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.

Application of Graphene in Tissue Engineering of the Nervous System.

Graphene is the thinnest two-dimensional (2D), only one carbon atom thick, but one of the strongest biomaterials. Due to its unique structure, it has many unique properties used in tissue engineering of the nervous system, such as high strength, flexibility, adequate softness, electrical conductivity, antibacterial effect, and the ability to penetrate the blood-brain barrier (BBB). Graphene is also characterized by the possibility of modifications that allow for even wider application and adaptation to cell cultures of specific cells and tissues, both in vitro and in vivo. Moreover, by using the patient's own cells for cell culture, it will be possible to produce tissues and organs that can be re-transplanted without transplant rejection, the negative effects of taking immunosuppressive drugs, and waiting for an appropriate organ donor.

Ciprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment-The Effect of Dose-Response on 2D and 3D Cell Cultures.

INTRODUCTION: Introducing new drugs for clinical application is a very difficult, long, drawn-out, and costly process, which is why drug repositioning is increasingly gaining in importance. The aim of this study was to analyze the cytotoxic properties of ciprofloxacin and levofloxacin on bladder and prostate cell lines in vitro. METHODS: Bladder and prostate cancer cell lines together with their non-malignant counterparts were used in this study. In order to evaluate the cytotoxic effect of both drugs on tested cell lines, MTT assay, real-time cell growth analysis, apoptosis detection, cell cycle changes, molecular analysis, and 3D cultures were examined. RESULTS: Both fluoroquinolones exhibited a toxic effect on all of the tested cell lines. In the case of non-malignant cell lines, the cytotoxic effect was weaker, which was especially pronounced in the bladder cell line. A comparison of both fluoroquinolones showed the advantage of ciprofloxacin (lower doses of drug caused a stronger cytotoxic effect). Both fluoroquinolones led to an increase in late apoptotic cells and an inhibition of cell cycle mainly in the S phase. Molecular analysis showed changes in BAX, BCL2, TP53, and CDKN1 expression in tested cell lines following incubation with ciprofloxacin and levofloxacin. The downregulation of topoisomerase II genes (TOP2A and TOP2B) was noticed. Three-dimensional (3D) cell culture analysis confirmed the higher cytotoxic effect of tested fluoroquinolone against cancer cell lines. CONCLUSIONS: Our results suggest that both ciprofloxacin and levofloxacin may have great potential, especially in the supportive therapy of bladder cancer treatment. Taking into account the low costs of such therapy, fluoroquinolones seem to be ideal candidates for repositioning into bladder cancer therapeutics.

Management of Intradiverticular Bladder Tumours: A Systematic Review.

The aim of this systematic review was to present available data on diagnostic and therapeutic options in intradiverticular bladder tumour cases. A literature search within the Medline database was conducted in March 2019 with combinations of the following search terms: bladder cancer, bladder tumour, bladder diverticulum, diverticulum, intradiverticular. Seventeen relevant articles were identified. Diagnostic and therapeutic options for intradiverticular bladder tumour follow the general management of bladder cancer patients. The most important differences include a higher rate of non-urothelial histology, higher rate of invasive cancers (stage T1 and higher), no stage T2 disease due to lack of a muscularis propria layer and potential role of partial cystectomy or diverticulectomy in the treatment. Among cystectomized patients, the survival is comparable to general bladder cancer patients after cystectomy. Data on accuracy of imaging and endoscopy in diagnosing intradiverticular bladder tumour are poor. There is no study comparing different treatment modalities in intradiverticular bladder tumour patients. Limitations of this review include low number and low evidence level of available studies, as well as low number and heterogeneity of enrolled subjects. Available literature data cannot be the basis for clinical recommendations in intradiverticular bladder tumour cases. While bladder cancer is the most common urinary tract malignancy and at least 1% of cases are intradiverticular, further research in this field is justified.

A systematic review of preventive and therapeutic options for symptoms of cystitis in patients with bladder cancer receiving intravesical bacillus Calmette-Guérin immunotherapy.

Local adverse effects are the most common clinical issues in patients with bladder cancer receiving intravesical BCG immunotherapy. The aim of this systematic review was to present available options for prevention and treatment of cystitis symptoms related to bacillus Calmette-Guérin (BCG) intravesical instillations. A literature search within the Medline database was conducted in June 2018 with the following search terms: adverse events, Bacillus Calmette-Guerin, BCG, bladder cancer, cystitis, dose, dwell time, dysuria, frequency, intravesical instillations, haematuria, pain, side effects, toxicity and urgency. Eighteen relevant original articles were identified, including 15 randomized controlled trials. Potentially effective options to prevent symptoms of cystitis are BCG dose reduction, intravesical hyaluronic acid instillations and oral prulifloxacin or ofloxacin administration. For the treatment of BCG-related cystitis, available options include oral pentosan polysulphate or a combination of intravesical hyaluronic acid and chondroitin sulphate. The included studies were characterized by high heterogeneity in terms of BCG strains, schedules and endpoints. Studies on treatment of BCG-related cystitis included only small number of patients. Studies on directed medical interventions did not consider the influence on the BCG efficacy. Among few proposed preventive or therapeutic options for symptoms of cystitis related to BCG, none was proven to be both definitively effective and oncologically safe.

