A geographic analysis of male urethral stricture aetiology and location

Authors


Correspondence: Daniel M. Stein, Department of Urology, Feinberg School of Medicine, Northwestern University, Tarry Building 16-703, 303 E. Chicago Ave., Chicago, IL 60611, USA.

e-mail: daniel-stein@fsm.northwestern.edu

Abstract

What's known on the subject? and What does the study add?

  • The incidence of specific aetiologies of urethral stricture disease has been reported from a variety of series throughout the world.
  • Most reported urethral stricture series are from single institutions or from a specific region of the world. We provide a multi-centred series to compare aetiologic incidence between differing regional populations.

Objective

  • To better understand distinct regional patterns in urethral stricture aetiology and location among distinct regional populations.

Patients and Methods

  • Data on 2589 patients who underwent urethroplasty from 2000 to 2011 were collected retrospectively from three clinical sites, including 1646 patients from Italy, 715 from India and 228 from the USA.
  • Data from all sites were single-surgeon series. As the data from the Italian and US cohorts were similar in aetiology, location and demographics, we combined these data to form group 1, and compared this group with men in the Indian cohort, group 2.
  • Age, stricture site and primary stricture aetiology were identified for each patient. Stricture site and primary aetiology were determined by the treating surgeon. Primary aetiology was defined as iatrogenic, trauma including pelvic-fracture-related urethral injury (PFUI), lichen sclerosus (LS), infectious, congenital, or unknown.

Results

  • There were more penile strictures (27 vs 5%) and fewer posterior urethral stenoses (9 vs 34%) in group 1.
  • There were more iatrogenic strictures identified in group 1 (35 vs 16%). When comparing the aetiology of iatrogenic strictures alone, more strictures in group 1 were attributable to failed hypospadias repair (49 vs 16%).
  • More patients presented with LS (22 vs 7%) and external trauma (36 vs 16%) in group 2.
  • Prevalence of strictures of infectious aetiology was low (1%) with similar proportions between the two groups.

Conclusions

  • We have shown that significant regional differences in stricture aetiology exist in a large multicentre cohort study. Group 1 had a higher proportion of penile strictures, largely owing to more iatrogenic strictures and, in particular, failed hypospadias repair. Group 2 had a higher proportion of PFUI and LS-associated urethal stricture.
  • Identified infection-related urethral stricture was rare in all cohorts.
  • Significant regional differences in stricture aetiology exist and should be considered when analysing international outcomes after urethroplasty. These data may also help the development of international disease prevention and treatment strategies.
Abbreviations
PFUI

pelvic-fracture-related urethral injury

LS

lichen sclerosus

Introduction

Urethral stricture disease is a relatively common problem in men, with an estimated prevalence of 229–627 per 100 000 males [1]. Historically, infection-related urethritis was the most commonly identified aetiology, accounting for 40% of urethral strictures; however, with improved public education, diagnosis and treatment there has been a shift such that urethritis is only identified as the cause of urethral stricture in a small proportion of cases. In the developed world, the majority of urethral strictures are now thought to be iatrogenic or idiopathic in aetiology [2, 3]; however, there is significant regional variation in stricture aetiology with different patterns noted in other parts of the world. Single-institution studies in a variety of countries have shown varied prevalence of aetiologies of urethral stricture [4-9].

Discrepancies in stricture aetiology may be related to access to quality healthcare, social and environmental settings, inherent regional differences and practice patterns, or variation in diagnosis. Differences in aetiology can lead to variation in the manifestation and treatment of urethral stenosis or stricture; therefore, a greater understanding of global patterns can allow more appropriate comparisons of interventions and outcomes between regions, improved understanding of disease pathogenesis, and better strategies for disease prevention and treatment. The purpose of the present study was to analyse a large multicentre, multiregional cohort of men with urethral stricture or urethral stenosis to demonstrate that regional patterns in stricture aetiology exist between distinctly different patient populations.

Patients and Methods

Data on patients who underwent urethroplasty from 2000 to 2011 were collected retrospectively from three clinical sites. The sites included the Department of Urology of the Northwestern University Feinberg School of Medicine in Chicago, USA; the Kulkarni Urethroplasty Centre in Pune, India; and the Centre for Reconstructive Urethral Surgery, Arezzo, Italy. Age, stricture site and primary stricture aetiology were identified for each patient. Stricture site and primary aetiology were determined by the treating surgeon at each clinical site. Primary aetiology was defined as iatrogenic, trauma (including pelvic-fracture-related urethral injury [PFUI]), lichen sclerosus (LS), infectious, congenital, or unknown. All sites were single-surgeon series. As they had similar aetiology, location and demographics, data from the Italian and US cohorts (group 1) were combined and compared with men in the Indian cohort (group 2). All statistical analysis was performed using IBM SPSS® v.19 with proportion estimate 95% CIs as listed, and a P value <0.05 was considered to indicate statistical significance.

