Zhiwen Chen

Muscle‐invasive bladder cancers (MIBC) are biologically heterogeneous and have widely variable conventional chemotherapy responses and clinical outcomes. This study demonstrates that XPC deficiency in bladder cancer cells can promote autophagy in response to the cisplatin‐mediated DNA damage response (DDR). This process is closely related to both the overexpression of KDM4A and the downregulation of PHRF1 induced by the overactivation of ATM phosphate. The overaccumulation of KDM4A can suppress PHRF1 expression and result in significant nuclear accumulation of the p53 protein. Notably, this study defines a new mechanism by which PHRF1 regulates p53 posttranslationally through the ubiquitin‐proteasome system. In XPC low expression cells, PHRF1 performs a more critical E3 ubiquitin ligase function than MDM2. Especially under conditions of cisplatin‐mediated DNA damage where MDM2 function is impaired, PHRF1 retains its functionality. In a mouse xenograft model, combining a KDM4 inhibitor with cisplatin results in superior antitumor effects compared with cisplatin alone. These findings provide new insights into the phenotypic plasticity of bladder cancer under drug resistance and highlight the potential of KDM4A inhibition and preservation of PHRF1 function in overcoming cisplatin resistance. Therefore, KDM4A or PHRF1 may be potential novel targets for the treatment of bladder cancer.

Over the past decade, there has been a significant increase in the use of robot-assisted radical cystectomy (RARC) with fully intracorporeal urinary diversion. Utilizing data from a single, high-volume institutional database, this study aimed to evaluate and compare perioperative outcomes and complications associated with intracorporeal urinary diversion (ICUD) versus extracorporeal urinary diversion (ECUD) following RARC. This study included 405 patients with bladder cancer who underwent RARC at our institution between July 2016 and April 2023. Data were retrospectively reviewed and compared between ICUD and ECUD groups. The 90-day major complications (MC90), 90-day overall complications (OC90), and perioperative and pathological outcomes were evaluated. Statistical analyses were performed using the Pearson chi-square test, Mann-Whitney U test, Kaplan-Meier tests, and multivariable regression analysis. Following RARC, 230 patients underwent ICUD and 175 underwent ECUD. No significant differences in demographics or oncological characteristics were observed between the two groups, except for a higher proportion of females in the ICUD group. Notably, ICUD was associated with significantly reduced median operative time (319 min vs. 370 min, p < 0.01) and lower median estimated blood loss (300 ml vs. 500 ml, p < 0.01). Postoperative recovery was faster in the ICUD group. However, the OC90, MC90, overall survival, and recurrence-free survival were comparable between the two groups. Compared with ECUD, ICUD significantly improved perioperative outcomes, including operative time, estimated blood loss, and postoperative recovery, without compromising long-term oncological survival or complication rates.

Purpose To compare the perioperative, functional, and oncological outcomes of the intracorporeal neobladder (ICNB) and extracorporeal neobladder (ECNB) technique following robot-assisted radical cystectomy (RARC). Methods We reviewed our single-institutional, prospectively collected database for consecutive patients who underwent RARC with an ileum neobladder from July 2016 to February 2023. Patients were divided into 2 groups according to the approach of reconstruction (ICNB or ECNB). The chi-squared test and Wilcoxon test were used to summarize categorical and continuous variables, respectively. survival and complication outcomes were analyzed using Kaplan-Meier curves, multivariate logistic regression and Cox hazards models. Result Among 304 patients, 190 ICNB patients and 114 ECNB patients were identified. A shorter median operative time (320 vs. 354 min; p = 0.001) and less median EBL (300 vs. 500 ml; p < 0.001) were recorded in the ICNB group. A significant difference in 90-d overall complications was detected between the 2 groups (49.5% vs. 61.4%; p = 0.043). Multivariate logistic regression analysis demonstrated that age, relapsed tumor and surgical approach (ECNB/ICNB) were individual predictive factors for 90-d overall complications. The functional outcomes and survival rates were comparable between the ICNB and ECNB groups. A Cox proportional hazards model indicated that higher pathological stage and pN status are predictors of both recurrence-free survival (RFS) and overall survival (OS). Conclusion Compared with ECNB, ICNB significantly improves perioperative outcomes without compromising functional or oncological outcomes.

