The Short-Term Efficacy of Dilatation Therapy Combined with Steroid After Internal Urethrotomy in the Management of Urethral Stenoses

Introduction

U rethral stricture is one of the most encountered causes of lower urinary tract symptoms among male patients. According to the data from the United States and England, men are more likely to have urethral stricture with aging. Although 1 in 10,000 men experiences urethral stricture by the age of 25 years, the incidence increases up to 1 in 1,000 by the age of 65. ¹ Etiologic factors for urethral stricture include perineal trauma, urethral catheterization, urologic instrumentation, and chronic inflammatory diseases, such as lichen sclerosus et atrophicus and sexually transmitted diseases. Most cases of urethral stricture, however, are idiopathic, and most patients probably have unrealized childhood trauma. ² The severity and duration of urethral stricture are closely associated with complications. ³

The treatment depends on the localization, length (in mm), and the form of the stricture. Recently, the most common technique for the management of urethral stricture is visual endoscopic internal urethrotomy (IU), which was first applied by Hans Sachse in 1971; in addition, dilatation, laser urethrotomy, and permanent urethral stent applications have also been used. ⁴ It is generally accepted that urethrotomy and dilatation have similar efficacies and provide 50% improvement when initially used for short bulbar urethral strictures. If re-treatment is necessary, it is rarely curative. The curative success rate for IU is significantly better for bulbar than pendulous urethral strictures. ^5,6

The short-term success rate of IU varies between 39% and 73% for urethral strictures shorter than 1.5 cm, whereas, long-term recurrence rate is 56%. ^{7 –10} Self-catheterization, intralesional steroids, or application of mitomycin have been tried to prevent recurrences; various results have been reported. ^11,12

The purpose of the present study was to compare recurrence rates of self-catheterization and self-catheterization with steroids after UI in patients with primary bulbar urethral stricture.

Patients and Methods

Forty-five male patients in whom bulbar urethral stricture had been diagnosed between March 2002 and February 2005 were included in the study. Urine culture was obtained, and uroflowmetry was performed for all patients. Uroflowmetry was performed at strong desire at least twice for each patient, and mean of flow rates were evaluated. If the shape of the uroflow curves voided and residual volumes checked by ultrasonography were considerably different between two consecutive tests at strong desire, a third test was performed. Strictures were determined with a stenotic pattern and a maximum flow rate (Qmax) < 10 mL/sec during uroflowmetry. Adequate medical treatment was administered to patients who had infections, and the localization, caliber, and length of the strictures were determined via retrograde urethrocystography and urethrocystoscopy.

Cold knife IU at the 12 o'clock position was performed for all patients under general anesthesia using a 21F Storz urethrotome. Patients with a stricture >1.5 cm in length, additional obstructive pathologic conditions, such as benign prostatic hyperplasia, bladder neck strictures, and patients with recurrent strictures or associated neurologic disorders that can adversely affect bladder dynamics or self-catheterization, were excluded. Informed consent based on a clear appreciation and understanding of the facts, implications, and future consequences of the study was obtained from all patients.

After IU, patients were randomized into three groups: Group 1 performed self-dilatation with an 18F hydrophilic urethral catheter covered with steroid ointment (triamcinolone acetonide 1%) for 2 weeks after IU; group 2 performed urethral self-dilatation with an 18F hydrophilic urethral catheter for 2 weeks after IU; and an 18F silicon urethral catheter was placed for patients in group 3 after IU for 3 days. The dilatation procedure was performed just before bedtime to achieve maximal local effects of steroids.

Randomization was performed by selection of closed envelopes that were kept in the operating room by the patient before the procedure. The patients were told to repeat the process in case of nocturia because of the concern that the washing effect of nocturia might restrict the effect of steroid treatment. The repeated dilatations were similarly performed in both self-dilatation groups, and patients were asked to note the number of nocturia episodes and redilatations, if required. For the 2 week period, seven patients in group 1 and five patients in group 2 had a total of 13 and 11 additional self-dilatations, respectively. None of the patients needed more than one additional dilation per night. For each self-dilatation, 1 gm of steroid that totally covered the catheter was applied from the 20-gm tubes.