Results

A total of 2589 patients were identified; 1646 patients from Italy, 715 from India, and 228 from the USA. The mean age was 41.4 years with a similar age distribution between geographic locations (Table 1).

Table 1. Stricture aetiology and location in 2594 patients.
 US/Italy (group 1), N = 1877India (group 2), N = 717P < 0.05
 95% CIn (%)95% CI
Aetiology, n (%)     
 Unknown776 (41.3)39.2–43.7169 (23.6)20.5–26.8Y
 Iatrogenic657 (35.0)32.7–37.1119 (16.6)13.8–19.2Y
Failed hypospadias repair319 (17.0)15.3–18.919 (2.6)1.5–3.8Y
Catheter185 (9.9)8.5–1.241 (5.7)4.2–7.5Y
Instrumentation117 (6.2)5.2–7.425 (3.5)2.2–4.9Y
Radiotherapy11 (0.6)0.3–0.91 (0.1)  
TURP25 (1.3)0.8–1.933 (4.6)3.1–6.1Y
 Trauma296 (15.8)14.1–17.4259 (36.1)32.6–39.6Y
 LS129 (6.9)5.6–8.0154 (21.5)18.3–24.5Y
 Infection15 (0.8)0.4–1.213 (1.8)0.8–2.8N
 Congenital4 (0.2)0.1–0.43 (0.4)0–1.0N
Location     
 Bulbar1046 (55.7)53.5–57.9303 (42.3)38.6–46.0Y
 Penile506 (27.0)24.9–28.938 (5.3)3.8–7.1Y
 Posterior170 (9.1)7.7–10.4247 (34.4)30.8–38.1Y
 Panurethral155 (8.3)7.0–9.5129 (18.0)15.2–20.8Y
Mean age, years42.741.9–43.438.236.9–39.4Y

Overall there were more penile strictures (27 vs 5%; 95% CI 25–29% and 4–7%, respectively) and fewer posterior urethral stenoses (9 vs 34%; 95% CI 8–10% and 31–38%, respectively) in group 1 than in group 2 (Fig. 1). Broadly categorized aetiologies for penile strictures were quite similar between the groups (Table 1) with a large proportion attributable to iatrogenic causes in both groups.

Figure 1.

Percent of subjects within each group corresponding to specific urethral stricture location and aetiology.

There were more iatrogenic strictures identified in group 1 than in group 2 (35 vs 16%; 95% CI 33–37% and 14–19%, respectively). When comparing the aetiology of iatrogenic strictures alone, significantly more strictures in group 1 were attributable to previous failed hypospadias repair (49 vs 16%; 95% CI 45–52% and 9–23%, respectively) than in group 2 (Figs 1, 2).

Figure 2.

Percent of specific iatrogenic aetiologies of patients with iatrogenic strictures within each group.

Conversely more patients presented with LS (22 vs 7%; 95% CI 18–25% and 6–8%, respectively) and external trauma (36 vs 16%; 95% CI 33–40% and 14–17%, respectively) in group 2.

The total number of men from all sites presenting with strictures of infectious aetiology was low (1%), with similar proportions in each group.

Discussion

In the present study, we provide a unique comparison of stricture aetiology between two cohorts of patients with urethral stricture disease. These populations have very different profiles with regard to socio-economics, healthcare exposure, geographic region and disease risk factors. Group 1, composed of patients from the USA and Italy, may represent a resource-rich ‘developed country’ setting while group 2, composed of patients from India may represent a ‘developing country’ setting. The results of the present study suggest that the aetiology of stricture disease appears to be affected by the geographic region.

Iatrogenic Strictures

Iatrogenic aetiology was the most commonly identified cause of urethral stricture in group 1 (35%), which is similar to other series in similar countries [2, 3, 10, 11]. The disparity between the groups may be attributable to regional factors contributing to increased healthcare interventions in this group. A large proportion of the iatrogenic strictures in group 1 were owing to hypospadias failures, accounting for 17% of all strictures and 48% of iatrogenic strictures. Hypospadias failures probably also partially account for the higher incidence of penile strictures in group 1. It is presumed that hypospadias is surgically repaired much more often in developed countries as opposed to developing countries and thus may contribute to the disparity in iatrogenic strictures between our groups.

Traumatic Strictures

Trauma was the most common aetiology identified in group 2 (36%), leading to a significantly higher rate of PFUI and subsequent urethral stenosis and trauma-induced urethral stricture. Given the retrospective nature of our data, we were limited to aetiological description of trauma with no distinction made between PFUI and other external trauma; however, 95% of traumatic injuries in group 2 were categorized as posterior, implying PFUI, compared with 56% of those in group 1. Furthermore, overall assessment of the data by site directors showed that the vast majority of traumatic presentations in group 2 were attributable to PFUI. The higher prevalence of PFUI in our Indian cohort is probably attributable in large part to the greater number of traffic-related accidents in a rapidly growing population. These dangerous traffic conditions, combined with a lack of appropriate emergent urological intervention, may increase the risk of PFUI and subsequent urethral stenosis [12, 13].