Purpose: To construct a radiomics-clinical nomogram model for predicting the risk of local and metastatic recurrence within 3 years after radical cystectomy (RC) of bladder cancer (BCa) based on the radiomics features and important clinical risk factors for arterial computed tomography (CT) images and to evaluate its efficacy. Methods: Preoperative CT datasets of 134 BCa patients (24 recurrent) who underwent RC were collected and divided into training (n = 93) and validation sets (n = 41). Radiomics features were extracted from a 1.5 mm CT layer thickness image in the arterial phase. A radiomics score (Rad-Score) model was constructed using the feature dimension reduction method and a logistic regression model. Combined with important clinical factors, including gender, age, tumor size, tumor number and grade, pathologic T stage, lymph node stage and histology type of the archived lesion, and CT image signs, a radiomics-clinical nomogram was developed, and its performance was evaluated in the training and validation sets. Decision curve analyses (DCA) the potential clinical usefulness. Results: The radiomics model is finally linear combined by 8 features screened by LASSO regression, and after coefficient weighting, achieved good predictive results. The radiomics nomogram developed by combining two independent predictors, Rad-Score and pathologic T stage, was developed in the training set [AUC, 0.840; 95% confidence interval (CI) 0.743–0.937] and validation set (AUC, 0.883; 95% CI 0.777–0.989). The calibration curve showed good agreement between the predicted probability of the radiomics-clinical model and the actual recurrence rate within 3 years after RC for BCa. DCA show the clinical application value of the radiomics-clinical model. Conclusion: The radiomics-clinical nomogram model constructed based on the radiomics features of arterial CT images and important clinical risk factors is potentially feasible for predicting the risk of recurrence within 3 years after RC for BCa.

Purpose To construct a radiomics-clinical nomogram model for predicting the risk of local and metastatic recurrence within 3 years after radical cystectomy (RC) of bladder cancer (BCa) based on the radiomic features and important clinical risk factors for arterial computed tomography (CT) images and to evaluate its efficacy. Methods Preoperative CT datasets of 134 BCa patients (24 recurrent) who underwent RC were collected and divided into training (n = 93) and validation sets (n = 41). Radiomics features were extracted from a 1.5 mm CT layer thickness image in the arterial phase. A radiomics score (Rad-Score) model was constructed using the recursive feature elimination approach and a logistic regression model. Combined with important clinical factors, including gender, age, tumor size, tumor number and grade, pathologic T stage, lymph node stage and histology type of the archived lesion, and CT image signs, a radiomics-clinical nomogram was developed, and its performance was evaluated in the training and validation sets. Decision curve analyses (DCA) the potential clinical usefulness. Results The radiomics feature, consisting of five recurrence-related features, achieved good predictive results. The radiomics nomogram developed by combining two independent predictors, Rad-Score and pathologic T stage, was developed in the training set [AUC, 0.840; 95% confidence interval (CI), 0.743–0.937] and validation set (AUC, 0.883; 95% CI, 0.777–0.989). The calibration curve showed good agreement between the predicted probability of the radiomics-clinical model and the actual recurrence rate within 3 years after radical cystectomy for BCa. DCA show the clinical application value of the radiomics clinical model. Conclusion The radiomics clinical nomogram model constructed based on the radiomics features of arterial CT images and important clinical risk factors is potentially feasible for predicting the risk of recurrence within 3 years after RC for BCa.

