Complications of Female Incontinence and Pelvic Reconstructive Surgery (Current Clinical Urology) 2nd ed.

20. Complications of Soft Tissue Bulking Agents Used in the Treatment of Urinary Leakage

Deborah J. Lightner  and John J. Knoedler1

(1)

Department of Urology, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA

Deborah J. Lightner

Email: lightner.deborah@mayo.edu

Abstract

Why are bulking agents used for stress urinary incontinence? Mentally-based urinary incontinence occurring with increases in intra-abdominal pressure is the sign qua non of stress urinary incontinence and results from urethral failure to resist increases in intra-abdominal pressure. The proximate cause may be related to poor anatomic support of the urethra and bladder neck; this generally responds well to pelvic floor resuspension procedures of various types. Urethral failure, however, may be also intrinsic, meaning the urethral closure pressure is inefficient at resisting increases in intra-abdominal pressures; this is generally treated with sphincter augmentation procedures, which include periurethral bulking agents [1]. Of course, while there is considerable overlap between these two causes of stress urinary incontinence, treatment success with bulking agents used in the patient with predominantly poor anatomic support do not differ markedly from the treatment success in the patient with predominantly intrinsic sphincteric deficiency (ISD) [2, 3]. Conventionally, however, the use of bulking agents is more widely applied if the urinary loss related to poor urethral function without hypermobility.

Introductory Comments

Why are bulking agents used for stress urinary incontinence? Meatally-based urinary incontinence occurring with increases in intra-abdominal pressure is the sign qua non of stress urinary incontinence and results from urethral failure to resist increases in intra-abdominal pressure. The proximate cause may be related to poor anatomic support of the urethra and bladder neck; this generally responds well to pelvic floor resuspension procedures of various types. Urethral failure, however, may be also intrinsic, meaning the urethral closure pressure is inefficient at resisting increases in intra-abdominal pressures; this is generally treated with sphincter augmentation procedures, which include periurethral bulking agents [1]. Of course, while there is considerable overlap between these two causes of stress urinary incontinence, treatment success with bulking agents used in the patient with predominantly poor anatomic support do not differ markedly from the treatment success in the patient with predominantly intrinsic sphincteric deficiency (ISD) [23]. Conventionally, however, the use of bulking agents is more widely applied if the urinary loss related to poor urethral function without hypermobility.

Due to the low long-term efficacy of these agents in the treatment of urinary incontinence, these agents are not frequently chosen as first line therapy. It is in the nuanced or more difficult clinical situation where these agents are considered: in the elderly [4], in the denervated sphincter of a spinal cord injured [56] or neobladder patient [7] who is leaking between catheterizations and/or is a Valsalva voider, in the multiply-operated urethra of a patient [8] who has failed multiple prior attempts at treatment, or has had partial urethrectomy [9], in the frozen pelvis and pipestem urethra after radiation therapy or for the patient in whom continence procedures have largely ameliorated his or her symptoms, but who still desires moderate improvement over his or her current level of continence [8]. Male patients with postprostatectomy incontinence may choose a bulking agent, carefully informed that the success rates are low [10]. Complications in each of these patient groups are of more consequence as appropriate and acceptable alternatives are few.

Bulking agents are used for soft tissue augmentation in many other specialties, including plastic surgery, dermatology, otolaryngology, and within urologic subspecialties, pediatric urology for ureteric reflux, in reconstructive urology for male sphincteric incontinence [1114] and in restoration of continence in catheterizable stomas [15]. There is renewed interest in bulking agents for fecal incontinence [16] and for GERD [17]. These soft tissue bulking agents continue to improve over their 70 year history. The commercially available agents currently are potentially more durable [18], generally safe, inducing a minimal local inflammatory reaction and with a low prevalence of significant adverse events.

