Ultrasound imaging of male urethral stricture disease: a narrative review of the available evidence, focusing on selected prospective studies.

PURPOSE: To synthetize the current scientific knowledge on the use of ultrasound of the male urethra for evaluation of urethral stricture disease. This review aims to provide a detailed description of the technical aspects of ultrasonography, and provides some indications on clinical applications of it, based on the evidence available from the selected prospective studies. Advantages and limitations of the technique are also provided. METHODS: A comprehensive literature search was performed using the Medline and Cochrane databases on October 2022. The articles were searched using the keywords "sonourethrography", "urethral ultrasound", "urethral stricture" and "SUG". Only human studies and articles in English were included. Articles were screened by two reviewers (M.F. and K.M.). RESULTS: Our literature search reporting on the role of sonourethrography in evaluating urethral strictures resulted in selection of 17 studies, all prospective, even if of limited quality due to the small patients' number (varied from 28 to 113). Nine studies included patients with urethral stricture located in anterior urethra and eight studies included patients regardless of the stricture location. Final analysis was based on selected prospective studies, whose power was limited by the small patients' groups. CONCLUSION: Sonourethrography is a cost-effective and safe technique allowing for a dynamic and three-dimensional urethra assessment. Yet, because of its limited value in detecting posterior urethral strictures, the standard urethrography should remain the basic 'road-map' prior to surgery. It is an operator-dependent technique, which can provide detailed information on the length, location, and extent of spongiofibrosis without risks of exposure to ionizing radiation.

Neoadjuvant chemotherapy with dose-dense MVAC in muscle-invasive bladder cancer: a tertiary center experience.

PURPOSE: Neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients has proven beneficial in overall survival. However, the optimal regimen is still a matter of debate. MATERIALS AND METHODS: In this retrospective analysis, we evaluate the results obtained in 42 patients treated in our center with 4 cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) followed by radical cystectomy from August 2015 to October 2020. All patients had cT2 or higher non-metastatic MIBC. Clinical and pathological outcomes are reported. RESULTS: Of the 42 patients, 90.5% were men (n = 38) and the mean age was 65 years. All of them had ECOG 0-1 at diagnosis and most tumors had an initial clinical stage T2N0 (76%). Thirty-six patients (85.7%) completed 4 cycles of neoadjuvant treatment, and 21.4% required a dose reduction. The most frequent adverse event (AE) was grade 1-2 asthenia (81%), while neutropenia was the most frequent grade 3 or higher AE (38%). Complete pathological response (ypT0, ypN0) was achieved in 50% of patients (n = 21), and down-staging was observed in 57.1% (n = 24). Only one patient presented radiological progressive disease during neoadjuvant treatment (2.4%), and after a mean follow-up time of 31.5 months, 33.3% of patients experienced disease recurrence. CONCLUSIONS: Neoadjuvant chemotherapy with 4 cycles of dd-MVAC is an effective regimen with high rates of pathological complete responses and down-staging along with an acceptable toxicity profile. DD-MVAC should be considered as an alternative to cisplatin and gemcitabine in patients with good clinical performance status.

Summary Paper of the Updated 2023 European Association of Urology Guidelines on Urological Trauma.

