- Email: [email protected]
A Critical Analysis of Bulbar Urethroplasty Stricture Recurrence: Characteristics and Management
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A Critical Analysis of Bulbar Urethroplasty Stricture Recurrence: Characteristics and Management Arman A. Kahokehr,*,† Michael A. Granieri, George D. Webster and Andrew C. Peterson From the Division of Urology, Duke University Medical Center, Durham, North Carolina, and New York University School of Medicine (MAG), New York, New York
Purpose: We evaluated the management of recurrent bulbar urethral stricture disease after urethroplasty at our institution. Materials and Methods: We performed an institution review board approved, retrospective case study of our urethroplasty database to collect stricture related and postoperative information with an emphasis on bulbar urethral stricture disease recurrence after urethroplasty between 1996 and 2012. Repair types included primary anastomotic, augmented anastomotic and onlay repair. Recurrence, which was defined as the need for intervention, was diagnosed with cystoscopy or retrograde urethrogram. Results: We identified 437 men who underwent urethroplasty of bulbar urethral stricture disease as performed by 2 surgeons from January 1996 to December 2012. Of the men 395 had available followup data. Recurrence was identified in 25 men (6.3%), of whom all presented with symptoms, including a weak stream in 23, urinary tract infection in 1 and pyelonephritis in 1. Median time to recurrence was 10 months. Recurrence was initially treated endoscopically in 23 of 25 cases (92%), dilatation in 12 and visual urethrotomy in 11. In 5 patients (22%) further recurrence developed after endoscopic treatment, which was managed by repeat urethroplasty in 2, self-calibration only in 2 and visual urethrotomy with subsequent self-calibration in 1. We identified 2 distinct phenotypes of recurrent stricture, including type Adshort focal recurrence, which may be salvaged with an endoscopic procedure, and type Bdthe long graft length type, which is less likely to be salvaged with endoscopy. Conclusions: Recurrence after urethroplasty is most likely to develop within the first 12 months. Type A short focal recurrence may be managed by a salvage endoscopic procedure, including dilation or visual urethrotomy. These data on the phenotype of recurrence may be useful for patient treatment. Key Words: urethral stricture, recurrence, mouth mucosa, tissue transplantation, salvage therapy
URETHROPLASTY is a highly successful treatment of BUSD with previously published recurrence rates ranging from 3% to 16.5% based on study setting and surgery complexity.1,2 Management of recurrence includes endoscopic treatment such as dilation
or DVIU and open surgical options such as repeat urethroplasty. However, there is no consensus on the management of recurrent stricture following urethral reconstruction of BUSD. It was postulated that recurrence after urethroplasty of BUSD
0022-5347/18/2006-0001/0 THE JOURNAL OF UROLOGY® Ó 2018 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
Dochead: Adult Urology
https://doi.org/10.1016/j.juro.2018.07.036 Vol. 200, 1-6, December 2018 Printed in U.S.A.
Abbreviations and Acronyms AAR ¼ augmented anastomotic repair BUSD ¼ bulbar urethral stricture disease DVIU ¼ direct visual internal urethrotomy EPA ¼ excision and primary anastomosis RUG ¼ retrograde urethrogram Accepted for publication July 2, 2018. No direct or indirect commercial incentive associated with publishing this article. The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. * Correspondence: Divisions of Urologic Surgery and Reconstructive Urology, Duke University Medical Center, 40 Duke Medicine Circle, DUMC Box 3146, Durham, North Carolina 27710 (telephone: 919-684-2516; FAX: 919-668-0321; e-mail: [email protected]). † Supported by a Boston Scientific research grant.
Editor’s Note: This article is the of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages and .
www.jurology.com
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BULBAR URETHROPLASTY STRICTURE RECURRENCE
may be located at the proximal or the distal anastomotic locations, often consisting of short annular fibrous rings.3 Our subjective clinical experience indicated that these recurrences can often be successfully managed by endoscopic techniques since the prior repair addressed the underlying diseased urethra and spongiofibrosis when present. We hypothesized that there may be different types of recurrent stricture phenotypes after urethroplasty for BUSD, which may be related to the success of managing these recurrences. The goal of this study was to assess our experience with the management of recurrence after urethroplasty of BUSD and examine recurrence characteristics and treatment outcomes.
Earlier in the series penile skin was also used for grafting, if available. It was harvested longitudinally along the ventral aspect of the penis and the defect was closed primarily. However, buccal mucosa is the preferred graft. It is harvested by the urologist and the defect is closed primarily. For long strictures without nearly or completely obliterated segments the onlay graft is placed dorsally as previously described,5 although in select cases ventral onlay grafting was also performed. Graft fixation and anastomosis are performed with interrupted 5-zero polyglactin. Muscle, Colles fascia, subcutaneous and skin tissues are closed with interrupted 4-zero polyglactin. No drain is placed.
Followup
We collected detailed data on each case. Data included patient demographics, stricture location and type, surgical repair type, postoperative complications, stricture related recurrence and detailed analysis of information from postoperative followup visits.
Pericatheter RUG was routinely performed approximately 2 to 3 weeks postoperatively. Following removal of the urethral catheter the patients returned at 3 and 12 months, and were offered an annual clinical visit thereafter. A symptom based followup protocol was established at Duke University. Assessment including the I-PSS (International Prostate Symptom score), the flow rate and post-void residual urine volume was performed routinely at each visit. If any symptoms such as urinary tract infection, a weak stream, etc were experienced, patients were seen sooner than scheduled. Patients were strongly encouraged to return to the clinic on an annual basis. When symptoms were identified, diagnostic office urethrocystoscopy and/or RUG was performed. Further investigation was tailored based on the clinical picture. The decision to perform the first initial salvage procedure was based on clinician preference since outcomes are similar after DVIU and dilation.6
Definition
Statistics
Stricture recurrence was defined as the need for further intervention in the postoperative period as diagnosed with cystoscopy and/or RUG. When symptoms suggestive of recurrence were suspected, urethrocystoscopy was usually initially performed. This was tailored based on patient symptom development and on the time line since urethroplasty. If the information required was not determined, this was always followed by the other synergistic test.
