Risk Factors and Timing of Early Stricture Recurrence After Urethroplasty

Accepted Manuscript Title: Risk Factors and Timing of Early Stricture Recurrence After Urethroplasty Author: Joceline S. Liu, Caroline Dong, Chris M. Gonzalez PII: DOI: Reference:

S0090-4295(16)30136-4 http://dx.doi.org/doi: 10.1016/j.urology.2016.04.033 URL 19762

To appear in:

Urology

Received date: Accepted date:

1-4-2016 26-4-2016

Please cite this article as: Joceline S. Liu, Caroline Dong, Chris M. Gonzalez, Risk Factors and Timing of Early Stricture Recurrence After Urethroplasty, Urology (2016), http://dx.doi.org/doi: 10.1016/j.urology.2016.04.033. 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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Risk Factors and Timing of Early Stricture Recurrence After Urethroplasty Joceline S. Liu MDa, Caroline Dong BSa, Chris M. Gonzalez MDb*

a

Department of Urology, Northwestern University Feinberg School of Medicine,

Chicago, IL b

Department of Urology, Case Western Reserve University, Cleveland, OH

*Corresponding author 11100 Euclid Ave. Mailstop LKSD 5046 Cleveland, OH 44106 Phone: (216) 844-3009 E-mail: [email protected]

Keywords: urethral stricture, stricture recurrence, surveillance

There are no conflicts of interest for the listed authors.

Abstract word count: 244 Text word count: 2196 ABSTRACT

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Objectives: To compare recurrence after urethroplasty, identifying associated risk factors for early recurrence. Materials and Methods: Among 262 urethroplasties (2001-2010) with ≥6 months of follow-up, we identified 65 patients (24.8%) with recurrence (defined by obstruction in the area of repair on cystoscopy). Results: Median stricture length was 4.5 cm (range 1-24 cm). Median follow-up was 85.2 (6.7-160.1) months, with median time to recurrence of 8.0 (0.5-88.0) months. Substitution urethroplasty was the most frequent repair (70.8%), followed by excision and primary anastomosis (23.1%). When graft was used, buccal was most common (66.0%), followed by abdominal wall skin (AWS) (24.5%). 21% of recurrences presented within 3 months, 40.0% by 6 months, 55.4% by 1 year, while 9.2% recurred more than 5 years later. Recurrences ≤6 months were significantly longer strictures (median 5.5 vs. 4.0 cm, p=0.009). Strictures ≤4 cm, ≤3 cm and ≤2 cm recurred at a median of 10.6, 18.2, and 30.3 months respectively (p=0.08). Most LS-related recurrences occurred within 6 months (62%). Patients recurring within 6 months were older, had history of LS or more likely had AWS. 40.0% suffered from multiple recurrences at a median of 12 months and were associated with longer stricture, prior instrumentation, substitution urethroplasty, AWS and LS. Conclusions: Half of recurrences following urethroplasty present within one year, with most declaring within 6 months. Early recurrence is associated with older age, LS, AWS and longer strictures. The duration and intensity of surveillance protocols following urethroplasty should be individualized in order to account for these characteristics.

INTRODUCTION

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Male urethral stricture disease is estimated between 200 and 1200 cases per 100,000 individuals, with its incidence increasing significantly over the age of 55.1 Urethral stricture disease is also associated with a substantial impact on patient quality of life and health-care costs, with estimated annual expenditures nearing 190 million in 2000 in the United States.1 While urethroplasty is considered the gold standard treatment for definitive correction of urethral stricture disease, it is still associated with stricture recurrence rates between 8.3-18.7%.2 Some of the most common etiologies of stricture disease include lichen sclerosis (LS), trauma, iatrogenic, and infection.3, 4 Of these etiologies, certain subpopulations with local tissue adversity can be associated with a higher risk of recurrence and complications, including a history of pelvic radiation, trauma or LS. Although it is accepted that postoperative monitoring for complications and recurrence are necessary following intervention, no consensus exists regarding the ideal method, frequency or duration of follow-up in these patients.5 Review of the literature demonstrates that over 50% of recurrences occur within one to two years of primary urethroplasty.6,7 However, specific information on the timing of recurrence within a two year window is unclear. Furthermore, it is reported that recurrence within 5 years of surgery accounts up to 29% of recurrences, while the remainder will recur in a delayed fashion.6, 8-11 The lack of clear data on the behavior of strictures following definitive repair has prompted us to reexamine stricture recurrence timing and associated risk factors. We hypothesize that longer strictures and those with LS are at risk for early recurrence (within 6 months) following urethroplasty. A better understanding of the timing of urethroplasty recurrence along with stricture etiology may help in the design of individualized surveillance protocols for high and low risk patients.

