Tissue Engineering Graft for Urethral Reconstruction: Is It Ready for Clinical Application?

Despite developing surgical techniques in urethral surgery, the outcome and complications are still unsatisfactory. Alternative treatment modality has been coming up, particularly in patients with longer stricture, under revision surgery, and penile stricture. Tissue engineering grafts are a promising approach for substituting urethral reconstruction. Over the decades, numerous preclinical studies have been published to show the efficacy and safety of different origins of materials, the presence of autologous cells (acellular matrices or autologous cell-seeded matrices), and the construction of engineered tissue (patch or tubularized constructs) on animal models. However, the results of these studies have not yet reached the intended level for daily clinical practice. A PubMed database search was performed for articles, using specific keywords, published between 1998 and 2022, with a selection on using tissue-engineered grafts for urethroplasty. Many materials have been used as a graft, such as acellular bladder matrix, small intestinal submucosa, acellular dermal matrix, and polyglycolic acid with or without cells, and were evaluated according to the functional and anatomical outcomes comprising complications. According to current literature, tubularized scaffolds constructed from co-cultured cells have promising results for the future. However, high-quality evidence through randomized controlled studies with larger sample sizes, with a long-term follow-up is required to determine accurate outcomes.

Ectopic Germinal Centres with B and T Cells and Follicular Dendritic Cell Networks in Urethral Stricture Tissue: Possible Avenue for Immunological Treatments.

BACKGROUND: The underlying cause of a urethral stricture can sometimes be obscure. It is possible that an injury to the urethra induces an immunological cascade that generates scar tissue and fibrosis, eventually resulting in a stricture. If such immunological reactions could be better elucidated, immunological therapies could possibly emerge. OBJECTIVE: To evaluate if ectopic germinal centres exist in urethral stricture disease. DESIGN SETTING AND PARTICIPANTS: Resected stricture specimens from 45 patients undergoing open bulbar urethroplasty with excision and anastomosis were assessed. Histopathological characteristics, such as fibrosis (grade I-III), inflammation, and sclerosis, were evaluated using immunostaining for CD3 (T cells), CD20 (B cells), and CD21 (follicular dendritic cells). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome measure was the presence or absence of a germinal centre. The secondary outcome was evaluation of any correlation between the degree of fibrosis and germinal centres. Fisher's exact test was used for univariate analysis. RESULTS AND LIMITATIONS: In six patients, ectopic germinal centres were found. In ten patients, there was no inflammation at all. There was no correlation found between the degree of fibrosis and the abundance of immunohistochemically detected immune cells. CONCLUSIONS: Ectopic germinal centres, with B and T cells as well as follicular dendritic cell networks, do exist in urethral stricture disease. This finding may open up for novel research avenues on the possibility of adopting immunological treatments for urethral stricture disease. PATIENT SUMMARY: In patients with a narrowing of the urethra due to any kind of trauma, we looked for the presence of centres of immunological reaction in urethral tissue. We identified these immunological centres (also called germinal centres) in some patients. This intriguing finding suggests that immunological treatments may have potential for men with scar tissue in a narrowed urethra.

Sclerosis as a predictive factor for failure after bulbar urethroplasty: a prospective single-centre study.

OBJECTIVE: The aim of this study was to assess whether sclerosis in histology following bulbar urethroplasty is a predictive factor for failure of surgery. MATERIALS AND METHODS: Resected stricture specimens from 45 patients undergoing open urethroplasty with excision and anastomosis were collected prospectively during 2011-2014. Histopathological characteristics, including fibrosis (grade I-III), inflammation and sclerosis, were evaluated using different routine staining. These specimens were compared to normal urethral resection specimens from patients undergoing sex-correction surgery. The uropathologist who conducted the analyses was blinded to the study design. RESULTS: The outcomes of the histological classifications were as follows: 19 patients had grade I fibrosis, of whom three had failures; 13 patients had grade II fibrosis, without any failures; and the most severe fibrosis, grade III, including sclerosis, was found in 13 patients (11 with sclerosis), with failure in eight. Sclerosis was a significant risk factor for restricture when comparing patients with sclerosis and those without sclerosis, and likewise when adjusting for age, inflammation and stricture length. CONCLUSION: Histological findings of sclerosis in the resected urethral stricture specimen indicate a significantly higher risk for restricture after urethroplasty surgery.

Outcomes of reintervention after failed urethroplasty.

OBJECTIVE: Urethroplasty is a procedure that has a high success rate. However, there exists a small subgroup of patients who require multiple procedures to achieve an acceptable result. This study analyses the outcomes of a series of patients with failed urethroplasty. MATERIALS AND METHODS: This is a retrospective review of 82 failures out of 407 patients who underwent urethroplasty due to urethral stricture during the period 1999-2013. Failure was defined as the need for an additional surgical procedure. Of the failures, 26 patients had penile strictures and 56 had bulbar strictures. Meatal strictures were not included. RESULTS: The redo procedures included one or multiple direct vision internal urethrotomies, dilatations or new urethroplasties, all with a long follow-up time. The patients underwent one to seven redo surgeries (mean 2.4 procedures per patient). In the present series of patients, endourological procedures cured 34% (28/82) of the patients. Ten patients underwent multiple redo urethroplasties until a satisfactory outcome was achieved; the penile strictures were the most difficult to cure. In patients with bulbar strictures, excision with anastomosis and substitution urethroplasty were equally successful. Nevertheless, 18 patients were defined as treatment failures. Of these patients, nine ended up with clean intermittent self-dilatation as a final solution, five had perineal urethrostomy and four are awaiting a new reintervention. Complicated cases need centralized professional care. CONCLUSION: Despite the possibility of needing multiple reinterventions, the majority of patients undergoing urethroplasty have a good chance of successful treatment.