Urethroplasty After Urethral Urolume Stent: An International Multicenter Experience

Accepted Manuscript Title: Urethroplasty after Urethral Urolume Stent: an International Multicenter Experience. Author: Javier C. Angulo, Sanjay Kulkarni, Joshi Pankaj, Dmitriy Nikolavsky, Pedro Suarez, Javier Belinky, Ramón Virasoro, Jessica DeLong, Francisco E. Martins, Nicolaas Lumen, Carlos Giudice, Oscar A. Suárez, Nicolás Menéndez, Leandro Capiel, Damian López-Alvarado, Erick A. Ramirez, Krishnan Venkatesan, Maha M. Husainat, Cristina Esquinas, Ignacio Arance, Reynaldo Gómez, Richard Santucci PII: DOI: Reference:

S0090-4295(18)30447-3 https://doi.org/10.1016/j.urology.2018.04.031 URL 21028

To appear in:

Urology

Received date: Accepted date:

22-3-2018 27-4-2018

Please cite this article as: Javier C. Angulo, Sanjay Kulkarni, Joshi Pankaj, Dmitriy Nikolavsky, Pedro Suarez, Javier Belinky, Ramón Virasoro, Jessica DeLong, Francisco E. Martins, Nicolaas Lumen, Carlos Giudice, Oscar A. Suárez, Nicolás Menéndez, Leandro Capiel, Damian LópezAlvarado, Erick A. Ramirez, Krishnan Venkatesan, Maha M. Husainat, Cristina Esquinas, Ignacio Arance, Reynaldo Gómez, Richard Santucci, Urethroplasty after Urethral Urolume Stent: an International Multicenter Experience., Urology (2018), https://doi.org/10.1016/j.urology.2018.04.031. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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TARGET JOURNAL: Urology TYPE OF ARTICLE: Original Article (Reconstructive Urology Section) TITLE:

Urethroplasty after urethral Urolume stent: an international multicenter

experience. AUTHORS: Javier C. Angulo (1), Sanjay Kulkarni (2), Joshi Pankaj (2), Dmitriy Nikolavsky (3), Pedro Suarez (4), Javier Belinky (5), Ramón Virasoro (6,7), Jessica DeLong (6), Francisco E. Martins (8), Nicolaas Lumen (9), Carlos Giudice (10), Oscar A. Suárez (11), Nicolás Menéndez (12), Leandro Capiel (7), Damian López-Alvarado (13), Erick A. Ramirez (13); Krishnan Venkatesan (14), Maha M. Husainat (15), Cristina Esquinas (1), Ignacio Arance (1), Reynaldo Gómez (16), Richard Santucci (15). AFFILIATION: (1) Departamento Clínico, Facultad de Ciencias Biomédicas, Universidad Europea de Madrid, Hospital Universitario de Getafe, Madrid, Spain; (2) Kulkarni Center for Reconstructive Urology, Pune, India; (3) SUNY Upstate Medical University, Syracuse, New York State, USA; (4) Sección Cirugía Reconstructiva Uretral. Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Argentina, Buenos Aires; (5) Hospital General de Agudos Carlos G. Durand, Buenos Aires, Argentina; (6) Eastern Virginia Medical School, Norfolk, Virginia, USA; (7) Centro de Educación Médica e Investigaciones Clínicas, Buenos Aires, Argentina; (8) Hospital de Santa María, Universidad de Lisboa, Lisboa, Portugal; (9) Ghent University Hospital, Ghent, Belgium; (10) Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; (11) Hospital San José Tecnológico de Monterrey, Universidad de Monterrey, Nuevo León, México; (12) Unidad Urológica Mar del Plata, Buenos Aires, Argentina; (13) Centro de Uretra Las Alamedas, México; (14) Washington Hospital Center, Washington, Philadelphia, USA; (15) Detroit Medical Center, Detroit Receiving Hospital, Detroit, Michigan, USA; (16) Hospital del Trabajador, Universidad Andrés Bello, Santiago de Chile, Chile. CORRESPONDENCE: Prof. Javier C. Angulo MD, PhD; Servicio de Urología, Hospital Universitario de Getafe, Carretera de Toledo Km 12.5, Getafe 28905, Madrid, Spain. E-mail: [email protected]; [email protected]

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SHORT TITLE: Urethroplasty after urethral stent WORD COUNT: 2.499 (Abstract 250 words excluded)

ACKNOWLEDGEMENTS: The authors acknowledge Mr. Juan Dorado (Análisis Estadísticos PerTICA S.L.) for statistical analysis, and Francisco Bulnes and Alberto Alós for bibliographical support. COMPETING INTERESTS: The authors have no competing interests. FUNDINGS: This study has no specific funding.