Objectives: To compare the occurrence of emptying dysfunction between surgical techniques for orthotopic neobladder suspended with round ligament (rONB) and the standard procedure (sONB). Patients and Methods: A prospective randomised controlled trial was performed in a single centre of female patients undergoing creation of an ONB using rONB or sONB. Patients were followed for ≥24 months after ONB. The primary endpoints were significant post‐void residual urine volume (sPVR) and need for clean intermittent catheterisation (CIC) at 24 months postoperatively. The secondary endpoints included early and late complications, urodynamic profile, and ONB continence. Results: Between January 2011 and October 2017, the trial enrolled 85 patients, of whom 82 were randomised. A total of 41 patients had a rONB and 41 a sONB. At 24 months, 17 of the 37 patients with a sONB and nine of the 39 patients with a rONB had a sPVR. The cumulative risk of a sPVR was significantly lower in the rONB group (23.1%) vs the sONB group (45.9%) (hazard ratio [HR] 0.43, 95% confidence interval [CI], 0.19–0.96; P = 0.040). In all, 15 of the 37 patients with a sONB and four of the 39 patients with a rONB needed CIC. The cumulative risk of requiring CIC was significantly lower in the rONB group (10.3%) vs the sONB group (40.5%) (HR 0.22, 95% CI 0.07–0.67; P = 0.008) at 24 months. Multivariable Cox regression analysis also showed that the rONB type was an independently protective factor for sPVR and CIC. The rates of early (0–90 days) and late complication (>90 days) were 54.1% and 13.5% in the sONB group, and 64.1% and 10.3% in the rONB group, respectively. There were no significant differences in complications, urodynamic profile or ONB continence. A major limitation is the small sample size at a single centre. Conclusion: Posterior support with round ligament for an ONB significantly improved the emptying of the ONB and resulted in a reduced need for CIC. The surgical modification is a feasible and safe technique without additional complication‐related surgeries.

Background: A routine blood examination is one of the most rapid, convenient and inexpensive clinical examinations that can reflect a patient’s inflammatory status and other blood conditions, and the prognostic value of routine preoperative blood parameters in MIBC patients is still unclear, so we evaluated the prognostic value of routine preoperative blood parameters in muscle-invasive bladder cancer (MIBC) following radical cystectomy (RC). Methods: Data on 202 patients with MIBC who underwent RC at our institution were retrospectively collected between October 2007 and August 2018. The median preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and hemoglobin (HGB) values were used as cutoffs to form the low and high NLR, low and high PLR, and low and high HGB groups, respectively. The clinicopathologic characteristics of each group were compared by chi-square and t tests. Kaplan-Meier survival and multivariate Cox regression analyses were used to analyze prognosis. Results: The median NLR, PLR and HGB values were 2.42, 112 and 125 g/L, respectively. Kaplan-Meier results showed that the low HGB group had poor progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). A high NLR and high PLR groups correlated only with poor OS. Multivariate Cox analyses showed that pathological T3/4 stage, positive lymph node status and low HGB were independent risk factors for PFS, CSS and OS, and age was the only independent risk factor for OS. Conclusion: Preoperative peripheral blood HGB is an independent risk factor for the prognosis of MIBC patients. These data suggest that HGB may be a useful prognostic marker for MIBC patients undergoing RC.

Background A routine blood examination is one of the most rapid, convenient and inexpensive clinical examinations that can reflect a patient’s inflammatory status and other blood conditions, and the prognostic value of routine preoperative blood parameters in MIBC patients is still unclear, so we evaluated the prognostic value of routine preoperative blood parameters in muscle-invasive bladder cancer (MIBC) following radical cystectomy (RC). Methods Data on 202 patients with MIBC who underwent RC at our institution were retrospectively collected between October 2007 and August 2018. The median preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and hemoglobin (HGB) values were used as cutoffs to form the low and high NLR, low and high PLR, and low and high HGB groups, respectively. The clinicopathologic characteristics of each group were compared by chi-square and t tests. Kaplan-Meier survival and multivariate Cox regression analyses were used to analyze prognosis. Results The median NLR, PLR and HGB values were 2.42, 112 and 125g/L, respectively. Kaplan-Meier results showed that the low HGB group had poor progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). A high NLR and high PLR groups correlated only with poor OS. Multivariate Cox analyses showed that pathological T3/4 stage, positive lymph node status and low HGB were independent risk factors for PFS, CSS and OS, and age was the only independent risk factor for OS. Conclusion Preoperative peripheral blood HGB is an independent risk factor for the prognosis of MIBC patients. These data suggest that HGB may be a useful prognostic marker for MIBC patients undergoing RC.