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BackgroundHemorrhagic cystitis (HC) is an inflammatory disease of the bladder with sustained hematuria for which there is currently no approved drug treatment. We evaluated a liposomal tacrolimus preparation (LP-10) in patients with refractory moderate to severe sterile HC.MethodsThis phase 2a dose-escalation study assessed the safety and efficacy of up to 2 intravesical instillations of LP-10 (2, 4, or 8 mg tacrolimus) in 13 patients with HC. Primary efficacy outcomes were changes from baseline in the number of bleeding sites on cystoscopy, microscopic urine analysis for red blood cells (RBCs), and hematuria on dipstick. Additional efficacy measures included urinary incontinence, frequency, and urgency on a 3-day diary and cystoscopy global response assessment (GRA). Blood samples for pharmacokinetic (PK) assessment were obtained in all patients.ResultsIntravesical LP-10 was well tolerated, with no treatment-related severe or serious adverse events (AEs) and only 3 drug-related AEs (artificial urinary sphincter malfunction, dysuria, and bladder spasms). LP-10 blood levels showed short durations of minimal systemic uptake. Treatment resulted in significant improvements in bleeding on cystoscopy, RBC counts in urine, hematuria on dipstick, and urinary incontinence. Bleeding on cystoscopy and urinary incontinence showed dose-dependent improvements that were more pronounced in the 4 mg and 8 mg dose groups. All dose groups showed a significant improvement in cystoscopy GRA.ConclusionLP-10 was well tolerated, with clinically relevant efficacy seen in improvements in cystoscopic bleeding, hematuria, and urinary incontinence. The benefit-risk profile supports the further clinical development of LP-10 at a tacrolimus dose of 4 mg.

BACKGROUND: Hemorrhagic cystitis (HC) is an inflammatory disease of the bladder with sustained hematuria for which there is currently no approved drug treatment. We evaluated a liposomal tacrolimus preparation (LP-10) in patients with refractory moderate to severe sterile HC. METHODS: This phase 2a dose-escalation study assessed the safety and efficacy of up to 2 intravesical instillations of LP-10 (2, 4, or 8 mg tacrolimus) in 13 patients with HC. Primary efficacy outcomes were changes from baseline in the number of bleeding sites on cystoscopy, microscopic urine analysis for red blood cells (RBCs), and hematuria on dipstick. Additional efficacy measures included urinary incontinence, frequency, and urgency on a 3-day diary and cystoscopy global response assessment (GRA). Blood samples for pharmacokinetic (PK) assessment were obtained in all patients. RESULTS: Intravesical LP-10 was well tolerated, with no treatment-related severe or serious adverse events (AEs) and only 3 drug-related AEs (artificial urinary sphincter malfunction, dysuria, and bladder spasms). LP-10 blood levels showed short durations of minimal systemic uptake. Treatment resulted in significant improvements in bleeding on cystoscopy, RBC counts in urine, hematuria on dipstick, and urinary incontinence. Bleeding on cystoscopy and urinary incontinence showed dose-dependent improvements that were more pronounced in the 4 mg and 8 mg dose groups. All dose groups showed a significant improvement in cystoscopy GRA. CONCLUSION: LP-10 was well tolerated, with clinically relevant efficacy seen in improvements in cystoscopic bleeding, hematuria, and urinary incontinence. The benefit-risk profile supports the further clinical development of LP-10 at a tacrolimus dose of 4 mg.

BACKGROUND: Bladder cancer poses a significant public health burden, with high recurrence and progression rates in patients with non-muscle-invasive bladder cancer (NMIBC). Current treatment options include bladder-sparing therapies (BST) and radical cystectomy, both with associated risks and benefits. However, evidence supporting optimal management decisions for patients with recurrent high-grade NMIBC remains limited, leading to uncertainty for patients and clinicians. The CISTO (Comparison of Intravesical Therapy and Surgery as Treatment Options) Study aims to address this critical knowledge gap by comparing outcomes between patients undergoing BST and radical cystectomy. METHODS: The CISTO Study is a pragmatic, prospective observational cohort trial across 36 academic and community urology practices in the US. The study will enroll 572 patients with a diagnosis of recurrent high-grade NMIBC who select management with either BST or radical cystectomy. The primary outcome is health-related quality of life (QOL) at 12 months as measured with the EORTC-QLQ-C30. Secondary outcomes include bladder cancer-specific QOL, progression-free survival, cancer-specific survival, and financial toxicity. The study will also assess patient preferences for treatment outcomes. Statistical analyses will employ targeted maximum likelihood estimation (TMLE) to address treatment selection bias and confounding by indication. DISCUSSION: The CISTO Study is powered to detect clinically important differences in QOL and cancer-specific survival between the two treatment approaches. By including a diverse patient population, the study also aims to assess outcomes across the following patient characteristics: age, gender, race, burden of comorbid health conditions, cancer severity, caregiver status, social determinants of health, and rurality. Treatment outcomes may also vary by patient preferences, health literacy, and baseline QOL. The CISTO Study will fill a crucial evidence gap in the management of recurrent high-grade NMIBC, providing evidence-based guidance for patients and clinicians in choosing between BST and radical cystectomy. The CISTO study will provide an evidence-based approach to identifying the right treatment for the right patient at the right time in the challenging clinical setting of recurrent high-grade NMIBC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03933826. Registered on May 1, 2019.

Background: Despite the publication of several meta-analyses regarding the efficacy of certain therapies in helping individuals with interstitial cystitis (IC) / bladder pain syndrome (BPS), these have not provided a comprehensive review of therapeutic strategies. The study aimed to determine the efficacy of various therapies for IC/BPS and identify potential moderating factors using randomized controlled trials (RCTs). Methods: We queried the PubMed, Cochrane, and Embase databases to identify prospective RCTs using inclusion criteria: 1) patients diagnosed with IC, 2) interventions included relevant treatments, 3) comparisons were a specified control or placebo, 4) outcomes were mean differences for individual symptoms and structured questionnaires. The pairwise meta-analysis and network meta-analysis (NMA) were performed to compare the treatments used in IC/BPS. Hedges' g standardized mean differences (SMDs) were used for improvement in all outcomes using random-effects models. Efficacy outcomes included individual symptoms such as pain, frequency, urgency, and nocturia, as well as structured questionnaires measuring IC/BPS symptoms. Results: A comprehensive literature search was conducted which identified 70 RCTs with 3,651 patients. The analysis revealed that certain treatments, such as instillation and intravesical injection, showed statistically significant improvements in pain and urgency compared to control or placebo groups in traditional pairwise meta-analysis. However, no specific treatment demonstrated significant improvement in all outcomes measured in the NMA. The results of moderator analyses to explore influential variables indicated that increasing age was associated with increased nocturia, while longer follow-up periods were associated with decreased frequency. Conclusion: This systematic review and meta-analysis provide insights into the efficacy of various treatments for IC. Current research suggests that a combination of therapies may have a positive clinical outcome for patients with IC, despite the fact that treatment for this condition is not straightforward. Trial registration: PROSPERO CRD42022384024 [ABSTRACT FROM AUTHOR]

