Objective: To assess the current etiology, features, and natural history of
urethral stricture disease in the developed world.
Methods: We analyzed the data from 1439 male patients with urethral stricture, who had undergone surgical treatment in our referral urethral center from 2000 to 2010. The preoperative evaluation included a detailed clinical history of stricture, uroflowmetry, retrograde and voiding cystourethrography, and urethroscopy. Statistical analysis was done for the stricture site, length, and etiology, patient age, and previous treatments.
Results: Strictures were posterior in 112 (7.8%) and anterior in 1327 (92.2%). In the anterior group, 439 were penile (30.5%), 675 bulbar (46.9%), 71 penile plus bulbar (9.9%), and 142 panurethral (4.9%). The main causes were iatrogenic in 556 (38.6%), unknown in 515 (35.8%), lichen sclerosus in 193 (13.4%), and trauma in 156 (10.8%). The main iatrogenic strictures were from catheterization in 234 (16.3%), hypospadias repair in 176 (12.2%), and transurethral surgery in 131 (9.1%). The stricture distribution increased until about 45 years and then decreased. Strictures were uncommon in those70 years old. The mean length was 4.15 cm; longer strictures were found in those with lichen sclerosus (7.45 cm) or after hypospadias repair (4.42 cm) and catheterization (4.40 cm). The mean length was also greater in the pretreated (4.34 cm) than in the untreated (3.64 cm) strictures.
Conclusions: Urethral stricture in developed countries mainly involves the anterior urethra, in particular the bulbar tract. The most common cause was iatrogenic. Hypospadias repair and lichen sclerosus represent emerging important causes. Finally, urethral stricture is not a disease of the elderly but involves all ages.
Male urethral stricture is one of the oldest and most difficult diseases known in urology. It has the potential for a significant economic impact and burden on each patient and society as a whole [ 1 ]. Nevertheless, a detailed assessment on this pathology is still lacking. This is due to the fact that the urethra is a complex organ, characterized by different areas each of which is prone to strictures of different type. Furthermore, in the last few decades its clinical history seems to have changed. Moreover, the differences between developed and developing countries should be considered. The literature contains few studies concerning the stricture etiology, with most information reported only in relation to the description of various reconstructive techniques [ 2 – 4 ] .
Only two recent publications focused on the specific topic of etiology but with small series of patients [ 5, 6 ].
Many questions about the characteristics of urethral strictures are still waiting for response and further study. What are the main causes of stricture today? How prevalent are the different causes? How do strictures of different site differ among themselves in terms of etiology, length or patient age? What are the ages most affected by the disease? May previous treatments worsen the strictures? The answers to these questions may help to prevent the development or worsening of the processes that cause the strictures.
We evaluated a large series of patients with urethral stricture to discover new information, in an effort to better understand the features and natural history of this complex urological disease in a developed country.
Materials and Methods
A retrospective study was performed in our Italian referral Center for urethral reconstruction, analyzing the whole database of male patients with urethral stricture who underwent surgical treatment between 2000 to 2010, indiscriminately of age. A total of 1439 patients were diagnosed, evaluated and surgically treated by the same urologist (E.P.). Preoperative evaluation included detailed clinical history of urethral stricture disease, physical examination, uroflowmetry, retrograde and voiding cystourethrography, and urethroscopy. With regard to the anatomical differences, we classified the strictures in posterior and anterior; the latter were further divided into 4 subgroups: penile, bulbar, pan-urethral (long and uninterrupted peno-bulbar strictures) and penile plus bulbar (interrupted and concomitant strictures in these urethral segments). According to the literature, the etiology was classified in unknown, congenital, infection, trauma, iatrogenic, LS and tumor. [ 2, 5-8 ]. The iatrogenic subgroup includes strictures subsequent to urological procedures involving the urethra: TS, prostate adenomectomy, prostatectomy, radiotherapy, HR, catheterization. Strictures were classified as catheterization when urethral catheter insertion was the only urethral manipulation. In many patients the catheterization had been performed a long time before stricture diagnosis or in an anesthetized, sedated or confused patient. Therefore exact data on the reason of catheterization, exact duration and catheter type, and whether catheterization was traumatic lack. In the cases classified as LS strictures Lichen Sclerosus had been pathologically confirmed by biopsy.
