Search Results (1,295)

Background: Despite clinical and pathological risk tools, predicting outcomes in non-muscle-invasive bladder cancer (NMIBC), particularly high-grade (HG) cases, remains challenging due to its unpredictable recurrence and progression. There is an urgent need for molecular biomarkers to enhance risk stratification and guide treatment. Methods: We assessed the prognostic potential of eight miRNAs (miR-9, miR-143, miR-182, miR-205, miR-27a, miR-369, let-7c, and let-7g) in a cohort of ninety patients with primary bladder cancer. Expression data were retrieved from our previously published studies. Kaplan–Meier’s and Cox’s regression analyses were used to evaluate the associations with overall survival (OS), metastasis-free survival (MFS), and clinical outcomes. Principal component analysis (PCA) was performed to identify informative miRNA combinations. Target gene prediction, pathway enrichment (DAVID), and drug–gene interaction mapping (DGIdb) were conducted in silico. Results: A high expression of let-7g and miR-9 was significantly associated with better OS in HG NMIBC and MIBC, respectively (p = 0.013 and p = 0.000). MiR-9 downregulation correlated with metastasis in MIBC (p = 0.018). Among all combinations, miR-205 and miR-27a best predicted intermediate-risk NMIBC progression and recurrence (r² = 0.982, p = 0.000). A functional analysis revealed that these miRNAs regulate key cancer-related pathways (MAPK, mTOR, and p53) through genes such as TP53, PTEN, and CDKN1A. Drug interaction mapping identified nine target genes (e.g., DAPK1, ATR, and MTR) associated with eight FDA-approved bladder cancer therapies, including cisplatin and gemcitabine. Conclusion: Let-7g, miR-9, miR-143, miR-182, and miR-205 emerged as promising biomarkers for outcome prediction in NMIBC. Their integration into liquid biopsy platforms could support non-invasive monitoring and personalized treatment strategies. These findings warrant validation in larger, prospective studies and through functional assays. Full article

Background: Bladder leiomyosarcoma is an extremely rare non-urothelial malignancy, accounting for less than 0.1% of all bladder tumors. It presents significant diagnostic and therapeutic challenges due to its aggressive nature and the absence of standardized treatment protocols. Case presentation: We report the case of a 61-year-old woman who presented with hematuria, dysuria, and suprapubic pain. Imaging revealed a large, locally invasive bladder mass, and histopathological examination following transurethral resection confirmed leiomyosarcoma. The patient underwent radical cystectomy with resection of adjacent bowel segments and urinary diversion. Histology showed a high-grade leiomyosarcoma (pT3N0) with extensive necrosis and a high mitotic index. Two months postoperatively, peritoneal dissemination was detected. Systemic chemotherapy with dacarbazine and doxorubicin initially led to the regression of metastases, but disease progression occurred within months, including lung, liver, and bone metastases. Palliative radiotherapy and second-line chemotherapy were initiated. As of now, 16 months have elapsed since surgery. Conclusions: This case underscores the aggressive clinical course of bladder leiomyosarcoma despite multimodal therapy and the urgent need for individualized management strategies. Given its rarity, this case contributes to the limited literature and highlights the importance of vigilant follow-ups and further studies to establish evidence-based treatment protocols. Full article

Background: Urothelial carcinoma is the second most common urological cancer, mainly affecting the bladder (90–95% of cases) while primary Upper Urinary Tract Urothelial Carcinomas (UTUC) are rare (5–10%). Socioeconomic and gender differences are known in urological cancers like urothelial carcinoma of the bladder, often based on national indices rating cities as single units. This study investigated factors influencing survival in patients with primary UTUC within Hamburg, Germany. Methods: We conducted a retrospective population-based cohort study using data extracted from the Hamburg cancer registry for all primary UTUC cases diagnosed between January 2004 and June 2021. Patient and tumor characteristics, socioeconomic status (measured by a neighborhood-level deprivation index), treatment patterns, and survival outcomes were analyzed. Kaplan–Meier analyses estimated survival probabilities, and a Cox Proportional Hazard Model with and without time transformation assessed survival factors. Results: The cohort included 727 patients (median age 74, 42.2% female), with a median follow-up of 2.2 years (IQR: 0.8–5.5 years). Relevant survival predictors were age, sex, and cancer stage. Older age was associated with reduced excess mortality risk (HR = 0.974), while female sex (HR = 1.472) and advanced stage (HR = 3.343) were associated with higher excess mortality risk. Socioeconomic status and diagnosis period had no measurable impact. Conclusions: Yet, a small sample size and single registry data may limit the generalizability of these results. Further research with larger cohorts is needed. Full article