Objective: Only a few numbers of studies have been published on the use of abobotulinumtoxinA (Dysport®) in idiopathic detrusor overactivity (IDO). This study reported the long-term follow-up of women with IDO who were treated with intravesical Dysport® injections. Methods: Two hundred and thirty-six patients with IDO who had failed first-line conservative and antimuscarinic therapy received 500–900 units of Dysport® between April 2014 and July 2015. All patients were followed up for 5 years after their initial injection and interviewed on the phone. Results: A total of 236 women with IDO aged from 18 years to 84 years (mean±standard deviation: 49.6±15.9 years) were included in our study. The median follow-up time for patients was 36.5 (range: 10–70) months, and the median recovery time after injection was 18.5 (range: 0–70) months. A total of 83 (35.2%) patients stated that they had subjective improvement of their symptoms whereas 84 (35.6%) patients did not report any improvement in symptoms. The initial International Consultation on Incontinence Questionnaire Overactive Bladder mean score was 6.9 (standard deviation 3.4). There was a positive association between the median recovery time and the components of the International Consultation on Incontinence Questionnaire Overactive Bladder questionnaire. Conclusion: In a sub-population of overactive bladder patients with IDO who have failed first-line therapy, a single intravesical Dysport® injection can resolve patient symptoms completely or reduce the symptoms to an acceptable level that can be controlled with antimuscarinics or re-injection on demands.

BackgroundImmune checkpoint inhibitors (ICI) improve overall survival (OS) in patients with locally advanced, unresectable, or metastatic urothelial carcinoma (aUC), but response rates can be modest. We compared outcomes between patients with and without prior intravesical Bacillus Calmette-Guerin (BCG), who received ICI for aUC, hypothesizing that prior intravesical BCG would be associated with worse outcomes.Patients and methodsWe performed a retrospective cohort study across 25 institutions in US and Europe. We compared observed response rate (ORR) using logistic regression; progression-free survival (PFS) and OS using Kaplan-Meier and Cox proportional hazards. Analyses were stratified by treatment line (first line/salvage) and included multivariable models adjusting for known prognostic factors.ResultsA total of 1026 patients with aUC were identified; 614, 617, and 638 were included in ORR, OS, PFS analyses, respectively. Overall, 150 pts had history of prior intravesical BCG treatment. ORR to ICI was similar between those with and without prior intravesical BCG exposure in both first line and salvage settings (adjusted odds radios 0.55 [P= .08] and 1.65 [P= .12]). OS (adjusted hazard ratios 1.05 [P= .79] and 1.13 [P= .49]) and PFS (adjusted hazard ratios 1.12 [P= .55] and 0.87 [P= .39]) were similar between those with and without intravesical BCG exposure in first line and salvage settings.ConclusionPrior intravesical BCG was not associated with differences in response and survival in patients with aUC treated with ICI. Limitations include retrospective nature, lack of randomization, presence of selection and confounding biases. This study provides important preliminary data that prior intravesical BCG exposure may not impact ICI efficacy in aUC.

While more than four decades have elapsed since intravesical Bacillus Calmette-Guérin (BCG) was first used to manage non-muscle invasive bladder cancer (NMIBC), its precise mechanism of anti-tumor action remains incompletely understood. Besides the classic theory that BCG induces local (within the bladder) innate and adaptive immunity through interaction with multiple immune cells, three new concepts have emerged in the past few years that help explain the variable response to BCG therapy between patients. First, BCG has been found to directly interact and become internalized within cancer cells, inducing them to act as antigen-presenting cells (APCs) for T-cells while releasing multiple cytokines. Second, BCG has a direct cytotoxic effect on cancer cells by inducing apoptosis through caspase-dependent pathways, causing cell cycle arrest, releasing proteases from mitochondria, and inducing reactive oxygen species-mediated cell injury. Third, BCG can increase the expression of programmed death ligand 1 (PD-L1) on both cancer and infiltrating inflammatory cells to impair the cell-mediated immune response. Current data has shown that high-grade recurrence after BCG therapy is related to CD8+ T-cell anergy or ‘exhaustion’. High-field cancerization and subsequently higher neoantigen presentation to T-cells are also associated with this anergy. This may explain why BCG therapy stops working after a certain time in many patients. This review summarizes the detailed immunologic reactions associated with BCG therapy and the role of immune cell subsets in this process. Moreover, this improved mechanistic understanding suggests new strategies for enhancing the anti-tumor efficacy of BCG for future clinical benefit.

Introduction: Benign Prostatic Hyperplasia (BPH) is mainly managed with alpha-blocker and 5 alpha reductase inhibitors. Non responders are offered surgery. To wait for the drug response is sometimes cumbersome for the patients with bothersome symptoms and may also lead to complications. On the other hand, some have minimal symptoms on drugs but silently develop obstructive complications. Aim: To understand the role of sonographic parameters of prostate and bladder of BPH patients in predicting and assessing response to medical treatment. Materials and Methods: This prospective cohort study was conducted in the Department of Urology at Army Hospital Research and Referral, New Delhi, India. The duration of the study was 15 months, from October 2017 to January 2019. A total of 100 consecutive patients of BPH with Prostate-specific Antigen (PSA) 35 cc were given three months of alpha-blocker and dutasteride. Based on there subjective response, they were grouped into Symptomatic Improved (SI) and Not Improved (NI) group. Values of sonographic parameters including Prostate Volume (PV), prostatic capsular artery Resistance Index (RI), Intravesical Protrusion of Prostate (IPP), Detrusor Wall Thickness (DWT) and Post-void Residual volume (PVR), as well as, International Prostate Symptom Score (IPSS) and Uroflowmetry (UFM) at baseline and after three months of treatment were analysed and compared in both the groups. The significance of change in parameters was analysed using paired t-test and two sample Student’s t-test. Results: The mean age of the study participants was 64.8±5.86 years. There was an association between IPSS and flow with initial reading of PV, PVR, DWT, RI and IPP. Post-treatment both, SI (n=74) and NI (n=26) group showed valuable difference in DWT, PV and PVR but it was significantly more in improved group. Significant change in RI was observed only in SI group and IPP did not change in either group. Area Under Curve (AUC) under Receiver Operating Characteristic (ROC) was suggestive of higher sensitivity for IPP in predicting drug outcome. Conclusion: Combined use of Ultrasonography (USG) and Kidney, Ureter, and Bladder (KUB) parameters as described above like RI, DWT, PV and IPP can be used to predict and assess the objective response to drug in BPH. This helps in determining therapeutic plan and the need for further medical therapy or surgical intervention.

