To investigate the efficacy and safety of single-port (SP) robotic nephroureterectomy (NUx) with bladder cuff excision. From September 2021 to August 2024, we reviewed all patients diagnosed with urothelial carcinoma who underwent robot-assisted laparoscopic NUx at our institution since the introduction of the SP robot. A total of 105 patients were included in the study, of whom 52 underwent surgical procedureusing the multi-port (MP) approach, whereas 53 underwent surgery using the SP approach. No statistically significant differences were found in patient characteristics, such as gender, body mass index, or tumor size. In terms of surgical outcomes, no statistically significant differences were found in key metrics, such as console time and estimated blood loss. However, a statistically significant difference was observed in total operative time, with an average difference of 45 minutes (222.25 ± 69.38 minutes in MP, 169.98 ± 49.63 minutes in SP, p = 0.000). The estimated blood loss was lower with the SP robot (144.91 mL ± 108.25 in MP, 96.68 ± 72.95 mL in SP, p = 0.004). During the one-year follow-up, no statistically significant differences in renal function loss or T stage were observed. NUx with bladder cuffing using the SP approach demonstrated feasibility compared with surgery performed using the MP approach. Notably, the ease of access during cuffing contributed significantly to reducing the total operative time.

BK polyomavirus-associated carcinoma of the kidney or bladder following cardiac or pulmonary transplantation has been reported in only 7 individuals, all but 1 being adults. We now report 2 additional pediatric patients, the first having received a lung transplant at the age of 21 months and developing a renal cell carcinoma at 14 years, and the second receiving a heart transplant at 20 months and developing a bladder urothelial carcinoma at 21 years.

Transurethral thulium laser resection via ureterorenoscope for pediatric low-grade urothelial carcinoma of the bladder: a case report.

Background: Urothelial carcinoma of the bladder is a significant global cause of morbidity and mortality. These tumors are classified into low-grade and high-grade lesions based on architectural patterns, cytological features, and nuclear atypia. Muscle invasion remains a critical determinant in treatment planning and prognosis. Aims and Objectives: The aim of this study is to evaluate the immunohistochemical expression of human epidermal growth factor receptor 2 (HER2)/neu in urothelial carcinoma of the bladder and to correlate this expression with various clinico-pathological parameters. The objectives include analyzing the age-wise, gender-wise, and site-wise distribution of urothelial carcinoma; correlating histopathological grade with tumor stage; assessing the relationship between urine cytology and tumor grade; and evaluating HER2/neu expression in relation to age, gender, tumor size, grade, stage, and invasiveness to aid in patient management. Materials and Methods: This study was conducted in the Department of Pathology, Stanley Medical College and Hospital, Chennai, over 1 year (September 2024–September 2025). Immunohistochemical evaluation of HER2/neu was performed on biopsy-proven urothelial carcinoma cases. Prospective and retrospective data were analyzed, and HER2/neu expression was correlated with clinical and pathological variables, including age, gender, tumor size, grade, stage, and invasiveness. Results: Urothelial carcinoma showed a peak incidence above 50 years. Males constituted 69% of cases. The lateral wall was the most common tumor site. Urine cytology demonstrated higher sensitivity for high-grade tumors. High-grade carcinomas were predominantly stage II-III, whereas low-grade lesions were more often stage I-II. Conclusion: HER2/neu expression showed significant correlation with tumor grade but not with invasiveness, stage, age, gender, or size. Overexpression may indicate a poorer prognosis and potential eligibility for targeted therapy.

Targeting autophagy to enhance Nectin-4-MMAE efficacy in gastric cancer.

