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Urinary bladder wound healing shares many features with skin healing, involving several molecular players, including microRNAs (miRs). This study investigated the role of miR-132 in urothelial cells. We analyzed miR-132 expression in rat bladder using in situ hybridization and conducted gain and loss of miR-132 function assays in primary human urothelial cells (HUCs). These assays included cell proliferation and migration studies. To explore the regulation of miR-132 expression, cells were treated with wound-healing-related factors such as interleukin 6 (IL-6), interleukin 10 (IL-10), and transforming growth factor beta-1 (TGF-β1). Predictive bioinformatics and a literature review identified potential miR-132 targets, which were validated through real-time polymerase chain reaction (RT-PCR) and Western blot analysis. miR-132 was found to promote cellular proliferation and migration during the early stages of urothelial wound repair. Its expression was modulated by key cytokines such as IL-6, IL-10, and TGF-β1. miR-132 played a crucial role in urothelial wound healing by enhancing cell proliferation and migration, regulated by cytokines, suggesting its action within a complex regulatory network. These findings highlight the therapeutic potential of targeting miR-132 in bladder injury repair, offering new insights into bladder repair mechanisms. [ABSTRACT FROM AUTHOR]

Introduction and Hypothesis: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition characterized by chronic inflammation that affects the bladder. The study was aimed at evaluating the effectiveness of intravesical platelet-rich plasma (PRP) injections in patients with IC/BPS. Methods: We conducted a comprehensive search strategy to involve studies that investigate the efficacy of intravesical PRP injections or instillations over different time intervals. Various outcome measures were assessed, including pain scores, functional outcomes, urodynamic parameters, and surface expressions on the urothelium. Results: Our search strategy revealed 1,125 studies. After screening, ten articles met the inclusion criteria. Intravesical PRP significantly reduced the visual analog scale (VAS) compared with baseline scores. Several clinical trials reported significant improvements in the global response rate (GRA), O'Leary–Sant Symptom (OSS) questionnaire, Interstitial Cystitis Symptom Index (ICSI), and Interstitial Cystitis Problem Index (ICPI). Urodynamic parameters such as maximum flow rate (Qmax) and post-voiding residual (PVR) showed significant improvements in some studies. Conclusion: The study concluded that intravesical PRP injections could be a promising effective treatment option for IC/BPS patients by their significant ability to reduce pain. However, improvement of urodynamic and functional outcomes is still not clear. Further large comparative trials are still warranted to assess the efficacy of PRP instillation. [ABSTRACT FROM AUTHOR]

Background: Bladder urothelial carcinoma, is considered the 7th most common cancer in males. It is classified into luminal and basal subtypes depending on molecular markers, influencing prognosis and treatment. Identifying reliable biomarkers like GATA3, CK20, and CK5/6 through immunohistochemical methods can aid in early detection, risk stratification, and personalized treatment strategies. This study aims for evaluation prognostic role of these mentioned markers in correlation with clinicopathological parameters in urothelial carcinomas. Methods: Tumor samples of forty cases were immunohistochemically stained for GATA3, CK5/6, and CK20. A cutoff of 20% positivity was used to determine subtype classifications, with staining patterns guiding the categorization into basal, luminal, double positive, or double negative groups. Results: In this study of 40 urothelial carcinoma patients tumors were classified into basal and luminal subtypes using GATA3, CK5/6 and CK20 markers. GATA3 expression showed no significant association with clinicopathological parameters; while, CK20 was associated with tumor size, and CK5/6 with T, N classification, and lymphovascular invasion. Significant differences in clinicopathological parameters were observed when subtypes were defined by CK5/6, GATA3 or CK20, particularly in tumor grade, T and N classification, and gender. Basal molecular subtypes was correlated with poor prognostic parameters. Conclusions: This study documented that use of triple markers could define the luminal and basal subtypes of urothelial carcinoma. Basal tumors have shown to be associated with the aggressive behavior and future studies may allow the development of new therapies in the context of molecular subtypes. [ABSTRACT FROM AUTHOR]

Aim: Bladder sensation is critical for coordinating voluntary micturition to maintain healthy bladder function. Sensations are initiated by the activation of sensory afferents that innervate throughout the bladder wall. However, the physiological complexity that underlies the initiation of bladder sensory signaling in health and disease remains poorly understood. This review summarises the latest knowledge of the mechanisms underlying the generation of bladder sensation and identifies key areas for future research. Methods: Experts in bladder sensory signaling reviewed the literature on how the lower urinary tract contributes to bladder sensation and identified key research areas for discussion at the 10th International Consultation on Incontinence—Research Society. Results: The importance of bladder sensory signals in maintaining healthy bladder function is well established. However, better therapeutic management of bladder disorders with exaggerated bladder sensation, including overactive bladder syndrome (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS) is limited by a lack of knowledge in a number of key research areas including; the contribution of different nerves (pudendal, pelvic, hypogastric) to filling sensations in health and disease; the relative contribution of stretch sensitive (muscular) and stretch‐insensitive (mucosal) afferents to bladder sensation in health and disease; the direct and indirect contributions of the muscularis mucosae to bladder contraction and sensation; and the impact of manipulating urothelial release factors on bladder sensation. Conclusion: Disturbances in bladder sensory signaling can have severe consequences for bladder sensation and function including the development of OAB and IC/BPS. Advancing therapeutic treatments for OAB and IC/BPS requires a deeper understanding of the mechanisms underlying the generation of bladder sensation, and key areas for future research have been identified. [ABSTRACT FROM AUTHOR]

Introduction: Inflammation and neuronal hypersensitivity are reactive protective mechanisms after urothelial injury. In lower urinary tract dysfunctions (LUTD), such as urinary tract infection (UTI), bladder pain syndrome with interstitial cystitis (BPS/IC) and neurogenic LUTD after spinal cord injury (SCI), chronic inflammation can develop. It is unclear how the protective reactionary inflammation escalates into chronic disease in some patients. Methods: During its 2023 meeting in Bristol, the International Consultation on Incontinence‐Research Society (ICI‐RS) reviewed the urothelial and inflammatory changes after UTI, BPS/IC and SCI. Potential factors contributing to the evolution into chronic disease were explored in a think‐tank. Results: Five topics were discussed. (1) Visceral fat metabolism participates in the systemic pro‐inflammatory effect of noradrenalin in BPS/IC and SCI. Sympathetic nervous system‐adipocyte‐bladder crosstalk needs further investigation. (2) Sympathetic hyperactivity also potentiates immune depression in SCI and needs to be investigated in BPS/IC. Gabapentin and tumor necrosis factor‐α are promising research targets. (3) The exact peripheral neurons involved in the integrative protective unit formed by nervous and immune systems need to be further identified. (4) Neurotransmitter changes in SCI and BPS/IC: Neurotransmitter crosstalk needs to be considered in identifying new therapeutic targets. (5) The change from eubiosis to dysbiosis in SCI can contribute to UTI susceptibility and needs to be unraveled. Conclusions: The think‐tank discussed whether visceral fat metabolism, immune depression through sympathetic hyperactivity, peripheral nerves and neurotransmitter crosstalk, and the change in microbiome could provide explanations in the heterogenic development of chronic inflammation in LUTD. High‐priority research questions were identified. [ABSTRACT FROM AUTHOR]

Objective: To develop a prognostically relevant scoring system for stage pT1 non‐muscle‐invasive bladder cancer (NMIBC) incorporating tumour budding, growth pattern and invasion pattern because the World Health Organisation grading system shows limited prognostic value in such patients. Patients and Methods: The tissue specimens and clinical data of 113 patients with stage pT1 NMIBC who underwent transurethral resection of bladder tumour were retrospectively investigated. Tumour budding, and growth and invasion patterns were evaluated and categorised into two grade groups (GGs). GGs and other clinical and histopathological variables were investigated regarding recurrence‐free survival (RFS), progression‐free survival (PFS), cancer‐specific survival (CSS) and overall survival (OS) using univariable and multivariable Cox regression analyses. Results: The integration of two tumour budding groups, two growth patterns, and two invasion patterns yielded an unfavourable GG (n = 28; 24.7%) that had a high impact on oncological outcomes. The unfavourable GG was identified as an independent RFS and OS predictor (P = 0.004 and P = 0.046, respectively) and linked to worse PFS (P = 0.001) and CSS (P = 0.001), irrespective of the European Association of Urology risk group. The unfavourable GG was associated with higher rates of BCG‐unresponsive tumours (P = 0.006). Study limitations include the retrospective, single‐centre design, diverse therapies and small cohort. Conclusions: We present a morphology‐based grading system for stage pT1 NMIBC that correlates with disease aggressiveness and oncological patient outcomes. It therefore identifies a highest risk group of stage pT1 NMIBC patients, who should be followed up more intensively or receive immediate radical cystectomy. The grading incorporates objective variables assessable on haematoxylin and eosin slides and immunohistochemistry, enabling an easy‐to‐use low‐cost approach that is applicable in daily routine. Further studies are needed to validate and confirm these results. [ABSTRACT FROM AUTHOR]