Background: Data for bladder-sparing treatment (BST) in bacillus Calmette-Guerin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC) patients report short-term outcomes limited to 1–2 yr. Objective: To assess long-term survival outcomes of BCG-unresponsive NMIBC patients treated with BST. Design, setting, and participants: BCG-unresponsive NMIBC patients diagnosed between January 2000 and September 2021 from an institutional NMIBC registry were evaluated. Intervention: Long-term survival outcomes for patients receiving BST, early radical cystectomy (RC), and delayed RC were compared. Outcome measurements and statistical analysis: The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). Results and limitations: In total, 114 patients with a median follow-up of 71.2 mo (interquartile range: 32.6–132.2) were analyzed. There were no significant differences in OS (hazard ratio [HR]: 1.40, 95% confidence interval [CI]: 0.68–2.89, p = 0.4) or CSS (HR: 0.88, 95% CI: 0.22–3.55, p = 0.9) between patients undergoing early RC (n = 38) and BST (n = 76). At 60 mo, BST patients had a high-grade recurrence-free rate, muscle-invasive disease/metastasis progression-free rate, and avoidance of RC rate of 37%, 83%, and 58%, respectively. Current smoker status (HR: 4.44, 95% CI: 1.41–13.97, p = 0.011) was the only variable predictive of high-grade recurrence following a multivariable analysis. The median time to RC from BCG-unresponsive date was 2.1 and 11.7 mo for those undergoing early RC and delayed RC (after BST), respectively. Patients treated with early RC had a higher incidence of cT1 disease (53% vs 36%, p = 0.049) and lymphovascular invasion (LVI; 11% vs 0%, p = 0.011) compared to patients treated with BST. Survival outcomes were similar between groups: 10-yr OS—58% versus 50% (HR: 1.40, 95% CI: 0.68–2.89, p = 0.4), and 10-yr CSS—81% versus 85% (HR: 0.88, 95% CI: 0.22–3.55, p = 0.9). Conclusions: An analysis of long-term survival of BCG-unresponsive NMIBC patients receiving BST suggests that it may be safe in patients without LVI and/or variant histology and nonsmokers. Survival outcomes for patients treated with BST may not be inferior to those receiving early RC. Patient summary: Bladder-sparing treatment can be offered to appropriately selected patients who have bacillus Calmette-Guerin (BCG)-unresponsive non–muscle-invasive bladder cancer. Long-term outcomes may not be inferior to those for patients who opt for early radical cystectomy.

Abstract Objectives This study aimed to investigate the anti‐PD‐1 inhibitor pembrolizumab as a potential agent for use in non‐muscle‐invasive bladder cancer (NMIBC) by conducting a Phase 1 safety run‐in study to assess the safety and tolerability of intravesical pembrolizumab after transurethral resection of the bladder tumour (TURBT). Patients and methods Eligible patients had recurrent NMIBC for which adjuvant treatment post TURBT was a reasonable treatment option, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0–1 and adequate end‐organ function. Pembrolizumab was administered by intravesical instillation once weekly for a total of six doses. Intra‐patient dose escalation was performed in three paired patient cohorts with doses starting at 50 mg and increasing through 100 mg to a maximum of 200 mg. Adverse events (AEs) were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 with dose limiting toxicity (DLT) defined as a clinically significant, drug‐related, Grade 4 haematological or Grade 3 or higher non‐haematological toxicity occurring within 7 days of administration of the first treatment at a given dose for that patient. Results Six patients were treated with no DLTs seen during dose escalation. Drug‐related AEs were of low grade and included dysuria and fatigue. All patients completed six doses of treatment as planned. Pharmacokinetic and pharmacodynamic assays did not detect any pembrolizumab in the serum following repeated intravesical administration, and no changes in peripheral immune cell populations were observed. Conclusions Administration of intravesical pembrolizumab was well tolerated and did not raise any safety concerns in patients with NMIBC following TURBT. There was no evidence of systemic absorption or systemic immune effects following intravesical administration. Further studies are required to assess whether intravesical administration has anti‐tumour activity.

This review article gives an overview of the current state of the art of bladder cancer imaging and then discusses in depth the scientific and technical merit of a novel imaging approach, tracing its evolution from murine cancer models to cancer patients. While the poor resolution of soft tissue obtained by widely available imaging options such as abdominal sonography and radiation-based CT leaves them only suitable for measuring the gross tumor volume and bladder wall thickening, dynamic contrast-enhanced magnetic resolution imaging (DCE MRI) is demonstrably superior in resolving muscle invasion. However, major barriers still exist in its adoption. Instead of injection for DCE-MRI, intravesical contrast-enhanced MRI (ICE-MRI) instills Gadolinium chelate (Gadobutrol) together with trace amounts of superparamagnetic agents for measurement of tumor volume, depth, and aggressiveness. ICE-MRI leverages leaky tight junctions to accelerate passive paracellular diffusion of Gadobutrol (604.71 Daltons) by treading the paracellular ingress pathway of fluorescein sodium and of mitomycin (

A 56-year-old man presented with subacute night sweats, fever, and weight loss with worsening dyspnea. Computed tomography (CT) scan demonstrated miliary pattern of nodules evenly distributed throughout all lung fields. Given the patients CT findings and temporal association with Bacille Calmette-Guerin (BCG) immunotherapy for bladder cancer, the patient was diagnosed with disseminated Mycobacterium bovis secondary to BCG bladder instillations.

Introduction: Benign Prostatic Hyperplasia (BPH) is mainly managed with alpha-blocker and 5 alpha reductase inhibitors. Non responders are offered surgery. To wait for the drug response is sometimes cumbersome for the patients with bothersome symptoms and may also lead to complications. On the other hand, some have minimal symptoms on drugs but silently develop obstructive complications. Aim: To understand the role of sonographic parameters of prostate and bladder of BPH patients in predicting and assessing response to medical treatment. Materials and Methods: This prospective cohort study was conducted in the Department of Urology at Army Hospital Research and Referral, New Delhi, India. The duration of the study was 15 months, from October 2017 to January 2019. A total of 100 consecutive patients of BPH with Prostate-specific Antigen (PSA) <4 ng/mL and prostate of >35 cc were given three months of alpha-blocker and dutasteride. Based on there subjective response, they were grouped into Symptomatic Improved (SI) and Not Improved (NI) group. Values of sonographic parameters including Prostate Volume (PV), prostatic capsular artery Resistance Index (RI), Intravesical Protrusion of Prostate (IPP), Detrusor Wall Thickness (DWT) and Post-void Residual volume (PVR), as well as, International Prostate Symptom Score (IPSS) and Uroflowmetry (UFM) at baseline and after three months of treatment were analysed and compared in both the groups. The significance of change in parameters was analysed using paired t-test and two sample Student's t-test. Results: The mean age of the study participants was 64.8±5.86 years. There was an association between IPSS and flow with initial reading of PV, PVR, DWT, RI and IPP. Post-treatment both, SI (n=74) and NI (n=26) group showed valuable difference in DWT, PV and PVR but it was significantly more in improved group. Significant change in RI was observed only in SI group and IPP did not change in either group. Area Under Curve (AUC) under Receiver Operating Characteristic (ROC) was suggestive of higher sensitivity for IPP in predicting drug outcome. Conclusion: Combined use of Ultrasonography (USG) and Kidney, Ureter, and Bladder (KUB) parameters as described above like RI, DWT, PV and IPP can be used to predict and assess the objective response to drug in BPH. This helps in determining therapeutic plan and the need for further medical therapy or surgical intervention. [ABSTRACT FROM AUTHOR]

