BACKGROUND:Early detection of urothelial carcinoma (UCa) remains challenging because of the limitations of current diagnostic methods. The objective of this study was to evaluate a novel, urine-based H4C6/TWIST1 methylation assay for its diagnostic accuracy in UCa. METHODS:In a prospective, multicenter study, 743 urine samples (387 patients with UCa and 356 controls) from four hospitals were analyzed. DNA was extracted from 3.5 mL of morning urine, and H4C6/TWIST1 methylation status was assessed by using quantitative polymerase chain reaction analysis. Histopathology served as the reference standard. RESULTS:The assay demonstrated high diagnostic accuracy, with 93.02% sensitivity (95% confidence interval, 90.01%-95.35%) and 92.13% specificity (95% confidence interval, 88.83%-94.71%). The positive and negative predictive values were 92.78% and 92.39%, respectively. Performance was particularly strong for high-grade tumors (97.64%) and muscle-invasive tumors (97.50%). Diagnostic efficacy was consistent across age, sex, and tumor location, covering both lower and upper urinary tract carcinomas. CONCLUSIONS:H4C6/TWIST1 methylation detection is a noninvasive, highly accurate, and consistent tool with significant clinical potential for the initial diagnosis and monitoring of UCa across all grades and stages.

To evaluate the effect of intraoperative administration of 1 g of tranexamic acid (TXA) on perioperative and postoperative outcomes in patients receiving antithrombotic therapy undergoing endoscopic enucleation of the prostate (EEP). This multicenter, prospective, observational study included 932 patients across 30 centers (December 2024–June 2025). Patients were divided into four groups based on TXA use and continuation or discontinuation of blood thinners during EEP. The primary endpoint was bleeding complications within 30 days, defined as a composite of transfusion, clot retention, bleeding requiring restart of continuous bladder washout (CBWO), or surgical reintervention to control hemostasis. Multivariable Logistic regression analysis identified independent predictors of bleeding complications. There were 534 patients in Group 1 (stopped blood thinners, no TXA given), 316 in Group 2 (on blood thinners, no TXA given), 69 in Group 3 (stopped blood thinners, TXA given), and 13 in Group 4 (on blood thinners, TXA given). Median total operative time was longest in Group 2 (88 min [IQR 70–127]) and shortest in Group 3 (55 min [IQR 39–69]). Hemostasis time was shortest in TXA groups (p < 0.001). Transfusions occurred in 0.6–7.7

Robotic surgical systems have revolutionized minimally invasive procedures, offering enhanced three-dimensional visualization, high precision, and stable operation, particularly beneficial for radical prostatectomy. However, high costs have hindered the adoption of robot-assisted radical prostatectomy (RARP) in grassroots hospitals in China. This retrospective study aimed to evaluate the efficacy and safety of the EDGE Surgical Robotic System in performing RARP. A total of 129 patients who underwent RARP at our center between November 2023 and March 2025 were analyzed, with outcomes assessed including port placement to docking time, operative time, estimated blood loss, complications, pathological results, safety indicators, length of hospital stay, catheterization duration, postoperative PSA level, and early urinary continence recovery rate. All surgeries were completed successfully without conversion to laparoscopic or open procedures, with a mean setup time of 36.9 min, operative time of 176.3 min, and estimated blood loss of 128.1 mL. The positive surgical margin (PSM) rate was documented at 31.0

The tumor downstaging and pathological complete response of bladder cancer were found to be improved with the application of neoadjuvant chemotherapy combined with immunotherapy. However, about 34.2

[This corrects the article on p. 1624 in vol. 8, PMID: 30210930.].

Purpose To evaluate the safety of endoscopic enucleation of the prostate (EEP) in benign prostatic hyperplasia (BPH) patients maintained on blood thinners compared to those who discontinued therapy, and to identify independent predictors of postoperative bleeding complications. Methods BPH patients on blood thinners planned for EEP were prospectively enrolled from 30 centers (December 2024-June 2025). Patients were divided into Group 1 (continued blood thinners, n = 329) and Group 2 (discontinued blood thinners, n = 603). Outcomes included bleeding complications, hospital stay, and functional results. Multivariable logistic regression identified predictors of postoperative bleeding (blood transfusion, need for restarting of continuous bladder washout, clot retention, surgical control of post-operative bleeding). Results The overall population had a median age of 70.0 years and prostate volume of 81.0 ml. Group 1 patients had higher comorbidity rates. Group 1 demonstrated significantly longer median operative times (87.0 vs. 70.0 min, p < 0.001) and increased bleeding-related complications, including continuous bladder washout restart (14.3% vs. 2.5%, p < 0.001), blood transfusion requirements (1.5% vs. 0.5%, p < 0.001), and hospital readmissions (10.0% vs. 4.1%, p < 0.001). Rates of surgical hemostasis intervention were similar (1.8% in Group 1 vs. 2.0% in Group 2, p = 0.92). No major thrombotic events occurred. Independent predictors of bleeding included longer operative time (OR 1.01, p < 0.001) and combination antiplatelet/anticoagulant therapy (OR 2.47, p = 0.04), while tranexamic acid was associated with lower odds (OR 0.18, p < 0.001). Conclusion EEP can be safely performed in patients on blood thinners with acceptable morbidity, though bleeding complications are higher. Combination therapy carries the highest risk, while tranexamic acid reduces bleeding complications.