CONTEXT: The European Association of Urology (EAU) Guidelines Panel for Urological Trauma has produced guidelines in order to assist medical professionals in the management of urological trauma in adults for the past 20 yr. It must be emphasised that clinical guidelines present the best evidence available to the experts, but following guideline recommendations will not necessarily result in the best outcome. Guidelines can never replace clinical expertise when making treatment decisions for individual patients regarding other parameters such as experience and available facilities. Guidelines are not mandates and do not purport to be a legal standard of care. OBJECTIVE: To present a summary of the 2023 version of the EAU guidelines on the management of urological trauma. EVIDENCE ACQUISITION: A systematic literature search was conducted from 1966 to 2022, and articles with the highest certainty evidence were selected. It is important to note that due to its nature, genitourinary trauma literature still relies heavily on expert opinion and retrospective series. EVIDENCE SYNTHESIS: Databases searched included Medline, EMBASE, and the Cochrane Libraries, covering a time frame between May 1, 2021 and April 29, 2022. A total of 1236 unique records were identified, retrieved, and screened for relevance. CONCLUSIONS: The guidelines provide an evidence-based approach for the management of urological trauma. PATIENT SUMMARY: Trauma is a serious public health problem with significant social and economic costs. Urological trauma is common; traffic accidents, falls, intrapersonal violence, and iatrogenic injuries are the main causes. Developments in technology, continuous training of medical professionals, and improved care of polytrauma patients reduce morbidity and maximise the opportunity for quick recovery.

Is a Course of Intermittent Self-dilatation with Topical Corticosteroids Superior at Stabilising Urethral Stricture Disease in Men and Improving Functional Outcomes over a Course of Intermittent Self-dilatation Alone? A Systematic Review and Meta-analysis.

Context: Intermittent self-dilatation (ISD) is a therapeutic strategy used to stabilise a urethral stricture and postpone or avoid further treatment. Adding corticosteroids to this mode of management might further enhance its outcomes by downregulation of collagen deposition and excessive scar tissue formation. Objective: To explore whether a course of ISD with topical corticosteroids is superior at stabilising urethral stricture disease in men and improving functional outcomes over a course of ISD alone. Evidence acquisition: This systematic review and meta-analysis was undertaken by the European Association of Urology Urethral Strictures Guideline Panel according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines (CRD42021256744). The primary benefit outcome was successful stabilisation of the urethral stricture. Treatment-related complications were the primary harm outcome. Evidence synthesis: In total, 978 records were screened for eligibility, ultimately leading to five included studies, all randomised controlled trials, comprising 250 patients, of whom 124 underwent a course of ISD with corticosteroids and 126 underwent a course of ISD alone, all after direct vision internal urethrotomy (DVIU). Successful stabilisation of the stricture was achieved in 77% and 64% of patients in the group with and without corticosteroids, respectively (p = 0.04). No extra complications related to the addition of corticosteroids to the ISD regimen were reported. The risk of bias of the included studies was generally unclear to high. Conclusions: Based on the currently available data, a course of ISD with topical corticosteroids appears to be safe and superior at stabilising a urethral stricture after DVIU in the short term to a course of ISD alone. However, given the unclear to high risk of bias in the included studies, further high-quality studies are needed to fully underpin this. Patient summary: This study shows that addition of topical corticosteroids to intermittent self-dilatation after direct vision internal urethrotomy can better stabilise the stricture in the short term.

Treatment Success After Urethroplasty: The Ongoing Quest for a Pragmatic and Universal Definition.

There is no consensus on the ideal definition of success after urethroplasty, which makes research, quality control, and comparisons challenging. Ongoing research endeavors are focused on achieving consensus regarding the optimal battery of outcomes for evaluation of patients after urethroplasty.

Epidemiology, Diagnosis and Management of Penile Cancer: Results from the Spanish National Registry of Penile Cancer.