The discussions herein will concentrate on the currently available FDA-approved bulking agents for periurethral use: calcium hydroxylapatite (Coaptite®, Merz Aesthetics, Inc., formerly BioForm Medical, Inc., Frankfurt, DE), pyrolytic carbon-coated zirconium beads (Durasphere® EXP, Carbon Medical Technologies, Inc., Saint Paul, MN, USA), and vulcanized silicone microimplant (Macroplastique®, Uroplasty, Inc., Minneapolis, MN, USA), each material purportedly forms a scaffold promoting secondary tissue infiltration with variable degrees of inflammatory reaction [1920] rather than the less desirable encapsulation [21], which risks extrusion [22]. The discontinuation of several older injected materials, including tetrafluoroethylene, autologous fat, and ethylene vinyl alcohol copolymer resulted from unreliable safety reports as well as the failure to deliver satisfactory rates of success [23]. They should not be used. Off-label use of other soft tissue bulking agents will be discussed to decry the practice.

Given these caveats of experience, the evaluation of future bulking agents, autologous myoblasts [24], or cartilage [25], or polyacrylamide hydrogel [26] (Bulkamid®, currently undergoing investigational studies, Contura International A/S, Soeborg, Denmark) should be subject to the same high degree of scrutiny regarding the unique complications related to the material as previous soft tissue bulking agents.

Of note, the complications seen in one surgical discipline generally mirror the experience of bulking agents across the spectrum of care. Polytetrafluoroethylene is one well-known example of granulomata formation [2730]. Local migration with radio-opaque carbon-coated zirconium beads is another [3133], although without clinical consequences. When considering newer periurethral agents, these should therefore be cross-linked for complications across specialties, as similar adverse events might occur in alternative applications.

Parenthetically, the discontinuation of Contigen (Bard™, Covington, GA, USA) was related to the lack of a primary supplier of the bovine product and neither due to lack of efficacy, nor significant complications with the material.

Complications from soft tissue bulking agents will be presented as local or systemic, acute or delayed in presentation, with emphasis on the extremely low risk of significant complications of any type.

Acute local complications of the current bulking agents used in a periurethral application are associated with very low rates of repetition complications. In 5–10% of patients, an uncomplicated or urinary tract infection from instrumentation, transient hematuria from the mucosal injection, transient urinary retention from periurethral edema can occur. A small French catheter is used if retention occurs, and applied for either intermittent catheterization or a short period of indwelling catheterization until resolution of this infrequent complication. Anecdotal concerns regarding the possible deformation of the injected bulking agents, leading to decreased efficacy, has lead to the recommendation that only a small French-sized catheter be used with acute transient urinary retention. As with any periurethral procedure for incontinence, there is an acceptable low incidence of de novo urge incontinence. In patients with either persistent acute urinary retention or secondary obstruction-related urge incontinence, the remote possibility of overbulking leading to obstruction should be considered. This can be treated early with simple aspiration [3435] with most agents. A transurethral approach is favored due to the theoretical, albeit never reported, risk of a secondary urethrovaginal fistula.

The type of complication is reported with periurethral bulking agents appear to be partially independent of the material used, in so far that local chronic complications of urethral prolapse, periurethral pseudoabscesses are reported in extremely low prevalence and are, at least, theoretically possible with each of these FDA-approved agents. This implies that some of these adverse events may be characteristic of the procedure and location and less likely resultant of the material.

Long-term local complications with the ­current commercially available bulking agents are also acceptably low and are reported only as small case series. A periurethral collection variously described as a pseudocyst [36] or pseudoabscess [37] or a noncommunicating diverticulum [38] each appear to reflect the same process and present with a palpable well circumscribed mass and secondary obstructive or irritative voiding symptoms. The mass may be tender or not. Several authors have reported that these collections may be infected [39], although the microbiological reports have not been conclusive. Imaging can be definitive [40] if clinically needed. Aspiration alone may lead to recurrence of the pseudoabscess, whereas transurethral unroofing of these periurethral masses is invariably associated with reoccurrence of their presenting symptom of stress urinary incontinence. The periurethral pseudocyst is thick-walled, containing cystic or loculated cavities which may or may not communicate with the urethral lumen; none have been associated with malignant or premalignant changes on explorations occurring up to 19 months postinjection [41]. Historically, pseudoabscess formation was thought secondary to delayed hypersensitivity to the bovine dermal product [42]; however, repeated skin tests do not show conversion [37]. Furthermore, pseudoabscesses can be reported with low prevalence with each of the bulking agents applied either peri- or transurethrally, suggesting that the etiology may be partially related to the specific urethral application. Consistent with this is the fact that pseudoabscess as described is not reported with either ureteral or dermatologic applications, although rarely, other local complication of overlying skin or mucosal erosion, and granulomata formation are common to each application site. Hence, the etiology of pseudoabscess remains enigmatic.