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MATERIALS AND METHODS We performed an institutional review board approved retrospective study of patients who underwent urethroplasty for urethral stricture disease at a single institution between 2001 and 2010. Using this institutional database including 262 urethroplasties, we identified 65 patients (24.8%) with stricture recurrence and at least six months of follow-up. Recurrence was defined by patient-reported urinary symptoms or signs confirmed by endoscopic evidence of obstruction in the area of repair < 16F in caliber. Inclusion criteria included male gender, age ≥18 years, urethroplasty performed at Northwestern Memorial Hospital between 2001 and 2010, follow-up of at least 6 months and confirmed endoscopic stricture recurrence. Patient data were retrospectively gathered from electronic medical records. Demographic information, etiology, comorbidities, smoking history, prior procedures, stricture characteristics, surgical intervention and outcomes were reviewed based on inpatient and outpatient history and physical, problem list, and progress notes. Etiology of stricture was also recorded, with iatrogenic classification assigned if the patient developed stricture with history of catheterization, transurethral instrumentation or procedure. Cases in which no identifiable cause of stricture was identified were classified as idiopathic. Primary outcome was time to stricture recurrence. Time to primary stricture recurrence was defined as date of endoscopic confirmation of stricture. Secondary outcomes analyzed included incidence and time to subsequent recurrences (labeled secondary stricture recurrence). Time to stricture recurrence was classified into chronologic categories: ≤3 months, ≤6 months, ≤1 year, >1 year and ≤5 years) and >5 years. Patient and stricture

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characteristics were compared relative to time to recurrence and incidence and timing of subsequent recurrences. Statistical analysis included use of Mann-Whitney U test and chi-squared test. For all statistical analyses, P < 0.05 was considered statistically significant. Analysis was performed using SPSS 21 for IBM (IBM Corp., Armonk, NY).

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RESULTS A total of 65 men with a median age of 45.0 years (range 25 to 76 years) experienced stricture recurrence following urethroplasty. Patient and stricture characteristics are presented in Table 1. Median urethral stricture length was 4.5 cm (range 1 to 24 cm). Patients were followed for a median of 85.2 months (range 6.7 to 160.1 months) with a median time to recurrence of 8.0 months (range 1.0 to 88.0 months). Most strictures had no identifiable cause and were classified as idiopathic strictures (33.8%), while 21.5% had a history of urethral instrumentation, 20.0% LS, and 15.4% a history of hypospadias. Most patients (55.4%) had undergone prior intervention for stricture, with the majority (77.8%) having a history of previous endoscopic management and several patients with a history of urethroplasty (30.6%) or hypospadias repair (5.6%). Substitution urethroplasty was the most frequent repair performed (70.8%), followed by EPA (23.1%). When graft was used, buccal mucosa was most common (66.0%), followed by abdominal wall skin (AWS) (24.5%) and penile skin (9.4%). Twenty-one percent (14/65) of stricture recurrences occurred within 3 months, 40.0% (26/65) within 6 months, 55.4% (36/65) within 1 year, while 35.4% (23/65) recurred between 1 and 5 years and 9.2% (6/65) recurred more than 5 years after repair. Patient and stricture characteristics are summarized based on primary outcome of time to stricture recurrence in Table 1. Overall, recurrences occurring earlier were associated with longer stricture length, reaching statistical significance when comparing cases recurring before and after 6 months (median stricture lengths 5.5 cm and 4.0 cm, respectively (p=0.009)). As demonstrated in Figure 1, the shortest strictures tended to

