Stesura Seveso Archivio Italiano di Urologia e Andrologia 2025; 97(3):14203 1 REVIEW many patients with various etiologies as trauma, infec- tion, ischemia, inflammation, instrumentation, or other unknown causes (1). Studies reported that it occurs in 200 in 100,000 people, with an increasing incidence rate in the last 50 years (2). The treatments recommended for patients with urethral strictures include urethrotomy, dilatation, and urethroplas- ty (3). Internal urethrotomy is used for urethral stricture with a length of less than 1.5 cm. However, the efficacy of internal urethrotomy is still being questioned because of its high stricture recurrence rate (4). A case-control study regarding urethral stricture in Indonesia by Gede et al. in 2017 stated that the urethral stricture recurrence after internal urethro- tomy was as high as 92.5% (5). Many treatment alternatives after internal urethrotomy have been widely studied to reduce the urethral stricture recurrence rate. Corticosteroid is one of the most commonly used drugs studied. It has been widely used in many centers to reduce scar formation. It is able to decrease collagen, glycosaminoglycan synthesis, and the expression of inflammatory mediators (6). Among corticosteroids, triamcinolone is regularly reported. However, results of this approach are conflicting. Many studies investigating the role of corticosteroids have been published (7-10). Therefore, we aimed to assess the efficacy of triamcinolone following internal urethrotomy in preventing urethral stricture recurrence. MATERIALS AND METHODS This study was a systematic review and meta-analysis per- formed and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. The protocol is registered in the PROSPERO database with the registration number CRD42020202254. Eligibility criteria We used the following inclusion criteria to determine the eligibility of studies: Introduction: Urethral stricture, character- ized by urethral narrowing due to fibrosis and scar tissue, is a common urological condition. It occurs in about 200 per 100,000 people, with increasing incidence over the past 50 years. Internal urethrotomy is commonly performed for short strictures, but its high recurrence rate has led to the exploration of adjunctive treatments like adjunct of triamci- nolone application. This study aimed to analyze the effect of tri- amcinolone as adjunctive therapy for internal urethrotomy on reducing urethral stricture recurrence in urethral stricture patients. Methods: A systematic search was conducted in PUBMED, ScienceDirect, and Google Scholar. This review was conducted according to the PRISMA guideline, and the protocol has been registered in the PROSPERO database (CRD42020202254). Results: Six RCTs, including 373 urethral stricture patients, were eligible for this study. Pooled results of the included studies showed a significant difference between the triamcinolone and control groups, indicating a lower recurrence rate in the triamcinolone group (OR = 0.49 95% CI 0.31-0.77, p = 0.002). A significant difference was seen in the ointment with clean intermittent catheterization (CIC) intervention subgroup (OR = 0.47 CI 95% 0.26-0.82, p = 0.009), but not in the submu- cosal injection subgroup (p > 0.05). The treatment and control groups had similar maximum urinary flow rate (Qmax) at six and twelve months (p > 0.05). Conclusions: Triamcinolone ointment with CIC reduced urethral stricture recurrence following internal urethrotomy, whereas submucosal injection did not. Both treatments do not increase the maximum urinary flow rate. KEY WORDS: Urethral stricture; Triamcinolone; Internal urethro- tomy; Systematic review. Submitted 29 July 2025; Acceptd 27 August 2025 INTRODUCTION Urethral stricture is one of the most commonly found urological problems, in which there is a narrowing of the urethra caused by fibrosis and scar tissue. It can occur in Triamcinolone application following internal urethrotomy for reducing urethral stricture recurrence rate: A systematic review and meta-analysis of randomized controlled trials Dimas Panca Andhika 1, 2, 3, Tarmono Djojodimedjo 1, 4, Furqan Hidayatullah 1, 4, Zakaria Aulia Rahman 1, 4, Ilham Akbar Rahman 1, 4, Prima Ardiansah Surya 1, 4, Mohammad Ayodhia Soebadi 1, 4 1 Department of Urology, Faculty of Medicine, Airlangga University, Surabaya, Indonesia; 2 Department of Anatomy, Histology, and Pharmacology, Faculty of Medicine, Airlangga University, Surabaya, Indonesia; 3 Universitas Airlangga Hospital, Surabaya, Indonesia; 4 Dr. Soetomo General-Academic Hospital, Surabaya, East Java, Indonesia. DOI: 10.4081/aiua.2025.14203 Summary Archivio Italiano di Urologia e Andrologia 2025; 97(3):14203 D. Panca Andhika, T. Djojodimedjo, F. Hidayatullah, et al. 2 (1) Randomized Controlled Trial (RCT) study design, (2) studies