Summary statistics are used to describe baseline characteristics. For nonparametric data the Mann-Whitney U test was used for unpaired independent samples. The Fisher exact or chi-square test was applied for categorical data and the 2-tailed test was used as appropriate. Statistical significance was considered at p <0.05 and analysis was performed with JMPÒ, version 13.
METHODS Patients We performed an institutional review board approved study of the Duke Urethroplasty Database of all patients who underwent urethroplasty of BUSD at our institution from January 1996 to December 2012 as performed by 2 surgeons. Repair types included EPA, AAR and onlay repair.
Data Collection
RESULTS
Operative Technique Intraurethral methylene blue is instilled routinely at the start of the case. The bulbospongiosus muscle is split in the midline. Intraoperative stricture length is recorded and a 20Fr urethral catheter is used to define the distal aspect of the stricture. EPA is performed based on the ability to construct a tension-free anastomosis. For longer strictures not amenable to EPA with a nearly or completely obliterated segment the diseased urethral tissue is excised and augmented anastomotic repair is done with substitution tissue as described previously.4 We first described augmented anastomotic repair in 2001. In this technique the nearly or completely obliterated portion is excised since this is important to prevent restenosis. The remaining nonobliterated stricture is widened by onlay substitution repair. This is a versatile repair technique. The graft was placed dorsally in most patients, although ventral onlay was performed in select patients. Dochead: Adult Urology
We limited our analysis to patients who underwent only bulbar urethral stricture repairs, excluding those with posterior, pendulous or meatal stricture disease as well as patients who presented with lichen sclerosus. During the study period 437 men underwent bulbar urethroplasty for BUSD as performed by a total of 2 surgeons. Followup data were available on 407 men (93%) but in 12 it could not be determined whether recurrence had developed. Median followup following initial urethroplasty surgery was 28 months (mean 25.7, range 3 to 112). Recurrence was identified in 25 of the 395 men (6.3%). All recurrences were identified by worsening symptoms, including a weak stream in 23 cases, urinary tract infection in 1 and pyelonephritis in 1. Median time to recurrence was 10 months (fig. 1).
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172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 ½F1 228
BULBAR URETHROPLASTY STRICTURE RECURRENCE
3
N
286 229 14 13 287 230 12 288 231 289 232 10 290 233 291 234 8 292 235 293 236 6 5 294 237 4 295 238 3 296 239 2 1 1 1 1 297 240 0 0 0 0 298 241 0 299 242 300 243 301 244 302 245 me since urethroplasty (months) 303 246 304 247 Figure 1. Months to diagnosed recurrence after bulbar urethroplasty. N, 25 patients. 305 248 306 249 307 250 Six of these 25 patients (24%) were treated with procedure had originally undergone more complex 308 251 urethroplasty in the past. The repair types associinitial urethroplasty (eg requiring substitution). 309 252 ated with recurrence were EPA in 10 men (40%), 310 253 AAR in 13 (52%) and ventral onlay repair in 2 (8%). 311 254 Recurrence was diagnosed by RUG and cystoscopy DISCUSSION 312 255 in 21 cases and by cystoscopy alone in 4. The 6.3% recurrence rate reported in our database 313 256 Table 1 shows demographic factors in patients ½T1 mirrors the rates currently reported in the contem314 257 with treatment success and those with recurrence. porary literature.7 Additionally, our experience in315 258 Stricture etiology varied between the groups with a dicates that a short and/or focal recurrence after 316 259 higher proportion of idiopathic, infective and radibulbar urethroplasty may be initially managed by 317 260 ation induced strictures in men who experienced various endoscopic techniques such as dilation or 318 261 recurrence (p ¼ 0.001). Most grafts were placed DVIU with an acceptable success rates. In this series 319 262 dorsally, given our extensive experience with this success was noted in 18 of 23 cases at a mean fol320 263 type of repair and ventrally placed grafts were lowup of 26 months. However, in men with a longer 321 264 associated with a higher recurrence rate (p ¼ 0.007). recurrence salvage with dilatation or DVIU is less 322 265 However, the overall low number of ventral repair likely to be successful, although repeat urethroplasty 323 266 in this series must be considered. is feasible. 324 267 Recurrence was initially treated endoscopically in Upon retrospective review it appeared that there 325 268 23 of 25 cases (92%), including dilation in 12 and DVIU are 2 distinct phenotypes of recurrent stricture, that 326 269 in 11. One patient was treated elsewhere and 1 elected is types A and B. Type A recurrence is a short focal 327 270 perineal urethrostomy due to multiple previous operrecurrence that is likely at the location of an anas328 271 ations. Mean followup after recurrence treatment was tomosis made during the original urethroplasty (fig. 329 272 26 months (median 11, range 3 to 127). Recurrence 2). This type presented earlier in our experience and ½F2 330 273 developed after endoscopic treatment in 5 patients in this analysis it represented a favorable prognosis 331 274 (22%), which was managed by successful repeat urefor a salvage endoscopic procedure. We believe that 332 275 throplasty in 2, self-calibration alone in 2, and visual this type is due to the excision of spongiofibrosis at 333 276 urethrotomy and subsequent self-calibration in 1. the time of urethroplasty, which we perform in most 334 277 Table 2 shows the characteristics of the 23 patients ½T2 cases. It leads to a less dense stricture upon recur335 278 who underwent a salvage procedure. Comparing rence at the anastomosis, which is likely a technical 336 279 recurrent stricture length in the 18 men in whom issue or other. Therefore, it may be more amenable 337 280 endoscopic intervention was successful vs the 5 in to endoscopic treatment after the recurrence is 338 281 whom it failed revealed that those in whom recurrence diagnosed clinically. 339 282 developed had longer strictures which presented later. Type B recurrence develops almost exclusively 340 283 However, the difference was not significant. Those in when substitution was performed. It is longer and 341 284 whom a repeat stricture developed after a salvage appears along part or all of the graft length and is 342 285 Dochead: Adult Urology
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BULBAR URETHROPLASTY STRICTURE RECURRENCE
Table 1 Recurrent Stricture