Abstract Purpose: To evaluate the outcomes and factors affecting success of urethroplasty in patients with stricture recurrence after Urolume® urethral stent. Material & Methods: Retrospective international multicenter study on patients treated with urethral reconstruction after Urolume® stent. Stricture and stent length, time between urethral stent insertion and urethroplasty, age, mode of stent retrieval, type of urethroplasty, complications and baseline and post-urethroplasty voiding parameters were analyzed. Successful outcome was defined as standard voiding, without need of any postoperative adjunctive procedure. Results: Sixty-three patients were included. Stent was removed at urethroplasty in 61 patients. Reconstruction technique was excision and primary anastomosis in 14(22.2%), dorsal onlay buccal mucosa graft (BMG) 9(14.3%), ventral onlay BMG 6(9.5%), dorsolateral onlay BMG 9(14.3%), ventral onlay plus dorsal inlay BMG 3(4.8%), augmented anastomosis 5(7.9%), pedicled flap urethroplasty 6(9.5%), 2-stage procedure 4(6.4%) and perineal urethrostomy 7(11.1%). Success rate was 81% at a mean 59.7+63.4months. Dilatation and/or internal urethrotomy was performed in 10(15.9%), redo-urethroplasty in 5(7.9%). Total IPSS, QoL, Qmax and PVR significantly improved (p<.0001).

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Complications occurred in 8(12.7%), all Clavien-Dindo <2. Disease-free survival rate after reconstruction was 88.1%,79.5% and 76.7% at 1,3 and 5-years respectively. Explant of individual strands followed by onlay BMG is the most common approach and was significantly advantageous over the other techniques (p=.018). Conclusions: Urethroplasty in patients with Urolume® urethral stents is a viable option of reconstruction with a high success rate and very acceptable complication rate. Numerous techniques are viable, however, urethral preservation, tine-by-tine stent extraction and use of BMG augmentation produced significantly better outcomes. KEYWORDS: Urethra, Stent, urethral stricture, Urethroplasty, Urolume

INTRODUCTION Urolume® urethral stent (American Medical Systems, Minnesota) was approved by the Food and Drug Administration in 1988 and distributed in many countries until 2011. Urolume stent placement was enthusiastically incorporated in the 1990’s as a minimally invasive therapy for recurrent bulbar strictures with promising early results in the absence of extensive periurethral fibrosis (1-4). However, long-term results showed progressive deterioration of the initial attractive results due to hyperplastic overgrowth with secondary restenosis, stent migration, encrustation, urinary infection and other side effects that impacted on quality of life including pain with erection and postvoid dribbling (5-7). At that time, most urologists erroneously believed the literature supported a reconstructive surgical ladder for urethral stricture management and urethroplasty, now readily accessible in most scenarios, was then too often performed only after repeat failure of endoscopic methods (8). The biocompatible, flexible and self-expanding Urolume endoprosthesis rapidly evolved to become an alternative to dilatation and internal urethrotomy for the treatment of recurrent bulbar strictures (9). After the initial excitement and widespread acceptance numerous centers reported on high recurrence and complication rates, and on the daunting task of dealing with removal of the

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embedded prosthesis. Treatment proposed for worsened stricture in seemingly devastated urethra was staged urethroplasty or even continent diversion (5,10). Currently, there is no consensus or agreement on a proper technique for repair of recurrent urethral stricture with retained Urolume endoprosthesis. The goal of this retrospective multi-institutional study is to analyze the outcomes of urethroplasty in this scenario and to compare various reconstructive options for treatment of recurrent stricture in patients with retained Urolume urethral stent. Our hypothesis is that urethroplasty involving stent retrieval in symptomatic patients is effective and safe, and that use of buccal mucosa tissue transfer techniques could facilitate a successful reconstruction in many of these cases. This multicenter international experience can be helpful for the reconstructive urologists that still today may face this infrequent challenging situation.