Pseudoabscess is described with virtually all bulking agents used in a periurethral application for stress urinary incontinence. This is not to discount that some agents are associated with this complication in an unacceptable percentage of those treated; dextranomer-hyaluronic acid is an agent particularly associated with granulomata [4344] and/or pseudoabscess formation [45].

The classical presentation of a pseudoabscess is outlined in this case: a otherwise healthy female with mixed urinary incontinence but without prior operative management opted for treatment of her stress urinary incontinence component with an injectable bulking agent; bovine glutaraldehyde-cross-linked collagen was chosen. After a negative skin test for bovine collagen allergy, a periurethral injection of a total of 5 cc was performed uneventfully. Six weeks later, she complained of terminal dysuria, her symptoms progressing rapidly to obstructive symptoms with straining to void, and increasing urethral discomfort and dysuria. Her physical examination demonstrated a large nonexpressible periurethral fluctuance. Urine analysis and urine culture were both negative for infection. Imaging demonstrated a large fluid collection periurethrally (Figs. 20.120.2, and 20.3).

A213469_1_En_20_Fig1_HTML.jpg

Fig. 20.1

CT imaging reveals a large periurethral fluid collection, Collagen pseudoabscesses can be challenging to diagnose on unenhanced CT imaging, the avascular fluid collection becomes readily apparent after administration of contrast agents. Also, the pseudoabscess is always considerably larger than the injected total bulking agent volume; these cases do not result from obstruction due to overbulking. Due to the acute nature of the process, the pseudoabscess was vaginally drained through a inverted-U incision, taking care to preserve the periurethral fascia. A simple longitudinal incision is made directly into the pseudoabscess, in order to establish complete drainage. The pseudoabscess fluid here is typical: nonodiferous viscous toothpaste-appearing fluid compresses adjacent tissues, with negative gram stains for bacteria and negative cultures even for fastidious organisms. The high pressures on the surrounding tissues are putatively the cause of the urethral pain, and reoccurrence of the pain should precipitate an evaluation for recurrence of the pseudoabscess (Image courtesy of Howard B. Goldman)

A213469_1_En_20_Fig2_HTML.jpg

Fig. 20.2

(a) An inverted-U incision for transvaginal drainage of a pseudoabscess assures a watertight ­secondary closure minimizing the risk of fistula. (b) The pseudoabscess should be expressed and drained completely; loculations can occur and should be adequately drained (Image courtesy of Howard B. Goldman)

A213469_1_En_20_Fig3_HTML.jpg

Fig. 20.3

Coronal image of a large periurethral pseudoabscess associated with obstructive voiding symptoms

Parenthetically, in this case, there was no pointing of the pseudoabscess towards the urethral lumen on cystoscopy as the cystoscopic presence of obvious thinning of the urethral luminal mucosa over pseudoabscess can facilitate performing a complete transurethral drainage of the pseudoabscess.

Pseudoabscess formation and subsequent drainage of the submucosal space into the true urethral lumen is the presumptive mechanism for another small set of chronic local complications: pseudodiverticulum formation [38].

Urethral prolapse has also been reported in case reports with several agents of both current and historic interest [4648]. Theoretically, this could occur with any bulking agent if it is causes separation of the supporting periurethral stroma. Treatment is local excision, if symptomatic.

Misdiagnosis of periurethral and bladder masses can occur if the history is not available [49]; imaging can be definitive [40].