No. pts Median age (range) No. tobacco use: Current or prior Never Unknown No. etiology:* Idiopathic Trauma Infection Radiation Iatrogenic No. diabetes mellitus: Yes No Unknown Median stricture length (range): Excision þ primary anastomosis Augmented anastomotic repair Onlay No. prior endoscopic treatments: 0 1 More than 1 (range) No. urethroplasty type: Excision þ primary anastomosis Augmented anastomotic repair Onlay No. graft location: Ventral Dorsal No. graft type: Buccal mucosa Penile skin Preputial skin No. extravasation: Retrograde urethrogram 1 Retrograde urethrogram 2 Median mos to recurrence (range) No. recurrence symptom: Urinary tract infection Pyelonephritis Voiding symptoms
Yes
No
p Value
25 48 (17e68)
370 43 (10e85)
e 0.167 (Mann-Whitney U test)
3 15 7
36 174 160
0.327
(chi-square test)
16 3 4 2 0
199 83 16 3 52
0.001
(chi-square test)
2 15 8 2 1.2 3.0 3.5
0.473
(chi-square test)
(1e5) (1e2) (1e5) (2e5)
18 191 161 2 1.0 2.0 2.5
(2e6)
21 106 243
1 16 18
(0.5e6) (0.5e3) (1e7) (2e4)
0.43 (Mann-Whitney U test)
0.803
(chi-square test)
(2e21)
10 13 2
216 133 21
0.118
(chi-square test)
4 11
6 148
0.007
(chi-square test)
8 7 0
114 38 2
0.049
(chi-square test)
19 1 Not applicable Not applicable
0.633
(Fisher exact test)
2 0 10 (2e112) 1 1 23
* No recurrent stricture in 353 patients and no patient had lichen sclerosis.
likely due to ischemic contracture (fig. 3). This type seems to present later and it is less likely to be salvaged by endoscopy (table 2). When deciding on the best initial salvage procedure after urethroplasty recurrence, these hypothesis generating data on the distinct phenotype of recurrence may be useful for patient treatment. For example, if there are 2 focal point strictures at the end of each anastomosis following substitution, this would be considered a long stricture according to some classifications. However, because this type of recurrence is likely to respond well to endoscopic management, it would be best categorized as 2 type A phenotypes as the graft length has not contracted due to ischemia. Growing data and guidelines support urethroplasty following an initial endoscopic treatment Dochead: Adult Urology
(DVIU or dilation) in previously untreated urethral stricture disease since ongoing further endoscopic treatment is unlikely to be successful.8e10 However, there are less data on managing recurrence after urethroplasty of BUSD. An initial salvage endoscopic procedure has a reasonable but not a perfect success rate. Because redo urethroplasty offers excellent durable results,11,12 some experts advocate proceeding directly to repeat urethroplasty after recurrence. However, when faced with a disappointed patient, it may be best to use a risk based strategy associated with the described type A vs B phenotypes as endoscopic salvage procedures have a reasonable success rate, however imperfect.13,14 It has been shown that when looking at salvage urethroplasty after all types of previous anterior urethra repairs, a higher risk of
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BULBAR URETHROPLASTY STRICTURE RECURRENCE
457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513
Table 2. Characteristics of 23 patients with recurrent stricture treated with endoscopic DVIU or dilation salvage procedure after bulbar urethroplasty Repeat Recurrence
No. pts Mean SD stricture length (cm) Mean SD stricture diagnosis after initial urethroplasty (mos) No. repair: Excision þ primary anastomosis Augmented anastomotic repair Onlay No. graft type: Buccal mucosa Penile skin No. graft technique: Dorsal Ventral
No
Yes
18 0.5 0.72 9.8 19.6
5 3.5 3.5 27 26.3
9 9 0
1 2 2
4 5
2 2
7 2
2 2
failure was associated with hypospadias related strictures, lichen sclerosis and 2 or more previously failed open surgeries.15 In a landmark study of the specifics of recurrent stricture disease following bulbar urethroplasty 22 patients (20%) were carefully analyzed using retrograde urethrogram, ultrasound and urethroscopy.3 Nearly 45% of recurrences were due to short (less than 1 cm) annular fibrosis at the proximal or distal anastomotic site, in contrast to a recurrence along an entire graft length. The investigators moved away from redo open reconstruction in this select group to DVIU of these shorter anastomotic recurrences once this difference in recurrence was recognized. Outcomes were successful outcomes in the majority of cases. In the current study we were able to present this principle by reviewing the outcomes of minimally invasive salvage procedure based on recurrence characteristics. Overall the literature suggests that all repeat urethroplasties of all anterior urethral recurrences, bulbar and pendulous combined, are associated with
5
a success rate of about 75%.16 We believe that since the data indicate a reasonable outcome in highly selected patients who undergo endoscopic treatment of type A recurrence, this is an appropriate first step in managing these recurrent strictures. Our clinical experience indicates that many patients with recurrence after definitive primary anastomotic or augmented urethroplasty prefer minimally invasive salvage, given the disadvantages of repeat open surgery. Based on the current data it appears that men with type A recurrence may do well with endoscopic intervention, abrogating the need for repeat open surgical intervention. When recurrence was defined and detected using routine flexible urethroscopy in all men whether or not they were symptomatic, a recent report concluded that DVIU seemed to perform better than dilation at a median of 5 months of followup.17 We await a longer followup date. In our study we found that patients with recurrence were more likely to have infective or radiotherapy induced strictures compared to those without recurrence. It was reported that infectious strictures are an independent risk factor for stricture recurrence following bulbar urethroplasty.7 It is possible that infection and radiation induced strictures are more likely associated with poor tissue integrity and, thus, with a higher risk of failed reconstruction and failed graft take. Limitations This study is limited due to the retrospective nature of the data collection, which may include recall bias during followup. In addition, many patients traveled for definitive treatment and chose to have additional long-term followup closer to the place of residence, making the attrition rate higher than desired. We did not perform routine urethrocystoscopy at our institution at the time that these urethroplasties were performed. Because routine urethrocystoscopy is currently not standardized or
Figure 2. Retrograde urethrogram shows short, type A annular recurrence 3 months after AAR repair with buccal mucosa. Patient underwent salvage DVIU with no further recurrence. A, before urethroplasty. B, recurrence after urethroplasty.