SUBJECTS AND METHODS Patient population and variables A retrospective fifteen-institution chart review was undertaken to analyze the records of all men with urethral stricture who had a Urolume endoprosthesis implanted with restenosis and complications leading to urethroplasty. Informed written consent was obtained and the study, approved by ethics committee (A05/17), was performed according to the Declaration of Helsinki. An institutionally approved database was used to collect data from patients treated with urethroplasty during the period 1995-2017. Inclusion criteria were male adults with symptomatic urethral stricture and previous Urolume implantation who decided to undergo definitive urethral reconstruction. Whenever possible, patients were contacted to confirm their consent to participate in the study and their follow-up was then updated. The patients included in this study were collected by contributing authors. All were identified and included by retrospective analysis of personal casuistry, with no specific procedure code and with no patient excluded for analysis. Exclusion criteria were patients with less than 6-month follow-up after surgery. All patients received urethroplasty, and the choice of repair was made

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according to surgeons’ preference and intraoperative findings regarding the amount of fibrosis and length of stricture. Successful outcome of urethroplasty was defined as ability to void, without need of any postoperative procedure including dilatation or DVIU and/or redo urethroplasty. We recorded birth date, reason to proceed with urethroplasty, length of stricture, date of stent insertion, site of the stent, length of the stent according to preoperative urethrocystogram, date of urethroplasty, mode of stent explant, type of urethroplasty performed, outcome measures before and after urethroplasy (IPSS, QoL, urine maximum flow and postvoid residual), proportion of patients with failed urethroplasty and time of follow-up. Postoperative 90-day complications (Clavien-Dindo) after urethroplasty were also recorded. Data were obtained from chart review. Post-operative voiding measurements recorded for comparison were those closest to 12 months after surgery. Statistical analysis Paired t-tests were used to compare preoperative and postoperative continuous variables. Wilcoxon signed-rank test was used to compare the preoperative and postoperative IPSS, QoL, Qmax and PVR. Chi-square contingency test and Fisher´s exact test compared differences between data, depending on scale of measure of evaluated variables. Survival analysis regarding urethroplasty failure was performed using KaplanMeier method with significance evaluated by two-sided log-rank test. Univariate and multivariate analysis was performed using hazard ratios and 95% Wald confidence limits for the variables investigated. The statistical analysis was developed using Statistical Analysis System 9.3 (SAS Institute Inc, Cary, NY, USA) and statistical significance was set at p<0.05 for all variables. RESULTS A total of 63 men with Urolume stent implant undergoing urethroplasty were included in the study. Table I represents the main clinical parameters evaluated. Seven patients (11.1%) had two stents placed, one immediately after the other in 5(7.9%) cases. Double stent was 3.0cm each in 5 cases (7.9%) and 2.5cm each in 2(3.2%). Single stent size was 3.0cm in 20(31.7%), 2.5cm in 16(25.4%), 2.0cm in 18(28.6%) and 1.5cm in