Bladder cancer remains a significant health challenge due to its high recurrence and progression rates. This study aims to evaluate the role of POLR3G in the development and progression of bladder cancer and the potential of POLR3G to serve as a novel therapeutic target. We constructed a bladder cancer model in Wistar rats by administering N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), which successfully induced a transition from normal mucosa to hyperplasia and ultimately to urothelial carcinoma. We observed a progressive upregulation of POLR3G expression during the bladder cancer development and progression. To investigate the functional role of POLR3G, we performed functional experiments in bladder cancer cell lines. The results demonstrated that knocking down POLR3G significantly inhibited cell proliferation, migration, and invasion. We further conducted RNA sequencing on POLR3G-knockdown bladder cancer cells, and Metascape was employed to perform the functional enrichment analysis of the differentially expressed genes (DEGs). Enrichment analysis revealed the enrichment of DEGs in the RNA polymerase and apoptotic cleavage of cellular proteins pathways, as well as their involvement in the Wnt and MAPK signaling pathways. The downregulation of Wnt pathway-related proteins such as Wnt5a/b, DVL2, LRP-6, and phosphorylated LRP-6 upon POLR3G knockdown was further confirmed by Western blotting, indicating that POLR3G might influence bladder cancer behavior through the Wnt signaling pathway. Our findings suggest that POLR3G plays a crucial role in bladder cancer progression and could serve as a potential therapeutic target. Future studies should focus on the detailed mechanisms by which POLR3G regulates these signaling pathways and its potential as a biomarker for early detection and prognosis of bladder cancer. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the prognostic role of blood-based nutritional biomarkers, including red blood cell (RBC count), hemoglobin (Hb), total protein (TP), albumin, the serum albumin to globulin ratio (AGR) and the prognostic nutritional index (PNI) in patients who underwent intravesical treatment for non-muscle invasive bladder cancer (NMIBC). A total of 501 NMIBC patients who received intravesical Bacillus Calmette-Guerin (BCG) treatment following transurethral resection of bladder tumor (TURBT) were included. The optimal cutoff values for these nutrition-based indicators were determined using receiver operating characteristic curve analysis. We observed a significantly higher recurrence-free survival (RFS) rate in patients with elevated levels of RBC count, Hb, TP, and albumin. Cox univariate and multivariate Cox regression analyses demonstrated that serum albumin (P = 0.002, HR = 0.51, 95%CI: 0.33–0.78), RBC count (P = 0.002, HR = 0.50, 95%CI: 0.32–0.77), TP (P = 0.028, HR = 0.62, 95%CI: 0.41–0.95), Hb (P = 0.004, HR = 0.53, 95%CI: 0.33–0.84), AGR (P = 0.003, HR = 0.46, 95%CI: 0.27–0.76) and PNI (P = 0.019, HR = 0.56, 95%CI: 0.35–0.91) were significant independent factors predicting RFS. These cost-effective and convenient blood-based nutritional biomarkers have the potential to serve as valuable prognostic indicators for predicting recurrence in NMIBC patients undergoing BCG-immunotherapy. [ABSTRACT FROM AUTHOR]

Background: A few studies regarding the epidemiology and risk factors of Non-muscle Invasive Bladder Cancer (NMIBC) are reported from Sub-Saharan African countries (SSA), including Somalia, and the African literature is scant on the management of NMIBC. The present study aims to evaluate the clinical-histopathological characteristics and factors associated with the survival rate of patients with NMIBC. Method: This six-year cohort study included 196 patients with NMIBC. It reviewed the clinical and histopathological characteristics and factors predicting cancer-specific survival for these patients. Results: The mean patient age was 59.01 ± 11.50 years, with a male-to-female ratio of 2.8:1. Urothelial carcinoma (UC) constituted the most common pathological type, accounting for 90.8%; Ta LG and T1HG were the most common histopathological tumour stage and grade (n = 90, 45.9%, vs. n = 56, 28.6%), respectively. The mean tumour size was 4.72 ± 2.81 cm. The cancer-specific mortality(CSM) was 13.3%. Age [2.252(2.310–2.943], p < 0.001], Gender [1.031(0.981-1.1.242),p < 0.001], tumour stage and grade [4.902(3.607–5.614),p < 0.001], tumour location [1.135(0.806–1.172),p < 0.001], number [0.510(0.410–0.920),p = 0.03], tumour size [1.523(0.936–1.541),p < 0.001], use of intravesical chemotherapy or BCG [2.810(1.972–4.381),p < 0.001], preoperative hydronephrosis grade [1.517(1.172–2.154),p < 0.001], and follow-up compliance [3.376(2.633–5.018),p < 0.001] were all associated with CSM. The 5-year overall survival was 57.1%, and cardiovascular diseases were the leading cause of mortality (n = 34), followed by diabetes (n = 28). Conclusion: Our study findings revealed that UC constituted the most common pathological subtype, though less than forty per cent of our patients receive intravesical adjuvant therapies, which are crucial to minimizing disease morbidity and mortality. Initiatives improving uro-oncological care, including subspecialty training in oncology and essential cancer therapies, better access to urology services, and cancer screening programs, are much needed for optimal management plans and care in the country. [ABSTRACT FROM AUTHOR]

We aimed to investigate the expression and motor modulatory roles of several mechano-sensitive channels (MSCs) in human ureter. Human proximal ureters were obtained from eighty patients subjected to nephrectomy. Expression of MSCs at mRNA, protein and functional levels were examined. Contractions of longitudinal ureter strips were recorded in organ bath. A fluorescent probe Diaminofluoresceins was used to measure nitric oxide (NO). RT-PCR analyses revealed predominant expression of Piezo1 and TRPV2 mRNA in intact ureter and mucosa. Immunofluorescence assays indicate proteins of MSCs (Piezo1/Piezo2, TRPV2 and TRPV4) were mainly distributed in the urothelium. Ca2+ imaging confirmed functional expression of TRPV2, TRPV4 and Piezo1 in cultured urothelial cells. Specific agonists of Piezo1 (Yoda1, 3–300 μM) and TRPV2 (cannabidiol, 3–300 μM) attenuated the frequency of ureteral contractions in a dose-dependent manner while the TRPV4 agonist GSK1016790A (100 nM–1 μM) exerted no effect. The inhibitory effects of Piezo1 and TRPV2 agonists were significantly blocked by the selective antagonists (Dooku 1 for Piezo1, Tranilast for TRPV2), removal of the mucosa, and pretreatment with NO synthase inhibitor L-NAME (10 μM). Yoda1 (30 μM) and cannabidiol (50 μM) increased production of NO in cultured urothelial cells. Our results suggest that activation of Piezo1 or TRPV2 evokes NO production and release from mucosa that may mediate mechanical stimulus-induced reduction of ureter contractions. Our findings support the idea that targeting Piezo1 and TRPV2 channels may be a promising pharmacological strategy for ureter stone passage or colic pain relief. [ABSTRACT FROM AUTHOR]

Background: Despite adequate transurethral resection of the bladder tumor (TURBT) followed by intravesical bacillus-calmette guérin (BCG), high-risk non-muscle-invasive bladder cancer (HR-NMIBC) is associated with high rates of recurrence and progression. Immune checkpoint inhibitors can improve antitumor activity in bladder cancer, but relevant evidence in HR-NMIBC is limited. Thus, we evaluated the efficacy and safety of the tislelizumab-based combination regimen in HR-NMIBC. Methods: A retrospective study included 21 patients diagnosed with HR-NMIBC between July 2020 and September 2022. All patients underwent TURBT followed by combination regimens of tislelizumab plus BCG with or without gemcitabine/cisplatin (GC) chemotherapy. Clinical Data on demographics and characteristics, treatment information, outcomes, and safety were collected and analyzed. Results: Among the 21 patients with HR-NMIBC, the median age was 63 years (range 39–85), with the majority of patients with stage T1 (16/21, 76.19%). The median treatment of tislelizumab was 5 cycles (range 1–12) and the median number of BCG instillations was 12 times (range 2–19). Of the 21 patients, 15 (71.43%) received combination chemotherapy with GC, with a median treatment of 2 cycles (range 0–7); others did not. Overall, after the median follow-up of 25 months (range 7–31), the estimated 2-year bladder recurrence-free survival rate was 78.64% (95% confidence intervals [CIs], 50.79–91.83%), 2-year cystectomy-free survival rate was 83.00% (95% CI 53.53–94.59%), and 2-year disease-free survival rate was 73.39% (95% CI 46.14–88.36%). Sixteen stage T1 patients achieved a distant metastasis-free survival rate of 95.45% (95% CI 71.87–99.34%) at 2 years. Fourteen (66.67%) patients experienced at least one treatment related-AEs (TRAEs), with 9.52% (2/21) of grade 3–4. Grade ≥ 3 TRAEs were hypophysitis (1/21, 4.76%) and myasthenia (1/21, 4.76%). No treatment-related deaths were observed. Conclusions: The study demonstrated promising clinical benefits and a manageable safety profile of tislelizumab-based combination regimen as a bladder-sparing treatment of HR-NMIBC. [ABSTRACT FROM AUTHOR]