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recur later. Of recurrences, short-segment strictures spanning ≤2 cm recurred at a median of 30.3 months, with progressively shorter time to recurrence with increasing stricture length; strictures 2-3 cm in length recurred at a median of 18.2 months, compared to 3-4 cm at 10.6 months, 4-5 cm at 5.3 months and 5-6 cm at 2.2 months (p=0.08). Most LS cases recurred early, with 38.5% within 3 months and 61.5% within 6 months. Patients recurring within 6 months were older (median 50.0 vs. 45.0 yrs, p=0.007) and more likely had AWS used (30.8% vs. 12.8%, p=0.08). Comparison of patient and stricture characteristics based on time to recurrence is summarized in Table 1. Hypertension (HTN) was more commonly diagnosed in patients with early recurrence, with 50% of patients recurring within 1 year, 53.8% within 6 months and 64.3% within 3 months. Conversely, no similar trend is seen with diabetes mellitus (DM), coronary artery disease (CAD) or smoking history. Forty percent (26/65) of patients suffered from multiple stricture recurrences at a median of 12 months (range 2-83 months) following the initial urethroplasty recurrence. No significant difference in time to recurrence following urethroplasty was observed when comparing patients with a single versus multiple recurrences (p=0.87, Table 2). Patients developing multiple recurrences had significantly longer strictures (median 6.5 vs. 4.0 cm, p=0.001), were more likely to have undergone prior intervention for their strictures (73.1% vs. 43.6%, p=0.02) and were more commonly patients who had been managed with urethroplasty using AWS graft (42.3% vs. 5.1%, p<0.001). LS was fivefold more likely in patients developing multiple recurrences (38.5%) compared to those developing a single recurrence (7.7%) (p=0.003). Stricture location, length of follow-up,

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smoking history, and type of prior intervention were not significantly associated with multiple recurrences.

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COMMENTS Urethroplasty is the gold standard of treatment for male urethral stricture disease, however recurrence remains a reality. The incidence and timing of stricture recurrence after definitive urethral reconstruction remains incompletely characterized. A review of the literature reports recurrence rates ranging from 8.3% to 18.7%, with wide variation in incidence likely related to differences in stricture and patient characteristics, surgical approach and technique, length of follow-up, and method of surveillance.2 Additionally, a lack of consensus regarding a standardized definition of stricture recurrence introduces ambiguity in the literature, making comparisons between studies difficult.12 As there is uncertainty in the expected outcomes following urethroplasty, there is no consensus regarding the ideal follow-up protocol, interval, or duration of surveillance beyond the general principle of regular follow-up postoperatively.5 Any proposed surveillance protocol will need to balance the yield of detecting recurrence while minimizing unnecessary invasive, potentially costly procedures for the patient. A recent multi-institutional study demonstrated that urethroplasty success rates may be lower than previously reported, when using an anatomic definition of recurrence, based on endoscopic evaluation.13 The rate of cystoscopic, or anatomic, stricture recurrence was increased relative to functional recurrence defined by patient-reported symptoms or retention, which more closely resembled the rates previously reported in the literature.13 This group reported an anatomic success rate of 86% following EPA and 78% after repairs using buccal mucosa at 12-month follow-up.13 Importantly, the 1-year compliance rate for follow-up cystoscopy was only 50%, highlighting the inherent difficulty of follow-up in patients irrespective of defined protocols.13 While the use of

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routine cystoscopy and surveillance for stricture recurrence may provide more accurate definitions of success rates, the clinical significance of asymptomatic anatomic recurrence and the high incidence of non-compliance with follow-up questions the acceptance of a regimented, standard post-urethroplasty protocol. There is value in the ability to further define patients at high-risk for recurrence and the associated time period, based on patient characteristics, disease, and reconstructive technique, allowing for design of individualized follow-up protocols. The ability to anticipate which patients are likely to recur after surgery, compared to remote recurrence could change the way in which patients are counseled about the natural history of their stricture disease and recovery, as well as aide in a more individualized, cost conscious follow-up protocol. Initially, studies suggested that most recurrences after anastomotic urethroplasty will occur within 2 years;7 however, several studies with extended follow-up suggest that a significant proportion may recur beyond those first two years.14 While evidence presented by Breyer et al. support the notion that most strictures after urethroplasty occur in the first year (57%), with an additional 28.5% up to five years postoperatively before reaching a relative plateau in stricture recurrence, the study demonstrated a consistent continuation of recurrence for the duration of followup.6 Andrich et al. compared stricture recurrence rates at 5, 10 and 15 years after urethroplasty, and reported most recurrences occurring within the first 5 years, with sustained stricture-free survival after that period in EPA patients, while success rates declined steadily in substitution urethroplasty cases.11 In contrast, in a cohort of substitution urethroplasty patients, Barbagli et al. report a 26.2% failure rate at a median