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2(3.2%). Sometimes recurrent bulbar stricture affected penile or membranous involvement. Mean time of stent duration before urethroplasty was 76.9+67.4 months (range 6-283). Prior data before urethral stent insertion such as initial stricture etiology or length were not available in most of the patients, because the stents were always inserted at other institutions. Stent was not removed at the time of urethroplasty in 2 cases (3.2%) because it was not considered necessary for a successful reconstruction as the stricture took place very close to but not contacting the stent, possibly due to long-standing stent migration or also to stricture disease progression distant to the stent. End-to-end anastomosis was performed in these patients. In the remaining 61(96.8%) the stent was removed at the time of urethroplasty, using either full-segment excision of the urethral segment containing the stent in 31 cases (49.2%) or through longitudinal section of the diseased segment and explant of individual metal strands in 30(47.6%). When explant was performed wire by wire, care was taken to remove the total 24 wires that compose a Urolume. In no case the stent was removed endoscopically. Choice of operative techniques The technique of urethroplasty was variable as can be expected from the experience of different surgeons through a long time-span, and due to individual patient and disease characteristics (Table I, Figure 1). The most commonly used procedure was excision and primary anastomosis (EPA), performed in 14 cases (22.2%). Pedicled flap urethroplasty using transverse island preputial skin flap was performed in 6(9.5%), complemented in 3 of these cases by dorsal onlay buccal mucosa graft (BMG). Augmented anastomotic urethroplasty using dorsal onlay BMG was used in 5(7.9%). Dorsal onlay BMG urethroplasty as described by Barbagli et al (11) was used in 9(14.3%). Ventral onlay BMG urethroplasty was performed in 6(9.5%), all with spongioplasty. Dorsolateral BMG using one-sided dissection according to Kulkarni et al (12) was used in 9(14.3%). A double BMG combining dorsal inlay plus ventral onlay was also used in 3(4.8%). Overall, BMG onlay-based primary reconstruction was used in 27(42.9%) of the patients. A 2-stage procedure with penile skin or BMG was performed in 4(6.4%) and definitive perineal urethrostomy was chosen in additional 7 cases (11.1%).

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The length of stricture was found significantly shorter (p=.003) in cases treated with EPA or augmented anastomosis (mean 3.2+1.7cm), compared to those treated with BMG onlay (4.5+2cm) and the rest of techniques (5+6cm). There was no association of other preoperative parameters with the choice of surgical techniques Surgical outcomes Total IPSS score, QoL, Qmax and PVR, expressed in median±intercuartile range, significantly improved (all p<.0001). IPSS score changed from 29±5.5 to 12±7 (∆IPSS 18.2±14.7); IPSS QoL from 5±1 to 1±1 (∆IPSS QoL -4±2); Qmax(ml/sec) from 4.2±5.4 to 16±6 (∆Qmax 13±7.8) and PVR(cc) from 180±160 to 33±70 (∆PVR -125±180). Age of the patient at the time of urethroplasty, type of stent, length of stent and surgical technique were not associated with differences in changes in voiding parameters. However, increasing length of stricture was inversely associated with an improvement in maximum flow rate (p=.036). Complications according to Clavien-Dindo classification occurred in 8 cases (12.7%), all minor (≤Grade2): postoperative urinary tract infection in 3 (4.8%), and upper digestive tract hemorrhage, deep venous thrombosis, urinary retention after surgery, urethrocutaneous fistula and hematoma in 1 case (1.6%) each. They were not associated with a particular technique. Risk of failure The net failure rate of urethroplasty in the series was 19% (12 cases), with dilatation and/or direct vision internal urethrotomy (DVIU) performed in 10(15.9%) and redo-urethroplasty in 5(7.9%) (3 cases underwent both). The failure rate differs among techniques (Fisher test, p<.0001) and those with highest success were BMG onlay and EPA, with 96.3 and 85.7% free of recurrence rate, respectively (Table II). Recurrence-free survival was 88.1%, 79.5% and 76.7% at 1, 3 and 5 years, respectively (Figure 1). No case failed after 4 years of surgery. Patient age at the time of urethroplasty (p=.53), length of stricture (p=.14) and length of stent (p=.11) did not affect the success of urethroplasty. However, a tendency for higher recurrence rate is observed in longer stents and longer strictures (Figure 2). Conversely, mode of stent retrieval was a