The aim of the work is to analyze the scientific literature data on the principles and state of rational antibiotic therapy use according to factors for the development of inflammatory changes in the urinary tract with the identification of the latter in the complex therapy for urolithiasis, taking into account the peculiarities of contact laser lithotripsy. The article presents the results of analytical processing of professional publications on current principles of rational antibiotic therapy in the surgical treatment for urolithiasis, taking into account factors that may influence the development of inflammatory changes in the urinary tract. It has been revealed that there is currently no clear understanding about chances of developing infectious processes during the treatment for urolithiasis of various localization, as well as the advisability and duration of using antibiotics in the comprehensive treatment of the disease. At the same time, antibiotic overuse has resulted in phenomena of resistance, side effects, and a number of other complicating factors needed to be addressed. Conclusions. An analysis of present approaches to antibacterial therapy, considering its rationality at different treatment stages, has been conducted concluding that clear criteria and indicators for the use of drugs have not been specified, but these data serve only as recommendations and have not been thoroughly examined. Data on searching for a solution to problematic aspects are also provided. [ABSTRACT FROM AUTHOR]

The transitional epithelial cells (urothelium) that line the lumen of the urinary bladder form a barrier between potentially harmful pathogens, toxins, and other bladder contents and the inner layers of the bladder wall. The urothelium, however, is not simply a passive barrier, as it can produce signaling factors, such as ATP, nitric oxide, prostaglandins, and other prostanoids, that can modulate bladder function. We investigated whether substances produced by the urothelium could directly modulate the contractility of the underlying urinary bladder smooth muscle. Force was measured in isolated strips of mouse urinary bladder with the urothelium intact or denuded. Bladder strips developed spontaneous tone and phasic contractions. In urothelium-intact strips, basal tone, as well as the frequency and amplitude of phasic contractions, were 25%, 32%, and 338% higher than in urothelium-denuded strips, respectively. Basal tone and phasic contractility in urothelium-intact bladder strips were abolished by the cyclooxygenase (COX) inhibitor indomethacin (10 µM) or the voltage-dependent Ca2+ channel blocker diltiazem (50 µM), whereas blocking neuronal sodium channels with tetrodotoxin (1 µM) had no effect. These results suggest that prostanoids produced in the urothelium enhance smooth muscle tone and phasic contractions by activating voltage-dependent Ca2+ channels in the underlying bladder smooth muscle. We went on to demonstrate that blocking COX inhibits the generation of transient pressure events in isolated pressurized bladders and greatly attenuates the afferent nerve activity during bladder filling, suggesting that urothelial prostanoids may also play a role in sensory nerve signaling. NEW & NOTEWORTHY: This paper provides evidence for the role of urothelial-derived prostanoids in maintaining tone in the urinary bladder during bladder filling, not only underscoring the role of the urothelium as more than a barrier but also contributing to active regulation of the urinary bladder. Furthermore, cyclooxygenase products greatly augment sensory nerve activity generated by bladder afferents during bladder filling and thus may play a role in perception of bladder fullness. [ABSTRACT FROM AUTHOR]

Background: Independent factors are needed to supplement vesical imaging‐reporting and data system (VI‐RADS) to improve its ability to identify muscle invasive bladder cancer (MIBC). Purpose: To assess the correlation between MIBC and diffusion kurtosis imaging (DKI) ratio, VI‐RADS, and other factors (such as tumor location). Study Type: Retrospective. Population: Sixty‐eight patients (50 males and 18 females; age: 70.1 ± 9.5 years) with bladder urothelial carcinoma. Field Strength/Sequence: 1.5 T, conventional diffusion‐weighted imaging (DWI), and DKI (single shot echo‐planar sequence). Assessment: Three radiologists independently measured the diffusion parameters of each bladder cancer (BCa) and obturator internus, including the mean apparent diffusion coefficient (ADCmean), mean kurtosis (MK), and mean diffusion (MD). And the ratio of diffusion parameters between BCa and obturator internus was calculated (diffusion parameter ratio = bladder cancer:obturator internus). Based on the VI‐RADS, the target lesions were independently scored. Furthermore, the actual tumor‐wall contact length (ACTCL) and absolute tumor‐wall contact length (ABTCL) were measured. Statistical Tests: Multicollinearity among independent variables was evaluated using the variance inflation factor (VIF). Multivariable logistic regression analysis was used to determine the independent risk factors of MIBC. The receiver operating characteristic curve was used to evaluate the efficacy of each variable in detecting MIBC. The DeLong test was used to compare the area under the curve (AUC). A P < 0.05 was considered statistically significant. Results: MKratio (median: 0.62) and VI‐RADS were independent risk factors for MIBC. AUCs for MKratio, VI‐RADS, and MKratio combined with VI‐RADS in assessing MIBC were 0.895, 0.871, and 0.973, respectively. MKratio combined with VI‐RADS was more effective in diagnosing MIBC than VI‐RADS alone. Data Conclusions: MKratio has potential to assist the assessment of MIBC. MKratio can be used as a supplement to VI‐RADS for detecting MIBC. Level of Evidence: 4 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Purpose: We aimed to assess the effectiveness of early single intravesical administration of epirubicin in preventing intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. Materials and Methods: Patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy between November 2018 and May 2022 were retrospectively reviewed. Intravesical epirubicin was administered within 48 hours if no evidence of leakage was observed. Epirubicin (50 mg) in 50 mL normal saline solution was introduced into the bladder via a catheter and maintained for 60 minutes. The severity of adverse events was graded using the Clavien-Dindo classification. We compared intravesical recurrence rate between the two groups. Multivariate analyses were performed to identify the independent predictors of bladder recurrence following radical nephroureterectomy. Results: Epirubicin (n=55) and control (n=116) groups were included in the analysis. No grade 1 or higher bladder symptoms have been reported. A statistically significant difference in the intravesical recurrence rate was observed between the two groups (11.8% at 1 year in the epirubicin group vs. 28.4% at 1 year in the control group; log-rank p=0.039). In multivariate analysis, epirubicin instillation (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20 to 0.93; p=0.033) and adjuvant chemotherapy (HR, 0.29; 95% CI, 0.13 to 0.65; p=0.003) were independently predictive of a reduced incidence of bladder recurrence. Conclusion This retrospective review revealed that a single immediate intravesical instillation of epirubicin is safe and can reduce the incidence of intravesical recurrence after radical nephroureterectomy. However, further prospective trials are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Preoperative discrimination between non-muscle-invasive bladder cancer (NMIBC) and the muscle invasive bladder cancer (MIBC) is a determinant of management. The purpose of this research is to employ radiomics to evaluate the diagnostic value in determining muscle invasiveness of compressed sensing (CS) accelerated 3D T2-weighted-SPACE sequence with high resolution and short acquisition time. Methods: This prospective study involved 108 participants who underwent preoperative 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted sequences. The cohort was divided into training and validation cohorts in a 7:3 ratio. In the training cohort, a Rad-score was constructed based on radiomic features selected by intraclass correlation coefficients, pearson correlation coefficient and least absolute shrinkage and selection operator. Multivariate logistic regression was used to develop a nomogram combined radiomics and clinical indices. In the validation cohort, the performances of the models were evaluated by ROC, calibration, and decision curves. Results: In the validation cohort, the area under ROC curve of 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted models were 0.87(95% confidence interval (CI):0.73-1.00), 0.79(95%CI:0.63–0.96) and 0.77(95%CI:0.60–0.93), respectively. The differences in signal-to-noise ratio and contrast-to-noise ratio between 3D-CS-T2-weighted-SPACE and 3D-T2-weighted-SPACE sequences were not statistically significant(p > 0.05). While the clinical model composed of three clinical indices was 0.74(95%CI:0.55–0.94) and the radiomics-clinical nomogram model was 0.88(95%CI:0.75-1.00). The calibration curves confirmed high goodness of fit, and the decision curve also showed that the radiomics model and combined nomogram model yielded higher net benefits than the clinical model. Conclusion: The radiomics model based on compressed sensing 3D T2WI sequence, which was acquired within a shorter acquisition time, showed superior diagnostic efficacy in muscle invasion of bladder cancer. Additionally, the nomogram model could enhance the diagnostic performance. [ABSTRACT FROM AUTHOR]