INTRODUCTION: Penile cancer (PC) is a rare malignancy with an overall incidence in Europe of 1/100,000 males/year. In Europe, few studies report the epidemiology, risk factors, clinical presentation, and treatment of PC. The aim of this study is to present an updated outlook on the aforementioned factors of PC in Spain. MATERIALS AND METHODS: A multicentric, retrospective, observational epidemiological study was designed, and patients with a new diagnosis of PC in 2015 were included. Patients were anonymously identified from the Register of Specialized Care Activity of the Ministry of Health of Spain. All Spanish hospitals recruiting patients in 2015 were invited to participate in the present study. We have followed a descriptive narration of the observed data. Continuous and categorical data were reported by median (p25th-p75th range) and absolute and relative frequencies, respectively. The incidence map shows differences between Spanish regions. RESULTS: The incidence of PC in Spain in 2015 was 2.55/100,000 males per year. A total of 586 patients were identified, and 228 patients from 61 hospitals were included in the analysis. A total of 54/61 (88.5%) centers reported ≤ 5 new cases. The patients accessed the urologist for visually-assessed penile lesions (60.5%), mainly localized in the glans (63.6%). Local hygiene, smoking habits, sexual habits, HPV exposure, and history of penile lesions were reported in 48.2%, 59.6%, 25%, 13.2%, and 69.7%. HPV-positive lesions were 18.1% (28.6% HPV-16). The majority of PC was squamous carcinoma (95.2%). PC was ≥cT2 in 45.2% (103/228) cases. At final pathology, PC was ≥pT2 in 51% of patients and ≥pN1 in 17% of cases. The most common local treatment was partial penectomy (46.9% cases). A total of 47/55 (85.5%) inguinal lymphadenectomies were open. Patients with ≥pN1 disease were treated with chemotherapy in 12/39 (40.8%) of cases. CONCLUSIONS: PC incidence is relatively high in Spain compared to other European countries. The risk factors for PC are usually misreported. The diagnosis and management of PC are suboptimal, encouraging the identification of referral centers for PC management.

Urethral management after artificial urinary sphincter explantation due to cuff erosion.

Introduction: The artificial urethral sphincter (AUS) is the gold standard treatment in cases of moderate-to-severe stress urinary incontinence in males. Cuff erosions are one of the most important distant complications of AUS implantation. The optimal urethral management has still not been established. Material and methods: Search terms related to 'urethral stricture', 'artificial urinary sphincter', and 'cuff erosion' were used in the PubMed database to identify relevant articles. Results: In this mini review we identified 6 original articles that assessed the urethral management after AUS explantation due to cuff erosion and included urinary diversion by transurethral and/or suprapubic catheterization, urethrorrhaphy, and in situ urethroplasty. We summarized the results of different management methods and their efficacy in terms of preventing urethral stricture formation. We highlight the need for better-quality evidence on this topic. Conclusions: The available data do not provide a clear answer to the question of optimal urethral management during AUS explantation. There is a great need to provide higher-quality evidence on this topic.

Reaching Consensus for Comprehensive Outcome Measurement After Urethral Stricture Surgery: Development of Study Protocol for Stricture-Fecta Criteria.

Urethral stricture disease is a very heterogeneous condition where different urethral segments can be involved as a result of diverse etiologies which come with variable prognosis. The surgical management of urethral strictures, and in particular urethroplasties can result in very diverse outcomes on many levels and, currently, there is absolutely no consensus about what should and what should not be considered a "success" after urethral surgery. In the wake of well-established quality criteria in urologic oncology, such as tri- or pentafecta outcomes, and given the lack of agreement on meaningful outcomes after urethral surgery, we aim to introduce our study protocol as the first step of a multistep research endeavor to reach consensus on comprehensive urethroplasty outcomes within a novel conceptual framework: the "stricture-fecta criteria". The development of stricture-fecta will be based on a Delphi consensus involving some of worldwide most influencing reconstructive urologists.

Arterial Fistulas in Urinary Diverted Patients: A Report of 5 Cases.

OBJECTIVE: Arterio-urinary fistulae are a rare but potentially lethal complication that may arise after pelvic surgery, such as radical cystectomy. Historically, open surgery was the gold standard treatment, but currently endovascular treatment has gained prominence. METHODS: We report our centre experience in endovascular treatment of cystectomy-related arterial fistulae and review the reported literature on the topic. During the postoperative period of radical cystoprostatectomy five patients presented different ranges of haematuria, and one presented rectal bleeding, four of them with haemodynamic instability. An urgent three-phase computed tomography was performed, showing active bleeding in 2 patients, while the rest of the patients presented indirect signs of fistulae. An angiography was performed, showing contrast extravasation in 60% of the cases and vessel wall irregularity in 40%. Five arteriourinary fistulae and one arterioenteric fistula were urgently treated with a covered stent placement, sealing the site of the fistula in the artery. RESULTS: Immediate results were satisfactory in all cases; however, one patient died secondary to fistula-related causes 15 days post-treatment. No stent thrombosis or rebleeding have been registered during follow-up. In this review, reported results and complications after covered stent placement are shown, and controversial topics such as antibiotic coverage and antithrombotic treatment after endovascular treatment are also reviewed.