Dochead: Adult Urology
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571 572 573 574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589 590 591 592 593 594 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 611 612 613 614 615 616 617 618 619 620 621 622 623 624 625 626 627 628 629 630 631 632
BULBAR URETHROPLASTY STRICTURE RECURRENCE
Figure 3. Retrograde urethrogram shows type B recurrence in patient with total of 6 prior failed multiple DVIUs plus dilations. AAR was done with penile skin and there was long recurrence along substitution length after 1 salvage DVIU. Patient performs self-calibration. A, before urethroplasty. B, recurrence after urethroplasty.
widely accepted, we currently perform a risk based approach. Furthermore, all urethroplasties and recurrence treatments were performed by 2 surgeons at 1 institution. Thus, we are aware that technical and treatment details do not reflect those at other centers specializing in BUSD treatment. Finally, we did not treat patients with lichen sclerosis as the primary etiology as the focus was on bulbar urethral stricture disease. Despite these limitations this study was based on a large cohort of patients who underwent urethroplasty and treatment of recurrence at a single tertiary center
where there is extensive urethroplasty experience. This enabled accurate evaluation of the recurrence incidence and of treatment outcomes.
CONCLUSIONS Recurrent urethral stricture following urethroplasty for BUSD may be managed by an endoscopic intervention such as dilation or DVIU with good success in most patients. Further research is needed to understand the distinct forms of recurrent stricture after urethroplasty.
REFERENCES 1. Hoy NY, Kinnaird A and Rourke KF: Expanded use of a dorsal onlay augmented anastomotic urethroplasty with buccal mucosa for long segment bulbar urethral strictures: analysis of outcomes and complications. Urology 2013; 81: 1357. 2. Barbagli G, Guazzoni G and Lazzeri M: One-stage bulbar urethroplasty: retrospective analysis of the results in 375 patients. Eur Urol 2008; 53: 828. 3. Barbagli G, Guazzoni G, Palminteri E et al: Anastomotic fibrous ring as cause of stricture recurrence after bulbar onlay graft urethroplasty. J Urol 2006; 176: 614. 4. Guralnick ML and Webster GD: The augmented anastomotic urethroplasty: indications and outcome in 29 patients. J Urol 2001; 165: 1496. 5. Barbagli G, Selli C, Tosto A et al: Dorsal free graft urethroplasty. J Urol 1996; 155: 123. 6. Steenkamp JW, Heyns CF and de Kock ML: Internal urethrotomy versus dilation as treatment for male urethral strictures: a prospective, randomized comparison. J Urol 1997; 157: 98.
Dochead: Adult Urology
7. Chapman D, Kinnaird A and Rourke K: Independent predictors of stricture recurrence following urethroplasty for isolated bulbar urethral strictures. J Urol 2017; 198: 1107. 8. Wessells H, Angermeier KW, Elliott S et al: Male urethral stricture: AUA guideline. J Urol 2017; 197: 182. 9. Greenwell TJ, Castle C, Andrich DE et al: Repeat urethrotomy and dilation for the treatment of urethral stricture are neither clinically effective nor cost-effective. J Urol 2004; 172: 275. 10. Heyns CF, Steenkamp JW, De Kock ML et al: Treatment of male urethral strictures: is repeated dilation or internal urethrotomy useful? J Urol 1998; 160: 356. 11. Siegel JA, Panda A, Tausch TJ et al: Repeat excision and primary anastomotic urethroplasty for salvage of recurrent bulbar urethral stricture. J Urol 2015; 194: 1316. 12. Gonzalez CM: Salvage surgery after failure of urethroplasty for stricture disease. J Urol 2015; 194: 1192.
13. Rosenbaum CM, Schmid M, Ludwig TA et al: Internal urethrotomy in patients with recurrent urethral stricture after buccal mucosa graft urethroplasty. World J Urol 2015; 33: 1337. 14. Ekerhult TO, Lindqvist K, Peeker R et al: Outcomes of reintervention after failed urethroplasty. Scand J Urol 2017; 51: 68. 15. Blaschko SD, McAninch JW, Myers JB et al: Repeat urethroplasty after failed urethral reconstruction: outcome analysis of 130 patients. J Urol 2012; 188: 2260. 16. Zaid UB, Lavien G and Peterson AC: Management of the recurrent male urethral stricture. Curr Urol Rep 2016; 17: 33. 17. Sukumar S, Elliott SP, Myers JB et al: Multiinstitutional outcomes of endoscopic management of stricture recurrence after bulbar urethroplasty. J Urol 2018; doi: 10.1016/ j.juro.2018.04.081.