Statistical analysis was performed using the S-PSS 12.0 software. Differences between groups of patients in medians for quantitative variables and differences in distributions for categorical variables were tested with the One-Way ANOVA analysis of variance and chi-square test, respectively. Data are presented as mean ± standard deviation (SD). An alpha value of 5% was considered as threshold for significance.
Out of 1439 patients, 1402 (97.4%) underwent urethroplasty and 37 (2.6%) IU. The main characteristics of the study data set are showed in table 1.
According to the structure site 112 patients (7.8%) presented a posterior urethral stricture and 1327 (92.2%) an anterior urethral stricture.
In the anterior stricture group, the urethral site was penile in 439 (30.5%) patients, bulbar in 675 (46.9%), pan-urethral in 142 (9.9%) and penile plus bulbar in 71 patients (4.9%).
We identified several causes of stricture. The majority were iatrogenic 556 (38.6%) and unknown 515 (35.8%). LS represents 13.5% of cases (193) and trauma 10.8% (156). Of the iatrogenic, the most frequent were catheterization 234 cases (16.3%), HR 176 (12.2%), and TS in 131 cases (9.1%).
In the penile urethra the main causes were: HR in 140 cases (31.9%), LS in 107 (24.4%), and catheterization in 71 (16.2%); in the bulbar urethra were unknown in 417 cases (61.8%), catheterization in 117 (17.3%) and TS in 59 (8.7%); in the pan-urethral were: LS in 69 (48.6%), unknown in 32 (22.5%) and catheterization in 23 (16.3%) cases.
The main cause of penile plus bulbar multifocal strictures were catheterization in 20 (28.2%) cases, LS in 17 (23.9%) and HR in 12 (16.8%). In the posterior urethra TS represents a minor cause (11 patients: 9.8%) while the main cause was pelvic trauma (81 patients: 72.3%); the stenoses from this last category are commonly denominated in literature “pelvic fracture urethral distraction defects (PFUDD)”. Others minor causes of strictures grouped in Others were congenital 0.7% (10 cases), infections 0.4% (6 cases), tumor 0.2% (3 cases), and for the others iatrogenic group were radiotherapy 0.1% (1 case), prostate adenomectomy 0.3% (5 cases), prostatectomy 0.6% (9 cases).
Mean age was 45.1 (±16.1) yrs (range 2-84) . Patients with bulbar strictures were significantly younger when compared to all the other groups of patients (p= 0.001) [Table 1]. The frequency distribution of strictures tends to increase until about 45 yrs (median value), then decreases over the years. The strictures resulted more frequent between 20 and 70 years and were uncommon outside this range (Figure 1). In the 0-10 age group the strictures were mainly localized in penile urethra, and in the 11-40 group, in the bulbar urethra. Over 41 years, the strictures were uniformly localized in penile and bulbar urethra. The pan-urethral strictures were more frequent in patients older than 51 years (Figure 1-A). The main cause of stricture was iatrogenic (particularly HR) in 0-20 age group, unknown in 21-50 and iatrogenic over 51 years (Figure 1-B). Patients with urethral strictures related to a previous transurethral surgery were significantly older when compared to the other groups (p= 0.001) [Table 2].
According to the different strictures etiologies, urethral strictures secondary to LS were significantly longer when compared to the other different etiologies (p=0.001) [Table 2]. Most of the pre-treated strictures were unknown 383 (36.1%), catheterization 177 (16.7%), HR 159 (15%) and LS 144 (13.6%).