Distention of the urinary bladder wall during filling stretches the urothelium and induces the release of chemical mediators, including adenosine 5′-triphosphate (ATP) and prostaglandins (PGs), that transmit signals between cells within the bladder wall. The urothelium also releases soluble nucleotidases (s-NTDs) that control the availability of ATP and its metabolites at receptor sites in umbrella cells and cells deeper in the bladder wall, as well as in the urine. This study investigated whether PGs regulate the intravesical breakdown of ATP by s-NTDs. Using a murine decentralized mucosa-only bladder model and an HPLC technology with fluorescence detection, we evaluated the decrease in ATP and increase in ADP, AMP, and adenosine (ADO) in intraluminal solutions (ILS) collected at the end of physiological bladder filling. PGD₂, PGE₂, and PGI₂, but not PGF_2α, inhibited the conversion of AMP (produced from ATP) to ADO, likely due to a suppressed intravesical release of s-AMPases. The effects of exogenous PGD₂, PGE₂, and PGI₂ were mediated by DP1/DP2, EP2, and IP prostanoid receptors, respectively. Activation of either DP1 or DP2 receptors by endogenous PGD₂ also led to AMP increase and ADO decrease in ILS-containing ATP substrate. Finally, PGs produced by either COX-1 or COX-2 inhibited the hydrolysis of AMP to ADO. Together, these observations suggest that (1) endogenous PGs (chiefly PGD₂, and to lesser degree PGE₂ and PGI₂) allow release of s-NTDs like s-ATPases and s-ADPases but impede the formation of ADO from intravesical ATP by inhibiting the release of s-NTDs/s-AMPases; (2) it is possible that high concentrations of PGD₂, PGE₂ and PGI₂, as anticipated in inflammation or bladder pain syndrome, delay the ADO production and prolong the action of excitatory purine mediators; and (3) either COX-1 and COX-2 are constitutively expressed in the mouse bladder mucosa or COX-2 is induced by distention of the urothelium during bladder filling. Full article

Platelet-rich plasma (PRP) therapy is a non-invasive, autologous treatment with regenerative potential in gynaecology beyond fertility applications. This review evaluates PRP in non-fertility-related gynaecological conditions affecting women’s quality of life (QoL). Methods: Following PRISMA-ScR guidelines, we searched Embase, CINAHL, Web of Science, Scopus, CENTRAL, and MEDLINE for studies on PRP in conditions such as vulvar lichen sclerosus (VLS), vulvovaginal atrophy (VVA), sexual dysfunction (SD), stress urinary incontinence (SUI), and interstitial cystitis/bladder pain syndrome (IC/BPS). Of 3660 records screened, 43 studies (randomised controlled trials, quasi-experimental, cohort, and case series) were included. Results: PRP improved symptoms and QoL in several conditions, particularly VLS and SD, and was generally well tolerated with minor adverse effects (e.g., injection-site pain, transient discomfort). Evidence for abnormal uterine bleeding (AUB) and pelvic organ prolapse (POP) was inconclusive. Considerable heterogeneity in preparation protocols and outcome measures limited cross-study comparison. Conclusions: PRP shows promise as a minimally invasive therapy for certain gynaecological conditions. Standardisation of preparation and administration, along with large-scale RCTs, is needed to determine long-term efficacy and safety. Full article

Purpose: Detrusor sphincter dyssynergia (DSD), a common lower urinary tract condition in patients with suprasacral spinal cord injury (SCI), can lead to urological complications and reduced quality of life. Urethral sphincter botulinum toxin A (BoNT-A) injection has been used to promote spontaneous voiding, albeit with limited success. This study aimed to identify predictive factors for treatment success. Methods: This retrospective analysis included 207 patients (157 males and 50 females) with chronic SCI and varying DSD grades treated with urethral sphincter BoNT-A injection. Each received 100 U of onabotulinumtoxinA via transurethral sphincter injection. The primary outcome was voiding efficiency (VE) and symptom improvement, assessed via global response evaluation 3 months post-treatment. Baseline videourodynamic parameters were used to predict success. Results: Successful outcomes were observed in 33.8% of patients. These patients were older and had higher voiding pressure, maximum flow rate (Qmax), voided volume, bladder contractility index, and VE, as well as lower post-void residual (PVR) volume and bladder outlet obstruction index. Patients with SCI and DSD grade 1 had the highest success rate (65.7%) compared to those with DSD grade 2 (14.3%) or 3 (7.1%). Patients with DSD grade 3 had the highest failure rate (55.8%). Multivariate analysis showed that higher Qmax and lower PVR significantly predicted success, consistent with lower DSD grades. Conclusion: Grade 1 DSD, higher Qmax, and lower PVR were associated with higher success after urethral BoNT-A injection, whereas grade 3 DSD predicted failure. Thus, careful patient selection is essential for effective DSD treatment with urethral BoNT-A injection. Full article