The different expression of key markers on urothelial holoclonal, meroclonal, and paraclonal cells in in vitro culture.

Urothelial cell populations which differ in morphology and proliferation capacities can be isolated from the urinary bladder. The goal of this study was to analyze a clonal, proliferative, and self-renewing potential of porcine urothelial cells and to compare expression of selected adhesion and tight junction molecules, urothelial and stem cell markers for the urothelial clone types. Urothelial cells were isolated from 10 porcine urinary bladders. Three different clone types: holoclone-, meroclone-and paraclone-like colonies were identified based on their morphology. To characterize and compare the urothelial clones the immunofluorescent stains were performed. Expression of pancytokeratin (PanCK), Ki-67 and p63 was higher for holoclone- like cells compared to meroclone-and paraclone-like cells (P < 0.05). Meroclone-like cells expressed higher levels of p63 compared to paraclone- like cells (P < 0.05). The level of Ki-67 and PanCK for meroclone- and paraclone- like cells was comparable (P > 0.05). ß1 and ß4 integrins were not expressed. Expression of zonula occludens-1 (ZO-1) in cell-cell junctions for paraclone-, meroclone-and holoclone-like cells was 17.6 ± 0.6, 14.7 ± 0.5, and 16.1 ± 0.4, respectively. The results of actin filaments (F-actin) expression were 253,634 ± 6,920 for meroclone-like cells, 198,512 ± 7,977 for paraclone-like cells and 133,544 ± 3,169 for holoclone-like cells. Three urothelial cell types with differing features can be isolated from the bladder. Holoclone-like cells are the richest in stem cells and should be used in further studies for construction of neo-bladder or neo-conduit using tissue engineering methods.

Technical developments in transurethral resection of bladder tumours.

Bladder cancer is one of the most common malignancies worldwide. The transurethral resection of bladder tumour (TURB) remains the gold standard in both diagnostics and treatment. Because of the importance of TURB in bladder cancer management and the fact that TURB is one of the most commonly performed urologic procedures, it is the subject of continuous technological development. The latest advances in the field of endourology are aimed at increasing surgical accuracy and thus reducing the risk of bladder tumour recurrence and progression. However, despite the constant progress in technology and technique, there are still a lack of good quality data showing the superiority of any of the methods. The aim of this paper is to present available data on new technological developments in surgical technique of TURB. Advantages and disadvantages of currently available methods are discussed, and literature showing their effectiveness and safety is shown.

Vascularization Potential of Electrospun Poly(L-Lactide-co-Caprolactone) Scaffold: The Impact for Tissue Engineering.

BACKGROUND Electrospun nanofibers have widespread putative applications in the field of regenerative medicine and tissue engineering. When compared to naturally occurring collagen matrices, electrospun nanofiber scaffolds have two distinct advantages: they do not induce a foreign body reaction and they are not at risk for biological contamination. However, the exact substrate, structure, and production methods have yet to be defined. MATERIAL AND METHODS In the current study, tubular-shaped poly(L-lactide-co-caprolactone) (PLCL) constructs produced using electrospinning technology were evaluated for their potential application in the field of tissue regeneration in two separate anatomic locations: the skin and the abdomen. The constructs were designed to have an internal diameter of 3 mm and thickness of 200 µm. Using a rodent model, 20 PLCL tubular constructs were surgically implanted in the abdominal cavity and subcutaneously. The constructs were then evaluated histologically using electron microscopy at 6 weeks post-implantation. RESULTS Histological evaluation and analysis using scanning electron microscopy showed that pure scaffolds by themselves were able to induce angiogenesis after implantation in the rat model. Vascularization was observed in both tested groups; however, better results were obtained after intraperitoneal implantation. Formation of more and larger vessels that migrated inside the scaffold was observed after implantation into the peritoneum. In this group no evidence of inflammation and better integration of scaffold with host tissue were noticed. Subcutaneous implantation resulted in more fibrotic reaction, and differences in cell morphology were also observed between the two tested groups. CONCLUSIONS This study provides a standardized evaluation of a PLCL conduit structure in two different anatomic locations, demonstrating the excellent ability of the structure to achieve vascularization. Functional, histological, and mechanical data clearly indicate prospective clinical utilization of PLCL in critical size defect regeneration.