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follow-up of 118 months, with 96.8% of recurrences presenting within 5 years after repair.15 We present the outcomes of 65 patients developing stricture recurrence following urethroplasty. The overall median time to recurrence in this cohort was 8 months, with over half of patients recurring within one year. Importantly, a significant proportion of patients experienced recurrence early in their postoperative course, with 21%, 40% and 55.4% within 3 months, 6 months, and 1 year, respectively. These results corroborate the existing literature on the majority of stricture recurrences occurring early after surgery, although our findings would suggest that even within that first year, most will recur within the first 6 months. Approximately one-third of patients (35.4%) recurred between 1 and 5 years, while a minority (9.2%) recurred beyond 5 years after repair. Overall, longer strictures were associated with an earlier time to recurrence, with progressively shorter strictures tending to recur at later time points in a near-linear fashion. Early stricture recurrence was also associated with cases of LS or those managed with AWS (non-genital skin) graft urethroplasty. Both of these factors have been associated with a higher risk for stricture recurrence,16 although specifics regarding timing of these recurrences have been less clear. Among the 26 patients experiencing multiple recurrences, patients were more likely to have undergone substitution urethroplasty for stricture repair, while EPA cases were less prone to develop multiple recurrences. While these associated factors are likely proxy indicators of strictures that are known to have poorer outcomes (i.e. patients with long-segment, refractory strictures requiring the use of graft tissue), recent studies have also suggested that EPA can be highly effective in salvage of recurrent strictures.9

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This study is not without limitations, which require mention. Although this study is limited in its retrospective nature at a single institution, we feel that the data presented on timing of stricture recurrence and an examination of predictive factors is an important assessment of postoperative outcomes in stricture disease. Our study is also limited by length of follow-up, which may prevent recognition of patient variables associated with delayed recurrence after urethroplasty, that are not realized here. Our study is complicated by the inconsistency or lack of a standard definition of recurrence, with our results reflecting incidence and timing of recurrence from a functional standpoint. Controversy exists regarding the optimal method of defining recurrence, with some suggesting regular endoscopy, others supporting urine flow rates and others still adhering to patient-reported symptoms.17,18 Our results may provide guidance for duration and intensity of postoperative surveillance, individualized follow-up protocol development, and patient counseling regarding the importance of regular follow-up for those at higher risk for delayed recurrence or multiple recurrences. Specifically, vigilant surveillance may be especially important in patients with risk factors for rapid recurrence, including those with LS, longer strictures or AWS graft. Conversely, patients with shorter strictures need to be appropriately counseled regarding their risk for potentially delayed recurrence beyond five years, with encouragement to follow-up with their urologist.

CONCLUSIONS Most stricture recurrences following urethroplasty will present within one year, with most declaring within 6 months. Early recurrence may be associated with older age, LS, AWS grafts and longer strictures. The duration and intensity of surveillance protocols

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following urethroplasty should be individualized in order to account for these characteristics.

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REFERENCES

1. 2. 3. 4. 5.

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14. 15. 16. 17. 18.