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predictive factor (p=.03) with full-segment urethral excision being at higher risk of recurrence than longitudinal urethral section and withdrawal of individual strands; HR=4.46 (95%CI 0.97-20-36). Stratification according to the surgical techniques used confirmed differences of statistical significance (p=.008). All binary combinations were tested but those that reached statistical significance were: BMG onlay vs. pedicled flap urethroplasty, favoring BMG onlay, HR=22.2 (95% CI 2.3-200); BMG onlay vs. perineal urethrostomy, again favoring BMG onlay, HR=12.9 (95% CI 1.35-125); and EPA vs. pedicled flap urethroplasty, favoring EPA, HR=6.6 (95% CI 1.1-40). In other words, BMG onlay behaved superiorly than pedicled flap urethroplasty and/or perineal urethrostomy, while EPA behaved superiorly than pedicled flap urethroplasty. When an individual technique was compared with the remaining pooled only one-stage procedure using onlay BMG after longitudinal section of the diseased segment and individual wire extraction revealed a statistically significant difference in recurrence-free survival (p=.018). Therefore, in univariate analysis BMG placement was a protective factor in the prediction of recurrence after treatment, HR=7.87 (95%CI 1.02-62.5). This effect was not observed when full segment excision and EPA was compared to the rest (p=.49) (Figure 2). Multivariate analysis revealed BMG onlay urethroplasty was the only independent protective factor against the recurrence in this series, HR=16.6 (95%CI 1.03-250). DISCUSSION Management of urethral stent failure for recurrent anterior urethral stricture is becoming an infrequent situation now that urethral stents are no longer used as primary treatment for urethral stenosis. Reported adverse events after stent placement included perineal pain, chronic urinary infections and sexual complaints (7,13). It is unknown how many stents have been explanted in the long term and there is no reliable data on contemporary patients with this type of endoprosthesis either. Our experience confirms a single-stage urethroplasty after stricture recurrence in these patients is a viable option with significantly-improved postoperative clinical and patient-reported outcomes, as well as acceptable long-term success rates.

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Technique of stent removal With respect to which is the most optimal way to extract the failed stent at the time of a definitive reconstruction the two options evaluated were en-block urethral excision vs urethral preservation and strands removal. Our study results suggest that enbloc segmental of the urethra should be avoided if possible and longitudinal section of the stented urethra with individual extraction of divided stent wires is advantageous. Reported histological changes associated with long-term stenting include severe polypoid hyperplasia and inflammatory infiltrate (9,16). This hyperplastic overgrowth cause restenosis either adjacent to or inside the prosthesis making interventions such as urethral dilatation or DVIU difficult (5,13).

Similarly, open stent explantation with

urethral reconstruction is a particularly challenging problem (7,14,15). The decision on how to perform stent retrieval can be difficult and management is usually decided on an individual basis, taking in consideration the degree of fibrosis, the length of the stricture and its concrete topography. The current study may help making informed decision in favor of the urethral preservation and against en-block urethra-stent resection Choice of Urethroplasty The optimal surgical technique to complete reconstruction after stent retrieval is another controversial matter. A wide variation of techniques has been described mainly dictated by the local circumstances and surgeons’ choice, and different alternatives for urethroplasty with stent removal appear valid options (14,15,17-20). Our study shows that on multivariate analysis BMG onlay urethroplasty is the most advantageous technique compared to EPA and fasciocutaneous flap repairs. Fisher and Santucci first described in 2006 a case treated with ventral onlay BMG urethroplasty with removal of the stent tine by tine as feasible option for a one-stage repair (18). Identification of the boundaries of the stricture was helped by catheter placement and flexible cystoscopy. The same year Zinman et al communicated simplified removal with urethral preservation and dorsal BMG onlay, thus also avoiding segmental urethrectomy (21). Gelman and Rodriguez reported 10 cases treated with different techniques and confirmed substitution dorsal onlay as a feasible option to plan a single-stage reconstruction even in longer strictures (19). Chapple and Bhargava reported a series of 14 patients and specified that

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the 4 cases treated with BMG onlay (3 dorsal, 1 ventral) were successful (15). Buckley and Zinman in 2012 reported the latest experience with removal of Urolume stent and simultaneous urethral reconstruction (22). They reported on 12 cases, 8 treated with BMG dorsal onlay, 3 with ventral onlay urethroplasty (with ancillary gracilis muscle flap in 2) and 1 perineal urethrostomy, with a global success rate of 83% at 4 years follow-up (22). In all cases the urethra was opened vertically over the stent and heavy scissors were used to cut directly down the stent length and the wires were removed without disrupting urethral integrity. Since then this approach avoiding segmental urethrectomy has gained popularity. Preservation of the affected segment and tine by tine extraction is the least invasive method of excision and allows a great range of substitution non-transecting reconstructive techniques using buccal mucosa. Dorsolateral dissection proposed by Kulkarni in BMG urethroplasty also allows the preservation of one-sided vascular supply to the urethra and its entire muscular and neurogenic support (12). As far as we know this is the first description of Kulkarni’s urethroplasty after stent retrieval (Appendix A, Supplementary Material). Limitations Our study is limited by its retrospective nature, and long time-span with large number of surgeons. Despite the great effort made for the multicenter collaboration total number of patients is still scarce for a large scale multivariate analysis. Also the patient cohort and treatment approaches vary greatly. In addition, the original etiology of the strictures requiring stent placement is unknown, and that could also affect the success rate of deferred urethroplasty. Besides, involvement of several surgeons with different surgical specificities may serve to capitalize on surgical skill diversity expertise. CONCLUSION To our knowledge we report the largest series with the longest follow-up of definitive urethral reconstruction after urethral stent explant, a disease that is fortunately disappearing. This multi-institutional experience confirms encouraging outcomes for urethroplasty in this situation. The issues raised still may help urologic reconstructive