Local tissue necrosis and subsequent erosion of the overlying mucosa has been described with a bulking agent leading to its removal from the market [2250]. Most currently available agents are rarely associated with this in small case series, as the submucosal injection may reduce blood supply to the thin overlying mucosal leading to erosion prior to tissue ingrowth. Fistulation to the vagina has been described [5152] as might occur rarely with any soft tissue expansion occurring in a limited space.

Chronic urinary retention may develop secondary to overbulking [5354]. The necessity of transurethral aspiration, or failing this, resection will lead to the reoccurrence of stress urinary incontinence. However, in the elderly, the author has seen the late development of urinary retention due to progressive loss of detrusor power, without intervening outlet obstruction or other complication of the outlet. These rare patients require treatment as clinically indicated for their detrusor failure; the bulking agent itself does not require other management.

Acute systemic complications are exceedingly rare. Any injected agent—injected at any pressure in juxtaposition to lymphatics or vessels—could be potentially migratory or embolic. Construction of bulking agents above a threshold size of 80 μm reduces but does not eliminate that potential risk [33]. There have been no reports of symptomatic embolic phenomenon with the currently available agents, in contradistinction to older agents, particularly dangerous is autologous fat [37]. The embolic and migratory potentials of agents injected adjacent to lymphatics and blood vessels has been a concern since the initial investigations of these agents [28]: it is generally accepted that bulking agents be larger than 80 μm in diameter to reduce the risk of these occurrences [55]. The injection of agents under pressure into a highly vascular area with abundant lymphatics is likely associated with migration and/or embolism, but clinical consequences have not been reported with Durasphere® EXP, Coaptite® or Macroplastique®. Asymptomatic particle migration, presumptively into lymphatics and submucosal tissues, has been described with those agents which are radiographically visible [33]. Submucosal urethral migration clearly occurs in men with traumatically injured sphincters treated with radiographically visible bulking agents, but these have a low therapeutic efficacy in this setting, limiting their use. Particle size is also directly related to phagocytic activity, with larger particle (herein, of Macroplastique) less likely to be phagocytosed [56]; there have been no clinically reported sequelae of this phenomenon.

There are no chronic systemic complications of soft tissue bulking agents reported, in large part because of the care taken to ensure that these agents are nonimmunogenic, hypoallergenic and biocompatible [21].

This is not to dismiss that fact that several agents are simply unsafe! Agents producing high-grade complications such as obstruction from the granulomata (as in polytetrafluoroethylene), truly embolic phenomenon (as in autologous fat [37]) should simply not be used. Likewise, agents with a high prevalence of adverse reactions (as in urethral erosion with ethylene vinyl alcohol copolymer [22], or pseudoabscess formation with dextranomer-hyaluronic acid [45]) should not be used, as has occurred with the use of these off-label.

In summary, the judicious use of the currently approved bulking agents, Coaptite, Durasphere, and Macroplastique, in the treatment of sphincteric incontinence are associated with an extremely low prevalence of local complications, the most serious of which occur chronically in the form of pseudoabscess formation and/or outlet obstruction. The treatment of these two complications is invariably associated with the reoccurrence of the urinary incontinence. The reader is cautioned that other bulking agents may not have the same clinical safety profile particularly when applied in the urethra; off-label use of other soft tissue bulking agents is specifically discouraged.

References

1.

Klarskov N, Lose G. Urethral injection therapy: what is the mechanism of action? Neurourol Urodyn. 2008;27(8):789–92.PubMedCrossRef

2.

Bent AE, Foote J, Siegel S, Faerber G, Chao R, Gormley EA. Collagen implant for treating stress urinary incontinence in women with urethral hypermobility. J Urol. 2001;166(4):1354–7.PubMedCrossRef

3.

Zullo MA, Plotti F, Bellati F, Muzii L, Angioli R, Panici PB. 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(3):898–902.PubMedCrossRef

4.

Zullo MA, Ruggiero A, Montera R, et al. An ultra-miniinvasive treatment for stress urinary incontinence in complicated older patients. Maturitas. 2010;65(3): 292–5.PubMedCrossRef

5.