The amount of steroids used for total dilatations was calculated by weighing and subtracting the amount of the remaining steroid in the tube. The mean amount of steroid used for patients with and without nocturia was 15.8 vs 14 gm, respectively, and was not different between groups. None of the patients were advised to repeat dilations if they encountered progressive resistance.

During follow-up, patients were examined via uroflowmetry, either when they complained about obstructive symptoms or at day 14 and 3-, 6-, 12-, and 18-month visits. The test was performed at least twice for all patients for whom the uroflowmetry had shown obstructive pattern. Patients who had a maximum flow rate of <10 mL/sec during uroflowmetry received an additional treatment and were considered as having recurrence. The groups were compared in terms of flow rates and recurrence. SPSS 12 was used for statistical analyses. The RM analysis of variance test was used for the comparison of Qmax values between the groups, whereas a chi-square test was used for the comparison of recurrences.

Results

The mean duration of follow-up for the participants was 16.4 months (range 6–18 months, standard deviation [SD] ± 2.97), and the mean age was 33.4 years (range 19–45 years, SD ± 7.6) When the patients were evaluated with special emphasis to the etiology, trauma was identified in 13 (28.9%) of 45 patients, infection was demonstrated in 5 (11.1%), instrumentation in 11 (24.4%), and 16 (35.6%) patients had unknown causes. No statistical difference was observed between the groups with respect to age or etiology (Table 1).

The mean length and caliber of stricture was calculated by retrograde urethrography and urethrocystoscopy. It was 8.4 ± 2.3 and 1.4 ± 0.2 mm, respectively. The patients were evenly distributed among groups in terms of length and calibration (Table 2).

The Qmax value for all the groups on day 14 was approximately 20 mL/sec. The 6, 12, and 18 month Qmax values of the groups, from highest to lowest, were: Group 1> group 2> Group 3; however, the differences were not statistically significant (P = 0.464, Table 3).

Recurrence of urethral stricture was determined in three patients in group 1, seven patients in group 2, and in nine patients in group 3. These results indicated treatment success rates of 80% in group 1, 53.3% in group 2, and 40% in group 3. Although there were differences between the groups in terms of recurrence, the differences were not statistically significant (Table 4). All 19 patients who had suspected recurrence after uroflowmetry underwent cystoscopic evaluation (8 by rigid and 11 by flexible cystoscope) to confirm the diagnosis. In all patients, recurrence was at the same location. Seven patients were deemed cured after the second UI, whereas four needed uretroplasty and two underwent repeated UIs. Six patients were lost to follow-up.

Discussion

IU has gained an important place for the management of urethral stricture since the 1980s. ^13,14 In patients in whom urethral stricture is suspected, the measurement of urinary flow is part of the initial assessment. Determination of Qmax <10 mL/sec on uroflowmetry provides a diagnosis of urethral stricture with 96% accuracy. ¹⁵ If the flow rate is <10 mL/sec, the patient is likely to have hematuria, recurrent urinary tract infections, and obstructive signs on ultrasonography. Therefore, such a group of patients should be treated effectively. ¹

IU is a widely accepted method for the initial management of short-segment urethral stricture. ¹⁶ When the reported outcomes of IU are reviewed, the curative success rates are clearly quite diverse. Santucci and McAninch ¹⁷ have reported a curative success rate of IU of approximately 20%, whereas Pansadoro and Emiliozzi ¹⁰ reported a curative success rate of 30% to 35%. These low success rates suggest the need for the development of additional new techniques to prevent wound contraction and thus recurrent stricture. Even the use of techniques such as Foley catheter placement, self-catheterization, and the use of urethral stents has unfortunately been proved to be insufficient in the long-term. Analyses demonstrate that a second IU does not increase the cure rate. ⁴ After the primary treatment, strictures can recur within weeks or months, but generally within 2 years. ^{18 –20}

Urethral strictures eventuate from hypertrophic scar tissue caused by fibroblast proliferation at the tunica propria. IU provides a secondary wound healing process by aiming to dissect the scarred epithelium. In the secondary wound healing, epithelization commences from the wound edges. If this epithelization can be compeleted before wound contraction, originating from the tunica propria that markedly narrows the lumen, IU may be successful. Wound contraction is provided by myofibroblasts, which have been differentiated from fibroblasts and in which many ultrastructural and functional properties are equivalent to smooth muscle cells. During the wound healing process, the migration and proliferation of fibroblasts begins on the second day and proliferation of collagen and fibroblasts continues for the following 2 weeks. ²¹ If any medication or intervention can delay wound contraction at this stage, the probability of recurrent stricture can decrease. ^4,11