Background & objectives: Tumor grade determines prognosis in urothelial carcinoma. The classification of low and high grade is based on nuclear morphological features that include nuclear size, hyperchromasia and pleomorphism. These features are subjectively assessed by the pathologists and are not numerically measured, which leads to high rates of interobserver variability. The purpose of this study is to assess the value of a computer-based image analysis tool for identifying predictors of tumor grade in bladder cancer. Methods: Four hundred images of urothelial tumors were graded by five pathologists and two expert genitourinary pathologists using a scale of 1 (lowest grade) to 5 (highest grade). A computer algorithm was used to automatically segment the nuclei and to provide morphometric parameters for each nucleus, which were used to establish the grading algorithm. Grading algorithm was compared to pathologists' agreement. Results: Comparison of the grading scores of the five pathologists with the expert genitourinary pathologists score showed agreement rates between 88.5% and 97.5%.The agreement rate between the two expert genitourinary pathologists was 99.5%. The quantified algorithm based conventional parameters that determine the grade (nuclear size, pleomorphism and hyperchromasia) showed > 85% agreement with the expert genitourinary pathologists. Surprisingly, the parameter that was most associated with tumor grade was the 10th percentile of the nuclear area, and high grade was associated with lower 10th percentile nuclei, caused by the presence of more inflammatory cells in the high-grade tumors. Conclusion: Quantitative nuclear features could be applied to determine urothelial carcinoma grade and explore new biologically explainable parameters with better correlation to grade than those currently used. [ABSTRACT FROM AUTHOR]

Urothelial damage and barrier dysfunction emerge as the foremost mechanisms in Hunner‐type interstitial cystitis/bladder pain syndrome (HIC). Although treatments aimed at urothelial regeneration and repair have been employed, their therapeutic effectiveness remains limited due to the inadequate understanding of specific cell types involved in damage and the lack of specific molecular targets within these mechanisms. Therefore, we harnessed single‐cell RNA sequencing to elucidate the heterogeneity and developmental trajectory of urothelial cells within HIC bladders. Through reclustering, we identified eight distinct clusters of urothelial cells. There was a significant reduction in UPK3A+ umbrella cells and a simultaneous increase in progenitor‐like pluripotent cells (PPCs) within the HIC bladder. Pseudotime analysis of the urothelial cells in the HIC bladder revealed that cells faced challenges in differentiating into UPK3A+ umbrella cells, while PPCs exhibited substantial proliferation to compensate for the loss of UPK3A+ umbrella cells. The urothelium in HIC remains unrepaired, despite the substantial proliferation of PPCs. Thus, we propose that inhibiting the pivotal signaling pathways responsible for the injury to UPK3A+ umbrella cells is paramount for restoring the urothelial barrier and alleviating lower urinary tract symptoms in HIC patients. Subsequently, we identified key molecular pathways (TLR3 and NR2F6) associated with the injury of UPK3A+ umbrella cells in HIC urothelium. Finally, we conducted in vitro and in vivo experiments to confirm the potential of the TLR3–NR2F6 axis as a promising therapeutic target for HIC. These findings hold the potential to inhibit urothelial injury, providing promising clues for early diagnosis and functional bladder self‐repair strategies for HIC patients. © 2024 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Urinary tract diseases are common in cats, and often require surgical reconstruction. Here, to explore the possibility of urinary tract reconstruction in cats using in-body tissue architecture (iBTA), biosheets fabricated using iBTA technology were implanted into the feline bladder and the regeneration process was histologically evaluated. The biosheets were prepared by embedding molds into the dorsal subcutaneous pouches of six cats for 2 months. A section of the bladder wall was removed, and the biosheets were sutured to the excision site. After 1 and 3 months of implantation, the biosheets were harvested and evaluated histologically. Implantable biosheets were formed with a success rate of 67%. There were no major complications following implantation, including tissue rejection, severe inflammation, or infection. Urinary incontinence was also not observed. Histological evaluation revealed the bladder lumen was almost entirely covered by urothelium after 1 month, with myofibroblast infiltration into the biosheets. After 3 months, the urothelium became multilayered, and mature myocytes and nerve fibers were observed at the implantation site. In conclusion, this study showed that tissue reconstruction using iBTA can be applied to cats, and that biosheets have the potential to be useful in both the structural and functional regeneration of the feline urinary tract. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prognostic value of T1 substaging in patients treated with bacillus Calmette‐Guérin (BCG) or immediate radical cystectomy (iRC). Materials and Methods: We performed an institutional review board‐approved retrospective study analysing non‐muscle‐invasive bladder cancer (NMIBC) patients with pT1 disease treated with either BCG or iRC between 2000 and 2020. Lamina propria (LP) invasion characteristics were extracted from the pathology report. The Kaplan–Meier method was used to calculate overall survival (OS), cancer‐specific survival (CSS) and metastasis‐free survival (MFS). Multivariable Cox models were used to determine the association between progression‐free survival (PFS) and characteristics in the BCG cohort. A logistic regression model explored the relationship between T1 substaging and upstaging to >pT2 at iRC. Results: A total of 411 T1 high‐grade patients were identified. LP invasion characteristics were as follows: not specified: 115 (28%); focal/superficial (F/S): 147 (35.8%); and extensive/multifocal (E/M): 149 (36.2%). Overall, 303 patients (73.7%) received BCG, and 108 patients (26.3%) underwent iRC. The median (interquartile range) follow‐up was 53 (32–96) months. Patients with E/M LP invasion were significantly more likely to undergo iRC (34% vs. 19%; P = 0.003). Patients with E/M LP invasion showed poorer MFS and CSS compared to those with F/S LP invasion when treated with BCG but not when treated with iRC. Among BCG‐treated patients, progression occurred in 41 patients and E/M LP invasion was independently associated with progression after BCG (hazard ratio 5.3, 95% confidence interval [CI] 2.2–13.1; P < 0.001). T1 substaging was not associated with upstaging at RC (odds ratio 3.15, 95% CI 0.82–12.12; P = 0.095). Conclusions: Extensive/multifocal LP invasion was associated with poor PFS, MFS and CSS in patients treated with BCG. T1 substaging provides valuable prognostic information and should be reported in pathology reports. [ABSTRACT FROM AUTHOR]

Urothelium forms a distensible yet impermeable barrier, senses and transduces stimuli, and defends the urinary tract from mechanical, chemical, and bacterial injuries. Biochemical and genetic labeling studies support the existence of one or more progenitor populations with the capacity to rapidly regenerate the urothelium following injury, but slow turnover, a low mitotic index, and inconsistent methodologies obscure progenitor identity. The progenitor properties of basal keratin 5 urothelial cells (K5-UCs) have been previously investigated, but those studies focused on embryonic or adult bladder urothelium. Urothelium undergoes desquamation and apoptosis after birth, which requires postnatal proliferation and restoration. Therefore, we mapped the fate of bladder K5-UCs across postnatal development/maturation and following administration of cyclophosphamide to measure homeostatic and reparative progenitor capacities, respectively. In vivo studies demonstrate that basal K5-UCs are age-restricted progenitors in neonates and juveniles, but not in adult mice. Neonatal K5-UCs retain a superior progenitor capacity in vitro, forming larger and more differentiated urothelial organoids than adult K5-UCs. Accordingly, K5-UC transcriptomes are temporally distinct, with enrichment of transcripts associated with cell proliferation and differentiation in neonates. Induction of urothelial proliferation is sufficient to restore adult K5-UC progenitor capacity. Our findings advance the understanding of urothelial progenitors and support a linear model of urothelial formation and regeneration, which may have significant impact on therapeutic development or tissue engineering strategies. NEW & NOTEWORTHY: Fate mapping reveals an important linear relationship, whereby bladder basal urothelial cells give rise to intermediate and superficial cells in an age-restricted manner and contribute to tissue repair. Neonatal basal cells reprise their role as superior progenitors in vitro and display distinct transcriptional signatures, which suggest progenitor function is at least partially cell intrinsic. However, the urothelium progenitor niche cannot be overlooked, since FGF7 rescues adult basal cell progenitor function. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy of an intravesical instillation of hyaluronic acid (HA) combined with epidermal growth factor (EGF) for the treatment of interstitial cystitis (IC) using a lipopolysaccharide (LPS)-induced IC animal model. Methods: A total of 24 female Sprague-Dawley rats were randomized to 4 groups: sham control, IC, HA, and treatment (HA/ EGF) groups. A polyethylene-50 tube was placed inside the bladder of each animal. IC was induced by twice-weekly instillations of LPS for 3 weeks, which resulted in chronic injury of the urothelium. Animals in the sham control group only received saline instillation. Treatment solutions of HA and HA/EGF were given on days 0, 7, and 14 after IC induction (400 μL of HA in a concentration of 0.4 mg/0.5 mL and 400 μL of NewEpi, a commercialized HA/EGF mixture containing 2 μg of EGF and 0.4 mg of sodium hyaluronate). Animals were sacrificed on day 21 for further examinations. Results: The HA/EGF group showed visible improvement in hematuria with a significant reduction of red blood cells in the urine compared to the HA group. Histological examination revealed that HA/EGF treatment reversed the abnormalities developed in IC, including infiltration of inflammatory cells, irregular re-epithelialization, and fibrotic tissue. Moreover, HA/ EGF significantly reduced the levels of proinflammation cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β) and substantially lowered the elevated oxidative stress biomarker malondialdehyde, yet restored the levels of antioxidant enzymes glutathione peroxidase and superoxide dismutase, with superior results than HA treatment. Cystometry studies indicated that HA/EGF significantly prolonged intercontraction interval and increased micturition volume. Conclusions: HA/EGF has been demonstrated as a more effective treatment for enhancing the urothelium lining and reducing inflammatory changes to alleviate clinical symptoms associated with IC in rats, compared to HA alone. [ABSTRACT FROM AUTHOR]