Introduction: The role of urethrectomy at the time of Robotic-Assisted or Open Radical Cystectomy (RARC, ORC) is controversial. Whether urethrectomy should be performed at the time of RARC/ORC or delayed up to a 3–6 month interval is unclear. We performed a retrospective cohort analysis of perioperative and survival outcomes in patients with high-risk NMIBCs or non-metastatic MIBCs at our institution who underwent either concomitant or deferred urethrectomy after RC. Materials and Methods: cTis-T1 or cT2-T4, N0-1, M0 BC patients who underwent RARC or ORC from 2009 to 2024 were reviewed. Clinical, demographic, tumour, and patient characteristics and perioperative variables were assessed across concomitant and delayed urethrectomy groups. Multivariate logistic analysis was performed to estimate the impact of significant variables on intraoperative and postoperative outcomes. Univariable Kaplan–Meier and multivariable Cox regression modelling was implemented to explore the relative effect of time of urethrectomy on progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Results: A total of n = 58 patients (n = 47 delayed vs. n = 11 concomitant) with similar demographic characteristics were included. The concomitant urethrectomy group experienced longer operative time and greater blood loss (379 ± 65 min and 430 ± 101 mL vs. 342 ± 82 min and 422 ± 125 mL, with p = 0.049 and p = 0.028, respectively). Hospital readmission rates were higher in the concomitant urethrectomy group (36.4% vs. 8.5%, p = 0.016; OR: 17.9; 95% CI 1.2–265; p = 0.036). In Cox regression analysis, the timing of urethrectomy had no influence on PFS, CSS, or OS (all p > 0.05). Conclusions: Our study suggests that urethrectomy can be safely deferred unless urothelial disease is clearly present pre- or intraoperatively without compromising survival outcome and with the advantage of reducing surgical morbidity at the time of RC. Full article

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of urothelial carcinoma (UC); however, their efficacy varies among patients. Identifying reliable biomarkers to predict response to ICIs remains challenging. We aimed to explore urinary microRNAs (miRNAs) as potential biomarkers for predicting ICI efficacy in patients with UC. Methods: We prospectively collected urinary samples from patients with UC before ICI initiation and investigated the predictive value of urinary miRNAs in patients with UC receiving ICIs. The expression levels of these miRNAs in pretreated urine samples were analyzed using next-generation sequencing. The patients were categorized as responders (those with stable disease or better for >6 months) or nonresponders (those who experienced disease progression within 6 months of treatment initiation). Urinary miRNA levels were compared between the groups to assess their potential as predictive biomarkers. Results: Elevated expression of miR-185-5p and miR-425-5p in the responder group was significantly associated with improved overall and progression-free survival in patients with bladder cancer treated with ICIs (p < 0.05). Conversely, higher levels of miR-30a-5p and miR-542-3p in the nonresponder group were correlated with a poorer response to ICIs, suggesting a potential role in immune resistance. Conclusions: miR-185-5p and miR-425-5p can serve as predictive biomarkers of favorable ICI efficacy in bladder cancer, whereas miR-30a-5p and miR-542-3p could be associated with resistance mechanisms. These findings highlight the potential of miRNA-based biomarkers, particularly those found in urine samples, to guide personalized immunotherapeutic strategies for UC treatment. Full article