Infectious Aetiology

In both groups, infection was an infrequently identified cause of urethral stricture. Rates of urethral stricture attributable to infection have previously been assumed to be a result of low access to care; however, significant variation in prevalence rates has been documented in cohorts from around the world (3–82%) [6, 9, 14-21]. Similarly to the US/Italy cohort, the Indian cohort had a low prevalence of stricture attributable to infection, despite potential disparities in socio-economics and access to healthcare. Our findings and variation in studies from around the world raise numerous questions with regard to the role of infection in stricture aetiology. In many regions of the world, the majority of cases of infectious urethritis are likely go untreated, yet stricture disease is not an epidemic. Furthermore, as we have shown in our cohorts, infectious aetiology is difficult to demonstrate, representing only a very small fraction of identified aetiology of stricture disease.

Lichen Sclerosus

The significant difference in the prevalence of LS supports the idea of regional variation. LS is a disease whose pathophysiology is poorly understood but it appears to be primarily an autoimmune phenomenon with a known genetic component [22]. Hypothesized triggers include chronic inflammation and infection [22]. In group 2, we found a significantly greater proportion of urethral stricture attributable to LS than in group 1 (22 vs 6.9%). This difference could possibly be explained by varied genetic predispositions in the different populations as well as different exposure to triggers. Mathur et al. [7] reported no cases of LS-induced urethral stricture in a cohort from Pradesh, India. This discrepancy within the same country may be the result of inherent differences in criteria for the diagnosis of LS or the result of exclusion criteria in the Pradesh series.

Idiopathic Strictures

The proportion of idiopathic strictures in the present series was significantly higher in group 1 (41 vs 24%). This relationship is consistent with reported prevalence of idiopathic strictures in other series, with a trend toward higher prevalence in developed countries (18–44%) [2, 3, 10, 11] than in developing countries (4–32%) [5, 7-9, 15-18, 20, 21]. Despite this difference, it must be acknowledged that these results may be purely attributable to differences in data collection. Variation may exist in certain regions of the world with regard to patient questioning and the methods in attributing aetiology of disease. In both groups, the majority of idiopathic strictures (82%) were bulbar which has been noted elsewhere in the literature [2, 3]. Hypotheses for the cause of idiopathic bulbar strictures have been proposed and include congenital origins or the possible manifestation of unrecognized paediatric trauma [2, 3, 23, 24]. Regional discrepancy between idiopathic strictures may possibly be attributable to genetic or developmental differences; however, further evaluation with detailed history and histological evidence would be needed to elucidate these differences.

Significance of Regional Differences in Stricture Aetiology

The region-specific aetiologies which give rise to varied presentations of urethral stricture are of important consideration, not only in treatment but also in educating the next generation of urologists. With increased globalization and immigration comes increased exposure to a wider patient population. It is important that we assure that urology residents in developed nations receive appropriate exposure to the more complex strictures frequently encountered in the developing world. Certain technical challenges, such as the transpubic approach that is rarely used in the developed world, could be re-emerging. It is also important to ensure that residents in developing nations have opportunities for training in reconstructive urology in developed nations to expose them to the standard of surgical care for urethral reconstruction.

Limitations

The limitations of the present study are important to consider for future research. The aetiology of each stricture was specific to the surgeon who evaluated the patient without standardization. For example, the aetiology definition ‘idiopathic’ in one group may have been defined differently in another group. Furthermore, retrospective data collection and limitations of charted data may have led to increased rates of idiopathic aetiologies. The definition of LS was not limited to histological evaluation across the sites and thus may have been biased by site surgeon definition. Lastly, all data collected were from patients presenting for urethroplasty, which may not be a completely representative population of all patients with urethral stricture. Further prospective comparison of time to treatment, type of treatment, and outcome of treatment by geography and aetiology is warranted.

In conclusion, we have shown that significant regional differences in stricture aetiology exist in a large multicentre cohort study. Our USA/Italy cohort had a higher proportion of penile strictures, largely because there were more iatrogenic strictures and in particular, failed hypospadias repair, while there was a higher proportion of PFUI and LS-associated urethal stricture in the Indian cohort. Infection-related urethral stricture was rare in all three cohorts of men.

Different areas of the world present different risk factors for stricture formation. These risk factors may include socio-economics, exposure to healthcare interventions, infrastructure, genetics, environment, or a number of other factors. Greater understanding of risk factors and regional variation may help identify the pathogenesis of certain manifestations of urethral stricture disease that are more poorly understood such as LS. Furthermore, regional variation should be considered when analysing international outcomes studies after urethroplasty. This information may help the development of disease prevention and treatment strategies.

Conflict of Interest

None declared.

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