Primary urethral carcinoma is an extremely rare malignancy, and evidence on its treatment and prognosis remains limited. This study aimed to clarify the treatment patterns, clinical outcomes, and prognostic factors for primary urethral carcinoma in Japan. This retrospective study across 10 institutions included 57 Primary urethral carcinoma cases between 2004 and 2022. Recurrence-free survival and overall survival were estimated using the Kaplan-Meier method, and overall survival-related factors were evaluated using univariate Cox regression analysis. The cohort comprised 24 men (42%) and 33 women (58%), with a median tumor size of 30 mm (interquartile range, 15-48 mm). Stage distribution was ≤ I in 17 (30%), II in 10 (18%), III in 8 (14%), and IV in 21 (38%) patients. Urothelial carcinoma, including cases with divergent differentiation, was the predominant histological subtype, identified in 17 men (71%) and 14 women (42%). The median follow-up time was 17.1 months (interquartile range, 6.4-37.7 months). Overall survival did not differ significantly between Stage I and Stage II disease (p = 0.499), whereas it was significantly shorter in patients with Stage III and Stage IV disease compared with Stage I (p = 0.030 and p < 0.001, respectively). Previous urinary catheter placement, urethral diverticulum, and elevated lactate dehydrogenase (> 220 IU/L) were significantly associated with poorer overall survival. Stage ≤ II Primary urethral carcinoma has favorable survival following definitive treatment, Stage III-IV disease showed poor outcomes, necessitating multimodal perioperative strategies (chemotherapy and/or radiotherapy).

Metastases to the gallbladder: Challenges of clinical and frozen section diagnosis.

A preoperative tool is warranted to predict renal function after radical nephroureterectomy, as this would optimize treatment plans and avoid postoperative end-stage renal disease. Therefore, this study aimed to develop an equation to predict postoperative renal function changes. We reviewed the medical records of 487 patients who were diagnosed with upper tract urothelial carcinoma treated by unilateral radical nephroureterectomy with bladder cuff excision between 2010 and 2020. Renal function was comprehensively evaluated preoperatively using 99mTc-mercaptoacetyltriglycine renal scintigraphy. Serum creatinine was evaluated before, and 3 and 6 months postoperatively. We then developed a predictive equation using Pearson linear correlation analysis. The median preoperative effective renal plasma flow was 241.30 mL/min., of which the lesion side accounted for 35.6% of the total. A predictive equation for changes in postoperative renal function was established. The preoperative lesion-side effective renal plasma flow ratio was significantly associated with an estimated glomerular filtration rate (eGFR) decline ratio at 3 months postoperatively (r = 0.613, P <0.001). Internal validation of the patients during 2021 confirmed that the equation could predict eGFR decline (r = 0.896) and radical nephroureterectomy-related cisplatin ineligibility (100%) at 3 months postoperatively. We established an equation that assists in predicting changes in postoperative eGFRs based on the preoperative lesion-side effective renal plasma flow ratio. This equation can also predict postoperative residual renal function.

Predictors and Patterns of Nonurothelial Recurrence After Nephroureterectomy for Upper Tract Urothelial Carcinoma (UCAN Collaboration): Erratum.

Identify the PANoptosis signature and prognostic model via a multimachine-learning computational framework for bladder urothelial carcinoma.

Background: Bladder urothelial carcinoma (BUC) remains a common urologic malignancy with substantial mortality. The tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), promotes extracellular matrix remodeling, angiogenesis, immune evasion, and treatment resistance, suggesting CAFs may serve as prognostic and predictive biomarkers. Objective: To evaluate the association between CAFs and overall survival (OS) in BUC and identify clinically relevant CAF-related markers. Methods: A PRISMA-guided systematic review was performed using PubMed, Cochrane Library, Taylor &amp; Francis, ProQuest, Scopus, and EMBASE (2015–2025). Eligible human studies assessing CAFs/CAF-signatures in BUC were included. Risk of bias was assessed using ROBINS-I. Results: Nine studies were included. Across cohorts, elevated CAF abundance or CAF-related markers consistently correlated with poorer outcomes. High CAF infiltration in TCGA-BLCA was associated with reduced OS (p=0.003) and advanced stage (p&lt;0.001). Stromal markers such as FAP (HR=2.06) and PDGFRβ (HR=1.75) predicted worse OS, with FAP-dominant phenotypes showing the lowest survival. myCAF- and iCAF-high subtypes were linked to shorter OS (e.g., iCAF cluster p=0.024). Multiple CAF-based gene signatures (e.g., 7-gene models) stratified mortality risk (multivariate HR up to 3.51; AUC 0.88). COL10A1 overexpression also predicted inferior OS. A fibroblast-related gene index (FRGI) showed strong performance in ICI-treated patients (1-year OS AUC=0.95) and was enriched in non-responders. Conclusion: CAF abundance and subtype composition are robust adverse prognostic indicators in BUC and show promise for risk stratification and treatment decision support, particularly for immunotherapy responsiveness.