Background:Accurate prediction of early recurrence is essential for disease management of patients with non-muscle-invasive bladder cancer (NMIBC). We aimed to develop and validate a deep learning-based early recurrence predictive model (ERPM) and a treatment response predictive model (TRPM) on whole slide images to assist clinical decision making. Methods:In this retrospective, multicentre study, we included consecutive patients with pathology-confirmed NMIBC who underwent transurethral resection of bladder tumour from five centres. Patients from one hospital (Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China) were assigned to training and internal validation cohorts, and patients from four other hospitals (the Third Affiliated Hospital of Sun Yat-sen University, and Zhujiang Hospital of Southern Medical University, Guangzhou, China; the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China; Shenshan Medical Centre, Shanwei, China) were assigned to four independent external validation cohorts. Based on multi-instance and ensemble learning, the ERPM was developed to make predictions on haematoxylin and eosin (H&E) staining and immunohistochemistry staining slides. Sharing the same architecture of the ERPM, the TRPM was trained and evaluated by cross validation on patients who received Bacillus Calmette-Guérin (BCG). The performance of the ERPM was mainly evaluated and compared with the clinical model, H&E-based model, and integrated model through the area under the curve. Survival analysis was performed to assess the prognostic capability of the ERPM. Findings:Between January 1, 2017, and September 30, 2023, 4395 whole slide images of 1275 patients were included to train and validate the models. The ERPM was superior to the clinical and H&E-based model in predicting early recurrence in both internal validation cohort (area under the curve: 0.837 vs 0.645 vs 0.737) and external validation cohorts (area under the curve: 0.761-0.802 vs 0.626-0.682 vs 0.694-0.723) and was on par with the integrated model. It also stratified recurrence-free survival significantly (p < 0.0001) with a hazard ratio of 4.50 (95% CI 3.10-6.53). The TRPM performed well in predicting BCG-unresponsive NMIBC (accuracy 84.1%). Interpretation:The ERPM showed promising performance in predicting early recurrence and recurrence-free survival of patients with NMIBC after surgery and with further validation and in combination with TRPM could be used to guide the management of NMIBC. Funding:National Natural Science Foundation of China, the Science and Technology Planning Project of Guangdong Province, the National Key Research and Development Programme of China, the Guangdong Provincial Clinical Research Centre for Urological Diseases, and the Science and Technology Projects in Guangzhou.

Background:Phosphorus metabolism might be associated with tumor initiation and progression. We aimed to screen out the phosphorus metabolism genes related to bladder cancer and construct a clinical prognosis model. Methods:The dataset used for the analysis was obtained from TCGA database. GO and KEGG enrichment analyses were subsequently applied to differentially expressed genes. Consensus clustering was utilized, and different clusters of the tumor immune microenvironment and other features were compared. The phosphorus metabolism-related genes involved in prognosis were screened out by univariate Cox regression, LASSO regression and multivariate Cox regression analysis, and a nomogram was constructed. The performance of the nomogram was validated using TCGA dataset and the GEO dataset, respectively. Results:Overall, 405 phosphorus metabolism-related differentially expressed genes from TCGA database were identified, which were associated with phosphorylation, cell proliferation, leukocyte activation, and signaling pathways. Two clusters were obtained by consistent clustering. After tumor immune microenvironment analysis, significant differences in immune cell infiltration between cluster 1 and cluster 2 were found. Four phosphorus metabolism-related genes (LIME1, LRP8, SPDYA, and MST1R) were associated with the prognosis of bladder cancer (BLCA) patients. We built a prognostic model and visualized the model as a nomogram. Calibration curves demonstrated the performance of this nomogram, in agreement with that shown by the ROC curves. Conclusion:We successfully identified four phosphorus metabolism-related genes associated with prognosis, providing potential targets for biomarkers and therapeutics. A nomogram based on these genes was developed. Nevertheless, this study is based on bioinformatics, and experimental validation remains essential.