comparing Triamcinolone with internal urethro- tomy alone, (3) men with urethral stricture treated with internal urethrotomy. Studies with the following criteria were excluded: (1) non- English articles, (2) animal studies, (3) unpublished arti- cles, and (4) abstract-only articles. Search strategy, study selection and data extraction We performed a systematic search in the MEDLINE, PubMed, ScienceDirect and Google Scholar databases. We used the keyword “Triamcinolone AND urethra OR Stricture”. We used Mendeley to combine the results from the databases and evaluate possible duplicates. The pri- mary screening of the studies was performed by reading the titles and abstracts. The studies that fit the inclusion criteria based on the title and abstract were evaluated in their full-text forms during the secondary review. Both the primary and secondary screenings in this systematic review were performed by three investigators. Any dis- putes between the investigators would have been resolved in a discussion. In the screening process of this review, there weren’t any inter-rater disagreements. Outcome measurement and data analysis The primary outcome was urethral stricture recurrence rate, whereas the secondary outcomes were maximum urinary flow rates examined in the 6th and 12th month after urethrotomy. The analyzed primary outcome was dichotomous and presented in an odds ratio (OR) with a confidence interval (CI) of 95%. The secondary outcomes were continuous and analyzed using a mean difference (MD). The heterogeneity between studies was calculated using I2. It was assumed that heterogeneity between stud- ies was statistically high if the I2 > 50%, then the random effects model analysis would be used. Otherwise, a fixed effecst model would be used. For statistical analysis RevMan version 5.4 (The Cochrane Collaboration, 2020) for Windows was used, presenting results in the form of Forest plots and narrative description. Risk of bias assessment Risk of bias was assessed using Cochrane Risk of Bias Tools for Randomized Trials 2 (9). Two reviewers conducted an independent bias assessment, with the results of the risk of bias being low risk, some concerns, and high risk. RESULTS In the initial search, as shown in Figure 1, 458 studies were obtained from the PubMed, Science-Direct, and Google scholar databases, and three studies were obtained from the references of previous meta-analysis. A total of 26 studies were extracted from the primary screen. The full paper version of the articles was evaluated in the sec- ondary screening to determine which studies fit the inclu- Figure 1. PRISMA flowchart of the study. Archivio Italiano di Urologia e Andrologia 2025; 97(3):14203 3 Triamcinolone following internal urethrotomy sion and exclusion criteria for this review. There were six articles that could be analyzed qualitatively and quantita- tively in this study. All studies were presented in the base- line characteristics table in Table 1. A total of 373 patients were included in this review. There were six RCT studies that met the inclusion criteria for this study. Overall, each study limited the length of the stricture to below 2 or 1.5 cm. Four studies evaluated the application of triamcinolone ointment with clean intermit- tent catheterization (CIC), whereas two studies adminis- tered submucosal triamcinolone injection. The etiologies of the strictures consisted mostly of infections and trau- mas. The strictures mostly occurred in the bulbar area, with a few studies reporting both bulbar and penile, as well as multiple strictures. Most studies excluded patients with a history of urethroplasty, except for Hosseini et al. (11). Complications were only found in the study by Tabassi et al. (12). Table 1. Baseline characteristics of studies. Author (Year) Group Sample Age Action Operator Intervention Previous Location Length of Stricture Complication Follow up (mean + SD) urethroplasty (number stricture etiology rate (n) (months) year (n) of strictures) Mazdak, (2010) Triamcinolone 23 37,1 ± 20,9 20fr DVIU Single Submucosal No previous Bulbar (NR) < 1,5 Trauma, No 24 (cold knife) operator triamcinolone urehtroplasty inflammatory, complications injection unknown Without 22 34 ± 19,9 None triamcinolone Regmi (2018) Triamcinolone 27 37,2 ± 1,6 21fr DVIU Single 16 fr CIC + No previous Bulbar or < 1,5 Trauma, No 12 (cold knife) operator triamcinolone urehtroplasty penile or inflammatory, complications ointment 1% both (NR) unknown Without 28 36 ± 1,7 16 fr CIC triamcinolone Tabassi (2011) Triamcinolone 34 42,38 DVIU NR Submucosal No previous Bulbar or < 1,5 Trauma, Infection (1), 24 (cold knife) triamcinolone urehtroplasty penile or catheterization, bleeding (3), injection both (NR) infection, extravasation (2) unknown Without 36 42 None Infection (2), triamcinolone bleeding (3), extravasation (2) Gucuk (2010) Triamcinolone 15 33,4 ± 7,6 21fr DVIU NR 18fr CIC + No previous Bulbar (NR) < 1,5 Trauma, No 18 (cold knife) triamcinolone urehtroplasty infection, complications ointment 1% instrumentation, unknown Without 15 18fr CIC riamcinolone Hosseini (2008) Triamcinolone 30 37,7 ± 17,1 DVIU Multi 18fr CIC + 18 Multiple (NR) < 1,5 Urethral No complications 12 (cold knife) operators triamcinolone distraction ointment 1% disease, straddle injury, urethral catheterization Without 34 34,5 ± 13,3 18fr CIC 17 triamcinolone Ergun (2015) Triamcinolone 30 60,7 DVIU Single 14fr until 20fr CIC No previous Bulbo- < 2 Iatrogenic No 24 (cold knife) operator + triamcinolone urehtroplasty membranous (endoscopic complications ointment (NR) urologic surgery, urethral catheterization), trauma, idiopathic Contratubex 30 57,8 14fr until 20fr CIC + contratubex ointment Without 30 61,2 14fr until 20fr CIC triamcinolone Without 19 47 ± 8,8 18fr CIC triamcinolone *DVIU: Direct Vision Internal Urethrotomy; CIC: Clean Intermittent Catheterisation; SD: Standard Deviation; Fr: French; NR: Not Reported. Archivio Italiano di Urologia e Andrologia 2025; 97(3):14203 D. Panca Andhika, T. Djojodimedjo, F. Hidayatullah, et al. 4 All studies included in the qualitative and quantitative analysis in this review were randomized controlled trial (RCT) studies; thus the Cochrane Risk of Bias Tools for Randomized Trials 2 was used (13), as shown in Figure 2. In this study, four studies had a low risk of bias. The studies conducted by Mazdak et al. (14) and Tabassi et al. (12) were at risk for randomization bias since the studies did not clearly explain the randomization process and whether the allocation process was blinded. Urethral stricture recurrence rate after triamcinolone application (ointment lubrication and injection) All six studies evaluated the application of triamcinolone after urethrotomy, as shown in Figure 3. The data of the studies were considered homogenous (I2 = 0%, p = 0.45). The fixed model analysis in the forest plot showed a lower urethral stricture incidence of the triamcinolone group (OR = 0.49 95% CI 0.31-0.77, p = 0.002). Further sub- group analyses were performed based on the methods of application, injection, and ointment. Urethral stricture recurrence rate after triamcinolone ointment lubrication There were four studies evaluating the application of tri- amcinolone ointment lubrication in Figure 3. The com- bined data obtained in each study was homogeneous (I2 = 0%, p = 0.45). The fixed effects model analysis in Figure 3 showed that there is a significant difference in urethral stricture incidence between the treatment and control groups (OR = 0.47 CI 95% 0.26-0.82, p = 0.009). Figure 2. Risk of bias assessment using Cochrane RoB Tool 2. Figure 3. Urethral stricture recurrence rate after triamcinolone application. Archivio Italiano di Urologia e Andrologia 2025; 97(3):14203 5 Triamcinolone following internal urethrotomy Urethral stricture recurrence rate after submucosal triamcinolone injection There were two studies evaluating submucosal triamci- nolone injection. The pooled odds ratio analysis in the subgroup of Figure 3 showed that the combined data obtained from each study were homogeneous (I2 = 33%, p = 0.22). The analysis was carried out using a fixed effect models, showing an insignificant difference (OR = 0.53 CI 95% 0.25-1.13, p = 0.10). Urethral recurrence rate and follow-up duration Figure 4 shows the visualization of the recurrence rate probability of the studies with different durations of fol- low-up. Maximum urinary flow rate (Qmax) in 6 months There were two studies reporting the mean maximum urinary flow rate after six months. The data of the studies were homogeneous with the value of (I2 = 0%, p = 0.84). The fixed effect model analysis in Figure 5 showed that there was no difference in Qmax between groups (MD = 0.91 CI 95% -0.82-2.63, p = 0.30). Maximum urinary flow rate (Qmax) in 12 months There were two studies describing the mean maximum uri- nary flow rate after 12 months as shown in Figure 6. The combined data obtained in each study were homogeneous (I2 = 0%, p = 0.52). The analysis was carried out by a fixed Figure 5. Maximum urinary flow rate (Qmax) at 6 months. Figure 6. Maximum urinary flow rate (Qmax) at 12 months. Figure 4. Recurrence rate probability of the studies with different durations of follow-up. Archivio Italiano di Urologia e Andrologia 2025; 97(3):14203 D. Panca Andhika, T. Djojodimedjo, F. Hidayatullah, et al. 6 effects model, showing no difference in Qmax between groups (MD = 0.77 CI 95%-1.52-3.05, p = 0.51). DISCUSSION Symptomatic urethral strictures impede voiding function and may significantly impact patient’s quality of life (15). The role of corticosteroids for urethral strictures and stenoses has