Myxoid pseudotumor is a pseudoneoplastic fibroblastic proliferation that has been described in the perinephric and renal sinus fat tissue. It is characterized by the presence of a myxoid matrix, intermingled with the adipocytes, and a hypocellular population of spindle-shaped and stellate cells. We report a myxoid pseudotumor involving the distal ureter, which broadens the spectrum of possible localizations of this lesion around the urinary tract. It occurred in an 80-year-old patient who underwent a nephroureterectomy indicated after an incidental radiological finding of a thickening of the distal left ureter wall which suggested a ureteral neoplasm. He had two voided urine and one ureteroscopic sample cytologies diagnosed as high-grade urothelial carcinoma, as well as a retrograde ureteroscopy ureteral biopsy which was diagnosed as urothelial carcinoma in situ. This emphasizes the problem of the possible misdiagnosis of myxoid pseudotumor as a ureteral infiltrative carcinoma due to the radiological findings being badly interpreted, compounded by the preoperative cytohistologic data on malignancy. A diffuse urothelial carcinoma in situ was seen in our specimen without infiltrative or papillary tumors. This would not support an obstructive pathogenetic mechanism as has been hypothesized for myxoid pseudotumor. [ABSTRACT FROM AUTHOR]

Purpose: To develop and validate a nomogram for preoperative prediction of lymph node metastasis in patients with progressive muscle-invasive bladder cancer. Materials and methods: We retrospectively recruited patients, divided them into training and validation cohorts, and gathered patient demographics, pathology data of transurethral bladder tumor resection specimens, imaging findings, and laboratory information. We performed logistic regression analyses, both single=variable and multi-variable, to investigate independent preoperative risk variables and develop a nomogram. Both internal and external validations were conducted to evaluate the predictive performance of this nomogram. Results: The training cohort consisted of 144 patients with advanced muscle- invasive bladder cancer, while the validation cohort included 62 individuals. The independent preoperative risk factors identified were tumor pathology grade, platelet count, tumor size on imaging, and lymph node size, which were utilized to develop the nomogram. The model demonstrated high predictive accuracy, as evidenced by the area under the receiver operating characteristic curve values of 0.898 and 0.843 for the primary and external validation cohorts, respectively. Calibration curves and decision curve analysis showed a good performance of the nomogram in both cohorts, indicating its high clinical applicability. Conclusion: A nomogram for preoperative prediction of lymph node metastasis in patients with advanced muscle-invasive bladder cancer was successfully developed; its accuracy, reliability, and clinical value were demonstrated. This new tool would facilitate better clinical decisions regarding whether to perform complete lymph node dissection in cases of radical cystectomy. [ABSTRACT FROM AUTHOR]

Introduction: [68 Ga]Ga-FAPI-46 PET/CT is a novel hybrid imaging method that previously showed additional diagnostic value in the assessment of distant urothelial carcinoma lesions. We hypothesized that patients with bladder cancer benefit from [68 Ga]Ga-FAPI-46 PET/CT prior to radical cystectomy for locoregional lymph node staging. Materials and methods: Eighteen patients underwent [68 Ga]Ga-FAPI-46 PET/CT for evaluation of lymph node (LN) status in predefined LN regions. Two hundred twenty-nine intraoperatively removed LN served as histopathological reference standard. Results: Urothelial carcinoma (UC) spread was found in ten LN in seven different regions (14.3%). Hereby, [68 Ga]Ga-FAPI-46 PET/CT was positive in four out of seven regions (57.1%) and showed significantly increased FAPI uptake compared to non-pathological regions. In the remaining three out of seven (42.9%) regions, [68 Ga]Ga-FAPI-46 PET/CT was rated negative since no pathological increased FAPI uptake was detected or the proximity of the urinary tract prevented a differentiation from physiological uptake. CT was inconspicuous in these three regions. In total, two FAP-positive LN regions were found without histopathological counterpart. Overall, sensitivity, specificity, positive predictive value, and negative predictive value were 57.1%, 95.2%, 66.7%, and 93.0% for PET imaging. Conclusion: In summary, this innovative [68 Ga]Ga-FAPI-46 PET/CT method showed high specificity and negative predictive value in patients with bladder UC with a future potential to optimize therapy planning. [ABSTRACT FROM AUTHOR]

Uncovering the function of understudied G protein-coupled receptors (GPCRs) provides a wealth of untapped therapeutic potential. The poorly understood adhesion GPCR Gpr126 (Adgrg6) is widely expressed in developing kidneys. In adulthood, Gpr126 expression is enriched in parietal epithelial cells (PECs) and epithelial cells of the collecting duct and urothelium. Whether Gpr126 plays a role in kidney disease remains unclear. Here, we characterized Gpr126 expression in diseased kidneys in mice, rats, and humans. RT-PCR data show that Gpr126 expression is altered in kidney disease. A quantitative RNAscope® analysis utilizing cell type-specific markers revealed that Gpr126 expression upon tubular damage is mainly increased in cell types expressing Gpr126 under healthy conditions as well as in cells of the distal and proximal tubules. Upon glomerular damage, an increase was mainly detected in PECs. Notably, Gpr126 expression was upregulated in an ischemia/reperfusion model within hours, while upregulation in a glomerular damage model was only detected after weeks. An analysis of kidney microarray data from patients with lupus nephritis, IgA nephropathy, focal segmental glomerulosclerosis (FSGS), hypertension, and diabetes as well as single-cell RNA-seq data from kidneys of patients with acute kidney injury and chronic kidney disease indicates that GPR126 expression is also altered in human kidney disease. In patients with FSGS, an RNAscope® analysis showed that GPR126 mRNA is upregulated in PECs belonging to FSGS lesions and proximal tubules. Collectively, we provide detailed insights into Gpr126 expression in kidney disease, indicating that GPR126 is a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Introduction: The combination of sequential intravesical gemcitabine and docetaxel (Gem/Doce) chemotherapy has been considered a feasible option for BCG (Bacillus Calmette-Guérin) treatment in non-muscle invasive bladder cancer (NMIBC), gaining popularity during BCG shortage period. We seek to determine the efficacy of the treatment by comparing Gem/Doce induction alone vs induction with maintenance, and to evaluate the treatment outcomes of two different dosage protocols. Methods: A bi-center retrospective analysis of consecutive patients treated with Gem/Doce for NMIBC between 2018 and 2023 was performed. Baseline characteristics, risk group stratification (AUA 2020 guidelines), pathological, and surveillance reports were collected. Kaplan–Meier survival analysis was performed to detect Recurrence-free survival (RFS). Results: Overall, 83 patients (68 males, 15 females) with a median age of 73 (IQR 66–79), and a median follow-up time of 18 months (IQR 9–25), were included. Forty-one had an intermediate-risk disease (49%) and 42 had a high-risk disease (51%). Thirty-seven patients (45%) had a recurrence; 19 (23%) had a high-grade recurrence. RFS of Gem/Doce induction-only vs induction + maintenance was at 6 months 88% vs 100%, at 12 months 71% vs 97%, at 18 months 57% vs 91%, and at 24 months 31% vs 87%, respectively (log-rank, p < 0.0001). Patients who received 2 g Gemcitabine with Docetaxel had better RFS for all-grade recurrences (log-rank, p = 0.017). However, no difference was found for high-grade recurrences. Conclusion: Gem/Doce induction with maintenance resulted in significantly better RFS than induction-only. Combining 2 g gemcitabine with docetaxel resulted in better RFS for all-grade but not for high-grade recurrences. Further prospective trials are necessary to validate our results. [ABSTRACT FROM AUTHOR]

This article discusses a case study involving a 14-year-old female miniature dachshund with a nodular lesion in the bladder mucosa. Further examination revealed dysplastic changes in the bladder neck and urethra, as well as the presence of a BRAFV595E mutation. The article explores the association between the mutation and dysplastic changes in the mucosa, as well as the presence of follicular cystitis. It also discusses the use of immunohistochemistry for diagnosis and highlights the similarities between canine and human bladder cancer. Further studies are needed to evaluate the involvement of BRAF mutation in malignant transformation and confirm the prognostic significance of BRAF mutations in dogs with flat urothelial lesions. [Extracted from the article]