The importance of CD4 + T cells in cancer immunotherapy has gained increasing recognition. Particularly, a specific subset of CD4 + T cells coexpressing the T helper type 1 (Th1) and Th17 markers has demonstrated remarkable antitumor potential. However, the underlying mechanisms governing the differentiation of these cells and their subsequent antitumor responses remain incompletely understood. Single-cell RNA sequencing (scRNA-seq) data reanalysis demonstrated the presence of Th 17 1 cells within tumors. Subsequent trajectory analysis found that these Th 17 1 cells are initially primed under Th17 conditions and then converted into IFN-γ-producing cells. Following the in vivo differentiation trajectory of Th 17 1 cells, we successfully established in vitro Th 17 1 cell culture. Transcriptomic profiling has unveiled a substantial resemblance between in vitro-generated Th 17 1 cells and their tumor-infiltrating counterparts. Th 17 1 cells exhibit more potent antitumor responses than Th1 or Th17 cells. Additionally, Th 17 1chimeric antigen receptor T (CAR-T) cells eradicate solid tumors more efficiently. Importantly, Th 17 1 cells display an early exhaustion phenotype while retaining stemness. Mechanistically, Th 17 1 cells migrate faster and accumulate more in tumors in an extracellular matrix protein 1 (ECM1)-dependent manner. Furthermore, we show that IFN-γ up-regulated IRF7 to promote the type I interferon response network and ECM1 expression but decreased the exhaustion status in Th 17 1 cells. Taken together, our findings position Th 17 1 cells as a great candidate for improving targeted immunotherapies in solid malignancies.

Purpose To retrospectively evaluate the tislelizumab-based chemoimmunotherapy combined with gemcitabine/cisplatin for bladder-sparing in patients with muscle-invasive bladder cancer (MIBC). Methods Forty-five patients who received bladder-sparing treatment or radical cystectomy (RC) for MIBC (cT2-T4a, NxM0) were retrospectively enrolled. All patients received maximal transurethral resection of bladder tumor (mTURBT), followed by four cycles of chemo-immunotherapy with tislelizumab (PD-L1 inhibitor), gemcitabine, and cisplatin. Clinical efficacy was evaluated to compare the benefit of bladder-sparing treatment on clinical CR (cCR) and RC for non-cCR patients. The primary outcomes were bladder intact disease-free survival (BIDFS) and overall survival (OS), and the secondary outcomes were adverse effects. The PD-L1 status and molecular subtypes of tumors were analyzed. Results The overall survival rate was 88.8% (95%CI: 79.6%, 98.0%) at 12 months, 85.7% (95%CI: 74.9%, 96.5%) at 18 months, and 66.6% (95%CI: 45.2%, 88.0%) at 24 months. Twenty-nine patients (64.4%) achieved cCR and their OS rate was 96.6% (95%CI: 89.9%, 100%). Sixteen patients were in the non-cCR group, and their OS rate was 75.0% (95%CI: 53.8%, 96.2%) at 12 months, 65.6% (95%CI: 40.3%, 90.9%) at 18 months, and 52.5% (95%CI: 21.9%, 83.1%) at 24 months. The BIDFS rate for patients who received bladder-sparing treatment was 96.0% (95%CI: 88.4%, 100%) from 12 to 24 months. Four patients (8.8%) were PD-L1 positive and 41 patients (91.2%) were PD-L1 negative. Conclusions Our retrospective study of patients with MIBC suggests that tislelizumab-based neoadjuvant therapy was a safe and effective bladder-sparing treatment.

Boron neutron capture therapy (BNCT) is a treatment method that focuses on improving the cure rate of patients with cancer who are difficult to treat using traditional clinical methods. By utilizing the high neutron absorption cross-section of boron, material rich in boron inside tumor cells can absorb neutrons and release high-energy ions, thereby destroying tumor cells. Owing to the short range of alpha particles, this method can precisely target tumor cells while minimizing the inflicted damage to the surrounding normal tissues, making it a potentially advantageous method for treating tumors. Globally, institutions have progressed in registered clinical trials of BNCT for multiple body parts. This review summarized the current achievements in registered clinical trials, Investigator-initiated clinical trials, aimed to integrate the latest clinical research literature on BNCT and to shed light on future study directions.