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A Critical Analysis of Bulbar Urethroplasty Stricture Recurrence: Characteristics and Management Arman A. Kahokehr,*,† Michael A. Granieri, George D. Webster and Andrew C. Peterson From the Division of Urology, Duke University Medical Center, Durham, North Carolina, and New York University School of Medicine (MAG), New York, New York
Purpose: We evaluated the management of recurrent bulbar urethral stricture disease after urethroplasty at our institution. Materials and Methods: We performed an institution review board approved, retrospective case study of our urethroplasty database to collect stricture related and postoperative information with an emphasis on bulbar urethral stricture disease recurrence after urethroplasty between 1996 and 2012. Repair types included primary anastomotic, augmented anastomotic and onlay repair. Recurrence, which was defined as the need for intervention, was diagnosed with cystoscopy or retrograde urethrogram. Results: We identified 437 men who underwent urethroplasty of bulbar urethral stricture disease as performed by 2 surgeons from January 1996 to December 2012. Of the men 395 had available followup data. Recurrence was identified in 25 men (6.3%), of whom all presented with symptoms, including a weak stream in 23, urinary tract infection in 1 and pyelonephritis in 1. Median time to recurrence was 10 months. Recurrence was initially treated endoscopically in 23 of 25 cases (92%), dilatation in 12 and visual urethrotomy in 11. In 5 patients (22%) further recurrence developed after endoscopic treatment, which was managed by repeat urethroplasty in 2, self-calibration only in 2 and visual urethrotomy with subsequent self-calibration in 1. We identified 2 distinct phenotypes of recurrent stricture, including type Adshort focal recurrence, which may be salvaged with an endoscopic procedure, and type Bdthe long graft length type, which is less likely to be salvaged with endoscopy. Conclusions: Recurrence after urethroplasty is most likely to develop within the first 12 months. Type A short focal recurrence may be managed by a salvage endoscopic procedure, including dilation or visual urethrotomy. These data on the phenotype of recurrence may be useful for patient treatment. Key Words: urethral stricture, recurrence, mouth mucosa, tissue transplantation, salvage therapy
URETHROPLASTY is a highly successful treatment of BUSD with previously published recurrence rates ranging from 3% to 16.5% based on study setting and surgery complexity.1,2 Management of recurrence includes endoscopic treatment such as dilation
or DVIU and open surgical options such as repeat urethroplasty. However, there is no consensus on the management of recurrent stricture following urethral reconstruction of BUSD. It was postulated that recurrence after urethroplasty of BUSD
0022-5347/18/2006-0001/0 THE JOURNAL OF UROLOGY® Ó 2018 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
Dochead: Adult Urology
https://doi.org/10.1016/j.juro.2018.07.036 Vol. 200, 1-6, December 2018 Printed in U.S.A.
Abbreviations and Acronyms AAR ¼ augmented anastomotic repair BUSD ¼ bulbar urethral stricture disease DVIU ¼ direct visual internal urethrotomy EPA ¼ excision and primary anastomosis RUG ¼ retrograde urethrogram Accepted for publication July 2, 2018. No direct or indirect commercial incentive associated with publishing this article. The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. * Correspondence: Divisions of Urologic Surgery and Reconstructive Urology, Duke University Medical Center, 40 Duke Medicine Circle, DUMC Box 3146, Durham, North Carolina 27710 (telephone: 919-684-2516; FAX: 919-668-0321; e-mail: [email protected]). † Supported by a Boston Scientific research grant.
Editor’s Note: This article is the of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages and .
www.jurology.com
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BULBAR URETHROPLASTY STRICTURE RECURRENCE
may be located at the proximal or the distal anastomotic locations, often consisting of short annular fibrous rings.3 Our subjective clinical experience indicated that these recurrences can often be successfully managed by endoscopic techniques since the prior repair addressed the underlying diseased urethra and spongiofibrosis when present. We hypothesized that there may be different types of recurrent stricture phenotypes after urethroplasty for BUSD, which may be related to the success of managing these recurrences. The goal of this study was to assess our experience with the management of recurrence after urethroplasty of BUSD and examine recurrence characteristics and treatment outcomes.
Earlier in the series penile skin was also used for grafting, if available. It was harvested longitudinally along the ventral aspect of the penis and the defect was closed primarily. However, buccal mucosa is the preferred graft. It is harvested by the urologist and the defect is closed primarily. For long strictures without nearly or completely obliterated segments the onlay graft is placed dorsally as previously described,5 although in select cases ventral onlay grafting was also performed. Graft fixation and anastomosis are performed with interrupted 5-zero polyglactin. Muscle, Colles fascia, subcutaneous and skin tissues are closed with interrupted 4-zero polyglactin. No drain is placed.
Followup
We collected detailed data on each case. Data included patient demographics, stricture location and type, surgical repair type, postoperative complications, stricture related recurrence and detailed analysis of information from postoperative followup visits.
Pericatheter RUG was routinely performed approximately 2 to 3 weeks postoperatively. Following removal of the urethral catheter the patients returned at 3 and 12 months, and were offered an annual clinical visit thereafter. A symptom based followup protocol was established at Duke University. Assessment including the I-PSS (International Prostate Symptom score), the flow rate and post-void residual urine volume was performed routinely at each visit. If any symptoms such as urinary tract infection, a weak stream, etc were experienced, patients were seen sooner than scheduled. Patients were strongly encouraged to return to the clinic on an annual basis. When symptoms were identified, diagnostic office urethrocystoscopy and/or RUG was performed. Further investigation was tailored based on the clinical picture. The decision to perform the first initial salvage procedure was based on clinician preference since outcomes are similar after DVIU and dilation.6
Definition
Statistics
Stricture recurrence was defined as the need for further intervention in the postoperative period as diagnosed with cystoscopy and/or RUG. When symptoms suggestive of recurrence were suspected, urethrocystoscopy was usually initially performed. This was tailored based on patient symptom development and on the time line since urethroplasty. If the information required was not determined, this was always followed by the other synergistic test.