Background: In the present study, we compared Narrow Band Imaging (NBI) and White Light Cystoscopy (WLC) in Non-muscle invasive bladder cancer (NMIBC) for detection and its impact on recurrence. Materials and methods: This prospective study was conducted in the department of Urology at a tertiary institution from August 2021 to April 2023. The main aim was to determine the benefit of addition of NBI during TURBT in NMIBC. All patients with Urinary Bladder Mass (size less than 5 cm on USG/CT) aged >18 years of age planned for TURBT were included. Results: Amongst 63 patients, the mean age was 59.84 ± 11.3 years; 80% were males. Sixty percent of patients had history of Tobacco consumption and Type II DM was the most common comorbidity (59%). Commonest symptom was gross haematuria. Posterior wall was most commonly involved and papillary lesions were commonest. A total of 125 lesions were identified on WLI, with mean 1.98 ± 1.75 and 78 additional lesions were identified only on NBI with mean 1.24 ± 1.63 lesions. Four patients had intra-operative complications. Five patients had recurrence at 6 weeks and eight patients had recurrence at 3 months. NBI had detected more lesions in patients who developed recurrence at 6 weeks and 3 months (mean: 1.41 and 1.43). Conclusion: NBI has additive role in detecting NMIBC lesions missed on WLI. NBI has significant role in preventing recurrence at 3 months and more so by detecting high grade tumours. [ABSTRACT FROM AUTHOR]

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Objective: The classic Okabayashi nerve-sparing radical hysterectomy involves complete resection of the posterior leaf of the vesicouterine ligament, whereas in the simplified nerve-sparing radical hysterectomy, only the vesical veins and some connective tissue of the posterior layer of the vesicouterine ligament are resected. This study aimed to compare bladder function and cervical carcinoma relapse-free survival between these two techniques. Methods: We conducted a retrospective, historical control study. All female patients aged >20 years who were diagnosed with cervical cancer stage IB1-IIB and underwent radical hysterectomy with pelvic lymphadenectomy between 2009 and 2022 were enrolled. Patients who had a history of other cancers and those who were treated with non-surgical approaches or non-radical hysterectomy were excluded. The primary outcome was relapse-free survival during the follow-up period. Results: A total of 114 patients who underwent curative-intent radical hysterectomy were included in this study. The median follow-up duration was 60 months. No significant difference was observed in relapse-free survival between the two surgical procedures. The simplified nerve-sparing radical hysterectomy was superior in terms of both motor and sensory bladder function outcomes. Conclusion: Resection of the posterior layer of the vesicouterine ligament, with the procedure limited to the vesical veins, is an effective and safe method for radical hysterectomy. It may be more useful for preserving the bladder function, without leading to unfavorable oncologic outcomes. [ABSTRACT FROM AUTHOR]

Background: Bone metastasis (BM) carries a poor prognosis for patients with upper-tract urothelial carcinoma (UTUC). This study aims to identify survival predictors and develop a prognostic nomogram for overall survival (OS) in UTUC patients with BM. Methods: The Surveillance, Epidemiology, and End Results database was used to select patients with UTUC between 2010 and 2019. The chi-square test was used to assess the baseline differences between the groups. Kaplan–Meier analysis was employed to assess OS. Univariate and multivariate analyses were conducted to identify prognostic factors for nomogram establishment. An independent cohort was used for external validation of the nomogram. The discrimination and calibration of the nomogram were evaluated using concordance index (C-index), area under receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). All statistical analyses were performed using SPSS 23.0 and R software 4.2.2. Results: The mean OS for UTUC patients with BM was 10 months (95% CI: 8.17 to 11.84), with 6-month OS, 1-year OS, and 3-year OS rates of 41%, 21%, and 3%, respectively. Multi-organ metastases (HR = 2.21, 95% CI: 1.66 to 2.95, P < 0.001), surgery (HR = 0.72, 95% CI: 0.56 to 0.91, P = 0.007), and chemotherapy (HR = 0.37, 95% CI: 0.3 to 0.46, P < 0.001) were identified as independent prognostic factors. The C-index was 0.725 for the training cohort and 0.854 for the validation cohort, and all AUC values were > 0.679. The calibration curve and DCA curve showed the accuracy and practicality of the nomogram. Conclusions: The OS of UTUC patients with BM was poor. Multi-organ metastases was a risk factor for OS, while surgery and chemotherapy were protective factors. Our nomogram was developed and validated to assist clinicians in evaluating the OS of UTUC patients with BM. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study is to assess the efficacy of the established computed tomography (CT)-based radiomics nomogram combined with radiomics and clinical features for predicting muscle invasion status in bladder cancer (BCa). Methods: A retrospective analysis was conducted using data from patients who underwent CT urography at our institution between May 2018 and April 2023 with urothelial carcinoma of the bladder confirmed by postoperative histology. There were 196 patients enrolled in all, and each was randomized at random to either the training cohort (n = 137) or the test cohort (n = 59). Eight hundred fifty-one radiomics features in all were retrieved. For feature selection, the significance test and least absolute shrinkage and selection operator (LASSO) approaches were utilized. Subsequently, the radiomics score (Radscore) was obtained by applying linear weighting based on the selected features. The clinical and radiomics model, as well as radiomics-clinical nomogram were all established using logistic regression. Three models were evaluated using analysis of the receiver operating characteristic curve. An area under the curve (AUC) and 95% confidence intervals (CI) as well as specificity, sensitivity, accuracy, negative predictive value, and positive predictive value were included in the analysis. Radiomics-clinical nomogram's performance was assessed based on discrimination, calibration, and clinical utility. Results: After obtaining 851 radiomics features, 12 features were ultimately selected. Histopathological grading and tortuous blood vessels were included in the clinical model. The Radscore and clinical histopathology grading were among the final predictors in the unique nomogram. The three models had an AUC of 0.811 (95% CI, 0.742–0.880), 0.845 (95% CI, 0.781–0.908), and 0.896 (95% CI, 0.846–0.947) in the training cohort and in the test cohort they were 0.808 (95% CI, 0.703–0.913), 0.847 (95% CI, 0.739–0.954), and 0.887 (95% CI, 0.803–0.971). According to the DeLong test, the radiomics-clinical nomogram's AUC in the training cohort substantially differed from that of the clinical model (AUC: 0.896 versus 0.845, p = 0.015) and the radiomics model (AUC: 0.896 versus 0.811, p = 0.002). The Delong test in the test cohort revealed no significant difference among the three models. Conclusions: CT-based radiomics-clinical nomogram can be a useful tool for quantitatively predicting the status of muscle invasion in BCa. [ABSTRACT FROM AUTHOR]

The clinical management of bladder cancer continues to present significant challenges. Bacillus Calmette–Guérin (BCG) immunotherapy remains the gold standard of treatment for non-muscle invasive bladder cancer (NMIBC), but many patients develop recurrence and progression to muscle-invasive disease (MIBC), which is resistant to BCG. This review focuses on the immune mechanisms mobilized by BCG in bladder cancer tumor microenvironments (TME), mechanisms of BCG resistance, the dual role of the BCG-triggered NFkB/TNFα/PGE2 axis in the regulation of anti-tumor and tumor-promoting aspects of inflammation, and emerging strategies to modulate their balance. A better understanding of BCG resistance will help develop new treatments and predictive biomarkers, paving the way for improved clinical outcomes in bladder cancer patients. [ABSTRACT FROM AUTHOR]

The urinary collecting system (UCS) consists of organized ducts that collect urine from the nephrons and transport it to the ureter and bladder. Understanding the histogenesis of the UCS is critical. Thirty human embryos between the Carnegie stages (CS) 18 and 23 were selected from the Congenital Anomaly Research Center, Kyoto, Japan. Epithelia of the UCS, ureter, and bladder of each sample were randomly selected. Histological findings of the epithelia were analyzed according to the following criteria: type of epithelium, presence or absence of glycogen, percentage of migrated nuclei, percentage of cells in mitosis, and the surrounding mesenchyme. A thickened epithelium lining a narrow luminal cavity was observed in the pre-expanded pelvic specimens at CS18-CS23. At CS23, after pelvic expansion, the UCS showed a thin epithelium with a large luminal cavity mainly located on the early branches, whereas the epithelium covering the subsequent branches had medium thickness. Histological characteristics differed depending on the UCS part and sample stage. The degree of differentiation was evaluated, revealing that in CS18-CS23 pre-expanded pelvis specimens, the undifferentiated epithelium was found in the zeroth to third/fifth generation, whereas at CS23, after pelvic expansion, a differentiated epithelium covered the UCS zeroth to seventh generation. In a comparison of the urothelial epithelium between the UCS, ureter, and bladder, we found that urinary tract differentiation may be initiated in the bladder, followed by the ureter, UCS zeroth to seventh generations, and finally, UCS eighth to end generations. An understanding of the histogenesis of embryonic stage UCS can aid in the clinical management of congenital urinary tract defects and other diseases. [ABSTRACT FROM AUTHOR]