Background: Bladder cancer is a common and heterogeneous malignancy of the urinary tract. Traditional chemotherapy using bivalent platinum drugs such as cisplatin(CDDP) is often limited by severe side effects and acquired resistance. To overcome these limitations, we explored a novel Pt(IV) prodrug, DNP, designed to release both cytotoxic cisplatin and the anti-inflammatory cyclooxygenase-2 (COX-2) inhibitor naproxen(NPX). Methods: We evaluated the cytotoxic activity of DNP using both two-dimensional (2D) monolayer and three-dimensional (3D) spheroid models of bladder cancer cells. Transcriptomic analysis via RNA-seq identified apoptosis- and inflammation-related signaling pathways modulated by DNP. RNA-seq-based transcriptomic profiling revealed that DNP regulates signaling pathways associated with apoptosis and inflammation. The anti-inflammatory effects were evaluated using a lipopolysaccharide (LPS)-induced macrophage model, while the in vivo antitumor efficacy was assessed in an orthotopic MB49 bladder cancer model. Results: Compared with CDDP, DNP significantly increased intracellular platinum accumulation and exhibited superior cytotoxicity. It effectively inhibited tumor proliferation, induced apoptosis, and attenuated inflammation both in vitro and in vivo. Conclusions: These findings suggest that DNP exerts dual antitumor effects through enhanced delivery of cytotoxic and anti-inflammatory agents, offering a promising strategy for bladder cancer therapy. Full article

Non-muscle invasive bladder cancer (NMIBC) accounts for about 75% of new bladder cancer diagnoses. Early detection improves survival, yet routine white-light cystoscopy is invasive, costly, and can miss up to 45% of flat or small lesions. These shortcomings have prompted development of label-free diagnostic tools that read the intrinsic optical, electrical, or mechanical signatures of urinary biomarkers without added labels. This review examines recent engineering advances in such platforms for NMIBC detection, focusing on analytical performance, readiness for clinical translation, and remaining barriers to adoption. We compare each technology with conventional cytology using key metrics such as limit of detection, diagnostic accuracy, analysis time, cohort size, and stage of clinical development. Surface-enhanced Raman spectroscopy and interferometric flow cytometry offer femtomolar sensitivity and more than 98% accuracy within minutes, while compact electrochemical sensors targeting NMP22, Galectin-1, and microRNAs reach sub-picogram levels on disposable chips. Standardized sample handling, multicenter validation, and robust cost-effectiveness data are now essential for these tools to advance point-of-care NMIBC surveillance. Full article

Background: Anorectal malformations (ARMs) are rare congenital anomalies requiring surgical correction and long-term multidisciplinary care. Despite advances in surgical techniques like posterior sagittal anorectoplasty (PSARP), patients often experience ongoing issues with bowel and urinary function and psychosocial well-being. Aim: To evaluate the long-term outcomes of bowel function, urinary function, and quality of life in patients born with anorectal malformation and treated at our center. Methods: A cross-sectional study evaluated 55 ARM patients treated at the University Hospital of Palermo between 2002 and 2020. Data on clinical characteristics, surgical management, bowel and urinary function, and quality of life were collected using the following validated tools: Rintala Bowel Function Score, PedsQL Family Impact Module, Fecal Incontinence Quality of Life Score, and Lower Urinary Tract Symptoms Questionnaire. Statistical analysis was performed using Fisher’s exact test and ANOVA. Results: Excellent bowel function was observed in 44% of patients, particularly those with low-type ARMs. A bowel management program (BMP) was required in 62% of cases, though 44% of these patients, especially adolescents, showed poor adherence. BMP non-adherence significantly correlated with lower quality of life and worse bowel function (p < 0.01). Bladder dysfunction was noted in 24% of patients, mainly younger ones. Conclusions: Tailored BMPs and transition care are important for long-term success in ARM patients. Adherence to BMPs improves continence and quality of life, highlighting the need for continuous, multidisciplinary follow-up from childhood into adulthood. Full article

Background: Fibromyalgia syndrome (FMS) is a complex condition with poorly understood pathophysiology, characterized by widespread pain and an increasing recognition of its associations with genitourinary symptoms. The objective of this study was to characterize the prevalence, phenotype, and common comorbidities of lower urinary tract symptoms (LUTS) in women with FMS. Methods: A retrospective observational study was conducted using electronic medical records of 440 women diagnosed with FMS at a single institution between 1 January 2018, and 1 January 2024. Study subjects were evaluated for diagnoses associated with LUTS, including interstitial cystitis (IC), overactive bladder (OAB), and stress urinary incontinence (SUI), alongside comorbidities such as irritable bowel syndrome (IBS), generalized anxiety disorder (GAD), and major depressive disorder (MDD). Multivariate analyses were performed to assess predictors of conditions associated with LUTS. Results: LUTS were identified in 37.0% of FM patients. GAD and IBS were significantly associated with conditions associated with LUTS (OR = 4.62; OR = 8.53, p < 0.001). SUI was present in 17.05% of patients, falling between survey-based and confirmed prevalence rates in the general population. IC was diagnosed in 2.95% of FMS patients. OAB was observed in 6.8% of patients and associated with GAD (OR = 5.98, p < 0.001). Conclusions: This study highlights a substantial burden of diagnoses associated with LUTS in patients with FMS. There is relatively high prevalence of SUI and IC in this dataset. IBS and GAD were commonly found to co-occur with one or more LUTS-associated condition. Future prospective studies are needed to investigate a multimodal approach to the treatment of LUTS in these patients. Full article