Summary statistics are used to describe baseline characteristics. For nonparametric data the Mann-Whitney U test was used for unpaired independent samples. The Fisher exact or chi-square test was applied for categorical data and the 2-tailed test was used as appropriate. Statistical significance was considered at p <0.05 and analysis was performed with JMPÒ, version 13.
METHODS Patients We performed an institutional review board approved study of the Duke Urethroplasty Database of all patients who underwent urethroplasty of BUSD at our institution from January 1996 to December 2012 as performed by 2 surgeons. Repair types included EPA, AAR and onlay repair.
Data Collection
RESULTS
Operative Technique Intraurethral methylene blue is instilled routinely at the start of the case. The bulbospongiosus muscle is split in the midline. Intraoperative stricture length is recorded and a 20Fr urethral catheter is used to define the distal aspect of the stricture. EPA is performed based on the ability to construct a tension-free anastomosis. For longer strictures not amenable to EPA with a nearly or completely obliterated segment the diseased urethral tissue is excised and augmented anastomotic repair is done with substitution tissue as described previously.4 We first described augmented anastomotic repair in 2001. In this technique the nearly or completely obliterated portion is excised since this is important to prevent restenosis. The remaining nonobliterated stricture is widened by onlay substitution repair. This is a versatile repair technique. The graft was placed dorsally in most patients, although ventral onlay was performed in select patients. Dochead: Adult Urology
We limited our analysis to patients who underwent only bulbar urethral stricture repairs, excluding those with posterior, pendulous or meatal stricture disease as well as patients who presented with lichen sclerosus. During the study period 437 men underwent bulbar urethroplasty for BUSD as performed by a total of 2 surgeons. Followup data were available on 407 men (93%) but in 12 it could not be determined whether recurrence had developed. Median followup following initial urethroplasty surgery was 28 months (mean 25.7, range 3 to 112). Recurrence was identified in 25 of the 395 men (6.3%). All recurrences were identified by worsening symptoms, including a weak stream in 23 cases, urinary tract infection in 1 and pyelonephritis in 1. Median time to recurrence was 10 months (fig. 1).
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172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 ½F1 228
BULBAR URETHROPLASTY STRICTURE RECURRENCE
3
N
286 229 14 13 287 230 12 288 231 289 232 10 290 233 291 234 8 292 235 293 236 6 5 294 237 4 295 238 3 296 239 2 1 1 1 1 297 240 0 0 0 0 298 241 0 299 242 300 243 301 244 302 245 me since urethroplasty (months) 303 246 304 247 Figure 1. Months to diagnosed recurrence after bulbar urethroplasty. N, 25 patients. 305 248 306 249 307 250 Six of these 25 patients (24%) were treated with procedure had originally undergone more complex 308 251 urethroplasty in the past. The repair types associinitial urethroplasty (eg requiring substitution). 309 252 ated with recurrence were EPA in 10 men (40%), 310 253 AAR in 13 (52%) and ventral onlay repair in 2 (8%). 311 254 Recurrence was diagnosed by RUG and cystoscopy DISCUSSION 312 255 in 21 cases and by cystoscopy alone in 4. The 6.3% recurrence rate reported in our database 313 256 Table 1 shows demographic factors in patients ½T1 mirrors the rates currently reported in the contem314 257 with treatment success and those with recurrence. porary literature.7 Additionally, our experience in315 258 Stricture etiology varied between the groups with a dicates that a short and/or focal recurrence after 316 259 higher proportion of idiopathic, infective and radibulbar urethroplasty may be initially managed by 317 260 ation induced strictures in men who experienced various endoscopic techniques such as dilation or 318 261 recurrence (p ¼ 0.001). Most grafts were placed DVIU with an acceptable success rates. In this series 319 262 dorsally, given our extensive experience with this success was noted in 18 of 23 cases at a mean fol320 263 type of repair and ventrally placed grafts were lowup of 26 months. However, in men with a longer 321 264 associated with a higher recurrence rate (p ¼ 0.007). recurrence salvage with dilatation or DVIU is less 322 265 However, the overall low number of ventral repair likely to be successful, although repeat urethroplasty 323 266 in this series must be considered. is feasible. 324 267 Recurrence was initially treated endoscopically in Upon retrospective review it appeared that there 325 268 23 of 25 cases (92%), including dilation in 12 and DVIU are 2 distinct phenotypes of recurrent stricture, that 326 269 in 11. One patient was treated elsewhere and 1 elected is types A and B. Type A recurrence is a short focal 327 270 perineal urethrostomy due to multiple previous operrecurrence that is likely at the location of an anas328 271 ations. Mean followup after recurrence treatment was tomosis made during the original urethroplasty (fig. 329 272 26 months (median 11, range 3 to 127). Recurrence 2). This type presented earlier in our experience and ½F2 330 273 developed after endoscopic treatment in 5 patients in this analysis it represented a favorable prognosis 331 274 (22%), which was managed by successful repeat urefor a salvage endoscopic procedure. We believe that 332 275 throplasty in 2, self-calibration alone in 2, and visual this type is due to the excision of spongiofibrosis at 333 276 urethrotomy and subsequent self-calibration in 1. the time of urethroplasty, which we perform in most 334 277 Table 2 shows the characteristics of the 23 patients ½T2 cases. It leads to a less dense stricture upon recur335 278 who underwent a salvage procedure. Comparing rence at the anastomosis, which is likely a technical 336 279 recurrent stricture length in the 18 men in whom issue or other. Therefore, it may be more amenable 337 280 endoscopic intervention was successful vs the 5 in to endoscopic treatment after the recurrence is 338 281 whom it failed revealed that those in whom recurrence diagnosed clinically. 339 282 developed had longer strictures which presented later. Type B recurrence develops almost exclusively 340 283 However, the difference was not significant. Those in when substitution was performed. It is longer and 341 284 whom a repeat stricture developed after a salvage appears along part or all of the graft length and is 342 285 Dochead: Adult Urology
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4
343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 ½F3 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399
BULBAR URETHROPLASTY STRICTURE RECURRENCE
Table 1 Recurrent Stricture