Hamid R, Arya M, Khastgir J, Patel HRH, Shah PJR. The treatment of male stress urinary incontinence with polydimethylsiloxane in compliant bladders following spinal cord injury. Spinal Cord. 2003;41(5):286–9.PubMedCrossRef

6.

Bennett JK, Green BG, Foote JE, Gray M. Collagen injections for intrinsic sphincter deficiency in the neuropathic urethra. Paraplegia. 1995;33(12):697–700.PubMedCrossRef

7.

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(1):244–6.PubMedCrossRef

8.

Appell RA, Davila GW. Treatment options for patients with suboptimal response to surgery for stress urinary incontinence. Curr Med Res Opin. 2007;23(2):285–92.PubMedCrossRef

9.

Plotti F, Zullo MA, Palaia I, Angioli R, Panici PB. Urinary incontinence after radical vulvectomy treated with macroplastique implantation. J Minim Invasive Gynecol. 2008;15(1):113–5.PubMedCrossRef

10.

Comiter CV. Surgery insight: surgical management of postprostatectomy incontinence—the artificial urinary sphincter and male sling. Nat Clin Pract Urol. 2007;4(11):615–24.PubMedCrossRef

11.

Brown JA, Elliott DS, Barrett DM. Postprostatectomy urinary incontinence: a comparison of the cost of conservative versus surgical management. Urology. 1998;51(5):715–20.PubMedCrossRef

12.

Imamoglu MA, Tuygun C, Bakirtas H, Yigitbasi O, Kiper A. The comparison of artificial urinary sphincter implantation and endourethral macroplastique injection for the treatment of postprostatectomy incontinence. Eur Urol. 2005;47(2):209–13.PubMedCrossRef

13.

Kylmala T, Tainio H, Raitanen M, Tammela TLJ. Treatment of postoperative male urinary incontinence using transurethral macroplastique injections. J Endourol. 2003;17(2):113–5.PubMedCrossRef

14.

Westney OL, Bevan-Thomas R, Palmer JL, Cespedes RD, McGuire EJ. Transurethral collagen injections for male intrinsic sphincter deficiency: the University of Texas-Houston experience. J Urol. 2005;174(3):994–7.PubMedCrossRef

15.

Roth CC, Donovan BO, Tonkin JB, Klein JC, Frimberger D, Kropp BP. Endoscopic injection of submucosal bulking agents for the management of incontinent catheterizable channels. J Pediatr Urol. 2009;5(4):265–8.PubMedCrossRef

16.

Maeda Y, Laurberg S, Norton C. Perianal injectable bulking agents as treatment for faecal incontinence in adults. Cochrane Database Syst Rev. 2010(5): CD007959.

17.

Ganz RA, Fallon E, Wittchow T, Klein D. A new injectable agent for the treatment of GERD: results of the Durasphere pilot trial. Gastrointest Endosc. 2009;69(2):318–23.PubMedCrossRef

18.

Ghoniem G, Corcos J, Comiter C, Westney OL, Herschorn S. Durability of urethral bulking agent injection for female stress urinary incontinence: 2-year multicenter study results. J Urol. 2010;183(4):1444–9.PubMedCrossRef

19.

Stenberg A, Larsson E, Lackgren G. Endoscopic treatment with dextranomer-hyaluronic acid for vesicoureteral reflux: histological findings. J Urol. 2003;169(3):1109–13.PubMedCrossRef

20.

Radley SC, Chapple CR, Lee JA. Transurethral implantation of silicone polymer for stress incontinence: evaluation of a porcine model and mechanism of action in vivo. BJU Int. 2000;85(6):646–50.PubMedCrossRef

21.

Dmochowski RR, Appell RA. Injectable agents in the treatment of stress urinary incontinence in women: where are we now? Urology. 2000;56(6 Suppl 1):32–40.PubMedCrossRef

22.