Epigenetic markers of ageing and cancer risk.

Objectiveto investigate the effect of tumor location on oncological outcomes in patients receiving robot-assisted radical nephroureterectomy (RANU) for upper urinary tract carcinoma (UTUC).MethodsA retrospective single-center cohort study of 54 patients with UTUC who underwent RANU by a single surgeon between July 2019 and July 2025, without neoadjuvant chemotherapy or previous or simultaneous cystectomy, were included. Patients were divided into two groups based on tumor location: 18 patients (33%) with ureteral tumors (Group 1) and 36 patients (67%) with renal pelvis tumors (Group 2). Demographics, perioperative data, and pathological results were analyzed. The primary endpoints Cancer-specific survival (CSS) and overall survival (OS) were estimated using Kaplan–Meier and univariable log-rank test.ResultsConsole time, blood transfusion, complications, and readmission were comparable in both groups. Group 1 experienced longer hospital stays (8 days vs. 6.5 days, p = 0.03). 48% of patients had ≥ pT2 disease, with a similar T-stage distribution across groups. Of 26 candidates for adjuvant therapy, 10 received chemotherapy with gemcitabine/cisplatin, 2 received nivolumab, and one patient received enfortumab vedotin with pembrolizumab. During a median 26.5-month follow-up, six patients developed bladder recurrence, (median 9 months) after RANU (p = 0.10), and four developed distant metastases (median 4 months) (p = 0.72), resulting in a disease-free survival of 81% (p = 0.08)Cancer-specific survival was 94%, overall survival 89%, with no significant group differences (p = 0.24 and 0.49).ConclusionIn our series, we observed that tumor location does not impact postoperative and oncological outcomes after RANU for UTUC, regardless of adjuvant therapy. However, further studies are needed to explore this proposed hypothesis.

Drug resistance, characterized by high heterogeneity and complex mechanisms, poses a significant challenge in cancer treatment. Stratifying resistant tumors into biologically and clinically meaningful subgroups can improve prognostic evaluation and help guide treatment decisions. However, the DNA methylation-based subtypes of resistant tumors have not yet been comprehensively characterized. DNA methylation profiles from resistant tumors were retrieved from public database including TCGA and GEO. For each tumor type resistant to a specific treatment drug, consensus clustering based on the most variable methylated probes was conducted to identify the DNA methylation subtypes of resistant tumors. For low-grade glioma (LGG) resistant to Temozolomide, consensus clustering of highly variable CpGs identified two subtypes: cancer resistance CpG island methylator phenotype-positive (CR_CIMP+) and -negative (CR_CIMP-). The CR_CIMP- subtype associates with poorer prognosis, reduced drug response, and more advanced histology, exhibiting higher tumor mutation burden and greater activity in drug resistance-related pathways, such as PI3K/AKT/mTOR signaling. CR_CIMP subtypes with distinct clinical or molecular features were also identified in pancreatic adenocarcinoma and bladder urothelial carcinoma resistant to Gemcitabine, as well as in non-small cell lung cancer resistant to anti-PD1/PD-L1 immunotherapy. Based on predicted drug responses, the study screens candidate drugs for each CR_CIMP subtype. Finally, a random forest model is proposed to predict CR_CIMP subtypes in LGG patients resistant to Temozolomide. This study uncovers DNA methylation subtypes within resistant tumors, enabling more precise stratification to inform prognosis and therapy selection.

Micropapillary urothelial carcinoma is a well-recognized subtype of urothelial carcinoma that is associated with an aggressive clinical course. Its recognition is critical for optimal management; however, strict diagnostic criteria are not always applied, resulting in interobserver variability in recognition and reporting. The genomic profiles of micropapillary urothelial carcinoma overlap with those of classic urothelial carcinoma, but show higher rates of alterations in the cell cycle regulators TP53 and RB1 and the receptor tyrosine kinase ERBB2. Recently approved therapeutic agents targeting cell surface markers such as HER2 and NECTIN4 provide promising novel and potentially more effective therapies for micropapillary urothelial carcinoma.