Santucci RA, Joyce GF and Wise M. Male urethral stricture disease. J Urol 2007; 177: 1667-74. Meeks JJ, Erickson BA, Granieri MA and Gonzalez CM. Stricture recurrence after urethroplasty: a systematic review. J Urol 2009; 182: 1266-70. Stein DM, Thum DJ, Barbagli G et al. A geographic analysis of male urethral stricture aetiology and location. BJU Int 2013; 112: 830-4. Wood DN, Andrich DE, Greenwell TJ and Mundy AR. Standing the test of time: the long-term results of urethroplasty. World J Urol 2006; 24: 250-4. Angermeier KW, Rourke KF, Dubey D, Forsyth RJ, Gonzalez CM. SIU/ICUD Consultation on Urethral Strictures: Evaluation and Follow-up. Urology 2014; 83: S8-17. Breyer BN, McAninch JW, Whitson JM et al. Multivariate analysis of risk factors for long-term urethroplasty outcome. J Urol 2010; 183: 613-7. Santucci RA, Mario LA and McAninch JW. Anastomotic urethroplasty for bulbar urethral stricture: analysis of 168 patients. J Urol 2002; 167:1715-9. Blaschko SD, McAninch JW, Myers JB, Schlomer BJ, and Breyer BN. Repeat urethroplasty after failed urethral reconstruction: outcome analysis of 130 patients. J Urol 2012; 188: 2260-4. Fichtner J, Filipas D, Fisch M, Hohenfellner R and Thüroff JW. Long-term outcome of ventral buccal mucosa onlay graft urethroplasty for urethral stricture repair. Urology 2004; 64: 648-50. Siegel JA, Panda A, Tausch TJ, Meissner M, Klein A, Morey AF. Repeat excision and primary anastomotic urethroplasty for salvage of recurrent bulbar urethral stricture. J Urol 2015; 194: 1316-22. Andrich DE, Dunglison N, Greenwell TJ and Mundy AR. The long-term results of urethroplasty. J Urol 2003; 170: 90-2. Yeung LL and Brandes SB. Urethroplasty practice and surveillance patterns: a survey of reconstructive urologists. Urology 2013; 82: 471-5. Erickson BA, Elliot SP, Voelzke BB et al. Multi-institutional 1-year bulbar urethroplasty outcomes using a standardized prospective cystoscopic follow-up protocol. Urology 2014; 84: 213-7. Han JS, Liu JS, Hofer MD et al. Risk of urethral stricture recurrence increases over time after urethroplasty. Int J Urol 2015; 22: 695-9. Barbagli G Kulkarni SB, Fossati N et al. Long-term followup and deterioration rate of anterior substitution urethroplasty. J Urol 2014; 192: 808-13. Liu JS, Han J, Said M et al. Long-term outcomes of urethroplasty with abdominal wall skin grafts. Urology 2015; 85: 258-62. Andrich DE and Mundy AR. Urethral strictures and their surgical treatment. BJU Int 2000; 86: 571-80. Erickson BA, Breyer BN and McAninch JW. The use of uroflowmetry to diagnose recurrent stricture after urethral reconstructive surgery. J Urol 2010; 184: 1386-90.

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LEGENDS Figure 1: Stricture length and median time to recurrence following urethroplasty. Patients with the shortest strictures tended to recur in a delayed fashion. A) With progressively longer stricture length, recurrence tended to occur more rapidly in a stepwise fashion. B) This trend in time to recurrence nears clinical significance (p=0.08). Spearman’s rho correlation utilized to determine statistical significance.

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Table 1: Patient and stricture characteristics of those experiencing recurrence relative to stricture length. Mann-Whitney U test utilized to determine statistical significance. CI = 95% confidence intervals. *P-values were calculated comparing the category of time to recurrence versus those recurring outside of the time point. **P-value was calculated comparing very late recurrence (>5 years) versus those recurring prior to 5 years. DM = diabetes mellitus; CAD = coronary artery disease; HTN = hypertension; DVIU = direct visual internal urethrotomy; EPA = excision and primary anastomosis; AWS = abdominal wall skin.

All recurrences (n=65)

p p ≤ 3 months value ≤ 6 months value (n=14) * (n=26) *

≤ 1 year (n=36)

p value *

1-5 years (n=23)

p value > 5 years (n=6) **

47.0 (32.8, 60.0)

0.18

42.0 (32.0, 54.0)

43.0 (32.0, 62.0)

0.92

0.2

4.0 (3.0, 6.0)

5.3 (4.0, 9.0)

0.47

0.48

79.3 (32.8, 110.3)

110.3 (97.8, 120.3)

0.06

Median (IQR) Age

45.0 (32.5, 58.5)

Stricture length (cm)

4.5 (3.8, 8.0)