been studied for decades (16-18). Triamcinolone is a long-acting synthetic glucocorticoid with anti-inflammatory and vasoconstricting properties. It is commonly used in many urological disorders as it is inexpensive and well-tolerated (19). Many studies have been exploring the possibilities of corticosteroids after internal urethrotomy, as the procedure does not provide an epithelial approximation, but only separates the scar tissues while relying on secondary healing (20). Triamcinolone is believed to be able to reduce scar for- mation by reducing collagen, glycosaminoglycan synthe- sis, and the expression of inflammatory mediators (21). A previously published meta-analysis evaluated the appli- cation of triamcinolone after internal urethrotomy (22). However, the review also evaluated a variety of other cor- ticosteroids. This review, on the other hand, focused only on clinical trials evaluating triamcinolone as an adjunc- tive treatment for internal urethrotomy. Urethral stricture recurrence rate after triamcinolone application (ointment lubrication and injection) The pooled results of all published RCTs evaluating the application of triamcinolone as an adjunctive treatment showed a lower probability of urethral stricture recur- rence (OR = 0.49 95% CI 0.31-0.77, p = 0.002). In early animal studies, the application of a single dose of steroid on a wound site was shown to decrease wound contrac- tion by up to 30% by the 28th day (23). The promising effects of corticosteroid on preventing scar tissues forma- tion were what led to investigations regarding its effect on strictures. In this review, we discovered that there are two routes of administration used, four studies evaluated tri- amcinolone ointment with CIC and two studies adminis- tered the steroid through a submucosal injection. Dividing the analysis into two subgroups provided inter- esting results. Urethral stricture recurrence rate after triamcinolone ointment lubrication There were four studies evaluating the use of triamci- nolone ointment following internal urethrotomy, which indicated the protective effect of topical triamcinolone (OR = 0.47 CI 95% 0.26-0.82, p = 0.009). Regarding the route of administration, Korhonen et al. reported that administering intralesional injections of steroids generat- ed poor results compared to self-dilatation (24). Self- dilatation using CIC following internal urethrotomy is considered an acceptable procedure to reduce treatment failure and had been recommended in the past to be per- formed within three to six months following the proce- dure (25). The studies included in this review showed the addition of triamcinolone to CIC significantly decreases the rate of stricture recurrence. Urethral stricture recurrence rate after submucosal triamcinolone injection Studies evaluating triamcinolone injection in urethral stricture are still limited. Only two trials examined sub- mucosal triamcinolone injection and found similar stric- ture probabilities (OR = 0.53 CI 95% 0.25-1.13, p = 0.10). These studies also included patients with multiple urethral strictures in the bulbar and pendular areas (26, 27). These findings are similar to a study by Korhonen et al. (24), who reported a higher rate of stricture recurrence in the triamcinolone injection group compared to the control group. Tabasssi et al. (28) believed that the insignificant findings in their study were because their subjects were not instructed to use CIC apart from given injections. Even though they could not demonstrate a decrease in recurrence rate, they claimed that the recur- rence of stricture after internal urethrotomy was post- poned due to the injection (28). However, the other study included in this meta-analysis by Mazdak et al. (14) reported favorable outcomes of triamcinolone injection. A previous study also reported the beneficial effects of cir- cular steroid injections as opposed to applying them directly into the structure (16). The difference in findings between the studies. Another evaluation in the future with more studies evaluating triamcinolone injection is warranted. Maximum urinary flow rate (Qmax) Uroflowmetry helps diagnose stricture and monitor its recurrence. If the symptoms and uroflowmetry findings suggested urethral stricture, retrograde urethrography would be performed to make a definitive diagnosis of the stricture as it can reveal the full length of the urethra to the stricture, passing through the urethral sphincter and prostatic urethra (29). There were two studies reporting the mean maximum urinary flow rate in six and twelve months. However, the findings of both follow-up periods were insignificant (p > 0.05). Gucuk et al. (30) reported that when the groups were compared with respect to Qmax values, the patients undergoing self-dilatation com- bined with triamcinolone