[Tissue engineering - experimental method of urinary bladder regeneration]. / Inzynieria tkankowa - eksperymentalna metoda regeneracji pecherza moczowego.

The most common cause of bladder reconstruction is radical cystectomy for invasive bladder cancer. Currently, bowel segments remains, the most widely used in reconstruction of urinary tract. Using of bowel as a "material" for bladder reconstruction is associated with numerous complications. Tissue engineering methods provide opportunities to construct bladder tissue in vitro from autologous cells obtained from non urinary tract system. So far, the most useful cell and matrix type for bladder reconstruction have not been defined. In this work actual knowledge about tissue engineering in bladder regeneration was presented.

Ablative therapies for small renal tumors.

Ablative therapies of renal tumors are steadily gaining popularity in clinical practice due to the many benefits they offer to patients. Moreover, ablative procedures hold promise in the field of uro-oncology for the best compromise between low invasiveness, high efficacy and advantages in terms of procedural costs. Reported outcomes with ablative therapies for small renal tumors are excellent and without significant differences for surgical procedures based on nephron-sparing surgery. Nevertheless, these methods for treatment of small renal tumors should still be confined to carefully selected patients. This review discusses the currently used ablative techniques in urology.

Precision strikes: PSMA-targeted radionuclide therapy in prostate cancer - a narrative review.

Introduction: Radio-ligand targeted therapy is a new and promising concept of treatment Castration resistant prostate cancer (CRPC). Only a few radio-pharmaceutics were approved for usage in treating prostate cancer, among the multiple others tested. We aimed to review and summarize the literature on the therapeutic isotopes specific for PSMA. Methods: We performed a scoping literature review of PubMed from January 1996 to December 2022. Results: 98 publications were selected for inclusion in this review. The studies contained in publications allowed to summarize the data on pharmacokinetics, therapeutic effects, side effects and the medical use of 225Ac and 177Lu radionuclides. The review also presents new research directions for specific PSMA radionuclides. Conclusion: Radioligand targeted therapy is a new and promising concept where Lu-177-PSMA-617 have promising outcomes in treatment according to standard of care.

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.

Comparison of Strain and Shear Wave Elastography in Prostate Cancer Detection.

The aim of the study was to compare strain elastography with shear wave elastography in prostate cancer detection by comparing data gained during elastography with histological analysis after prostatectomy. Thirty patients with prostate cancer qualified for radical prostatectomy were enrolled into the study. All patients underwent transrectal strain elastography and shear wave elastography during pre-surgical evaluation. In each prostate, 36 regions were evaluated separately whether there was a suspicious prostate cancer lesion or not. Subsequently, the same regions were analyzed during histological analysis of the resected gland. Strain elastography and shear wave elastography (overall stiffness cutoff value = 35 kPa) in our study were characterized by overall sensitivities of 58.9% and 65.3% and specificities of 71.8% and 70.2%, respectively. Cutoff values specific to the zones in the shear wave elastography examination (peripheral zone: 35 kPa, transitional zone: 45 kPa) were characterized by an overall prostate cancer detection sensitivity and specificity of 63.4% and 73% respectively. Shear wave elastography examination revealed a higher sensitivity versus strain elastography, 63.4% versus 58.9% (p = 0.038, p < 0.05), and comparable specificity, 73.0% versus 71.8% (p = 0.547, p > 0.05), respectively. Sensitivity in prostate cancer detection for both methods is higher for larger lesions (except Gleason score 5 massive lesions in strain elastography). Controversially we observed a decrease in sensitivity for strain elastography in the detection of lesions with a large diameter and a Gleason score of 5 near the prostate capsule. Overall sensitivity in the diagnosis of prostate cancer is more significant for shear wave elastography versus strain elastography.

Feasibility and accuracy of prostate cancer risk calculators in prediction of prostate cancer, extraprostatic extension as well as the risk of lymph nodes metastasis.

