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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.

Background: A congenital disease is for life. Posterior hypospadias, the severe form of hypospadias with a penoscrotal, scrotal, or perineal meatus, is a challenging condition with a major impact on lifelong quality of life. Aim: Our network meeting is aimed to identify what is currently missing in the lifelong treatment of posterior hypospadias, to improve care, quality of life, and awareness for these patients. Methods: The network meeting "Lifelong Posterior Hypospadias" in Utrecht, The Netherlands was granted by the European Joint Programme on Rare Diseases–Networking Support Scheme. There was a combination of interactive sessions (hackathons) and lectures. This paper can be regarded as the last phase of the hackathon. Results: Surgery for hypospadias remains challenging and complications may occur until adulthood. Posterior hypospadias affects sexual function, fertility, and hormonal status. Transitional care from childhood into adulthood is currently insufficiently established. Patients should be more involved in defining desired treatment approach and outcome measures. For optimal outcome evaluation standardization of data collection and registration at European level is necessary. Tissue engineering may provide a solution to the shortage of healthy tissue in posterior hypospadias. For optimal results, cooperation between basic researchers from different centers, as well as involving clinicians and patients is necessary. Conclusions: To improve outcomes for patients with posterior hypospadias, patient voices should be included and lifelong care by dedicated healthcare professionals guaranteed. Other requirements are joining forces at European level in uniform registration of outcome data and cooperation in basic research. [ABSTRACT FROM AUTHOR]

Even though more than 30 years have passed since the eradication of smallpox, high titers of smallpox-specific antibodies are still detected in the blood of subjects vaccinated in childhood. In fact, smallpox-specific antibody levels are maintained in serum for more than 70 years. The generation of life-long immunity against infectious diseases such as smallpox and measles has been thoroughly documented. Although the mechanisms behind high persisting antibody titers in the absence of the causative agent are still unclear, long lived plasma cells (LLPCs) play an important role. Most of the current knowledge on LLPCs is based on experiments performed in mouse models, although the amount of data derived from human studies is increasing. As the results from mouse models are often directly extrapolated to humans, it is important to keep in mind that there are differences. These are not only the obvious such as the life span but there are also anatomical differences, for instance the adiposity of the bone marrow (BM) where LLPCs reside. Whether these differences have an effect on the function of the immune system, and in particular on LLPCs, are still unknown. In this review, we will briefly discuss current knowledge of LLPCs, comparing mice and humans.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to evaluate outcomes and possible risk factors for failure of open urethroplasty due to penile urethral strictures. Materials and methods. A retrospective chart review was undertaken of 90 patients with penile stricture undergoing 109 open urethroplasties between 2000 and 2011. In 80 urethroplasties, a one-stage procedure was performed: 68 of these had a pediculated penile skin flap, nine had a free buccal mucosal graft and three had a free skin graft. A two-stage procedure using buccal mucosa was performed in 29 urethroplasties. Failure was defined as when further urethral instrumentation was needed. Results. The mean age in the one-stage and two-stage groups were 50 and 54 years, respectively. The success rates in the corresponding groups were 65% and 72%, with follow-up times of 63 and 40 months, respectively. Multivariable analyses disclosed body mass index (BMI) and previous urethral surgery to be significant risk factors for failure in the one-stage group. Failure over time significantly decreased during the study period. Conclusions. Both one- and two-stage penile urethroplasty demonstrated success rates in line with previous reports. Limited experience, high BMI and previous urethral surgery appear to be associated with less favourable outcome. [ABSTRACT FROM AUTHOR]