Hurtado EA, McCrery RJ, Appell RA. Complications of ethylene vinyl alcohol copolymer as an intraurethral bulking agent in men with stress urinary incontinence. Urology. 2008;71(4):662–5.PubMedCrossRef

23.

Haab F, Zimmern PE, Leach GE. Urinary stress incontinence due to intrinsic sphincteric deficiency: experience with fat and collagen periurethral injections [Erratum appears in J Urol. 1997;158(1):188]. J Urol. 1997;157(4):1283–6.PubMedCrossRef

24.

Mitterberger M, Marksteiner R, Schwaiger W, et al. Can autologous myoblasts be used as a potential bulking agent? BJU Int. 2008;102(11):1731–6.PubMedCrossRef

25.

Bent AE, Tutrone RT, McLennan MT, Lloyd LK, Kennelly MJ, Badlani G. Treatment of intrinsic sphincter deficiency using autologous ear chondrocytes as a bulking agent. Neurourol Urodyn. 2001;20(2):157–65.PubMedCrossRef

26.

Lose G, Sorensen HC, Axelsen SM, Falconer C, Lobodasch K, Safwat T. An open multicenter study of polyacrylamide hydrogel (Bulkamid) for female stress and mixed urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2010;21(12):1471–7.CrossRef

27.

Aragona F, D’Urso L, Scremin E, Salmaso R, Glazel GP. Polytetrafluoroethylene giant granuloma and adenopathy: long-term complications following subureteral polytetrafluoroethylene injection for the treatment of vesicoureteral reflux in children. J Urol. 1997;158(4):1539–42.PubMedCrossRef

28.

Malizia Jr AA, Reiman HM, Myers RP, et al. Migration and granulomatous reaction after periurethral injection of polytef (Teflon). JAMA. 1984;251(24):3277–81.PubMedCrossRef

29.

Hubmer MG, Hoffmann C, Popper H, Scharnagl E. Expanded polytetrafluoroethylene threads for lip augmentation induce foreign body granulomatous reaction. Plast Reconstr Surg. 1999;103(4):1277–9.PubMedCrossRef

30.

Toth G, Rubeiz H, Macdonald RL. Polytetrafluoroethylene-induced granuloma and brainstem cyst after microvascular decompression for trigeminal neuralgia: case report. Neurosurgery. 2007;61(4):E875–7; discussion E877.

31.

Altomare DF, La Torre F, Rinaldi M, Binda GA, Pescatori M. Carbon-coated microbeads anal injection in outpatient treatment of minor fecal incontinence. Dis Colon Rectum. 2008;51(4):432–5.PubMedCrossRef

32.

Tjandra JJ, Chan MKY, Yeh HCH. Injectable silicone biomaterial (PTQ) is more effective than carbon-coated beads (Durasphere) in treating passive faecal incontinence—a randomized trial. Colorectal Dis. 2009;11(4):382–9.PubMedCrossRef

33.

Pannek J, Brands FH, Senge T. Particle migration after transurethral injection of carbon coated beads for stress urinary incontinence. J Urol. 2001;166(4):1350–3.PubMedCrossRef

34.

Petrou SP, Pak RW, Lightner DJ. Simple aspiration technique to address voiding dysfunction associated with transurethral injection of dextranomer/hyaluronic acid copolymer. Urology. 2006;68(1):186–8.PubMedCrossRef

35.

Hartanto VH, Lightner DJ, Nitti VW. Endoscopic evacuation of Durasphere. Urology. 2003;62(1): 135–7.PubMedCrossRef

36.

Wainstein MA, Klutke CG. Periurethral pseudocyst following cystoscopic collagen injection. Urology. 1998;51(5):835–6.PubMedCrossRef

37.

Sweat SD, Lightner DJ. Complications of sterile abscess formation and pulmonary embolism following periurethral bulking agents. J Urol. 1999;161(1): 93–6.PubMedCrossRef

38.

Clemens JQ, Bushman W. Urethral diverticulum following transurethral collagen injection. J Urol. 2001;166(2):626.PubMedCrossRef

39.

