PURPOSE: The lack of personalized management of bladder cancer (BlCa) results in patients' lifelong post-treatment monitoring with invasive interventions, underlying the urgent need for tailored and minimally invasive health care services. On the basis of our previous findings on miR-143/145 cluster methylation in bladder tumors, we evaluated its clinical significance in pretreatment cell-free DNA (cfDNA) of patients with BlCa. MATERIALS AND METHODS: Methylation analysis was performed in our screening cohort (120 patients with BlCa; 20 age-matched healthy donors) by bisulfite-based pyrosequencing. Tumor recurrence/progression for patients with non–muscle-invasive bladder cancer, and progression and mortality for patients with muscle-invasive bladder cancer (MIBC) were used as clinical end point events in survival analysis. Bootstrap analysis was applied for internal validation of Cox regression models and decision curve analysis for assessment of clinical benefit on disease prognosis. RESULTS: Decreased methylation of MIR145 core promoter in pretreatment cfDNA was associated with short-term disease progression (multivariate Cox: hazard ratio [HR], 2.027 [95% CI, 1.157 to 3.551]; P = .010) and poor overall survival (multivariate Cox: HR, 2.098 [95% CI, 1.154 to 3.817]; P = .009) of patients with MIBC after radical cystectomy (RC). Multivariate models incorporating MIR145 promoter methylation in cfDNA with tumor stage clearly ameliorated patients' risk stratification, highlighting superior clinical benefit in MIBC prognostication. CONCLUSION: Reduced pretreatment cfDNA methylation of MIR145 core promoter was markedly correlated with increased risk for short-term progression and worse survival of patients with MIBC after RC and adjuvant therapy, supporting modern personalized and minimally invasive prognosis. Methylation profiling of MIR145 core promoter in pretreatment cfDNA could serve as a minimally invasive and independent predictor of MIBC treatment outcome and emerge as a promising marker for blood-based test in BlCa.

Prostate cancer (PCa) is a global health concern, being a leading cause of cancer-related mortality among males. Early detection and accurate prognosis are crucial for effective management. This study delves into the diagnostic and prognostic potential of 28S rRNA-derived fragments (rRFs) in PCa. Total RNA extracted from 89 PCa and 53 benign prostate hyperplasia (BPH) tissue specimens. After 3’-end polyadenylation, we performed reverse transcription to create first-strand cDNA. Using an in-house quantitative real-time PCR (qPCR) assay, we quantified 28S rRF levels. Post-treatment biochemical relapse served as the clinical endpoint event for survival analysis, which we validated internally through bootstrap analysis. Our results revealed downregulated 28S rRF levels in PCa compared to BPH patients. Additionally, we observed a significant positive correlation between 28S rRF levels and higher Gleason scores and tumor stages. Furthermore, PCa patients with elevated 28S rRF expression had a significantly higher risk of post-treatment disease relapse independently of clinicopathological data. In conclusion, our study demonstrates, for the first time, the prognostic value of 28S rRF in prostate adenocarcinoma. Elevated 28S rRF levels independently predict short-term PCa relapse and enhance risk stratification. This establishes 28S rRF as a potential novel molecular marker for PCa prognosis.

Dorsal vein thrombophlebitis, or penile Mondor disease, is a rare benign penile condition presenting with cord-like induration at the dorsum of the penis. This induration is caused by an isolated thrombosis of the dorsal superficial vein of the penis. As symptoms are not typical and many patients are asymptomatic, it is often underdiagnosed. Causes include trauma, infection, sexual activity, genital surgery, and cancer. Differential diagnosis includes Peyronie’s disease and sclerosing lymphangitis, and diagnosis remains crucial as it facilitates the treatment plan and reassures the patient. Treatment consists of conservative measures, such as oral nonsteroidal anti-inflammatory medications (NSAIDs) and anticoagulation, and surgical management, with excision of the thrombosed vein. We present a case report of penile Mondor disease following circumcision, with the aim to provide educational ultrasound images of this rare entity. The patient, 32 years old, on the sixth postoperative day, developed a cord-like induration, along with pain, at the dorsum of the penis. Physical examination revealed a cord-like mass on the dorsal aspect of the penis. Penile triplex demonstrated a lack of endoluminal flow signals of the superficial dorsal veins, which were uncompressible. Triplex of the femoral and iliac veins showed no sign of thrombosis. Clinical presentation, along with imaging findings, facilitated the diagnosis of Mondor disease. The patient was treated conservatively with sexual abstinence and NSAIDs, and 6 weeks after the presentation, the patient was asymptomatic, without evidence of the disease in clinical examination.

Alterations of DNA methylation represent one of the earliest molecular events in bladder tumorigenesis and are strongly associated with treatment efficacy and prognosis. Herein, we investigated DNA methylation landscape of MIR141 promoter and elucidated its clinical relevance in bladder cancer (BlCa) patients. miRNA-seq was performed to analyze miRNA profile in bladder tumors. Expression analysis of miR-141-3p and methylation profiling of MIR141 promoter were performed in 15 patient-derived xenografts (PDXs) mouse models, and in our screening patients' cohort (n=133). TCGA-BLCA (n=412) was used as independent validation cohort. Survival analysis was performed employing tumor relapse/progression as clinical endpoints in non-muscle-invasive BlCa (NMIBC; TaT1), and mortality in muscle-invasive BlCa (MIBC; T2-T4) patients. Internal validation was conducted through bootstrap analysis, and the clinical benefit of the findings was evaluated using decision curve analysis. miRNA-seq highlighted miR-141-3p as one of the most significantly downregulated miRNAs in muscle-invasive and high-grade tumors, while PDXs, TCGA-BLCA and the screening cohort revealed its robust epigenetic regulation through MIR141 core promoter methylation. In line with miR-141-3p loss, hypermethylation of MIR141 core promoter was associated with advanced stage and high-grade tumors, reduced survival in PDXs, and significantly higher risk of TaT1 patients for short-term progression to muscle-invasive disease. Moreover, multivariate models highlighted MIR141 promoter hypermethylation as independent predictor for NMIBC short-term progression, displaying superior clinical benefit in patients' prognostication. Overall, MIR141 core promoter methylation results in miR-141-3p loss in bladder tumors and correlates with patients' poor treatment outcome, offering improved risk-stratification and addressing heterogeneity of disease prognosis beyond traditional markers.