Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic non-small-cell lung cancer (NSCLC) but can cause a broad spectrum of immune-related adverse events (irAEs) affecting multiple organ systems. Although common irAEs are well characterized, immune-related cystitis is rare and may pose a significant diagnostic challenge, particularly when urine cytology demonstrates atypical urothelial cells that mimic high-grade urothelial carcinoma. We present the case of a 55-year-old man with metastatic squamous cell carcinoma of the lung who developed hematuria and non-bacterial cystitis during pembrolizumab therapy in the setting of multiple other irAEs, including hypophysitis resulting in secondary adrenal insufficiency and hypothyroidism. Following the onset of hematuria, computed tomography (CT) of the abdomen and pelvis demonstrated an acute cystitis picture. Importantly, there was no evidence of urinary calculi or progression of pelvic metastatic disease to otherwise explain his symptoms. Urine cytology subsequently showed marked urothelial atypia concerning for high-grade urothelial carcinoma, creating a significant diagnostic dilemma. Cystoscopic evaluation, however, revealed a normal bladder mucosa without erythema, lesions, or findings suggestive of carcinoma in situ; no biopsy was performed. The absence of an identifiable urothelial malignancy or bacterial infection, together with the temporal association with pembrolizumab and the patient's concurrent multisystem irAEs, supported an immune-related etiology. This case highlights the potential for ICI-associated cystitis to produce cytologic atypia that closely mimics high-grade urothelial carcinoma and underscores the importance of integrating cytomorphologic findings with clinical history, radiologic and cystoscopic findings, microbiologic studies, and treatment history to avoid misdiagnosis. Recognition of this rare irAE is essential for appropriate management and prevention of unnecessary interventions.

This manuscript aims to provide an overview of minimally invasive treatment for overactive bladder (OAB) in men, highlighting how concomitant bladder outlet obstruction in men can complicate management and lead to underutilization of these therapies in this patient population.

The full morphologic spectrum of divergent differentiations in urothelial carcinoma is still unknown. Herein, we describe two cases of pilomatrix-like high grade carcinomas (PiMLC) involving bladder. Case #1 was a 55-year-old male with a bladder tumor with basaloid nests, geographic necrosis, and shadow cells. The tumor cells were positive for LEF1, β-catenin (nuclear/cytoplasmic staining), CK5/6, CD10, BerEP4, p63 (focal-to-patchy) and AMACR (patchy), and negative for CK7, GATA3, CDX2, INSM1, chromogranin, synaptophysin, p40, CK20, calponin, CD117, S100, smooth muscle actin, p16 and high-risk HPV in-situ hybridization. PD-L1 and Her2 were negative. Trop-2 immunostain showed modest expression (H-score: 75). There were rare microscopic foci of surface disease with a similar basaloid appearance that were also positive for LEF1 and negative for GATA3. Genomic profiling of the tumor revealed an APC mutation, suggesting β-catenin/Wnt pathway dysregulation. Additionally, mutations in TERT, CDKN2A, and TP53 were present. The patient was transitioned to hospice shortly after initiating chemotherapy. Case #2 was a 78-year-old male with a large bladder mass with basaloid nests and abundant shadow cells. Conventional UC was focally present. The tumor cells were positive for p63, β-catenin (nuclear/cytoplasmic staining), CK14 (focal), and CK20 (focal), and negative for GATA3, Uroplakin, NUT, and Her2. Genomic profiling of the tumor revealed a CTNNB1 mutation, suggesting β-catenin/Wnt pathway dysregulation. Additionally, mutations in RB1, KMT2A, and TP53 were present. Overall, these two cases describe PiMLC of urinary bladder with evidence supporting novel pilomatrix-like divergent differentiation from urothelial carcinoma.

Cystitis is common during pregnancy and requires effective antibiotic treatment to prevent complications. Gastric bypass surgery alters gastrointestinal anatomy and may impair oral drug absorption, raising concerns about antibiotic effectiveness. We therefore aimed to examine antibiotic use for cystitis and the risk of treatment failure in pregnant women with prior gastric bypass. In this nationwide Danish register-based study, we compared 1985 pregnancies among women with prior gastric bypass with 1 400 174 pregnancies among women without bariatric surgery. We assessed redeemed prescriptions for cystitis-related antibiotics and potential treatment failure defined as repeated antibiotic prescriptions within 14 days, hospital-recorded cystitis or severe urinary tract complications (pyelonephritis or urosepsis). Pregnant women with prior gastric bypass more frequently redeemed cystitis-related antibiotics than those without bariatric surgery (22.6% vs. 12.7%). Among antibiotic-exposed pregnancies, prior gastric bypass was associated with an increased risk of potential treatment failure, including repeated antibiotic prescriptions (adjusted odds ratio [aOR] 1.69, 95% confidence interval [CI] 1.22-2.30) and hospital-recorded cystitis (aOR 2.22, 95% CI 1.24-3.67), while severe complications were rare. These findings suggest that antibiotic treatment may be less effective or that the clinical course is more complicated in this group, highlighting a need for closer monitoring and tailored treatment strategies.