52.0 (46.3, 75.0)

0.01

50.0 (42.5, 66.3)

0.007

5.8 (4.0, 9.0) 0.14 5.5 (4.0, 9.8) 0.009 5.0 (4.0, 8.8)

Recurrence Timing Follow-up (months)

85.2 (47.6, 113.9)

74.6 (44.6, 116.5)

0.7

88.1 (41.8, 113.6)

0.72

80.6 (47.3, 113.1)

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Time to recurrence (months) Time to secondary recurrence (months)

<0.00 <0.00 <0.00 8.0 (3.9, 29.4) 1.6 (1.0, 2.6) 1 3.0 (1.2, 4.9) 1 4.6 (1.9, 6.4) 1

12.0 (3.9, 29.0)

3.2 (2.0, 13.3) 0.03 4.5 (3.2, 23.0) 0.2 5.0 (3.5, 21.0) 0.12

27.3 (16.0, 36.5)

77.6 (68.6, 95.2)

<0.00 1

21.5 (13.5, 50.8)

3.0 (1.5, 3.0)

0.34

n (%) Multiple Recurrences

26 (40.0)

5 (35.7)

0.71

11 (42.3)

0.76

15 (41.7)

0.76

8 (34.8)

3 (50.0)

0.6

DM

10 (15.4)

2 (14.3)

0.89

3 (11.5)

0.49

4 (11.1)

0.29

5 (21.7)

1 (16.7)

0.93

CAD

10 (15.4)

3 (21.4)

0.48

5 (19.2)

0.48

6 (16.7)

0.75

3 (13.0)

1 (16.7)

0.93

HTN

26 (40.0)

9 (64.3)

0.04

14 (53.8)

0.06

18 (50)

0.07

7 (30.4)

1 (16.7)

0.22

Smoking History

22 (33.8)

5 (25.7)

0.87

9 (34.6)

0.92

10 (27.8)

0.25

10 (43.5)

2 (33.3)

0.98

Comorbid Conditions

Stricture History and Treatment Stricture

0.99

0.42

0.41

0.89

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Location Penile

22 (33.8)

5 (35.7)

7 (26.9)

5 (36.0)

10 (43.5)

2 (33.4)

Bulbar

40 (61.5)

8 (57.1)

18 (69.2)

25 (69.4)

11 (47.8)

4 (66.7)

3 (4.6)

1 (7.1)

1 (3.8)

6 (16.7)

2 (8.7)

0 (0)

6 (9.2)

2 (14.3)

0.46

3 (11.5)

0.6

3 (8.3)

0.78

2 (8.7)

1 (16.7)

0.51

Lichen Sclerosus

13 (20.0)

5 (35.7)

0.1

8 (30.8)

0.08

9 (25.0)

0.27

3 (13.0)

1 (16.7)

0.83

Iatrogenic

14 (21.5)

6 (42.9)

0.03

7 (26.9)

0.39

9 (25.0)

0.45

4 (17.4)

1 (16.7)

0.76

Idiopathic

22 (33.8)

0 (0)

0

6 (23.1)

0.14

10 (27.8)

0.25

10 (43.5)

2 (33.3)

0.98

Hypospadias

10 (15.4)

1 (7.1)

0.34

2 (7.7)

0.16

5 (13.9)

0.71

4 (17.4)

1 (16.7)

0.93

Previous intervention

36 (55.4)

10 (71.4)

0.18

16 (61.5)

0.42

21 (58.3)

0.6

12 (52.2)

3 (50.0)

0.78

Dilation/DVIU

28 (43.1)

8 (57.1)

0.23

12 (46.2)

0.69

18 (50.0)

0.81

9 (39.1)

3 (50.0)

0.72

Bulbomembran ous Etiology Trauma

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Urethroplasty

11 (16.9)

2 (14.3)

0.77

4 (15.4)

0.79

6 (16.7)

0.95

4 (17.4)

1 (16.7)

0.99

Hypospadias Repair

2 (3.1)

1 (7.1)

0.32

1 (3.8)

0.77

1 (2.8)

0.88

1 (4.3)

0 (0)

0.65

15 (23.1)

4 (28.6)

0.59

5 (19.2)

