Development of a Nomogram Model to Predict the Risk of Stricture Recurrence after Urethroplasty: A Retrospective Study

Objective: A retrospective study was performed to analyse the influencing factors of stricture recurrence after urethroplasty and to establish a predictive nomogram model. Methods: The clinical data of patients who underwent urethroplasty in our hospital from January 2021 to June 2023 were retrospectively analysed. Depending on whether stenosis occurs six months after surgery, the patients were divided into recurrence and nonrecurrence groups. Logistic regression analysis was performed on the indicators with statistically significant differences between the two groups in single factor analysis to analyse the influencing factors of postoperative recurrence risk of stricture. X64.4.1.3 version R language and external source packages were used to build the nomogram model. The nomogram was internally validated through 10-fold cross-validation, and C-index was calculated. The area under the curve (AUC) of the receiver operating characteristic curve was employed to evaluate the results of the internal validation. Results: Amongst 105 patients who underwent urethroplasty in our hospital, 15 patients with recurrence were included in the recurrence group, and 90 patients without recurrence were included in the nonrecurrence group. The length of stricture segment, history of urethroplasty and smoking history within 3 months before surgery were risk factors for stricture recurrence, with odds ratio (OR) values of 1.874 (95% CI: 1.103–5.725), 1.670 (95% CI: 1.105–2.904) and 1.740 (95% CI: 1.456–5.785), respectively. The constructed nomogram obtained an average AUC of 0.842 and an average C-index of 0.794, calculated after 200 times of 10-fold cross-validation. Conclusions: From the data of this study, it can be deduced that the influencing factors of stricture recurrence after urethroplasty include the length of stricture segment, history of urethroplasty and smoking history of 3 months before surgery... (AU)

Synchronous genitourinary lichen sclerosus signals a distinct urinary microbiome profile in men with urethral stricture disease.

PURPOSE: Alterations in the urinary microbiome have been associated with urological diseases. The microbiome of patients with urethral stricture disease (USD) remains unknown. Our objective is to examine the microbiome of USD with a focus on inflammatory USD caused by lichen sclerosus (LS). METHODS: We collected mid-stream urine samples from men with LS-USD (cases; n = 22) and non-LS USD (controls; n = 76). DNA extraction, PCR amplification of the V4 hypervariable region of the 16S rRNA gene, and sequencing was done on the samples. Operational taxonomic units (OTUs) were defined using a > 97% sequence similarity threshold. Alpha diversity measurements of diversity, including microbiome richness (number of different OTUs) and evenness (distribution of OTUs) were calculated and compared. Microbiome beta diversity (difference between microbial communities) relationships with cases and controls were also assessed. RESULTS: Fifty specimens (13 cases and 37 controls) produced a 16S rRNA amplicon. Mean sample richness was 25.9 vs. 16.8 (p = 0.076) for LS-USD vs. non-LS USD, respectively. LS-USD had a unique profile of bacteria by taxonomic order including Bacillales, Bacteroidales and Pasteurellales enriched urine. The beta variation of observed bacterial communities was best explained by the richness. CONCLUSIONS: Men with LS-USD may have a unique microbiologic richness, specifically inclusive of Bacillales, Bacteroidales and Pasteurellales enriched urine compared to those with non-LS USD. Further work will be required to elucidate the clinical relevance of these variations in the urinary microbiome.

Cells Involved in Urethral Tissue Engineering: Systematic Review.

The urethra is part of the lower urinary tract and its main role is urine voiding. Its complex histological structure makes urethral tissue prone to various injuries with complicated healing processes that often lead to scar formation. Urethral stricture disease can affect both men and women. The occurrence of this pathology is more common in men and thus are previous research has been mainly oriented on male urethra reconstruction. However, commonly used surgical techniques show unsatisfactory results because of complications. The new and progressively developing field of tissue engineering offers promising solutions, which could be applied in the urethral regeneration of both men´s and women´s urethras. The presented systematic review article offers an overview of the cells that have been used in urethral tissue engineering so far. Urine-derived stem cells show a great perspective in respect to urethral tissue engineering. They can be easily harvested and are a promising autologous cell source for the needs of tissue engineering techniques. The presented review also shows the importance of mechanical stimuli application on maturating tissue. Sufficient vascularization and elimination of stricture formation present the biggest challenges not only in customary surgical management but also in tissue-engineering approaches.

Combination of the fetal urinary metabolome and peptidome for the prediction of postnatal renal outcome in fetuses with PUV.

Most of biomarker panels, extracted from single omics traits, still need improvement since they display a gray zone where prediction is uncertain. Here we verified whether a combination of omics traits, fetal urinary metabolites and peptides analyzed in the same sample, improved prediction of postnatal renal function in fetuses with posterior urethral valves (PUV) compared to individual omics traits. Using CE-MS, we explored the urinary metabolome of 13 PUV fetuses with end stage renal disease (ESRD) and 12 PUV fetuses without postnatal ESRD at 2 years postnatally. This allowed the selection of 24 differentially abundant metabolite features which were modelled into predictive classifiers, alone or in combination with 12 peptides previously identified as predictive of ESRD. Validation in 35 new fetuses showed that the combination of peptides and metabolites significantly outperformed the 24 metabolite features with increased AUC (0.987 vs 0.905), net reclassification improvement (36%) and better sensitivity accuracy (86% vs 60%). In addition, the two trait combination tended to improve, but without reaching statistical significance, the already high performances of the 12 peptide biomarkers (AUC 0.967, accuracy 80%). In conclusion, this study demonstrates the potential of cumulating different omics traits in biomarker research where single omics traits fall short. SIGNIFICANCE: Although increasingly proposed in disease-diagnosis and -prognosis because of their improved efficacy over single markers, panels of body fluid biomarkers based on single omics analysis still fail to display perfect accuracy, probably due to biological variability. Here, we hypothesized that combination of different omics traits allowed to better capture this biological variability. As proof of concept, we studied the added value of fetal urine metabolites and peptides using CE-MS, starting from the same urine sample, to predict postnatal renal outcome in fetuses with posterior urethral valves. We observed that the prognostic power of combined metabolite and peptide markers was clearly higher than that of metabolites alone and slightly, but non-significantly, improved compared to the peptides alone. To our knowledge, this report is the first to demonstrate that combining multiomics traits extracted from (fetal) urine samples displays clear promise for kidney disease stratification.