Out of 1439 patients enrolled in our study, 1060 (73.6%) had received previous treatments in other centers, while 379 (26.4%) were evaluated for the first time by our group [Table 3]. Patients who had received previous treatments were significantly older and presented longer strictures when compared to patients who were treated for the first time by our group (p= 0.001). Overall the mean urethral length resulted to be 4.15 (±3.4) cm. Pan-urethral strictures (12.19±2.8 cm) were significantly longer when compared to the other groups of urethral strictures (p= 0.001[Table1]
What is the most common site of stricture?
Our paper confirmed that urethral stricture in developed countries mainly involves the anterior urethra (92.2%), in particular the bulbar tract (46.9%), whilst the posterior urethra is involved only in 7.8% [ 5, 6, 8 ]. This explains why general urologists manage mainly bulbar strictures and more rarely penile strictures. Otherwise, the rarest posterior strictures are treated in highly specialized centers [ 7 ].
What is the most common cause of stricture today?
Past articles on stricture etiology are characterized by small series of patients and show that in the past few decades, among the male population of developed nations it has been registered a reduction of inflammatory causes in favour of the iatrogenic and unknown, whilst in developing nations the main causes are traumatic and inflammatory [ 2, 5, 9 ]. Our large series proved that the main cause of strictures was iatrogenic (38.6%): mostly catheterization (16.3%) and TS (9.1%). This should determine the urologists to be particularly careful when handling the urethra in order to reduce the trauma that could cause future strictures [ 5, 10, 11 ].
The data that a certain percentage of stenoses are catheter -induced might lead to suggest a restriction on the indications for potentially harmful catheterizations, avoidance of needless catheterizations and, if necessary, the use of small catheters for short durations or to suprapubic cystotomy when a prolonged drainage of urine is required. On the other hand, several authors have supposed that the urethral ischemia, activating the stenosing spongiofibrosis, might be caused by the combination of an indwelling catheter with a reduced local blood flow in hypovolemic states as in the open-heart surgery or similar haemodynamic situations. This pathogenesis was considered responsible for urethral stricture in a relevant number of patients undergoing cardiosurgery and, consequently, these authors suggested the use of suprapubic cystostomy instead of an urethral catheter which increases the urehral ischemia [ 12-14].
Iatrogenic strictures subsequent to HR represent 12.2%, so pediatric surgeons should inform parents that children undergoing HR might develop strictures in the future, and therefore should be monitored from this point of view.
This data seems to confirm that HR has a high rate of complications of which we only know the tip of the iceberg. In particular, out of 176 patients with HR strictures, 34 (19.3%) had an association with LS and this makes treatment more difficult to manage. Interestingly, there were less radiation-induced strictures than we would have expected for a developed country; on the other hand this finding is consistent with literature [ 5 ]. A large part (35.8%) of our strictures remains of unknown etiology, especially in the bulbar tract; perhaps some of these strictures are caused by unrecognized childhood perineal traumas or are congenital [ 15 ].
Another explanation could be inflammation from “undetected” infections that lie in the Littre’s glands located mainly in the mid/proximal bulb [ 8, 16 ]. However, we observed that the “detected” infectious causes (0.4%) have been reduced considerably, probably thanks to the widespread use of condoms in developed countries. Anyway, experts should make an effort to clarify this large group of unknown bulbar strictures.
In Western countries today, the most common cause for inflammatory strictures is LS.
The virtual increasing of this dermatological-urological pathology is probably due to its relatively recent identification and classification as a cause of urethral disease. However, the incidence of urethral involvement in male patients with genital LS and the percentage of LS strictures out of the total number of strictures remains unknown. In our series it represents 13.5%. In particular, it is the main cause (48.6%) of long pan-urethral strictures and the second cause (24.4%) of penile strictures after HR. The pathology progressively affects prepuce, glans and meatus. Meatal stenosis would lead to high pressure voiding and inflammation of the periurethral glands with potential progressive pan-urethral involvement [ 8, 17 ]. This would explain why we have never observed single bulbar strictures in LS without involvement of distal urethra.