Abstract Background Bladder cancer (BC) treatments are known to be invasive; nevertheless, research into the long‐term effects is limited and in the context of sexual function often male focussed. Female sexual dysfunction (FSD) has been reported in up to 75% of female patients. This systematic scoping review examines the literature on sexual consequences of BC in female patients. Objective This study aimed to systematically evaluate the evidence on female sexual function in BC to identify areas of unmet need and research priorities. Evidence Acquisition We performed a critical review of PubMed, PsychMed, CINAHL, MEDLINE and the Cochrane Library in March 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) extension for Scoping Reviews statement following Levac et al. methodology. Identified reports were reviewed according to the Critical Appraisal Skills Programme (CASP) criteria. 45 publications were included. Evidence Synthesis There was an inconsistent use of patient‐reported outcome measures (PROMs), with commonly used PROMs having a narrow symptom focus. However, common symptoms emerged: loss of desire, orgasmic disorders, vaginal dryness, dyspareunia, difficult intromission, reduced clitoral sensation, psychological concerns related to diagnosis, fear of contamination and body image. Sexual activity was reduced in most groups, despite women expressing a motivation to retain sexual function. The degree of symptom distress associated with FSD is underreported. Evidence emerged regarding a gap for women in clinician counselling and follow‐up. Conclusions The patient's perspective of FSD in BC patients is poorly understood and under‐addressed in clinical practice. There have been very few qualitative studies of FSD in BC. Any intervention designed to address the problem must start with greater understanding of both the patients' and clinicians' perspective. Lay Summary We examined the evidence on sexual consequences of BC in women. It is apparent that despite common themes of sexual dysfunction emerging, the problem is poorly understood and addressed in clinical practice.

This review article gives an overview of the current state of the art of bladder cancer imaging and then discusses in depth the scientific and technical merit of a novel imaging approach, tracing its evolution from murine cancer models to cancer patients. While the poor resolution of soft tissue obtained by widely available imaging options such as abdominal sonography and radiation-based CT leaves them only suitable for measuring the gross tumor volume and bladder wall thickening, dynamic contrast-enhanced magnetic resolution imaging (DCE MRI) is demonstrably superior in resolving muscle invasion. However, major barriers still exist in its adoption. Instead of injection for DCE-MRI, intravesical contrast-enhanced MRI (ICE-MRI) instills Gadolinium chelate (Gadobutrol) together with trace amounts of superparamagnetic agents for measurement of tumor volume, depth, and aggressiveness. ICE-MRI leverages leaky tight junctions to accelerate passive paracellular diffusion of Gadobutrol (604.71 Daltons) by treading the paracellular ingress pathway of fluorescein sodium and of mitomycin (<400 Daltons) into bladder tumor. The soaring cost of diagnosis and care of bladder cancer could be mitigated by reducing the use of expensive operating room resources with a potential non-surgical imaging option for cancer surveillance, thereby reducing over-diagnosis and over-treatment and increasing organ preservation. [ABSTRACT FROM AUTHOR]

Simple Summary: Bladder cancer (BCa) requires the investigation of alternative therapies. Prior to clinical testing, researchers require the use of animal models to thoroughly investigate their therapeutic efficacy. To appropriately mimic cancer response, the cancer must be developed and treated within the relevant organ. This creates an obstacle with BCa, as cancer presence and progression are difficult to evaluate due to its location. Therefore, non-invasive techniques have been developed that allow for visualization of the cancer from outside the bladder. These techniques include bioluminescence imaging (BLI), micro-ultrasound imaging (MUI), magnetic resonance imaging (MRI), and positron emission tomography (PET). This paper reviews these imaging techniques when used independently or in conjunction in an animal model where BCa is developed within the bladder. Bladder cancer (BCa) is the sixth most prevalent cancer in men and seventeenth most prevalent cancer in women worldwide. Current treatment paradigms have limited therapeutic impact, suggesting an urgent need for the investigation of novel therapies. To best emulate the progression of human BCa, a pre-clinical intravesical murine model is required in conjunction with existing non-invasive imaging modalities to detect and evaluate cancer progression. Non-invasive imaging modalities reduce the number of required experimental models while allowing for longitudinal studies of novel therapies to investigate long-term efficacy. In this review, we discuss the individual and multi-modal use of non-invasive imaging modalities; bioluminescence imaging (BLI), micro-ultrasound imaging (MUI), magnetic resonance imaging (MRI), and positron emission tomography (PET) in BCa evaluation. We also provide an update on the potential and the future directions of imaging modalities in relation to intravesical murine models of BCa. [ABSTRACT FROM AUTHOR]

Interferon alpha (IFNα) gene therapy is emerging as a new treatment option for patients with non-muscle invasive bladder cancer (NMIBC). Adenoviral vectors expressing IFNα have shown clinical efficacy treating bacillus Calmette-Guerin (BCG)-unresponsive bladder cancer (BLCA). However, transient transgene expression and adenoviral immunogenicity may limit therapeutic activity. Lentiviral vectors can achieve stable transgene expression and are less immunogenic. In this study, we evaluated lentiviral vectors expressing murine IFNα (LV-IFNα) and demonstrate IFNα expression by transduced murine BLCA cell lines, bladder urothelium, and within the urine following intravesical instillation. Murine BLCA cell lines (MB49 and UPPL1541) were sensitive to IFN-mediated cell death after LV-IFNα, whereas BBN975 was inherently resistant. Upregulation of interleukin-6 (IL-6) predicted sensitivity to IFN-mediated cell death mediated by caspase signaling, which when inhibited abrogated IFN-mediated cell killing. Intravesical therapy with LV-IFNα/Syn3 in a syngeneic BLCA model significantly improved survival, and molecular analysis of treated tumors revealed upregulation of apoptotic and immune-cell-mediated death pathways. In particular, biomarker discovery analysis identified three clinically actionable targets, PD-L1, epidermal growth factor receptor (EGFR), and ALDHA1A, in murine tumors treated with LV-IFNα/Syn3. Our findings warrant the comparison of adenoviral and LV-IFNα and the study of novel combination strategies with IFNα gene therapy for the BLCA treatment.