Crosstalk between TGF-ß1 and CXCR3 signaling during urethral fibrosis.

Urethral fibrosis is an important pathological feature of urethral stricture. TGF-ß1 and CXC chemokine receptor 3 (CXCR3) signaling have been reported as the critical pathways involved in the pathology of fibrosis. Here, we collected the urine samples from the patients with recurring urethral stricture, recurring stricture treated by cystostomy, and age- and gender-matched healthy people. ELISA detection revealed that TGF-ß1 level was significantly up-regulated for the urethral stricture patients. By contrast, flow cytometry, real-time PCR detection, and immunofluoresecent staining showed that urethral stricture resulted in decreased expression of CXCR3. TGF-ß1 treatment could increase cell proliferation and migration ability of urethra fibroblasts, whereas IP-10/CXCR3 signaling showed the opposite effect. Further, we found a crosstalk between TGF-ß1 and CXCR3 signaling in the regulation of urethral fibrosis. Thus, pharmacological intervention of TGF-ß1 or CXCR3 signaling has a potential as the therapeutic target for the prevention of urethral fibrosis.

The role of urinary TGF-ß1, TNF-α, IL-6 and microalbuminuria for monitoring therapy in posterior urethral valves.

BACKGROUND: Long-term renal deterioration is common in patients with posterior urethral valves (PUV), and early identification of detrimental factors can help in counselling patients as well as in guiding future therapy. The aim of our study was (1) to evaluate urinary transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) levels and microalbuminuria before and after ablation of PUV and (2) to examine the effect of early induction of angiotensin-converting enzyme inhibitors (ACE-I) on renal recovery. METHODS: The study included 30 patients with diagnosed PUV. Urinary cytokines were measured pre-operatively and post-operatively for 1 year. The study group was subdivided into two subgroups at 6 months after surgery. Group 1 included 16 patients whose urinary TGF-ß1 level showed a declining trend. Group 2 included 14 patients whose urinary TGF-ß1 showed a rising trend or plateaued; these patients were started on ACE-I therapy, which they received for at least 6 months. RESULTS: Urinary TGF-ß1, TNF-α and microalbumin levels were high in patients with PUV. In Group 1 patients, urinary TGF-ß1, TNF-α and microalbumin levels fell significantly following valve ablation and continued to decline for 12 months. In Group 2 patients, after an initial fall following valve ablation, urinary TGF-ß1, TNF-α and microalbumin showed a continued rise until 6 months post-surgery. After ACE-I therapy, there was 53.43 % fall in urinary TGF-ß1, 43.15 % fall in microalbuminuria, 28.57 % improvement in split renal function and 35.80 % improvement in GFR. CONCLUSIONS: Based on our results, urinary TGF-ß1, urinary TNF-α and microalbuminuria can be used as biomarkers for the early recognition of ongoing renal damage in patients with PUV. ACE-I plays a role in retarding renal damage in these patients.

[Urethroplasty in 2 stages using skin grafts]. / Uréthroplastie en 2 temps par greffe cutanée.

OBJECTIVE: To present the technique and results of 2-stage mesh-graft urethroplasty, as described by Schreiter in 1984. METHODS: 11 patients with a stricture of the anterior urethra were treated according to this urethroplasty (pedicle skin flap). The site of the stricture was penile in 4 cases and perineoscrotal in 7 cases, and the mean length was 7.7 cm (range: 3 to 12.5). RESULTS: 10 patients were treated in 2 stages, while the remaining patient has a persistent perineal urethrostomy. With a mean follow-up of 3.5 years (range: 14 to 77 months), 9 patients obtained a satisfactory result with no radiographic recurrence, but with persistent nocturia (x 2/night), a mean peak flow rate of 12.8 ml/s, and a mean residual urine of 55 ml present in 8 our of 9 cases. One complete failure was observed, following complete recurrence of the stricture due to the limited dimensions of the skin flap at the 2nd stage. CONCLUSION: This technique constitutes a useful salvage solution after failure of a one-stage urethroplasty. It can be used to treat extensive strictures of the anterior urethra by reconstituting a good quality urethral lumen with well vascularized tissue. It also has the advantage of avoiding the presence of hair follicles and allows the two stages to be performed at a brief interval.

A new uroflowmeter for routine clinical use.

A uroflowmeter has been produced using a simple strain gauge transducer system with a performance that has been optimised to provide various micturition parameters with an accuracy consistent with the known physiological range. The total cost of the uroflowmeter is around L140 including the digital read-out. The results from over 300 patients have been collected and the flow curves of over 100 of these have been obtained. It is hoped that we can define a set of clinically significant parameters from each flow curve and correlate these against their associated urological conditions. Since, with the majority of patients, only one test is carried out, the parameters would also have to be significant for a single result.