Interstitial cystitis (IC) and overactive bladder (OAB) are chronic pelvic conditions with shared symptoms of urinary urgency, increased frequency, and nocturia with pain in the bladder. IC is characterized by bladder pain and inflammation without a clear etiology, whereas OAB involves detrusor overactivity in the absence of infection. Despite this symptomatic overlap, IC and OAB differ in underlying pathophysiology and require distinct treatment and medical care. A specific diagnostic strategy is currently lacking and highlights the need of a robust diagnostic method for effective treatment. Raman spectroscopy provides sensitive and nondestructive molecular fingerprints; when combined with artificial intelligence (AI)-driven analysis of spectral data, it offers a promising approach to overcoming the limitations of exclusion-based diagnoses. In this study, urinary samples were collected from healthy individuals (n = 117), IC patients (n = 19), and OAB patients (n = 45) for the acquisition of Raman spectra using Au-ZnO nanorod surface-enhanced Raman spectroscopy (SERS) chips. To obtain biological interpretable Raman spectra per group and high accuracy of classification performance, the linear models PCA-PLS-DA and PCA-LDA and tree-based nonlinear models XGBoost and LightGBM were applied and reached up to 92% accuracy with interpretable and pathologic relative Raman features for discriminating among healthy control, IC, and OAB. This approach suggests that urine-based SERS Raman spectra combined with machine learning could serve as a promising diagnostic platform to support disease-specific clinical decision.

Bladder cancer (BC), a highly prevalent malignancy of the urinary tract, imposes a considerable clinical burden because of its high recurrence rates and a substantial risk of disease progression. Accumulating evidence suggests that microbiome dysbiosis is associated with the initiation and progression of BC through potentially bidirectional interactions. Recent advances in high-throughput sequencing technologies have facilitated a more comprehensive characterization of the urinary microbiome, thereby revealing its potential involvement in the pathogenesis of BC. This review summarizes the proposed mechanisms through which microbial communities may contribute to BC carcinogenesis, including chronic inflammation, microbial metabolite production, and epigenetic regulation. We further critically evaluate the established mechanisms of Bacillus Calmette-Guérin (BCG) immunotherapy-a standard intravesical immunotherapy for patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC)-and examine the emerging application of microbiome profiling as a source of candidate noninvasive biomarkers and potential correlates or modulators of immune checkpoint inhibitor (ICI) response. Additionally, we elucidate the associations between microbiota heterogeneity and immunotherapy response, offering novel insights into microbiome-targeted therapeutic strategies for BC.

Bladder cancer arising in a defunctionalized bladder after urinary diversion is rare. We report a 42-year-old man who developed pure small cell carcinoma 20 years after diversion for childhood trauma. Lower abdominal discomfort and increasing intravesical fluid accumulation prompted reevaluation. Preoperative biopsy was interpreted as urothelial carcinoma, whereas the cystectomy specimen revealed pure small cell carcinoma. He underwent radical cystectomy followed by adjuvant etoposide and cisplatin chemotherapy and remained recurrence-free for 15 years. This case highlights the importance of long-term follow-up, reassessment of new or worsening clinical findings, and recognition of potential sampling limitations of a small biopsy specimen.

Inflammatory diseases of the urinary system, including urinary tract infection (UTI), catheter-associated urinary tract infection (CAUTI), interstitial cystitis/bladder pain syndrome (IC/BPS), and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), are associated with high recurrence, complex pathogenesis, and limited therapeutic durability. Conventional treatments are constrained by antimicrobial resistance, biofilm persistence, intracellular bacterial reservoirs, urine washout, urothelial and prostatic barriers, indwelling device surfaces, and heterogeneous neuroimmune inflammatory mechanisms. Nanoparticles provide versatile platforms to address these challenges through tunable physicochemical properties, controlled release, local retention, tissue penetration, and intrinsic material functions. This review summarizes the pathological basis and therapeutic limitations of major inflammatory urinary disorders and discusses recent advances in organic, inorganic, and hybrid nanoplatforms. In infectious diseases, nanoparticles can enhance antibiotic delivery, promote biofilm penetration and intracellular pathogen clearance, and functionalize catheter or stent surfaces with antibacterial, antibiofilm, and anti-encrustation properties. In noninfectious disorders, they support intravesical retention, glycosaminoglycan-layer repair, oxidative-stress modulation, immune regulation, pain-pathway intervention, and prostatic or rectal delivery. Emerging applications in upper UTI and renal inflammatory injury further expand their therapeutic scope. Finally, we discuss current translational barriers, including model fidelity, long-term safety, manufacturing control, clinical evidence, and rational functional integration.

Herpes zoster-associated voiding dysfunction is an uncommon complication but may occur when the sacral dermatomes are involved. In immunocompromised patients, including kidney transplant recipients receiving immunosuppressive therapy, urinary retention may predispose patients to secondary urinary tract infections such as pyelonephritis. Prompt recognition and appropriate management are therefore essential. We report the case of a woman with a history of living-donor kidney transplantation who developed urinary retention and pyelonephritis following herpes zoster involving the buttock. She had been receiving maintenance immunosuppressive therapy with methylprednisolone, mizoribine, and cyclosporine. After the diagnosis of herpes zoster, antiviral therapy was initiated. Several days later, she developed dysuria caused by urinary retention, which was successfully managed with corticosteroid therapy and temporary urinary catheterization. However, she subsequently developed fever and was diagnosed with acute pyelonephritis on hospital day 7. Intravenous antibiotic therapy resulted in gradual clinical improvement, and inflammatory markers and urinary findings normalized by hospital day 15. This case highlights that sacral herpes zoster can cause neurogenic bladder dysfunction, resulting in urinary retention and subsequent pyelonephritis, particularly in immunocompromised patients. Careful monitoring of urinary symptoms and early intervention may help prevent serious infectious complications in this high-risk population.