Urinary tract infection (UTI) afflicts millions of patients globally each year. While the majority of UTIs are successfully treated with orally administered antibiotics, the impact of oral antibiotics on the host microbiota is under close research scrutiny and the potential for dysbiosis is a cause for concern. Optimal treatment of UTI relies upon the selection of an agent which displays appropriate pharmacokinetic-pharmacodynamic (PK-PD) properties that will deliver appropriately high concentrations in the urinary tract after oral administration. Alternatively, high local concentrations of antibiotic at the urothelial surface can be achieved by direct instillation into the urinary tract. For antibiotics with the appropriate physicochemical properties, this can be of critical importance in cases for which an intracellular urothelial bacterial reservoir is suspected. In this review, we summarise the underpinning biopharmaceutical barriers to effective treatment of UTI and provide an overview of the evidence for the deployment of the intravesical administration route for antibiotics. [ABSTRACT FROM AUTHOR]

Background. A magnetic ball is a toy for children that can cause physical injury when used improperly. The injury of urethra and bladder caused by magnetic ball is rarely reported. Case. Here we present a case of self-inflicted intravesical insertion of 83 magnetic balls by a 10-year-old boy. Preliminary diagnosis was made by a plain radiograph of the pelvis and ultrasonic examination of bladder and all the magnetic balls were removed under cystoscopy successfully. Conclusions. For children with recurrent bladder irritation, the possibility of bladder foreign body should be considered. Surgery is an effective method. For patients without serious complications, cystoscopy is the gold standard for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Purpose: Intravesical BCG (bacille Calmette–Guérin) instillation in patients with non-muscle-invasive bladder cancer decreases the risk for tumor recurrence and progression. After one BCG product was discontinued, a chronic global BCG shortage occurred. We focused on identifying a reduced dose of BCG that could maintain efficacy and reduce adverse effects. Materials and Methods: We conducted a comprehensive literature search of PubMed, Embase, the Cochrane Library, CINAHL, Web of Science, and Scopus to identify randomized controlled trials through April 2021. The odds ratios (ORs) and 95% confidence intervals (CIs) for the low and standard doses in nine studies were compared. A low dose was defined as a low volume of BCG compared with the standard BCG dose (Armand Frappier, 120 mg; Connaught, 81 mg; Danish 1331, 120 mg; modified Danish 1331, 120 mg; Tokyo 172, 80 mg). Results: The low-dose group experienced aggravated recurrence (OR, 1.45; 95% CI, 1.09–1.94; p=0.01) but similar progression (OR, 1.11; 95% CI, 0.76–1.62; p=0.59), similar cancer-specific survival (OR, 1.02; 95% CI, 0.60–1.75; p=0.93), similar overall survival (OR, 1.09; 95% CI, 0.76–1.56; p=0.65), favorable adverse effects (OR, 0.41; 95% CI, 0.28–0.62; p

BackgroundIntravesical Mitomycin-C (MMC) following transurethral resection of bladder tumor (TURBT), while efficacious, is associated with side effects and poor utilization. Continuous saline bladder irrigation (CSBI) has been examined as an alternative. In this study we sought to compare the rates of recurrence and/or progression in patients with NMIBC who were treated with either MMC or CSBI after TURBT.MethodsWe retrospectively reviewed records of patients with NMIBC at our institution in 2012-2015. Perioperative use of MMC (40 mg in 20 mL), CSBI (two hours), or neither were recorded. Primary outcome was time to recurrence or progression. Descriptive statistics, chi-squared analysis, Kaplan-Meier survival analysis, and Cox multivariable regression analyses were performed.Results205 patients met inclusion criteria. Forty-five (22.0%) patients received CSBI, 71 (34.6%) received MMC, and 89 (43.4%) received no perioperative therapy. On survival analysis, MMC was associated with improved DFS compared with CSBI (p = 0.001) and no treatment (p = 0.0009). On multivariable analysis, high risk disease was associated with increased risk of recurrence or progression (HR 2.77, 95% CI: 1.28-6.01), whereas adjuvant therapy (HR 0.35, 95% CI: 0.20-0.59) and MMC (HR 0.43, 95% CI: 0.25-0.75) were associated with decreased risk.ConclusionsPostoperative MMC was associated with improved DFS compared with CSBI and no treatment. The DFS benefit seen with CSBI in other studies may be limited to patients receiving prolonged irrigation. New intravesical agents being evaluated may consider saline as a control given our data demonstrating that short-term CSBI is not superior to TURBT alone.

Purpose: To assess the comparative effectiveness and toxicity of intravesical gemcitabine instillation for non-muscle invasive bladder cancer (NMIBC). Materials and Methods: We performed a comprehensive literature search on 11 September 2020. We included RCTs in which participants received intravesical gemcitabine for primary or recurrent NMIBC. Two review authors independently assessed the included studies and extracted data for the primary outcomes (time to recurrence, time to progression, grade III to V adverse events) and the secondary outcomes (time to death from bladder cancer, time to death from any cause, grade I or II adverse events, and disease-specific quality of life). We performed statistical analyses using a random-effects model and rated the certainty of the evidence using GRADE. Results: We found seven studies with 1,222 participants. Gemcitabine may reduce the risk of recurrence over time, but may have a similar effect on progression and grade III to V adverse events compared to saline. Gemcitabine may reduce recurrence and progression compared to mitomycin. We are uncertain about the effect of gemcitabine on the grade III to V adverse events compared to mitomycin. Gemcitabine may reduce recurrence and progression compared to giving BCG again in recurrent high-risk NMIBC after BCG treatment. Conclusions: Based on the findings of this review, gemcitabine may have a favorable impact on recurrence and progression-free survival than saline and mitomycin but we are uncertain about how major adverse events compare. The same is true when comparing gemcitabine to BCG in individuals with high-risk diseases who have previously failed BCG.

PurposeThis study aims to compare the outcomes of extravesical (EVUR) and intravesical (IVUR) ureteric reimplantation for primary vesicoureteral reflux (VUR) via systematic review and meta-analysis.MethodsLiterature review from Medline, Embase, and Cochrane since inception to March 2022 was performed. Meta-analysis was conducted on eligible randomized controlled trials (RCT) and observational cohort studies (OCS) comparing outcomes between EVUR and IVUR.ResultsTwelve studies were included, comprising 577 patients (778 ureters) operated by EVUR and 395 patients (635 ureters) by IVUR. Pre-operative VUR grade, postoperative VUR persistence and hydronephrosis was not statistically significant. EVUR had shorter operative time [mean differences (MD) −22.91 min; 95% confidence interval (CI), −44.53 to −1.30, P = 0.04] and hospital stay (MD −2.09 days; 95% CI, −2.82 to −1.36, P < 0.00001) compared to IVUR. Bilateral EVUR had higher risk of postoperative acute urinary retention (ARU) (8.1%) compared to bilateral IVUR (1.7%) (OR = 4.40; 95% CI, 1.33–14.58, P = 0.02). No patient undergoing unilateral EVUR or IVUR experienced ARU.ConclusionBoth EVUR and IVUR are equally effective in correcting primary VUR. Operative time and hospital stay are shorter after EVUR compared to IVUR. However, bilateral EVUR is associated with higher risk of postoperative ARU.