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surgeons to make appropriate decisions to manage these patients. Although definite surgical decision must be individualized best results are associated to preservation of the urethra avoiding en-bloc removal of diseased tissue. Instead longitudinal section, tine by tine removal and reconstruction using onlay BMG urethroplasty is the most favorable option.

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REFERENCES 1. Milroy EJ, Chapple CR, Cooper JE, Eldin A, Wallsten H, Seddon AM, Rowles PM. A new treatment for urethral strictures. Lancet. 1988;1:1424-7. 2. Milroy EJ, Chapple C, Eldin A, Wallsten H. A new treatment for urethral strictures: a permanently implanted urethral stent. J Urol. 1989;141:1120-2. 3. Chapple CR, Rickards D, Milroy EJG. Permanently implanted urethral stents. Semin Intervent Radiol. 1991;8:284-94. 4. Milroy E, Allen A. Long-term results of urolume urethral stent for recurrent urethral strictures. J Urol. 1996;155:904-8. 5. Hussain M, Greenwell TJ, Shah J, Mundy A. Long-term results of a self-expanding wallstent in the treatment of urethral stricture. BJU Int. 2004;94:1037-9. 6. Baert L, Verhamme L, Van Poppel H, Vandeursen H, Baert J. Long-term consequences of urethral stents. J Urol. 1993;150:853-5. 7. Palminteri E, Gacci M, Berdondini E, Poluzzi M, Franco G, Gentile V. Management of urethral stent failure for recurrent anterior urethral strictures. Eur Urol. 2010;57:61521. 8. Bullock TL, Brandes SB. Adult anterior urethral strictures: a national practice patterns survey of board certified urologists in the United States. J Urol. 2007;177:685-90. 9. Badlani GH, Press SM, Defalco A, Oesterling JE, Smith AD. Urolume endourethral prosthesis for the treatment of urethral stricture disease: long-term results of the North American Multicenter UroLume Trial. Urology. 1995;45:846-56. 10. Shah DK, Kapoor R, Badlani GH; North American Study Group. Experience with urethral stent explantation. J Urol. 2003;169:1398-400.

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11. Barbagli G, Sansalone S, Kulkarni SB, Romano G, Lazzeri M. Dorsal onlay oral mucosal graft bulbar urethroplasty. BJU Int. 2012;109:1728-41. 12. Kulkarni S, Barbagli G, Sansalone S, Lazzeri M. One-sided anterior urethroplasty: a new dorsal onlay graft technique. BJU Int. 2009;104:1150-5. 13. Wilson TS, Lemack GE, Dmochowski RR. UroLume stents: lessons learned. J Urol. 2002;167:2477-80. 14. Eisenberg ML, Elliott SP, McAninch JW. Management of restenosis after urethral stent placement. J Urol. 2008;179:991-5. 15. Chapple CR, Bhargava S. Management of the failure of a permanently implanted urethral stent-a therapeutic challenge. Eur Urol. 2008;54:665-70. 16. Bailey DM, Foley SJ, McFarlane JP, O'Neil G, Parkinson MC, Shah PJ. Histological changes associated with long-term urethral stents. Br J Urol. 1998;81:745-9. 17. Parsons JK, Wright EJ. Extraction of UroLume endoprostheses with one-stage urethral reconstruction. Urology. 2004;64:582-4. 18. Fisher MB, Santucci RA. Extraction of UroLume endoprosthesis with one-stage urethral reconstruction using buccal mucosa. Urology. 2006;67:423.e9-423.e10. 19. Gelman J, Rodriguez E Jr. One-stage urethral reconstruction for stricture recurrence after urethral stent placement. J Urol. 2007;177:188-91. 20. Elkassaby AA, Al-Kandari AM, Shokeir AA. The surgical management of obstructive stents used for urethral strictures. J Urol. 2007;178:204-7. 21. Zinman LN, Stoffel JT and Malone M. Simplified UroLume stent removal with urethral preservation and dorsal buccal graft onlay (or without segmental urethrectomy). J Urol, suppl., 2006;175:40, abstract 124.