In recent years, a surge in studies investigating N6-methyladenosine (m6A) modification in human diseases has occurred. However, the specific roles and mechanisms of m6A in kidney disease remain incompletely understood. This study revealed that m6A plays a positive role in regulating renal fibrosis (RF) by inducing epithelial-to-mesenchymal phenotypic transition (EMT) in renal tubular cells. Through comprehensive analyses, including m6A sequencing, RNA-seq, and functional studies, we confirmed the pivotal involvement of zinc finger E-box binding homeobox 2 (ZEB2) in m6A-mediated RF and EMT. Notably, the m6A-modified coding sequence of ZEB2 mRNA significantly enhances its translational elongation and mRNA stability by interacting with the YTHDF1/eEF-2 complex and IGF2BP3, respectively. Moreover, targeted demethylation of ZEB2 mRNA using the dm6ACRISPR system substantially decreases ZEB2 expression and disrupts the EMT process in renal tubular epithelial cells. In vivo and clinical data further support the positive influence of m6A/ZEB2 on RF progression. Our findings highlight the m6A-mediated regulation of RF through ZEB2, revealing a novel therapeutic target for RF treatment and enhancing our understanding of the impact of mRNA methylation on kidney disease.

Background The pathological examination of lymph node metastasis (LNM) is crucial for treating prostate cancer (PCa). However, the limitations with naked -eye detection and pathologist workload contribute to a high misseddiagnosis rate for nodal micrometastasis. We aimed to develop an arti fi cial intelligence (AI) -based, time -eff i cient, and high -precision PCa LNM detector (ProCaLNMD) and evaluate its clinical application value. Methods In this multicentre, retrospective, diagnostic study, consecutive patients with PCa who underwent radical prostatectomy and pelvic lymph node dissection at fi ve centres between Sep 2, 2013 and Apr 28, 2023 were included, and histopathological slides of resected lymph nodes were collected and digitised as whole -slide images for model development and validation. ProCaLNMD was trained at a dataset from a single centre (the Sun Yat-sen Memorial Hospital of Sun Yat-sen University [SYSMH]), and externally validated in the other four centres. A bladder cancer dataset from SYSMH was used to further validate ProCaLNMD, and an additional validation (human -AI comparison and collaboration study) containing consecutive patients with PCa from SYSMH was implemented to evaluate the application value of integrating ProCaLNMD into the clinical work fl ow. The primary endpoint was the area under the receiver operating characteristic curve (AUROC) of ProCaLNMD. In addition, the performance measures for pathologists with ProCaLNMD assistance was also assessed. Findings In total, 8225 slides from 1297 patients with PCa were collected and digitised. Overall, 8158 slides (18,761 lymph nodes) from 1297 patients with PCa (median age 68 years [interquartile range 64 - 73]; 331 [26%] with LNM) were used to train and validate ProCaLNMD. The AUROC of ProCaLNMD ranged from 0.975 (95% con fi dence interval 0.953 - 0.998) to 0.992 (0.982 - 1.000) in the training and validation datasets, with sensitivities > 0.955 and speci fi cities > 0.921. ProCaLNMD also demonstrated an AUROC of 0.979 in the cross -cancer dataset. ProCaLNMD use triggered true reclassi fi cation in 43 (4.3%) slides in which micrometastatic tumour regions were initially missed by pathologists, thereby correcting 28 (8.5%) missed -diagnosed cases of previous routine pathological reports. In the human -AI comparison and collaboration study, the sensitivity of ProCaLNMD (0.983 [0.908 - 1.000]) surpassed that of two junior pathologists (0.862 [0.746 - 0.939], P = 0.023; 0.879 [0.767 - 0.950], P = 0.041) by 10 - 12% and showed no difference to that of two senior pathologists (both 0.983 [0.908 - 1.000], both P > 0.99). Furthermore, ProCaLNMD signi fi cantly boosted the diagnostic sensitivity of two junior pathologists (both P = 0.041) to the level of senior pathologists (both P > 0.99), and substantially reduced the four pathologists ' slide reviewing time ( - 31%, P < 0.0001; - 34%, P < 0.0001; - 29%, P < 0.0001; and - 27%, P = 0.00031). Interpretation ProCaLNMD demonstrated high diagnostic capabilities for identifying LNM in prostate cancer, reducing the likelihood of missed diagnoses by pathologists and decreasing the slide reviewing time, highlighting its potential for clinical application.