No. pts Median age (range) No. tobacco use: Current or prior Never Unknown No. etiology:* Idiopathic Trauma Infection Radiation Iatrogenic No. diabetes mellitus: Yes No Unknown Median stricture length (range): Excision þ primary anastomosis Augmented anastomotic repair Onlay No. prior endoscopic treatments: 0 1 More than 1 (range) No. urethroplasty type: Excision þ primary anastomosis Augmented anastomotic repair Onlay No. graft location: Ventral Dorsal No. graft type: Buccal mucosa Penile skin Preputial skin No. extravasation: Retrograde urethrogram 1 Retrograde urethrogram 2 Median mos to recurrence (range) No. recurrence symptom: Urinary tract infection Pyelonephritis Voiding symptoms
Yes
No
p Value
25 48 (17e68)
370 43 (10e85)
e 0.167 (Mann-Whitney U test)
3 15 7
36 174 160
0.327
(chi-square test)
16 3 4 2 0
199 83 16 3 52
0.001
(chi-square test)
2 15 8 2 1.2 3.0 3.5
0.473
(chi-square test)
(1e5) (1e2) (1e5) (2e5)
18 191 161 2 1.0 2.0 2.5
(2e6)
21 106 243
1 16 18
(0.5e6) (0.5e3) (1e7) (2e4)
0.43 (Mann-Whitney U test)
0.803
(chi-square test)
(2e21)
10 13 2
216 133 21
0.118
(chi-square test)
4 11
6 148
0.007
(chi-square test)
8 7 0
114 38 2
0.049
(chi-square test)
19 1 Not applicable Not applicable
0.633
(Fisher exact test)
2 0 10 (2e112) 1 1 23
* No recurrent stricture in 353 patients and no patient had lichen sclerosis.
likely due to ischemic contracture (fig. 3). This type seems to present later and it is less likely to be salvaged by endoscopy (table 2). When deciding on the best initial salvage procedure after urethroplasty recurrence, these hypothesis generating data on the distinct phenotype of recurrence may be useful for patient treatment. For example, if there are 2 focal point strictures at the end of each anastomosis following substitution, this would be considered a long stricture according to some classifications. However, because this type of recurrence is likely to respond well to endoscopic management, it would be best categorized as 2 type A phenotypes as the graft length has not contracted due to ischemia. Growing data and guidelines support urethroplasty following an initial endoscopic treatment Dochead: Adult Urology
(DVIU or dilation) in previously untreated urethral stricture disease since ongoing further endoscopic treatment is unlikely to be successful.8e10 However, there are less data on managing recurrence after urethroplasty of BUSD. An initial salvage endoscopic procedure has a reasonable but not a perfect success rate. Because redo urethroplasty offers excellent durable results,11,12 some experts advocate proceeding directly to repeat urethroplasty after recurrence. However, when faced with a disappointed patient, it may be best to use a risk based strategy associated with the described type A vs B phenotypes as endoscopic salvage procedures have a reasonable success rate, however imperfect.13,14 It has been shown that when looking at salvage urethroplasty after all types of previous anterior urethra repairs, a higher risk of
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BULBAR URETHROPLASTY STRICTURE RECURRENCE
457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513
Table 2. Characteristics of 23 patients with recurrent stricture treated with endoscopic DVIU or dilation salvage procedure after bulbar urethroplasty Repeat Recurrence
No. pts Mean SD stricture length (cm) Mean SD stricture diagnosis after initial urethroplasty (mos) No. repair: Excision þ primary anastomosis Augmented anastomotic repair Onlay No. graft type: Buccal mucosa Penile skin No. graft technique: Dorsal Ventral
No
Yes
18 0.5 0.72 9.8 19.6
5 3.5 3.5 27 26.3
9 9 0
1 2 2
4 5
2 2
7 2
2 2
failure was associated with hypospadias related strictures, lichen sclerosis and 2 or more previously failed open surgeries.15 In a landmark study of the specifics of recurrent stricture disease following bulbar urethroplasty 22 patients (20%) were carefully analyzed using retrograde urethrogram, ultrasound and urethroscopy.3 Nearly 45% of recurrences were due to short (less than 1 cm) annular fibrosis at the proximal or distal anastomotic site, in contrast to a recurrence along an entire graft length. The investigators moved away from redo open reconstruction in this select group to DVIU of these shorter anastomotic recurrences once this difference in recurrence was recognized. Outcomes were successful outcomes in the majority of cases. In the current study we were able to present this principle by reviewing the outcomes of minimally invasive salvage procedure based on recurrence characteristics. Overall the literature suggests that all repeat urethroplasties of all anterior urethral recurrences, bulbar and pendulous combined, are associated with
5
a success rate of about 75%.16 We believe that since the data indicate a reasonable outcome in highly selected patients who undergo endoscopic treatment of type A recurrence, this is an appropriate first step in managing these recurrent strictures. Our clinical experience indicates that many patients with recurrence after definitive primary anastomotic or augmented urethroplasty prefer minimally invasive salvage, given the disadvantages of repeat open surgery. Based on the current data it appears that men with type A recurrence may do well with endoscopic intervention, abrogating the need for repeat open surgical intervention. When recurrence was defined and detected using routine flexible urethroscopy in all men whether or not they were symptomatic, a recent report concluded that DVIU seemed to perform better than dilation at a median of 5 months of followup.17 We await a longer followup date. In our study we found that patients with recurrence were more likely to have infective or radiotherapy induced strictures compared to those without recurrence. It was reported that infectious strictures are an independent risk factor for stricture recurrence following bulbar urethroplasty.7 It is possible that infection and radiation induced strictures are more likely associated with poor tissue integrity and, thus, with a higher risk of failed reconstruction and failed graft take. Limitations This study is limited due to the retrospective nature of the data collection, which may include recall bias during followup. In addition, many patients traveled for definitive treatment and chose to have additional long-term followup closer to the place of residence, making the attrition rate higher than desired. We did not perform routine urethrocystoscopy at our institution at the time that these urethroplasties were performed. Because routine urethrocystoscopy is currently not standardized or
Figure 2. Retrograde urethrogram shows short, type A annular recurrence 3 months after AAR repair with buccal mucosa. Patient underwent salvage DVIU with no further recurrence. A, before urethroplasty. B, recurrence after urethroplasty.