Traditional clinical modalities for diagnosing bladder urothelial carcinoma (BUC) remain limited due to their invasive nature, significant costs, discomfort associated with cystoscopy, and low sensitivity to urine cytology. Therefore, there is an urgent need to identify highly sensitive, specific, and noninvasive biomarkers for the early detection of this neoplasm. Hypermethylated TWIST1/Vimentin promoter may be a noninvasive biomarker using urine sample. We assessed the TWIST1/Vimentin promoter methylation status in urine samples using the Methylated Human TWIST1 and Vimentin Gene Detection Kit (Jiangsu MicroDiag Biomedicine Co., Ltd., China). The samples were collected from five groups: group 1 consisted of patients with BUC, group 2 contained other patients with urologic tumors, group 3 consisted of patients with benign diseases (e.g., urinary tract infections, lithiasis, and benign prostatic hyperplasia), Group 4 included UTUC (upper tract urothelial carcinoma) patients and group5 comprised healthy individuals. The study encompassed 77 BUC patients, and we evaluated the degree of methylation of the TWIST1/Vimentin gene in their urine samples. Notably, TWIST1/Vimentin positivity was significantly elevated in comparison to groups 2, 3 and 5 (all p < 0.001) at a rate of 77.9%, but no significant difference was observed when compared to group 4. In the relationship between TWIST1/Vimentin methylation and clinicopathological features of BC patients from our center, we found there was no significant association between TWIST1/Vimentin status and proteinuria and/or hematuria, and hypermethylation of TWIST1 / VIM genes was found in both high and low tumor grade and in both non-muscle invasive bladder cancer (stages Tis, Ta, or T1) and muscle-invasive bladder cancer (stage T2 or above). In the multivariable analysis for cancer detection, a positive TWIST1/Vimentin methylation were significantly linked to a heightened risk of BC. Moreover, TWIST1/Vimentin promoter methylation demonstrated an ability to detect BUC in urine samples with a sensitivity of 78% and a specificity of 83%. Our findings reveal that hypermethylation of the TWIST1/Vimentin promoter occurs in bladder urothelial carcinoma, and its high sensitivity and specificity suggest its potential as a screening and therapeutic biomarker for urothelial carcinoma of the bladder. [ABSTRACT FROM AUTHOR]

Introduction Bacillus Calmette-Guerin (BCG) Moreau is under-represented in literature and comparisons with other BCG strains are rare. Material and methods We conducted a retrospective data analysis in patients with intermediate or high-risk non-muscle invasive bladder cancer (NMIBC) to assess effectiveness and safety of BCG Moreau Polish substrain to BCG RIVM. The primary objective was to describe the real-world effectiveness of BCG Moreau in the treatment of patients with NMIBC in terms of recurrence free survival (RFS) 2 years posttreatment initiation compared to BCG RIVM. Results The database to be analysed comprised of 967 patients with NMIBC. The primary endpoint was met since BCG Moreau was non-inferior to BCG RIVM in terms of RFS [HR: 0.920 (95%CI: 0.725; 1.168)]. There was no statistically significant difference in all secondary endpoints including time to recurrence, progression-free survival, time to progression, and overall survival. The safety profile of BCG Moreau Polish substrain was consistent with side effects and frequency of complications observed with BCG RIVM and study reports in the literature. Conclusions BCG Moreau was effective and safe in the treatment of patients with intermediateor high-risk non-muscle invasive bladder cancer. There was no statistically significant difference in treatment outcome between BCG Moreau and BCG RIVM strains based on real-world data. [ABSTRACT FROM AUTHOR]

Background: The presence of tertiary lymphoid structures (TLS) is related with good prognosis of various cancers including bladder cancer. The majority of bladder tumors are identified as non-muscle-invasive bladder cancer (NMIBC) when they are discovered in their early stages. We aimed to evaluate the prognostic value and clinical relevance of TLS in NMIBC. Materials and Methods: This cohort included 130 NMIBC samples, with 39 (30%) having TLS, as confirmed by hematoxylin and eosin and immunohistochemistry staining. The chi-square test was utilized to examine the relationship between TLS and the biomarkers and clinicopathologic characteristics of NMIBC. Results: It was found that TLS has significant association with pT stage, Ki-67 expression, and COX-2 expression. Using Kaplan-Meier analysis and Gehan-Breslow-Wilcoxon test, we found that the presence of TLS is associated with longer recurrencefree survival and overall survival of NMIBC patients. Moreover, we used bioinformatics to analyze the association of TLS marker L1CAM and bladder cancer. L1CAM is downregulated in bladder cancer, linked to an advanced stage of the disease, and indicates a poorer prognosis for those who have bladder cancer. In bladder cancer, there is a positive correlation between its expression and B cell infiltration. We also indicated that NMIBC with TLS have a higher level of TLS than that without TLS. Conclusion: To conclude, the presence of TLS is an important favorable prognostic indicator in NMIBC. A further understanding on TLS can provide new insights to improve immunotherapy for bladder cancer. [ABSTRACT FROM AUTHOR]

Aims: Treatment options for advanced urothelial carcinoma (aUC) rapidly evolved: besides immunomodulative therapeutic options and inhibitors targeting Fibroblast growth factor receptor (FGFR) alterations, two new antibody‐drug conjugates (ADC), sacituzumab govitecan (SG) and enfortumab vedotin (EV), have been approved. However, little is known about the associations of specific aUC properties and the surface target expression of TROP2 and NECTIN‐4. Our aim was to characterize associations of TACSTD2/TROP2 and NECTIN‐4/NECTIN‐4 protein and gene expression with morphomolecular and clinicopathological characteristics of aUC in two large independent cohorts. Methods and results: The TCGA BLCA (n = 405) and the CCC‐EMN (n = 247) cohorts were retrospectively analysed. TROP2/TACSTD2 and NECTIN‐4/NECTIN‐4 are highly expressed at the protein and transcript level in aUC, and their expression status did not correlate with patient survival in both cohorts. NECTIN‐4/NECTIN‐4 expression was higher in luminal tumours and reduced in squamous aUCs. NECTIN‐4 was negative in 10.6% of samples, and 18.4% of samples had low expression (H‐score <15). The TROP2 negativity rate amounted to 6.5%. TACSTD2 and NECTIN‐4 expression was reduced in neuroendocrine‐like and/or protein‐based double‐negative tumours. TROP2‐ and NECTIN‐4‐negative tumours included one sarcomatoid and four neuroendocrine aUC. FGFR3 alterations and PD‐L1 expression on tumour and immune cells did not associate with TROP2 or NECTIN‐4 expression. Conclusions: TACSTD2/TROP2 and NECTIN‐4/NECTIN‐4 are widely expressed in aUC, independent of FGFR3 alterations or PD‐L1 expression, thus representing a suitable target for ADC treatment in the majority of aUC. The expression loss was associated with aggressive morphomolecular aUC subtypes, i.e. neuroendocrine(‐like) and sarcomatoid aUC. [ABSTRACT FROM AUTHOR]

Muscle-invasive bladder cancer (MIBC) remains a pressing health concern due to conventional treatment failure and significant molecular heterogeneity, hampering the development of novel targeted therapeutics. In our quest for novel targetable markers, recent glycoproteomics and bioinformatics data have pinpointed (glucose transporter 1) GLUT1 as a potential biomarker due to its increased expression in tumours compared to healthy tissues. This study explores this hypothesis in more detail, with emphasis on GLUT1 glycosylation patterns and cancer specificity. Immunohistochemistry analysis across a diverse set of human bladder tumours representing all disease stages revealed increasing GLUT1 expression with lesion severity, extending to metastasis, while remaining undetectable in healthy urothelium. In line with this, GLUT1 emerged as a marker of reduced overall survival. Revisiting nanoLC-EThcD-MS/MS data targeting immature O-glycosylation on muscle-invasive tumours identified GLUT1 as a carrier of short glycosylation associated with invasive disease. Precise glycosite mapping uncovered significant heterogeneity between patient samples, but also common glycopatterns that could provide the molecular basis for targeted solutions. Immature O-glycosylation conferred cancer specificity to GLUT1, laying the molecular groundwork for enhanced targeted therapeutics in bladder cancer. Future studies should focus on a comprehensive mapping of GLUT1 glycosites for highly specific cancer-targeted therapy development for bladder cancer. [ABSTRACT FROM AUTHOR]