Furthermore, intervention on a meatal or penile stricture in the early stages of the disease, instead of useless dilations, may be useful in stopping the large diffusion of urethral involvement. Another interesting observation is that we did not find LS in the posterior urethra, in accordance with the theory that the disease does not involve the different epithelium of this tract. This data confirms the need for further study on this disease in order to understand the etiopathogenetic processes and find appropriate treatment. Trauma was a recognized cause in 10.8% (respectively 5.6% of the anterior strictures and 72.3% of the posterior), in contrast with the higher incidence of up to 31% of traumatic strictures in developing countries with poor traffic regulations [ 18 ].
Despite the high number of pre-treated patients and with a long history of stricture, tumor was present only in 0.2% of cases. On the other hand, the literature has not confirmed the assumption that the prolonged state of inflammation of stenotic tissues and the repeated traumatic procedures (such as dilatations) could increase the risk of developing urethral cancer.
Is urethral stricture a typical disease of old age?
The strictures were frequent between 20 and 70 years and rare outside this range, contrary to the belief that the incidence of stricture increases proportionally with the age, especially in patients older than 55 years [ 8 ]. Urethral stricture is not a typical disease of the elderly but it involves all ages, carrying a potential impact on the patient’s sexual activity and quality of life and presenting a social cost.
Based on site and age groups (Figure 1-A), the strictures resulted mainly localized in penile urethra under 10 years and in bulbar urethra between 11 and 40 years; over 41 years they were uniformly localized in penile and bulbar urethra. Most of the long pan-urethral strictures were present over 51 years (mean 55.6 years). Based on stricture etiology and age groups (Figure 1-B), the strictures resulted mainly iatrogenic (in particular HR) under 20 yrs, unknown between 21 and 50 years, iatrogenic (mainly catheterization and TS) over 51 yrs.
Which are the longer strictures?
In our series mean length resulted highest for pan-urethral (12.19 cm) and LS strictures (7.45 cm). Length of strictures is higher in the pre-treated patients (mean 4.34 cm) versus untreated ones (mean 3.64 cm). The mean length (5.30 cm) and the mean age (49.8 yrs) were greater in patients undergoing dilatations. This data is in agreement with the old assumption that elderly men with a history of prior instrumentation develop longer strictures than younger and untreated men. All this suggests that inappropriate and repeated procedures (i.e. IU and dilations) could potentially transform a simple and short stenosis in a longer and more complex stricture [ 19 ]. Because most of the patients who were referred to our centre had undergone dilations and/or IU, our study confirms the existence of a trend among urologists, who initially resort to minimally invasive procedures instead of opting for urethroplasty as a first choice procedure. There were more penile urethroplasties performed prior to referral to our center than there were bulbar urethroplasties. This may reflect the fact that penile urethroplasties are more difficult to perform and prone to fail considering the scarcity of spongious tissue. Conversely, bulbar urethral repairs are more amenable to anastomotic urethroplasty, easier to perform and less prone to fail because of the abundant spongiosum.
Finally, we believe that considering stenoses from a length/site standpoint only and as idiopathic for the most part is an outdated concept. In our study we have investigated the actual percentage of the emerging causes of stenosis on the largest series of patients ever analyzed. These demographic news might help to prevent the development or worsening of the urethral stricture disease, and might help the experts to decide the most adequate therapeutic strategy. However, the limitation of our study is that results may not accurately reflect all urethral stricture disease patients, but rather describe only those that are severe enough to require surgery in a referral reconstructive center.
Urethral stricture in developed countries mainly involves the anterior urethra, in particular the bulbar tract. The most common causes of strictures are iatrogenic, so particular care must be taken when handling the urethra. HR and LS represent important emerging causes, responsible for the majority of penile and pan-urethral strictures which are also commonly acknowledged as the most difficult to treat. Urethral stricture is not a disease of the elderly but involves all ages.