0.55

10 (27.8)

0.32

4 (17.4)

1 (16.7)

0.7

Graft Urethroplasty

46 (70.8)

9 (64.3)

0.55

18 (69.2)

0.83

23 (63.9)

0.18

18 (78.3)

5 (83.3)

0.48

Staged

26 (40.0)

6 (42.9)

0.81

11 (42.3)

0.76

15 (41.7)

0.76

9 (39.1)

2 (33.3)

0.73

35 (53.8)

6 (42.9)

0.36

14 (53.8)

1

19 (52.8)

0.85

13 (56.5)

3 (50.0)

0.84

5 (7.7)

1 (7.1)

0.93

2 (7.7)

1

2 (5.6)

0.48

1 (4.3)

2 (33.3)

0.01

13 (20.0)

3 (21.4)

0.88

8 (30.8)

0.08

9 (25.0)

0.27

4 (17.4)

0 (0)

0.2

Surgery Performed EPA

Graft Source Buccal mucosa Genital AWS

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Table 2: Predictors of patients at risk for multiple stricture recurrences. Time to first stricture recurrence was not a significant predictor of the development of multiple subsequent recurrences (p=0.87). Conversely, predictors of multiple recurrences included longer stricture length (p=0.001), history of any previous stricture intervention (p=0.02), lichen sclerosus (p=0.003) and a history of CAD (p=0.005). Mann-Whitney U test utilized to determine statistical significance. CI = 95% confidence intervals. DM = diabetes mellitus; CAD = coronary artery disease; HTN = hypertension; DVIU = direct visual internal urethrotomy; EPA = excision and primary anastomosis; AWS = abdominal wall skin. Multiple recurrences (n=26)

Single recurrence (n=39)

p value

46.5 (32.8, 60.8)

43.0 (32.0, 58.0)

0.45

6.5 (4.4, 12.0)

4.0 (3.5, 6.0)

0.001

Median (IQR) Age Stricture length (cm)

0.36

Recurrence Timing Follow-up (months)

86.8 (65.7, 113.5)

85.3 (30.8, 115.0)

0.87

7.5 (4.5, 32.9)

9.0 (3.3, 25.0)

0.71

≤ 3 months

5 (19.2)

9 (23.1)

0.76

3-6 months

6 (23.1)

6 (15.4)

0.76

6 months - 1 year

4 (15.4)

6 (15.4)

0.53

Time to recurrence (months)

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1-5 years

8 (30.8)

15 (38.5)

> 5 years

3 (11.5)

3 (7.7)

Stricture History and Treatment

0.6

n (%)

Stricture Location

0.35

Penile

9 (34.6)

13 (33.3)

Bulbar

17 (65.4)

23 (59.0)

0 (0)

3 (7.7)

Previous intervention

19 (73.1)

17 (43.6)

0.02

Dilation/DVIU

14 (53.8)

14 (35.9)

0.16

DVIU

1 (3.8)

3 (7.7)

0.53

Urethroplasty

7 (26.9)

4 (10.3)

0.08

Hypospadias Repair

1 (3.8)

1 (2.6)

0.77

Trauma

3 (11.5)

3 (7.7)

0.6

Lichen Sclerosus

10 (38.5)

3 (7.7)

0.003

Iatrogenic

2 (7.7)

12 (30.8)

0.03

Idiopathic

7 (26.9)

15 (38.5)

0.34

Bulbomembranous

Etiology

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22

Hypospadias

4 (15.4)

6 (15.4)

1

2 (7.7)

13 (33.3)

0.02

22 (84.6)

24 (61.5)

0.05

18 (69.2)

8 (20.5)

<0.001

17 (65.4)

18 (46.2)

0.13

1 (3.8)

4 (10.3)

0.35

11 (42.3)

2 (5.1)

<0.001

DM

2 (7.7)

8 (20.5)

0.16

CAD

0 (0)

10 (25.6)

0.005

HTN

8 (30.8)

18 (46.2)

0.22

Smoking History

8 (30.8)

14 (35.9)

0.67

Surgery Performed EPA Graft Urethroplasty Staged Graft Source Buccal mucosa Genital AWS Comorbid Conditions

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