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22. Buckley JC, Zinman LN. Removal of endoprosthesis with urethral preservation and simultaneous urethral reconstruction. J Urol. 2012;188:856-60.

LEGENDS TO THE FIGURE Figure 1. Two examples of different surgical approach: en-bloc segmental resection followed by augmented anastomotic urethroplasty (A-C) and Kulkarni one-sided dissection with dorsolateral BMG graft after tine-by-tine extraction (D-F). Figure 2. Ten-year failure-free survival rate of urethroplasty: (A) total series; (B) length of stricture; (C) mode of stent retrieval; (D) different techniques of urethroplasty; (E) patients treated with buccal mucosal graft onlay vs. pooled patients treated with other types of urethroplasty; (F) patients treated with excision and primary anastomosis vs. pooled patients treated with other types of urethroplasty.

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Table 1. Descriptive data of patients included in the study Clinical parameter n (%) Total series Mean age+SD, years Mean stricture length+SD, cm Main reason of removal Recurrent stricture Urinary infection Perineal pain Urinary retention Urethral bleeding Site of urethra affected Penile urethra Bulbar urethra Membranous urethra Number of stents Single Double Mode of explant No removal Full segment excision Section and individual wire extraction Type of urethroplasty Excision primary anastomoses Augmented anastomotic Dorsal onlay BMG Ventral onlay BMG Dorsolateral onlay BMG Double dorsal onlay ± ventral inlay BMG Pedicled flap ± dorsal BMG 2-stage reconstruction Perineal urethroplasty Mean follow-up ± SD,months Urethral dilatation ± DVIU Yes No Redo urethroplasty Yes No Failure Yes No

63 (100) 60.9 ± 9.4 4.1 ± 2.1 55 (87.3) 16 (25.4) 14 (22.2) 11 (17.5) 2 (3.2) 5 (7.8) 60 (93.7) 8 (12.5) 7 (11.1) 56 (88.9) 2 (3.2) 31 (49.2) 30 (47.6) 14 (22.2) 5 (7.9) 9 (14.3) 6 (9.5) 9 (14.3) 3 (4.8) 6 (9.5) 4 (6.4) 7 (11.1) 59.7 ± 63.4 10 (15.9) 53 (84.1) 5 (7.9) 58 (92.1) 12 (19.05) 51 (80.95)

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Table II: Success and failure rate of urethroplasty for each technique used. Excision Buccal mucosa Augmented Perineal primary Pedicled flap 2-stage repair graft onlay (*) anastomotic urethroplasty anastomoses

TOTAL

n

%

N

%

n

%

n

%

N

%

n

%

n

%

26

96.3

12

85.7

4

80

3

50

2

50

4

57.1

51

80.95

Failure

1

3.7

2

14.3

1

20

3

50

2

50

3

42.9

12

19.05

TOTAL

27

100

14

100

5

100

6

100

4

100

7

100

63

100

Success

(*) Different types of buccal mucosa graft onlay (dorsal, ventral, lateral, ventral plus dorsal) grouped vs. rest: Fisher exact test; p<.0001

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SUPPLEMENTARY MATERIAL Appendix A: Video showing urethral reconstruction in a patient with two Urolume stents. One-sided dorsolateral dissection with longitudinal urethral section and tine-by-tine wire removal was followed by dorsolateral buccal mucosa graft repair following Kulkarni’s technique.

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Figure 1.tif

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Figure 2 corrected.tif

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