Introduction: The aim of this article was to evaluate the accuracy of European Randomized study of Screening for Prostate Cancer (ERSPC 4) and Prostate Cancer Prevention Trial (PCPT 2.0) risk calculator on predicting high-grade prostate cancer (HGPCa) and accuracy of Partin and Briganti nomograms on organ confined (OC) or extraprostatic cancer (EXP), seminal vesicles invasion (SVI) and risk of lymph nodes metastasis. Material and methods: A cohort of 269 men aged between 44-84 years, who underwent radical prostatectomy was retrospectively analysed. Based on estimated calculator risk, patients were divided into risk groups: low (LR), medium (MR) and high (HR). Results obtained with calculators were compared to post-surgical final pathology outcome. Results: In ERPSC4, the average risk for HGPC was LR = 5%, MR = 21%, and HR = 64%. In PCPT 2.0, the average risk for HG was: LR - 8%, MR - 14%, and HR - 30%. In the final results, HGPC was observed in: LR = 29%, MR = 67%, and HR = 81%. In Partin, LNI was estimated to occur in: LR = 1%, MR = 2%, and HR = 7.5% and in Briganti: LR = 1.8%, MR = 11.4%, and HR = 44.2% while finally it was found in: LR = 1.3%, MR = 0%, and HR = 11.6%. Conclusions: ERPSC 4 and PCPT 2.0 corresponded well with each other as well as Partin and Briganti. ERPSC 4 was more accurate in predicting HGPC than PCPT 2.0. Partin was more accurate as for LNI than Briganti. In this study group a large underestimation was observed in reference to Gleason grade.

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.

Quinolones as a Potential Drug in Genitourinary Cancer Treatment-A Literature Review.

Quinolones, broad-spectrum antibiotics, are frequently prescribed by urologists for many urological disorders. The mechanism of their bactericidal activity is based on the inhibition of topoisomerase II or IV complex with DNA, which consequently leads to cell death. It has been observed that these antibiotics also act against the analogous enzymes present in eukaryotic cells. Due to their higher accumulation in urine and prostate tissue than in serum, these drugs seem to be ideal candidates for application in genitourinary cancer treatment. In this study, an extensive literature review has been performed to collect information about concentrations achievable in urine and prostate tissue together with information about anticancer properties of 15 quinolones. Special attention was paid to the application of cytotoxic properties of quinolones for bladder and prostate cancer cell lines. Data available in the literature showed promising properties of quinolones, especially in the case of urinary bladder cancer treatment. In the case of prostate cancer, due to low concentrations of quinolones achievable in prostate tissue, combination therapy with other chemotherapeutics or another method of drug administration is necessary.

A Personalized Approach to Radical Cystectomy Can Decrease Its Complication Rates.

The aim of this study was to assess the influence of a patient's general status on perioperative morbidity and mortality after radical cystectomy, and to assess which of the used scales is best for the prediction of major complications. The data of 331 patients with muscle-invasive bladder cancer, who underwent radical cystectomy, were analyzed. The general status was assessed according to the American Society of Anesthesiologists (ASA), Charlson Comorbidity Index (CCI), Eastern Cooperative Oncology Group (ECOG), and Geriatric-8 (G-8) scales. Complications were classified according to the Clavien-Dindo classification system. In a group of patients with the highest complication rate according to the Clavien-Dindo scale, (i) statistically more patients rated high according to the ASA and ECOG scales, (ii) patients had significantly higher CCI scores (minor complications (I-II), and (iii) there were significantly more patients rated as frail with G8-predominantly those with 11 points or fewer in the scale. A patient's general status should be assessed before the start of therapy because patients with a high risk of death or serious complications (evaluated with any rating scale) should be offered conservative treatment. None of the scales can describe the risk of cystectomy, because the percentage of patients with major complications among those who achieved worse score results on any scale was not significantly different from the percentage of patients with major complications in the general group.

Tissue engineering in reconstructive urology-The current status and critical insights to set future directions-critical review.

Advanced techniques of reconstructive urology are gradually reaching their limits in terms of their ability to restore urinary tract function and patients' quality of life. A tissue engineering-based approach to urinary tract reconstruction, utilizing cells and biomaterials, offers an opportunity to overcome current limitations. Although tissue engineering studies have been heralding the imminent introduction of this method into clinics for over a decade, tissue engineering is only marginally applied. In this review, we discuss the role of tissue engineering in reconstructive urology and try to answer the question of why such a promising technology has not proven its clinical usability so far.

Management with Santorini's Plexus Should Be Personalized during Prostatectomy.

The aim of this study is to compare the results of laparoscopic prostatectomy in terms of management with Dorsal Venosus Complex (DVC)/Santorini's plexus as it is still an open question in the field of urology. For this purpose, 457 patients after prostatectomy derived from two high volume centers were compared. In one center, patients underwent DVC ligation in all cases, whereas in the second center, this step was omitted. Subsequently, the histological and functional results were compared. Results showed that DVC management has an impact on blood loss and the duration of the surgery. In addition, omitting DVC ligation is demonstrated to reduce positive margin rate within the apex if the cancer was localized in this region. The continence and erectile function were similar in the 12-month follow up.