McLennan MT, Bent AE. Suburethral abscess: a complication of periurethral collagen injection therapy. Obstet Gynecol. 1998;92(4 Pt 2):650–2.PubMedCrossRef

40.

Bridges MD, Petrou SP, Lightner DJ. Urethral bulking agents: imaging review. AJR Am J Roentgenol. 2005;185(1):257–64.PubMed

41.

Leonard MP, Canning DA, Epstein JI, Gearhart JP, Jeffs RD. Local tissue reaction to the subureteral injection of glutaraldehyde cross-linked bovine collagen in humans. J Urol. 1990;143(6):1209–12.PubMed

42.

Hanke CW, Higley HR, Jolivette DM, Swanson NA, Stegman SJ. Abscess formation and local necrosis after treatment with Zyderm or Zyplast collagen implant. J Am Acad Dermatol. 1991;25(2 Pt 1): 319–26.PubMedCrossRef

43.

Bedir S, Kilciler M, Ozgok Y, Deveci G, Erduran D. Long-term complication due to dextranomer based implant: granuloma causing urinary obstruction. J Urol. 2004;172(1):247–8.PubMedCrossRef

44.

Abdelwahab HA, Ghoniem GM. Obstructive suburethral mass after transurethral injection of dextranomer/hyaluronic acid copolymer. Int Urogynecol J Pelvic Floor Dysfunct. 2007;18(11):1379–80.PubMedCrossRef

45.

Lightner DJ, Fox J, Klingele C. Cystoscopic injections of dextranomer hyaluronic acid into proximal urethra for urethral incompetence: efficacy and adverse outcomes. Urology. 2010;75(6):1310–4.PubMedCrossRef

46.

Ko EY, Williams BF, Petrou SP. Bulking agent induced early urethral prolapse after distal urethrectomy. Int Urogynecol J Pelvic Floor Dysfunct. 2007;18(12):1511–3.PubMedCrossRef

47.

Khalil A, Ghazeeri G, Chammas M, Usta I, Awwad J, Seoud M. Teflonoma presenting as a cystourethrocele. Clin Exp Obstet Gynecol. 2001;28(1):58–9.PubMed

48.

Harris RL, Cundiff GW, Coates KW, Addison WA, Bump RC. Urethral prolapse after collagen injection. Am J Obstet Gynecol. 1998;178(3):614–5.PubMedCrossRef

49.

Kulkarni S, Davies AJW, Treurnicht K, Dudderidge TJ, Al-Akraa M. Misplaced macroplastique injection presenting as a vaginal nodule and a bladder mass. Int J Clin Pract Suppl. 2005;147(Suppl):85–6.PubMedCrossRef

50.

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(8):869–73.PubMedCrossRef

51.

Carlin BI, Klutke CG. Development of urethrovaginal fistula following periurethral collagen injection. J Urol. 2000;164(1):124.PubMedCrossRef

52.

Pruthi RS, Petrus CD, Bundrick Jr WS. New onset vesicovaginal fistula after transurethral collagen injection in women who underwent cystectomy and orthotopic neobladder creation: presentation and definitive treatment. J Urol. 2000;164(5):1638–9.PubMedCrossRef

53.

Bernier PA, Zimmern PE, Saboorian MH, Chassagne S. Female outlet obstruction after repeated collagen injections. Urology. 1997;50(4):618–21.PubMedCrossRef

54.

McKinney CD, Gaffey MJ, Gillenwater JY. Bladder outlet obstruction after multiple periurethral polytetrafluoroethylene injections. J Urol. 1995;153(1):149–51.PubMedCrossRef

55.

Henly DR, Barrett DM, Weiland TL, O’Connor MK, Malizia AA, Wein AJ. Particulate silicone for use in periurethral injections: local tissue effects and search for migration. J Urol. 1995;153(6):2039–43.PubMedCrossRef

56.

Solomon LZ, Birch BR, Cooper AJ, Davies CL, Holmes SA. Nonhomologous bioinjectable materials in urology: ‘size matters’? BJU Int. 2000;85(6):641–5.PubMedCrossRef