For many decades, the treatment of metastatic urothelial carcinoma (mUC) was dominated by platinum-based chemotherapy. However, the introduction of immune checkpoint inhibitors in combination with modern antibody-drug conjugates (ADCs) and FGFR3 inhibitors has replaced this "old" standard due to significantly better efficacy. Although these therapies are targeted therapies, biomarker-driven therapy decisions are rarely used to date. The currently available biomarkers are also only helpful in isolated therapy situations. However, this could change fundamentally for ADCs in view of the pronounced expression variability of potential target structures such as NECTIN4, HER2, EGFR, and TROP2. The presence of activating FGFR3 mutations or fusions already defines aclearly delineated, albeit still small, therapeutic niche that could also gain importance in localized stages of urothelial carcinoma in the future. In order to be able to use these therapeutic innovations in atargeted and precise manner in the future, biomarker-based stratification of urothelial carcinomas is likely to play agreater role. Current developments thus open up considerable potential for true precision oncology.

Enfortumab vedotin (EV) exhibited superior efficacy in the EV-301 trial; however, real-world outcomes stratified by trial eligibility criteria remain unclear. We evaluated the real-world efficacy of EV in Japanese patients with metastatic urothelial carcinoma (mUC) via EV-301 eligibility stratification and restricted mean survival time (RMST) analysis. This multicenter retrospective study analyzed 115 Japanese mUC patients treated with EV following platinum-based chemotherapy and immune checkpoint inhibitors. Patients were categorized as eligible (n=81, 70.4%) or ineligible (n=34, 29.6%) based on EV-301 criteria. The primary endpoint was overall survival (OS) evaluated via RMST at multiple time points. Reconstructed individual patient data from EV-301 enabled comparative analysis, with Bayesian power prior methodology integrating evidence sources. Eligible patients exhibited significantly higher OS than ineligible ones (HR 2.19, 95% CI 1.24-3.89, P=.009). RMST analysis at 12months revealed OS of 9.65months (95% CI 8.67-10.63) and 7.11months (4.79-9.44) in eligible and ineligible patients, respectively. Significant RMST differences were observed between the eligible and ineligible groups at 6months (1.18months, P=.017) and 12months (2.54months, P=.049). Bayesian analysis with moderate borrowing (α=0.5) revealed posterior RMST of 9.40months (95% credible intervals 8.80-9.98) at 12months. Eligible patients showed comparable RMST outcomes to EV-301 trial participants, with no significant differences. EV exhibited real-world efficacy in Japanese mUC patients comparable to the eligible patients' outcomes in the EV-301 trial. Ineligible patients showed statistically inferior outcomes.