Purpose An overexpression of nerve growth factor (NGF) in the urothelium is discussed to lead to neuronal hyperinnervation of the bladder detrusor. The aim was to assess the sensory and sympathetic innervation of the detrusor in unclosed exstrophic bladders patients with known overexpression of NGF in the urothelium. Methods Full-thickness bladder biopsies were prospectively obtained from 34 infants at delayed primary bladder closure between 01/2015 and 04/2020. The bladder biopsies were immunohistochemically stained with antibodies against S100, calcitonin gene-related peptide (anti-CGRP), Neuroflament 200 (anti-NF200), and tyrosine-hydroxylase (anti-TH). Specimens from 6 children with congenital vesicoureterorenal refux (VUR) served as controls. Results There was no statistically signifcant diference in nerve fber density in any of the immunohistochemical assessments (anti-S100 [p=0.210], anti-CGRP [p=0.897], anti-NF200 [p=0.897]), and anti-TH [p=0.956]) between patients with BE and patients with VUR. However, we observed a trend toward lower nerve fber densities in exstrophic detrusor. Conclusion Overall our results showed an unharmed innervation pattern in this cohort but a lower density of nerve fbers in the detrusor compared to controls. Further studies in patients after successful primary closure are needed to clarify the potential impact of the urothelial overexpression of NGF modulating the innervation pattern in exstrophic bladders. [ABSTRACT FROM AUTHOR]

Objective: Cytologic evaluation of the upper urinary tract (UUT) can be challenging due to instrumentation artefacts. This study retrospectively reviewed UUT specimens using The Paris System for Reporting Urinary Cytopathology, second edition (TPS 2.0), compared it with the original reporting system (ORS) and correlated it with histopathologic follow‐up. Methods: An institutional database was reviewed for the UUT biopsy/resection histopathologic specimens, and we included 52 UUT cytology specimens pertinent to these cases in the study. These specimens were blindly reviewed and reclassified using TPS 2.0. The correlation between TPS 2.0, ORS and histopathologic follow‐up was assessed. Results: The UUT cytology specimens corresponded to 21 (40.4%) high‐grade urothelial carcinoma (HGUC), 27 (51.9%) low‐grade urothelial carcinoma (LGUC) and 4 (7.7%) benign cases on follow‐up. For HGGC cases, the associated TPS categories included unsatisfactory (n = 1, 4.8%), negative for HGUC (NHGUC; n = 3, 14.3%), atypical urothelial cells (AUC; n = 6, 28.6%), suspicious for HGUC (SHGUC; n = 3, 14.3%) and HGUC (n = 8, 38.1%), while ORS categorised the specimens as unsatisfactory (n = 1, 4.8%), negative for malignant cells (NFMC; n = 3, 14.3%), AUC (n = 5, 23.8%), low‐grade urothelial carcinoma (LGUC; n = 0, 0%), SHGUC (n = 5, 23.8%) and HGUC (n = 7, 33.3%). The risks of high‐grade malignancy among cytologic categories were similar between ORS and TPS (p > 0.05). The majority of LGUC were classified as AUC similarly by ORS and TPS (55.6% vs. 59.3%). Conclusions: Our study demonstrated comparable performance between TPS 2.0 and ORS for UUT cytology specimens. Cytological diagnosis of UUT specimens remains challenging, especially for LGUC. [ABSTRACT FROM AUTHOR]

The scaffolding protein programmed cell death protein 10 (Pdcd10) has been demonstrated to play a critical role in renal epithelial cell homeostasis and function by maintaining appropriate water reabsorption in collecting ducts. Both ureter and kidney collecting duct systems are derived from the ureter bud during development. Here, we report that cadherin-16 (Cdh16)- cre drives gene recombination with high specificity in the ureter, but not the bladder, urothelium. The consequences of Pdcd10 deletion on the stratified ureter urothelium were investigated using an integrated approach including messenger RNA (mRNA) expression analysis, immunocytochemistry, and high-resolution confocal and electron microscopy. Loss of Pdcd10 in the ureter urothelium resulted in increased expression of uroplakins (Upks) and keratins (Krts), as well as hypertrophy of the ureter urothelium with an associated increase in the number of proliferation marker protein Ki-67 (Ki67)-expressing cells specifically within the basal urothelium layer. Ultrastructural analysis documented significant modification of the intracellular membrane system, including intracellular vesicle genesis and transport along the basal- to umbrella-cell-layer axis. Additionally, Pdcd10 loss resulted in swelling of Golgi compartments, disruption of mitochondrial cristae structure, and increased lysosomal fusion. Lack of Pdcd10 also resulted in decreased fusiform vesicle formation in umbrella cells, increased secretion of exosome vesicles, and alteration in microvillar structure on apical membranes. Our findings indicate that Pdcd10 expression and its influence on homeostasis is associated with modulation of endomembrane trafficking and organelle biogenesis in the ureter urothelium. [ABSTRACT FROM AUTHOR]

Improving the segmentation of bladder mucosa and serosa is a significant advancement for enhancing the diagnosis and treatment of bladder cancer, leading to a better understanding of the disease and improved decision-making accuracy for physicians. However, the primary aim of multi-region segmentation in bladder cancer is to facilitate the staging of the disease, specifically distinguishing between muscle-invasive bladder cancer and nonmuscle-invasive bladder cancer. This differentiation is crucial as urothelial cancers become increasingly aggressive as they infiltrate and penetrate the bladder wall. Yet, none of the existing segmentation methods have effectively addressed this critical issue. In our study, an attention U-Net with an adversarial mechanism is proposed, combining with two-layer level sets, to address these challenges. The attention U-Net with an adversarial mechanism captures the inner and outer boundaries of the bladder, including the tumor. Moreover, a two-layer level sets is proposed to further catching subpixels of the bladder wall and gets results with Dice score of 0.91. By calculating the convexity of the two-level sets, the two types of tumor are successfully classified, achieving an experimental accuracy of 0.88. This innovative approach significantly contributes to the field of bladder cancer segmentation and classification, providing valuable insights for improved diagnosis and treatment strategies. [ABSTRACT FROM AUTHOR]

The GUSTO clinical trial (Gene expression subtypes of Urothelial carcinoma: Stratified Treatment and Oncological outcomes) uses molecular subtypes to guide neoadjuvant therapies in participants with muscle‐invasive bladder cancer (MIBC). Before commencing the GUSTO trial, we needed to determine the reliability of a commercial subtyping platform (Decipher Bladder; Veracyte) when performed in an external trial laboratory as this has not been done previously. Here, we report our pre‐trial verification of the TCGA molecular subtyping model using gene expression profiling. Formalin‐fixed paraffin‐embedded tissue blocks of MIBC were used for gene expression subtyping by gene expression microarrays. Intra‐ and inter‐laboratory technical reproducibilities, together with quality control of laboratory and bioinformatics processes, were assessed. Eighteen samples underwent analysis. RNA of sufficient quality and quantity was successfully extracted from all samples. All subtypes were represented in the cohort. Each sample was subtyped twice in our laboratory and once in a separate reference laboratory. No clinically significant discordance in subtype occurred between intra‐ or inter‐laboratory replicates. Examination of sample histopathology showed variability of morphological appearances within and between subtypes. Overall, these results show that molecular subtyping by gene expression profiling is reproducible, robust and suitable for use in the GUSTO clinical trial. [ABSTRACT FROM AUTHOR]

This article provides guidelines for the macroscopic examination of various specimens from the genitourinary system, including prostate, renal, testicular, bladder, ureter, urethra, lymph node, and penile specimens. It emphasizes the importance of accurate measurement, documentation, and sampling to detect clinically important abnormalities and ensure appropriate patient management. The article acknowledges the global variation in clinical practice and suggests that recommendations should be considered in the context of local clinical requirements. It also highlights the rarity of penile cancers and recommends consultation with a specialist center for their management. [Extracted from the article]

This article discusses the treatment of low-grade non-muscle-invasive bladder cancer (NMIBC) and the potential for deintensifying treatment to avoid overtreatment while maintaining oncological safety. The study found that the majority of patients with low-grade NMIBC do not experience progression to high-grade disease, suggesting the potential for treatment de-intensification. Factors such as age were associated with an increased risk of high-grade recurrence. The study highlights the need for personalized follow-up and management for patients with low-grade NMIBC and suggests the use of less invasive approaches in selected patients. However, the study has limitations due to its retrospective design and limited sample size. Further research is needed to confirm these findings and provide more robust evidence. [Extracted from the article]

This article discusses alternative instillation techniques for sequential intravesical gemcitabine and docetaxel (Gem/Doce) treatment for non-muscle-invasive bladder cancer (NMIBC). The standard Gem/Doce treatment protocol can be challenging for some patients due to bladder capacity or detrusor overactivity issues. The article presents two alternative instillation methods, the split-dosing method and the gravity method, which aim to improve patient adherence and tolerability. The study found that these modified instillation methods were safe and effective, with similar recurrence-free survival rates compared to the standard method. The authors hope that these findings will have a positive impact on real-world practice and the increasing utilization of Gem/Doce. [Extracted from the article]