Bladder cancer treatment remains a challenge to every oncologist. We report the case of a 57‐year‐old man with BCG‐refractory bladder cancer who had a complete response to intravesical gemcitabine to highlight the role of gemcitabine as a bladder sparing treatment in BCG‐failure patients. [ABSTRACT FROM AUTHOR]

Recreational use of substituted cathinones continues to be an emerging public health problem in the United States; cathinone derivatives α-pyrrolidinopentiophenone (α-PVP) and 3,4-methylenedioxypyrovalerone (MDPV), which have been linked to human fatalities and show high potential for abuse liability in animal models, are of particular concern. The objective of this study was to develop an immunotherapeutic strategy for attenuating the effects of α-PVP and MDPV in rats, using drug-conjugate vaccines created to generate antibodies with neutralizing capacity. Immunoconjugates (α-PVP-KLH and MDPV-KLH) or the control carrier protein, keyhole limpet hemocyanin (KLH), were administered to groups (N = 12) of male Sprague-Dawley rats on Weeks 0, 2 and 4. Groups were administered α-PVP or MDPV (0.0, 0.25, 0.5, 1.0, 5.0 mg/kg, i.p.) in acute drug challenges and tested for changes in wheel activity. Increased wheel activity produced by α-PVP or MDPV in the controls was attenuated in the α-PVP-KLH and MDPV-KLH vaccinated groups, respectively. Rectal temperature decreases produced by MDPV in the controls were reduced in duration in the MDPV-KLH vaccine group. A separate group (N = 19) was trained to intravenously self-administer α-PVP (0.05, 0.1 mg/kg/inf) and vaccinated with KLH or α-PVP-KLH, post-acquisition. Self-administration in α-PVP-KLH rats was initially higher than in the KLH rats but then significantly decreased following a final vaccine booster, unlike the stable intake of KLH rats. The data demonstrate that active vaccination provides functional protection against the effects of α-PVP and MDPV, in vivo, and recommend additional development of vaccines as potential therapeutics for mitigating the effects of designer cathinone derivatives.

Abstract Bladder cancer treatment remains a challenge to every oncologist. We report the case of a 57‐year‐old man with BCG‐refractory bladder cancer who had a complete response to intravesical gemcitabine to highlight the role of gemcitabine as a bladder sparing treatment in BCG‐failure patients.

IntroductionNon-muscle-invasive bladder cancer (NMIBC) is a common and heterogeneous disease; many patients develop recurrent or progress to muscle-invasive disease. Intravesical drug therapy is a pillar in the current management of NMIBC; notwithstanding, Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) have numerous limitations including international supply issues, and local and systemic toxicity. Here we review novel intravesical therapeutic options and drug delivery devices with potential for clinical use in the treatment of NMIBC.MethodsPubMed, ClinicalTrials.gov and Cochrane Library searches were undertaken. Systematic reviews, meta-analyses, randomised controlled trials, single-arm clinical trials and national/international conference proceedings were included.ResultsNovel intravesical drugs, including chemotherapeutic agents, immune checkpoint inhibitors, monoclonal antibodies and gene therapies, have demonstrated varying efficacy in the treatment of NMIBC. Current evidence for the majority of treatments is mostly limited to single-arm trials in patients with recurrent NMIBC. Various novel methods of drug delivery have also been investigated, with encouraging preliminary results supporting the intravesical delivery of hyperthermic MMC and MMC hydrogel formulations.ConclusionsNovel therapeutic agents and drug delivery systems will be important in the future intravesical management of NMIBC. As our understanding of the molecular diversity of NMIBC develops, molecular subtyping will become fundamental in the personalisation of intravesical treatments. Further randomised studies are urgently required to investigate the efficacy of novel intravesical treatments and novel regimens, in comparison to current standards-of-care, particularly in the context of international BCG shortages.

Bacillus Calmette–Guérin is frequently the treatment of choice of superficial bladder cancer. Exposing the urinary bladder of elderly patients with bladder cancer to the BCG vaccine reduced the risk of Alzheimer's disease (AD) substantially. Vaccines against other infectious microorganisms by other vaccination methods showed a similar but a lesser effect. This suggests that immune effects on AD are antigenically non-specific, likely being a metabolic result of immune system activation, similar to that shown for Juvenile diabetes. In this mini review we point to the benefit of BCG vaccine. We then briefly highlight the pathological involvement of the immune system in the AD both, in the peripheral and the central (brain) compartments. Given the uncertain prophylactic mechanism of the BCG effect against AD we propose to take advantage of the therapeutically planned bladder exposure to BCG. Based on pathological aggregation of wrongly cleaved amyloid precursor protein (APP) resistant to the unfolded protein response (UPR) which results in amyloid beta plaques we predict that BCG may impact the UPR signaling cascade. In addition pathways of innate immunity training concerned with energy metabolism, predict capability of activated immune cells to substitute deranged astrocytes that fail to support neuronal energy metabolism. This mini review points to ways through which immune cells can mediate between BCG vaccination and AD to support the wellness of the central nervous system. [ABSTRACT FROM AUTHOR]

Bacillus Calmette–Guérin is frequently the treatment of choice of superficial bladder cancer. Exposing the urinary bladder of elderly patients with bladder cancer to the BCG vaccine reduced the risk of Alzheimer’s disease (AD) substantially. Vaccines against other infectious microorganisms by other vaccination methods showed a similar but a lesser effect. This suggests that immune effects on AD are antigenically non-specific, likely being a metabolic result of immune system activation, similar to that shown for Juvenile diabetes. In this mini review we point to the benefit of BCG vaccine. We then briefly highlight the pathological involvement of the immune system in the AD both, in the peripheral and the central (brain) compartments. Given the uncertain prophylactic mechanism of the BCG effect against AD we propose to take advantage of the therapeutically planned bladder exposure to BCG. Based on pathological aggregation of wrongly cleaved amyloid precursor protein (APP) resistant to the unfolded protein response (UPR) which results in amyloid beta plaques we predict that BCG may impact the UPR signaling cascade. In addition pathways of innate immunity training concerned with energy metabolism, predict capability of activated immune cells to substitute deranged astrocytes that fail to support neuronal energy metabolism. This mini review points to ways through which immune cells can mediate between BCG vaccination and AD to support the wellness of the central nervous system.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition affecting approximately 3% of the female population. IC/BPS is defined as an unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms for more than six weeks duration, in the absence of infection or other identifiable cause. This condition is known to have a profound negative impact on quality of life. There are few well-studied treatment options and no cure for this condition, which is therefore challenging to treat. The purpose of this narrative review is to summarise the contemporary literature, including the Canadian Urological Association (CUA) and American Urological Association (AUA) guidelines, on various treatment options that exist for IC/BPS, including conservative therapies, oral therapies, intravesical therapies, and more invasive surgical options. Most importantly, this review highlights the need for an individualised, multimodal approach to the treatment of IC/BPS.