Cystoscopy remains the gold standard for diagnosing bladder lesions; however, its diagnostic accuracy is operator dependent and prone to missing subtle abnormalities such as carcinoma in situ or misinterpreting mimic lesions (tumor, inflammation, or normal variants). Artificial intelligence-based image-analysis systems are emerging, yet conventional models remain limited to single tasks and cannot produce explanatory reports or articulate diagnostic reasoning. Multimodal large language models (MM-LLMs) integrate visual recognition, contextual reasoning, and language generation, offering interpretive capabilities beyond conventional artificial intelligence. This study aims to rigorously evaluate state-of-the-art MM-LLMs for cystoscopic image interpretation and lesion classification using clinician-defined stress-test datasets enriched with rare, diverse, and challenging lesions, focusing on diagnostic accuracy, reasoning quality, and clinical relevance. Four MM-LLMs (OpenAI-o3 and ChatGPT-4o [OpenAI]; Gemini 2.5 Pro and MedGemma-27B [Google]) were evaluated under blinded, randomized procedures across two tasks: (1) free-text image interpretation for anatomic site, findings, lesion reasoning, and final diagnosis (n=401) and (2) seven-class tumor-like lesion classification (n=113) within a multiple-choice framework (cystitis, polyps, papilloma, papillary urothelial carcinoma, carcinoma in situ, non-urothelial carcinoma, and none of the above). Three raters independently scored outputs using a 5-point Likert scale, and classification metrics (accuracy, sensitivity, specificity, Youden J index (Youden J), and Matthews correlation coefficient [MCC]) were calculated for lesion detection, biopsy indication, and malignancy endpoints. For optimization, model performance was compared between zero-shot and text-based in-context learning prompts that were prefixed with brief descriptions of tumor features. The 401-image test set spanned 40 subcategories, with 322 (80.3%) containing abnormal findings in the image interpretation task. OpenAI-o3 demonstrated strong reasoning, with high satisfaction for anatomy (339/401, 84.5%) and findings (305/401, 76%), but lower satisfaction for lesion reasoning (211/401, 52.5%) and final diagnosis (193/401, 48.2%), indicating increasing difficulty with higher-order synthesis. Mean Likert score differences (OpenAI-o3 minus Gemini 2.5 Pro) were +0.27 for findings (adjusted P value: q=0.002), +0.24 for lesion reasoning (q=0.047), and +0.19 for final diagnosis. For clinically relevant endpoints in the full set, OpenAI-o3 achieved the most balanced performance, with lesion detection accuracy of 88.3%, sensitivity of 92%, specificity of 73.1%, Youden J of 0.650, and MCC of 0.635. In 7-class tumor-like lesion classification, OpenAI-o3 achieved accuracies of 73.5% for biopsy indication and 62.8% for malignancy, with a balanced sensitivity-specificity trade-off, outperforming other models. Notably, OpenAI-o3 performed best on prevalent malignant lesions. ChatGPT-4o and Gemini 2.5 Pro showed high sensitivity but low specificity, whereas MedGemma-27B underperformed. In-context learning improved OpenAI-o3 microaverage accuracy (40.7%→46.0%; MCC 0.311→0.370) but yielded only slight specificity gains and minimal accuracy change in other models, likely constrained by the absence of paired image-text context. MM-LLMs demonstrate meaningful assistive potential in generating interpretable cystoscopy free-text rationales and supporting biopsy triage and training. However, performance in difficult differential diagnoses remains modest and requires further optimization before safe clinical integration.

The association between the tumor immune microenvironment (TiME) in upper tract urothelial carcinoma (UTUC) and its prognosis remains unclear. We investigated the relationship between TiME and UTUC recurrence patterns. We evaluated 90 patients who underwent nephroureterectomy for UTUC and divided them into nonrecurrence, distant metastasis, and intravesical recurrence-only groups. We assessed the association of the TiME with clinicopathological factors using surgical tissues and the prognosis of the three groups via multiplex fluorescence immunohistochemistry. The median age was 71years (44-89), and 58 (64%) were male. Intratumoral CD4+ T cell density was significantly higher in the nonrecurrence group (p = 0.0004) than the other groups, whereas intra- and peritumoral regulatory T cell (Treg; CD3+CD4+FoxP3+cell) density was higher in the distant metastases group than the intravesical recurrence-only group (p = 0.0025). In the multivariate analysis, pathological T stage and CD4+ T cells, and pathological T stage and Treg were independent predictors of recurrence-free survival (p = 0.045, p = 0.017) and metastatic-free survival (p = 0.027, p = 0.011), respectively. Our study demonstrated that CD4+ T cells and Tregs in the TiME of patients with UTUC were independent predictors of high-risk recurrence together with high pathological stage. The analysis of TiME in surgical specimens may provide an objective indicator of the efficacy of adjuvant therapy in UTUC.

Localised upper tract urothelial carcinoma (UTUC) presents a diagnostic challenge due to its biological heterogeneity and anatomical complexity. Early detection and precise risk stratification are crucial for improved prognosis. The combination of histology, urine cytology, and biopsy plays a central role in preoperative diagnosis. Histopathological analysis allows for the determination of tumour grade, with the distinction between low-grade and high-grade tumours being particularly important. Urine cytology demonstrates high specificity for high-grade tumours, but limited sensitivity for low-grade lesions. Molecular markers such as FGFR3 and TP53 mutations, as well as microsatellite instability (MSI) in Lynch syndrome, can contribute to risk stratification and assessment of tumour behaviour. Endoscopic resection represents an effective organ-preserving therapy, particularly for non-invasive tumours. Despite higher recurrence rates compared with radical nephroureterectomy (RNU), it can be a valuable option for patients with chronic renal insufficiency given its organ-sparing approach. However, close follow-up is essential to detect recurrences early.