Dochead: Adult Urology
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6
571 572 573 574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589 590 591 592 593 594 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 611 612 613 614 615 616 617 618 619 620 621 622 623 624 625 626 627 628 629 630 631 632
BULBAR URETHROPLASTY STRICTURE RECURRENCE
Figure 3. Retrograde urethrogram shows type B recurrence in patient with total of 6 prior failed multiple DVIUs plus dilations. AAR was done with penile skin and there was long recurrence along substitution length after 1 salvage DVIU. Patient performs self-calibration. A, before urethroplasty. B, recurrence after urethroplasty.
widely accepted, we currently perform a risk based approach. Furthermore, all urethroplasties and recurrence treatments were performed by 2 surgeons at 1 institution. Thus, we are aware that technical and treatment details do not reflect those at other centers specializing in BUSD treatment. Finally, we did not treat patients with lichen sclerosis as the primary etiology as the focus was on bulbar urethral stricture disease. Despite these limitations this study was based on a large cohort of patients who underwent urethroplasty and treatment of recurrence at a single tertiary center
where there is extensive urethroplasty experience. This enabled accurate evaluation of the recurrence incidence and of treatment outcomes.
CONCLUSIONS Recurrent urethral stricture following urethroplasty for BUSD may be managed by an endoscopic intervention such as dilation or DVIU with good success in most patients. Further research is needed to understand the distinct forms of recurrent stricture after urethroplasty.
REFERENCES 1. Hoy NY, Kinnaird A and Rourke KF: Expanded use of a dorsal onlay augmented anastomotic urethroplasty with buccal mucosa for long segment bulbar urethral strictures: analysis of outcomes and complications. Urology 2013; 81: 1357. 2. Barbagli G, Guazzoni G and Lazzeri M: One-stage bulbar urethroplasty: retrospective analysis of the results in 375 patients. Eur Urol 2008; 53: 828. 3. Barbagli G, Guazzoni G, Palminteri E et al: Anastomotic fibrous ring as cause of stricture recurrence after bulbar onlay graft urethroplasty. J Urol 2006; 176: 614. 4. Guralnick ML and Webster GD: The augmented anastomotic urethroplasty: indications and outcome in 29 patients. J Urol 2001; 165: 1496. 5. Barbagli G, Selli C, Tosto A et al: Dorsal free graft urethroplasty. J Urol 1996; 155: 123. 6. Steenkamp JW, Heyns CF and de Kock ML: Internal urethrotomy versus dilation as treatment for male urethral strictures: a prospective, randomized comparison. J Urol 1997; 157: 98.
Dochead: Adult Urology
7. Chapman D, Kinnaird A and Rourke K: Independent predictors of stricture recurrence following urethroplasty for isolated bulbar urethral strictures. J Urol 2017; 198: 1107. 8. Wessells H, Angermeier KW, Elliott S et al: Male urethral stricture: AUA guideline. J Urol 2017; 197: 182. 9. Greenwell TJ, Castle C, Andrich DE et al: Repeat urethrotomy and dilation for the treatment of urethral stricture are neither clinically effective nor cost-effective. J Urol 2004; 172: 275. 10. Heyns CF, Steenkamp JW, De Kock ML et al: Treatment of male urethral strictures: is repeated dilation or internal urethrotomy useful? J Urol 1998; 160: 356. 11. Siegel JA, Panda A, Tausch TJ et al: Repeat excision and primary anastomotic urethroplasty for salvage of recurrent bulbar urethral stricture. J Urol 2015; 194: 1316. 12. Gonzalez CM: Salvage surgery after failure of urethroplasty for stricture disease. J Urol 2015; 194: 1192.
13. Rosenbaum CM, Schmid M, Ludwig TA et al: Internal urethrotomy in patients with recurrent urethral stricture after buccal mucosa graft urethroplasty. World J Urol 2015; 33: 1337. 14. Ekerhult TO, Lindqvist K, Peeker R et al: Outcomes of reintervention after failed urethroplasty. Scand J Urol 2017; 51: 68. 15. Blaschko SD, McAninch JW, Myers JB et al: Repeat urethroplasty after failed urethral reconstruction: outcome analysis of 130 patients. J Urol 2012; 188: 2260. 16. Zaid UB, Lavien G and Peterson AC: Management of the recurrent male urethral stricture. Curr Urol Rep 2016; 17: 33. 17. Sukumar S, Elliott SP, Myers JB et al: Multiinstitutional outcomes of endoscopic management of stricture recurrence after bulbar urethroplasty. J Urol 2018; doi: 10.1016/ j.juro.2018.04.081.
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