Contemporary Management of Male Anterior Urethral Strictures by Reconstructive Urology Experts-Results from an International Survey among ESGURS Members.

Assessment of anterior urethral stricture (US) management of European urology experts is relevant to evaluate the quality of care given to the patients and plan future educational interventions. We assessed the practice patterns of the management of adult male anterior US among reconstructive urology experts from European countries. A 23-question online survey was conducted among European Association of Urology Section of Genito-Urinary Reconstructive Surgeons (ESGURS) members. A total of 88 invitations were sent by email at two different times (May and October 2019). Data were prospectively collected from May 2019 to December 2019. The response rate was 55.6%. Most of the responders were between 50 and 59 y.o. and mainly from University Public Teaching/Academic Hospitals. A total of 73.5% treated ≥20 patients/year with US. Retrograde urethrogram (RUG) was the commonest diagnostic tool, followed by uroflowmetry (UF) +/− post-void residual (PVR). Urethroplasty using grafts was the most frequent treatment (91.8%). Of responders, 55.3% performed >20 urethroplasties/year. Anastomotic urethroplasties were performed by 83.7%, skin flap repairs by 61.2%, perineal urethrostomy by 77.6% and non-transecting techniques by 63.3%. UF was the most common follow-up tool. Most of the responders considered urethroplasty as the primary option when indicated. Male anterior US among ESGURS members are treated mainly using urethroplasty graft procedures. RUG is preferred for diagnosis, and UF for follow-up.

Gold Glyconanoparticles Combined with 91-99 Peptide of the Bacterial Toxin, Listeriolysin O, Are Efficient Immunotherapies in Experimental Bladder Tumors.

This study presents proof of concept assays to validate gold nanoparticles loaded with the bacterial peptide 91-99 of the listeriolysin O toxin (GNP-LLO91-99 nanovaccines) as immunotherapy for bladder tumors. GNP-LLO91-99 nanovaccines showed adjuvant abilities as they induce maturation and activation of monocyte-derived dendritic cells (MoDCs) to functional antigen-presenting cells in healthy donors and patients with melanoma or bladder cancer (BC), promoting a Th1 cytokine pattern. GNP-LLO91-99 nanovaccines were also efficient dendritic cell inducers of immunogenic tumor death using different bladder and melanoma tumor cell lines. The establishment of a pre-clinical mice model of subcutaneous BC confirmed that a single dose of GNP-LLO91-99 nanovaccines reduced tumor burden 4.7-fold and stimulated systemic Th1-type immune responses. Proof of concept assays validated GNP-LLO91-99 nanovaccines as immunotherapy by comparison to anti-CTLA-4 or anti-PD-1 antibodies. In fact, GNP-LLO91-99 nanovaccines increased percentages of CD4+ and CD8+ T cells, B cells, and functional antigen-presenting DCs in tumor-infiltrated lymphocytes, while they reduced the levels of myeloid-derived suppressor cells (MDSC) and suppressor T cells (Treg). We conclude that GNP-LLO91-99 nanovaccines can work as monotherapies or combinatory immunotherapies with anti-CTLA-4 or anti-PD-1 antibodies for solid tumors with high T cell infiltration, such as bladder cancer or melanoma.

Histological Comparison of Buccal and Lingual Mucosa Grafts for Urethroplasty: Do They Share Tissue Structures and Vascular Supply?