An adult female bottlenose dolphin (Tursiops truncatus) housed at a public oceanarium presented with acute anorexia and lethargy. A blood analysis demonstrated mild leukocytosis, marked azotemia, hyperkalemia, and hyperphosphatemia suggestive of acute kidney injury or renal insufficiency. Ultrasound examination of the dolphin revealed ascites, pleural effusion, bilateral nephrolithiasis, mild hydronephrosis, and bilateral hydroureter consistent with bilateral post-renal obstruction. Initial treatment consisted of antibiotics, oral fluids, and anti-inflammatory treatment. Further imaging diagnosed bilateral obstructing ureteroliths at both ureteral orifice junctions of the urinary bladder. The dolphin’s azotemia and hyperkalemia were nonresponsive to traditional medical management; therefore, peritoneal dialysis was performed for emergent clinical stabilization. Peritoneal dialysis was conducted over 3 days and facilitated the patient to undergo laser lithotripsy of the offending ureteral obstruction. The dolphin made a full recovery following months of intensive medical treatment for complications from peritoneal dialysis and secondary peritonitis. This is the first documented case of successful, though complicated, peritoneal dialysis in a cetacean. Full article

Background: Neurogenic bladder (NB) in children may lead to recurrent urinary tract infections (UTIs), renal deterioration, and a reduced quality of life. Clean intermittent catheterization (CIC) is the standard of care, but in some patients, CIC may be unfeasible due to anatomical, sensory, or compliance issues. Button cystostomy (BC) has emerged as a minimally invasive, bladder-preserving alternative. This study aimed to assess the feasibility, safety, and outcomes in the long-term of BC in pediatric NB patients. Methods: Retrospective analysis was conducted on children with NB who underwent endoscopic BC placement between January 2020 and December 2024 in a tertiary pediatric center. Demographic data, operative time, complications, and follow-up outcomes were collected. All procedures used an endoscopic approach with cystoscopic guidance for safe device placement. Results: Thirty-three patients (25 males; median age 7.96 years) underwent BC placement. Most had spinal dysraphism (63.6%). The mean operative time was 48.5 ± 6 min. During a mean follow-up of 2.1 ± 1.4 years, five patients (15.2%) had febrile UTIs and two had minor leakage. No major complications occurred. Four buttons were removed due to clinical improvement (N = 1), the fashioning of a continent derivation (N = 1) and implantation of a sacral neuromodulator (N = 2); two patients accepted CIC. Satisfaction was reported by 93.9% of families. Conclusions: BC is an effective, minimally invasive alternative for urinary drainage in children with NB, even when compared to continent diversion techniques such as the Mitrofanoff, due to its lower invasiveness, greater feasibility, and lower complication rate. Broader adoption may be warranted, but prospective studies are needed to confirm long-term outcomes. Full article

Bladder cancer (BC) is the most frequent cancer of the urinary system and one of the most common malignancies in the world. In the last decade, many studies have been conducted to better understand the pathophysiological mechanisms of BC to find innovative markers for disease monitoring and treatment. In this study, we aim to identify miRNAs whose expression is associated with specific tumoral characteristics and risks of disease progression. Forty-one BC patients were enrolled in this study. The expression of 84 miRNAs was evaluated by qRT-PCR analysis on tumoral and peritumoral tissues. The results highlighted the association of the miRNA-17-92 cluster with BC, with miR-17-5p, miR-18a-5p, miR-19a-3p, and miR-20a-5p (members of this cluster) being upregulated in the tumoral tissue and correlated with muscle invasion and tumor grading. Taken together, our study identified a panel of 26 dysregulated miRNAs in BC, some of which may be associated with aggressiveness and the risk of progression of this malignancy. Full article