Objective: To report the magnitude, the financial and the economic impact of Bacillus Calmette-Guérin (BCG) shortage in our institute and transfer of non-muscle invasive bladder cancer (NMIBC) patients to higher centers to receive the treatment. Methods: This is a retrospective study, between January 2015 and December 2017, the cases of NMIBC diagnosed at Aseer Central Hospital, Abha, Saudi Arabia were studied. Demographic features, clinical presentations, histopathological features, and the BCG therapy shortage and its economic impact were addressed. Results: Over a three years study review of 62 urothelial bladder cancer, NMIBC was diagnosed in 55 (89%) patients. Forty-three (78%) patients were males and 12 (22%) patients were females. The mean age ± standard deviation (SD) (range) in this cohort was 59 ± 12 years (38–87). Gross hematuria was the main presentation in 51 (92%) patients of this cohort. Dysuria and other lower urinary tract symptoms were the presentations in 18 (32%) patients. Smoking history was positive in 33 (60%) patients and the rest 22 (40%) patients denied any form of tobacco consumptions. The BCG eligible were 46 (84%) patients of all NMIBC patients in this study. Twenty-seven (59%) patients of them received BCG in our institute. The rest 19 (41%) patients were opted to be transferred to a higher medical center to receive the BCG because of the BCG shortage in our center. The financial cost of traveling to receive the six-weeks induction BCG therapy was on average of 7200 Saudi riyals (1.745 €) for every patient. Conclusions: The BCG shortage in our institute is almost approaching half of eligible BCG cases. This has had an economic impact on the health budget. Such health catastrophe could be mitigated with proper health plans of a provision of the BCG to all tertiary care centers. Alternative therapies for such cases should be considered in cases of global BCG shortage.

Urinary tract infection (UTI) afflicts millions of patients globally each year. While the majority of UTIs are successfully treated with orally administered antibiotics, the impact of oral antibiotics on the host microbiota is under close research scrutiny and the potential for dysbiosis is a cause for concern. Optimal treatment of UTI relies upon the selection of an agent which displays appropriate pharmacokinetic-pharmacodynamic (PK-PD) properties that will deliver appropriately high concentrations in the urinary tract after oral administration. Alternatively, high local concentrations of antibiotic at the urothelial surface can be achieved by direct instillation into the urinary tract. For antibiotics with the appropriate physicochemical properties, this can be of critical importance in cases for which an intracellular urothelial bacterial reservoir is suspected. In this review, we summarise the underpinning biopharmaceutical barriers to effective treatment of UTI and provide an overview of the evidence for the deployment of the intravesical administration route for antibiotics.

While more than four decades have elapsed since intravesical Bacillus Calmette-Guérin (BCG) was first used to manage non-muscle invasive bladder cancer (NMIBC), its precise mechanism of anti-tumor action remains incompletely understood. Besides the classic theory that BCG induces local (within the bladder) innate and adaptive immunity through interaction with multiple immune cells, three new concepts have emerged in the past few years that help explain the variable response to BCG therapy between patients. First, BCG has been found to directly interact and become internalized within cancer cells, inducing them to act as antigen-presenting cells (APCs) for T-cells while releasing multiple cytokines. Second, BCG has a direct cytotoxic effect on cancer cells by inducing apoptosis through caspase-dependent pathways, causing cell cycle arrest, releasing proteases from mitochondria, and inducing reactive oxygen species-mediated cell injury. Third, BCG can increase the expression of programmed death ligand 1 (PD-L1) on both cancer and infiltrating inflammatory cells to impair the cell-mediated immune response. Current data has shown that high-grade recurrence after BCG therapy is related to CD8 + T-cell anergy or 'exhaustion'. High-field cancerization and subsequently higher neoantigen presentation to T-cells are also associated with this anergy. This may explain why BCG therapy stops working after a certain time in many patients. This review summarizes the detailed immunologic reactions associated with BCG therapy and the role of immune cell subsets in this process. Moreover, this improved mechanistic understanding suggests new strategies for enhancing the anti-tumor efficacy of BCG for future clinical benefit., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Introduction: Urothelial carcinoma, especially localized bladder cancer, has a substantial prevalence in Brazil with 9,480 new cases each year and 3,903 deaths, therefore progress is required in its management in order to decrease its recurrence and progression, and improve survival. Material and Methods: Medical oncologists, radiation oncologists, and urologists from Brazil conducted a meeting to vote the best approaches available in this country in the diagnosis, staging, and treatment of localized and locally advanced urothelial bladder carcinoma. The panel drew up 73 questions and answers were chosen considering the feasibility according to the access to drugs and the procedures used in this country. Each answer reaching 75% of voters was considered a consensus. The results of this consensus were compared with evidence published in the medical literature and rated with a level of evidence and grade of recommendation using the Oxford classification. Results: Transurethral resection of bladder tumors confirms the diagnosis of and provides initial treatment for non-muscle-invasive bladder cancers. Repeated resection is necessary in selected cases and should not delay further treatment. The use of intravesical Bacillus Calmette-Guérin is performed according to risk stratification, showing a significant reduction in tumor recurrence and progression, and improved disease-specific survival in intermediate- and high-risk patients. Radical cystectomy should be considered for high-progression risk cases after Bacillus Calmette-Guérin treatment failure and for localized muscle-invasive bladder cancer. Conclusion: Management of urothelial carcinoma often requires a multidisciplinary team with surgical and clinical approaches, based on the expertise of professionals and evidence from the literature.

Intravesical therapy with bacillus Calmette-Guérin has proven effects for reducing recurrence, progression, and death from non-muscle-invasive bladder cancer. These advantages are seen mainly when appropriate maintenance therapy is used for 1-3 years, in the context of appropriate patient selection, tumor management, and symptom support for potential side effects.

A common health-care problem worldwide, urinary tract infection (UTI), represents a disease of significant impact on every country's economy, being the most common cause of hospitalization among elderly people and the most common cause of antibiotic prescription in primary care. Diagnosing and managing upper and lower UTI have always been a challenge to physicians, given its high prevalence, risk of recurrence and improper treatment, and the fact of worldwide increase in antibiotic resistance, necessitating implementation of a proper antibiotic stewardship. Urinary infections are twice more likely to occur in females compared to males and its prevalence increases with increasing age. The following is a comprehensive review paper about UTI in females, discussing the various factors leading to a complicated infection. The various etiologies and microbiologies of UTI are also highlighted. In addition to various usual antibiotic regimens for treating UTI, a significant number of nonantimicrobial treatment modalities are highlighted and described in this manuscript, including the novel use of intravesical antibiotics and vaccines for suppression treatment. Finally, a pathway is suggested for the proper diagnosis and treatment that ensures antibiotic stewardship in order to decrease long-term complications.

Reports of foreign body in the bladder are rare. Various objects have been retrieved. Diagnosis is mainly by history of lower urinary tract symptoms and low abdominal pain combined with relevant radiological investigations. Treatment depends on the size, nature, and configuration of the object. The approach may be endoscopic or through open surgery depending on the above highlighted factors.