Background: Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma. Approximately 15-20% of RMS cases arise from the bladder and prostate (B/P). The optimal treatment strategy for B/P RMS remains unclear. Objective: To retrospectively evaluate the applicability of our procedure performed to treat paediatric patients with B/P RMS. Design, setting, and participants: This is a retrospective analysis from a single tertiary referral hospital. From August 2003 to March 2021, 62 children pathologically diagnosed with B/P RMS underwent radical cystectomy and orthotopic detaenial sigmoid neobladder reconstruction in our centre. Surgical procedure: Surgical procedures included laparoscopic radical cystectomy and detaenial sigmoid neobladder reconstruction, which is demonstrated in the accompanying video. Measurements: Demographic, clinical, and follow-up data were collected. Perioperative and long-term oncological and functional outcomes were reported. A logistic regression analysis was also performed. Results and limitations: All surgeries, including three intracorporeal laparoscopic surgeries, were completed successfully. Of the 62 patients, 54 were alive without evidence of disease recurrence or metastasis at the last follow-up. Five of the 14 >12-yr-old boys reported that they experienced erections. Two female patients >12 yr old reported that they menstruated. However, this was a retrospective study conducted at a single centre with limited surgeon experience. Conclusions: Our results confirmed the safety and feasibility of primary orthotopic sigmoid neobladder reconstruction after radical cystectomy for paediatric patients with B/P RMS. Good outcomes in terms of oncological control and functional recovery were achieved. The high histocompatibility and tissue adaptability of children are inspiring. Patient summary: We describe our stepwise technique of radical cystectomy and detaenial sigmoid neobladder reconstruction for paediatric patients with bladder and prostate rhabdomyosarcoma. With this technique, we were able to achieve good functional recovery without compromising cancer control and significantly increasing complications.

OBJECTIVE:To explore the application prospect and clinical efficacy of transurethral plasmakinetic enucleation of the Giant prostatic hyperplasia.METHODS:The clinical data of 5 patients with Giant prostatic hyperplasia treated by transurethral plasmakinetic enucleation in our department from december 2021 to january 2023 were retrospectively analyzed.RESULTS:All 5 patients successfully completed the operation, aged 69－80 years (73.2±4.32),PSA level was 8.07～42.90ng/ml (22.81±13.97), prostate volume was 321.05－534.26g (388.34±84.26), enucleation time was 120－240 min (174±61.48), Gland processing time 40－120 min（63±32.71). There were 1 case of perforation of prostate capsule and severe hematuria，3 cases of blood transfusion. 2 cases of transient urinary incontinence were improved after 2 weeks and 4 months postoperative respectively. International Prostate Symptom Score (IPSS),and quality of life score (QoL) and Maximum urine flow rate(Qmax) were significantly improved compared with preoperative parameters.CONCLUSION:It is safe and effective to treat GPH with plasma enucleation through urethra with skilled plasma enucleation technique.

OBJECTIVES:To investigate the effect of progressive pre-disconnection of urethral mucosal flap during transurethral plasmakinetic enucleation of prostate (TUPEP) on early recovery of urinary continence.METHODS:Clinical data of patients with benign prostatic hyperplasia (BPH) admitted in Zhujiang Hospital of Southern Medical University during February and May 2022 were collected. All the patients underwent TUPEP, and the progressive pre-disconnection of urethral mucosal flap was performed in the procedure. The total operation time, enucleation time, postoperative bladder irrigation time and catheter indwelling time were recorded. Urinary continence was evaluated 24 h, 1 week, and 1, 3, 6 months after the removal of urinary catheter.RESULTS:All surgeries were successfully completed at one time with less intraoperative bleeding, and there were no complications such as rectal injury, bladder injury or perforation of prostate capsule. The total operation time was (62.2±6.5) min, the enucleation time was (42.8±5.2) min, the postoperative hemoglobin decrease by (9.5±4.5) g/L, the postoperative bladder irrigation time was (7.9±1.4) h, and the postoperative catheter indwelling time was 10.0 (9.2, 11.4) h. Only 2 patients (3.6%) had transient urinary incontinence within 24 h after catheter removal. No urinary incontinence occurred at 1 week, and 1, 3, 6 months after operation, and no safety pad was needed. The Qmax at 1 month after operation was 22.3 (20.6, 24.4) mL/s, international prostate symptom scores were 8.0 (7.0, 9.0), 5.0 (4.0, 6.0) and 4.0 (3.0, 4.0) at 1, 3 and 6 months after surgery, and quality of life scores at 1, 3 and 6 months after surgery were 3.0 (2.0, 3.0), 2.0 (1.0, 2.0) and 1.0 (1.0, 2.0), all of these indicators were better than those before surgery (all P<0.01).CONCLUSIONS:In the treatment of BPH, the application of progressive pre-disconnection of urethral mucosal flap in TUPEP can completely remove the hyperplastic glands and promote early recovery of postoperative urinary continence with less perioperative bleeding and decreased surgical complications.