Comparable outcomes were published using a buccal mucosa graft (BMG) from the cheek and a lingual mucosa graft (LMG) from the sublingual area, for urethral augmentation or substitution. To date, no histological comparison between both grafts has been conducted. We histologically assessed BMG and LMG harvested during urethral surgeries, aiming to compare graft properties and vascular support. We conducted a prospective single cohort study, including oral mucosa urethroplasty patients. During surgery, graft dimensions and donor sites were collected, and a 0.5 × 0.5 cm sample was obtained from the prepared graft. Formalin-fixed paraffin-embedded samples were sliced at 4 micrometres (µm) and hematoxylin-eosin stained. Using a telepathology tool, all slides were digitalized and measured from 10× to 40× magnification. In each graft, global and individual layers thicknesses were assessed, including vascular density and area. Descriptive and comparative (parametrical and non-parametrical) statistical analysis occurred. We collected 57 grafts during 33 urethroplasties, with 30 BMG and 22 LMG, finally, included. The mean age was 56.6 (SD 15.2) years, and the mean graft length was 5.8 (SD 1.7) cm and the width was 1.7 (SD 0.4) cm. The median graft thickness was 1598.9 (IQR 1200-2100) µm, the mean epithelium layer was 510.2 (SD 223.7) µm, the median submucosa was 654 (IQR 378-943) µm. the median muscular was 477.6 (IQR 286-772) µm, the median vascular area was 5% (IQR 5-10), and the median adipose tissue area was 5% (IQR 0-20). LMG were significantly longer and narrower than BMG. Total graft thickness was similar between LMG and BMG, but the epithelium and submucosa layers were significantly thinner in LMG. The muscular layer was significantly thicker in LMG. Vascular density and vascular areas were not significantly different between both types of grafts. LMG showed significantly less adipose tissue compared with BMG. Our findings show LMG and BMG for urethroplasty surgeries share the same thickness and blood supply, despite having significantly different graft sizes as well as mucosal and submucosal layers thickness.

Use of grafting materials during penile prosthesis implantation in patients with Peyronie's disease-a systematic review.

Severe Peyronie's disease (PD) and concomitant erectile dysfunction (ED) may require plaque incision/excision and grafting (PIG) as an adjunct to penile prosthesis implantation (IPP). Currently, there is no available consensus on the best graft material to use. Our aim was to systematically review graft materials used as patches following PIG + IPP. Literature search was performed in March 2021. Only original articles in English with a series of 10 or more patients were included. Overall, a total of 17 studies were included, corresponding to a cohort of 662 patients. The mean age ranged from 45 to 65 years and most patients had curvatures >45°. Average penile lengthening ranged from 1 to 3.5 cm, average residual curvatures from 0 to 20% and decreased glans sensitivity from 0 to 20%. Eighty to 100% of patients were satisfied with cosmetic and functional results. PIG + IPP with the use of various grafts offers promising results for the treatment of patients suffering from severe PD with concomitant ED. Unfortunately, the absence of high quality and comparative studies makes it difficult to establish the optimum graft. Therefore, the level of experience of the surgical team with one or more methods should guide their choice.

European Association of Urology Guidelines on Urethral Stricture Disease Part 3: Management of Strictures in Females and Transgender Patients.