Objective: To report the magnitude, the financial and the economic impact of Bacillus Calmette-Guérin (BCG) shortage in our institute and transfer of non-muscle invasive bladder cancer (NMIBC) patients to higher centers to receive the treatment. Methods: This is a retrospective study, between January 2015 and December 2017, the cases of NMIBC diagnosed at Aseer Central Hospital, Abha, Saudi Arabia were studied. Demographic features, clinical presentations, histopathological features, and the BCG therapy shortage and its economic impact were addressed. Results: Over a three years study review of 62 urothelial bladder cancer, NMIBC was diagnosed in 55 (89%) patients. Forty-three (78%) patients were males and 12 (22%) patients were females. The mean age ± standard deviation (SD) (range) in this cohort was 59 ± 12 years (38–87). Gross hematuria was the main presentation in 51 (92%) patients of this cohort. Dysuria and other lower urinary tract symptoms were the presentations in 18 (32%) patients. Smoking history was positive in 33 (60%) patients and the rest 22 (40%) patients denied any form of tobacco consumptions. The BCG eligible were 46 (84%) patients of all NMIBC patients in this study. Twenty-seven (59%) patients of them received BCG in our institute. The rest 19 (41%) patients were opted to be transferred to a higher medical center to receive the BCG because of the BCG shortage in our center. The financial cost of traveling to receive the six-weeks induction BCG therapy was on average of 7200 Saudi riyals (1.745 €) for every patient. Conclusions: The BCG shortage in our institute is almost approaching half of eligible BCG cases. This has had an economic impact on the health budget. Such health catastrophe could be mitigated with proper health plans of a provision of the BCG to all tertiary care centers. Alternative therapies for such cases should be considered in cases of global BCG shortage. [ABSTRACT FROM AUTHOR]

Posterior urethral valves are the most common cause of bladder outlet obstruction in male newborns. Initial catheter drainage alleviates the urethral obstruction before definitive management by valve ablation. Newborns with posterior urethral valves often present with hypercontractile bladders that may inhibit upper tract drainage despite bladder catheterization. Anticholinergic agents are commonly used to treat detrusor hyperactivity, with oxybutynin being the most commonly used. We report the first case of a newborn with posterior urethral valves and ureterovesical junction obstruction caused by detrusor hypertrophy who underwent urgent intravesical instillation of oxybutynin at high doses in an attempt to avoid a diversion procedure.

Objective: Only a few numbers of studies have been published on the use of abobotulinumtoxinA (Dysport®) in idiopathic detrusor overactivity (IDO). This study reported the long-term follow-up of women with IDO who were treated with intravesical Dysport® injections., Methods: Two hundred and thirty-six patients with IDO who had failed first-line conservative and antimuscarinic therapy received 500-900 units of Dysport® between April 2014 and July 2015. All patients were followed up for 5 years after their initial injection and interviewed on the phone., Results: A total of 236 women with IDO aged from 18 years to 84 years (mean±standard deviation: 49.6±15.9 years) were included in our study. The median follow-up time for patients was 36.5 (range: 10-70) months, and the median recovery time after injection was 18.5 (range: 0-70) months. A total of 83 (35.2%) patients stated that they had subjective improvement of their symptoms whereas 84 (35.6%) patients did not report any improvement in symptoms. The initial International Consultation on Incontinence Questionnaire Overactive Bladder mean score was 6.9 (standard deviation 3.4). There was a positive association between the median recovery time and the components of the International Consultation on Incontinence Questionnaire Overactive Bladder questionnaire., Conclusion: In a sub-population of overactive bladder patients with IDO who have failed first-line therapy, a single intravesical Dysport® injection can resolve patient symptoms completely or reduce the symptoms to an acceptable level that can be controlled with antimuscarinics or re-injection on demands., Competing Interests: The authors declare no conflict of interest., (© 2024 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V.)

A common health-care problem worldwide, urinary tract infection (UTI), represents a disease of significant impact on every country's economy, being the most common cause of hospitalization among elderly people and the most common cause of antibiotic prescription in primary care. Diagnosing and managing upper and lower UTI have always been a challenge to physicians, given its high prevalence, risk of recurrence and improper treatment, and the fact of worldwide increase in antibiotic resistance, necessitating implementation of a proper antibiotic stewardship. Urinary infections are twice more likely to occur in females compared to males and its prevalence increases with increasing age. The following is a comprehensive review paper about UTI in females, discussing the various factors leading to a complicated infection. The various etiologies and microbiologies of UTI are also highlighted. In addition to various usual antibiotic regimens for treating UTI, a significant number of nonantimicrobial treatment modalities are highlighted and described in this manuscript, including the novel use of intravesical antibiotics and vaccines for suppression treatment. Finally, a pathway is suggested for the proper diagnosis and treatment that ensures antibiotic stewardship in order to decrease long-term complications. [ABSTRACT FROM AUTHOR]

To determine the effectiveness of instillation of single dose of intravesical mitomycin C in patients with low grade non-muscle invasive bladder tumor (NMIBT). Study Design: Retrospective cross-sectional study. Setting: Tabba kidney institute Karachi. Period: 2016 to Jan-2018. Materials and Methods: A total of 76 patients with first time diagnosis of non-invasive bladder tumor were included. Data of patients of SNMIBT who underwent transuretheral resection of bladder tumor (TURBT) and received single dose instillation of mitomycin C (MMC, 40 mg) within 24 hours after resection from 2016 to Jan-2018 were included in this analysis. All these patients were followed for 6 months after TURBT, cystoscopy was performed at 3 and 6 monthly to check and record any recurrence or progression. Results: Out of 76 cases, 43 (56.57%) had one lesion, 27 (35.52%) had two lesion and 6 (7.89%) cases had three lesion. Single dose intravesical mitomycin C was effective in 81.57% (62/76) cases, recurrence occurred in 6 (7.89 %) cases and progression of disease in 8 (10.52%) cases. Conclusion: The results of present study confirmed the positive effect of instillation of single immediate dose of MMC in patients with low risk superficial bladder tumor. 81.57% patients will not require any further treatment if MMC-40 is given immediately following TURBT. [ABSTRACT FROM AUTHOR]

Background: Urinary symptoms are common for people with neurogenic lower urinary tract dysfunction (NLUTD). No nonprescription approach has been proven safe and effective for self-management of urinary symptoms. Our objective was to describe the safety and tolerability of Lactobacillus rhamnosus GG (LGG®) instilled intravesically for self-management of inflammatory urinary symptoms in adults and children with NLUTD due to spinal cord injury or disease (SCI/D) and who use intermittent catheterization (IC). Methods: A total of 103 individuals with SCI/D enrolled in an 18-month study consisting of three 6-month stages: baseline (weekly observation of urinary symptoms); intervention (self-instilled intravesical LGG® in response to more cloudy or foul-smelling urine); and washout (weekly observation of urinary symptoms). Urinary symptoms were assessed using the Urinary Symptom Questionnaire for people with neurogenic bladder using intermittent catheters (USQNB-IC). Safety was based on serious adverse events and adverse events (S/AEs) and trends in symptoms. Tolerability was defined as the independence of AE experience and willingness to use/pay for this intervention. Results: A total of 74 (77%) adults and 6 (86%) of children completed the study, of whom 64 instilled LGG® for a total of 357 instillations (range 1-41 per person). There were 59 S/AEs, 44% (26/59) of which were categorized as infectious genitourinary. There was no statistical relationship between S/AEs and use or dose of the intervention. Conclusions: One or two doses of self-instilled intravesical LGG® in response to more cloudy or foul-smelling urine was safe and well tolerated among this sample of adults and children with SCI/D who have NLUTD and use IC. [ABSTRACT FROM AUTHOR]