showed improvements, even though the difference with the patients of the control group was not statistically significant. In this paper the flow rate evaluation may suffer from selection bias since patients not treated with triamcinolone had earlier and more frequent recurrences (53% in the control group compared to 20% group) and subjectes where recurrence has occurred were excluded from the evaluation of max- imum urinary flow rate. The review has several limitations. Three studies evaluat- ed multiple strictures and diverse etiologies, even though they were still within the anterior urethra. Furthermore, the studies analyzed have included patients beyond the contemporary indications for direct vision internal ure- throtomy, which limit its use to bulbar strictures. The dif- ferent catheter sizes used by the patients were also a potential bias regarding the actual effects of the ointment combined with the dilatation caused by the clean inter- mittent catheterization. The study by Hosseini et al. also included patients with a history of urethroplasty which could affect the outcome of the urethrotomy al. (11) Studies evaluating submucosal injection were only a few Archivio Italiano di Urologia e Andrologia 2025; 97(3):14203 7 Triamcinolone following internal urethrotomy with contrasting results, indicating a possible biased result. The differences in time to urethral stricture recur- rence were also different among studies. As more clinical trials will become available in the future, an updated sys- tematic review which overcome these limitations should be performed. CONCLUSIONS The administration of submucosal triamcinolone injec- tion did not improve the urethral stricture recurrence rate after internal urethrotomy, whereas the administration of triamcinolone ointment with clean intermittent catheteri- zation could decrease urethral stricture recurrence. However, the administration of both triamcinolone oint- ment and injection did not improve maximum urinary flow rate. REFERENCES 1. Anger JT, Buckley JC, Santucci RA, et al. Trends in stricture man- agement among male medicare beneficiaries: Underuse of urethro- plasty? Urology. 2011; 77:481-485. 2. Hampson LA, McAninch JW, Breyer BN. Male urethral strictures and their management. Nat Rev Urol. 2014; 11:43-50. 3. McDougal W, Wein AJ, Kavoussi LR, et al. Campbell-Walsh Urology Eleven Edition Review: Urethral Stricture Disease. 2016. 4. Naudé AM, Heyns CF. What is the place of internal urethrotomy in the treatment of urethral stricture disease? Nat Clin Pract Urol. 2005; 2:538-545. 5. 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Authors' contributions: DPA: Led the conceptualization of the systematic review, designed the methodology, performed the data synthesis, and drafted the manuscript, and ensured all revisions were addressed. MAS: Conducted the literature search, screened studies for inclusion, and contributed to data extraction and analysis. Assisted in drafting and critically revising the manu- script.TD: Performed the data extraction, contributed to the qual- ity assessment of included studies, and participated in manuscript writing and revisions. FH: Assisted in the systematic literature search, data analysis, and contributed to manuscript drafting and revisions. ZAR: Supported the data analysis, assisted in reviewing the included studies, and contributed to manuscript revisions. IAR: Contributed to the literature search, data extraction, and performed statistical analysis. Also provided input on the manu- script's structure and revisions. 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One-stage transperineal repair of pan-urethral stricture with dorsally placed buccal mucosal grafts: results, complications, and surgical technique. Urol J. 2011; 8:307-312. 29. Mundy AR, Andrich DE. Urethral strictures. BJU Int. 2011; 107:6-26. 30. Gücük A, Tuygun C, Burgu B, et al. The short-term efficacy of dilatation therapy combined with steroid after internal urethrotomy in the management of urethral stenoses. J Endourol. 2010; 24:1017- 1021. Correspondence Dimas Panca Andhika dimaspanca26@gmail.com Mohammad Ayodhia Soebadi (Corresponding author) yodisoebadi@gmail.com Department of Urology, Faculty of Medicine, Airlangga University, Surabaya, Indonesia Department of Anatomy, Histology, and Pharmacology, Faculty of Medicine, Airlangga University, Surabaya, Indonesia Universitas Airlangga Hospital, Surabaya, Indonesia Tarmono Djojodimedjo tar_urology@yahoo.com Furqan Hidayatullah furqanhidayatullah26@gmail.com Zakaria Aulia Rahman zakariaaulia04@gmail.com Ilham Akbar Rahman ilhamakbaarr@gmail.com Prima Ardiansah Surya prima.ardiansah1922@gmail.com Department of Urology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia Universitas Airlangga Teaching Hospital, Surabaya, East Java, Indonesia