Steroids are known to decrease the amount of collagen fibers and fibroblasts and inhibit the proliferation of fibroblasts in wound tissue. In an animal model used by Richters and associates ²² after the local application of a single dose of steroid on a wound site, it was determined that a reduction up to 30% in wound contraction occurs by day 28, and a reduction up to 50% occurs in the amount of myofibroblasts by day 4. It is known that fibroblast reactions can experimentally and clinically be suppressed by steroids. ²² Because of such effects, local administration of steroids may be beneficial for the treatment of urethral stricture by preventing wound contraction and, thus, recurrence. Also, beneficial effects might positively affect the outcome after hypospadias repair and urethroplasty. ²¹

Karhonen and colleagues ¹² have indicated that the results of patients who were treated with intralesional steroid injections after IU are poor, and self-dilatation may be a better adjuvant therapy, whereas in a study performed in a selected group of 96 cases, Sarpe and coworkers ²³ have reported the beneficial effects of circular steroid injections instead of applying steroids directly into the stricture. In our opinion, two issues should capture attention concerning clinical practice for patients who are receiving intralesional treatment: The effect of injections is short and it is hard to repeat them; and injections themselves may contribute to scar formation via the traumatic effect of the needle. Based on these issues, we planned a treatment modality that would eliminate the above-mentioned disadvantages. In the current study, we hypothesized an advantage of a combined therapy of self-dilatation and steroids by eliminating the factors mentioned above.

The present study is a prospective, randomized study in which self-dilatation has been combined with steroids after IU. In the present study, it appears that dilatation combined with steroids made a striking but statistically insignificant contribution with respect to Qmax values and curative efficacy; therefore, long-term studies in large groups would enhance the objectivity of the outcomes.

In the present study, among all the groups in which patients were alike in terms of initial mean Qmax values, the best mean Qmax values at 6, 12, and 18 months were observed in the dilatation + steroid group. When the groups were compared with respect to Qmax values, it was observed that self-dilatation combined with steroids made an important contribution to Qmax, although the difference was not statistically significant.

When evaluated with respect to efficacy, the success rate of IU, which was about 40% alone, was increased up to 80% by self-dilatation combined with steroids. This grandiose difference may be considered to be very important to maintain the achieved efficacy of IU. Certainly, corroboration of these clinical results by histopathologic studies will provide more objective outcomes.

The limitations of the study include small number of patients with a relatively short follow-up period. Some of the recurrences, however, occur usually within 3 to 12 months of IU. Repeated IU might be useful in patients who have a stricture recurrence more than 6 months after the initial procedure, but if a stricture recurs within 3 months, repeated IU offers no long-term cure. ²⁴ We believe that a mean follow-up of 16.4 months covers this critical period. The majority of recurrences in this study, however, occurred at 18 months. It warrants mentioning that longer follow-up is crucial and internal urethrotomy should not be considered curative in the majority of patients.

From this study, which can be considered as a short-term description of treatment results, one can assume that the use of steroids posturethrotomy at least delays the recurrence of stricture disease. For results regarding the effect of steroids in actual cure, further long-term studies are necessary. Another limitation is the lack of standard flexible cystoscopic evaluation. If the uroflow patterns and Qmax values are satisfactory and the patient has no complaints practically, however, we believe that cystoscopic evaluation can be postponed. None of our patients without a complaint chose to undergo cystoscopic evaluation.

Conclusion

An efficacy of 35% for IU, which is the primarily applied treatment method in short urethral stricture, is not acceptable. Therefore, research for adjuvant therapies continues. One approach may be self-dilatation combined with steroids, This method is easily applicable as an adjuvant therapy without complications. Such an approach may at least delay the recurrence of stricture disease. For curative, long-term effects, this technique deserves to be tested on large groups of patients with special emphasis on objective verification of the safety and efficacy profile.