CONTEXT: Urethral stricture management guidelines are an important tool for guiding evidence-based clinical practice. OBJECTIVE: To present a summary of the 2021 version of the European Association of Urology (EAU) guidelines on management of urethral strictures in females and transgender patients. EVIDENCE ACQUISITION: The panel performed a literature review on these topics covering a time frame between 2008 and 2018 and used predefined inclusion and exclusion criteria for study selection. Key papers beyond this time period could be included as per panel consensus. A strength rating for each recommendation was added based on the review of the available literature and after panel discussion. EVIDENCE SYNTHESIS: Management of urethral strictures in females and transgender patients has been described in a few case series in the literature. Endoluminal treatments can be used for short, nonobliterative strictures in the first line. Repetitive endoluminal treatments are not curative. Urethroplasty encompasses a multitude of techniques and adaptation of the technique to the local conditions of the stricture is crucial to obtain durable patency rates. CONCLUSIONS: Management of urethral strictures in females and transgender patients is complex and a multitude of techniques are available. Selection of the appropriate technique is crucial and these guidelines provide relevant recommendations. PATIENT SUMMARY: Although different techniques are available to manage narrowing of the urethra (called a stricture), not every technique is appropriate for every type of stricture. These guidelines, developed on the basis of an extensive literature review, aim to guide physicians in selecting the appropriate technique(s) to treat a specific type of urethral stricture in females and transgender patients. TAKE HOME MESSAGE: Although different techniques are available to manage urethral strictures, not every technique is appropriate for every type of stricture. Management of urethral strictures in females and transgender patients is complex and a multitude of techniques are available. Selection of the appropriate technique is crucial and these guidelines provide relevant recommendations.

What is the role of single-stage oral mucosa graft urethroplasty in the surgical management of lichen sclerosus-related stricture disease in men? A systematic review.

PURPOSE: The benefits and harms of the available types of surgical management for lichen sclerosus-related (LS) strictures remain unclear and, thus, clear and robust clinical practice recommendations cannot be given. MATERIALS AND METHODS: To assess the role of single-stage OMGU in the management of LS strictures and explore how its benefits and harms compare with the alternative management options. Medline, Embase and Cochrane controlled trial databases (CENTRAL, CDSR) were systematically searched. Randomized (RCTs) and nonrandomized studies (NRCSs) comparing single-stage OMGU with other surgical management options for LS strictures and single-arm studies on single-stage OMGU were included. Risk of bias (RoB) was assessed. RESULTS: Of the 1912 abstracts identified, 15 studies (1 NRCS and 14 single-arm studies) were included, recruiting in total 649 patients. All studies were at high RoB. In the only NRCS available, stricture-free rate (SFR) for single-stage and staged OMGU was 88% vs 60%, respectively (p = 0.05), at a mean follow-up of 66.5 months. SFR range for single-stage OMGU in single-arm studies was 65-100% (mean/median follow-up, 12-59 months). Single-stage OMGU had low complication rates and beneficial impact on LUTS and QoL. CONCLUSIONS: The present SR highlights the methodological limitations of the available literature. In the absence of adverse local tissue conditions, and taking into consideration benefit-harm balance and surgeon's skills and expertise, single-stage OMGU can be justified in patients with LS strictures.

Sexual function after anterior urethroplasty: a systematic review.

BACKGROUND: Urethral surgery outcomes are often evaluated by assessing urinary flow and urethral patency. However, sexual consequences may appear after urethroplasty, impairing quality of life and patient's perception of success.The aim of this study is to assess the relationship between anterior urethral reconstruction and postoperative sexual dysfunction, including the proposed factors predicting sexual outcomes. METHODS: We searched in PubMed database using the terms: "anterior urethroplasty", bulbar urethroplasty" or "penile urethroplasty", and "sexual dysfunction", "erectile function" or "ejaculation". Articles were independently evaluated for inclusion based on predetermined criteria. Systematic data extraction was followed by a comprehensive summary of evidence. RESULTS: Thirty-eight studies were included for final analysis. No randomised trial on the topic was found. Urethral surgery might affect different aspects of sexual function: erectile function, ejaculatory function, penile shape and length, and genital sensitivity, leading to severe sexual dysfunction. Patient perception of sexual impairment was related to post-operative satisfaction. CONCLUSIONS: Sexual dysfunction after anterior urethral reconstruction is an important issue that must be appropriately discussed during preoperative patient counselling. Reported outcomes after anterior urethroplasty should include sexual consequences and relevance, evaluated using validated tools.