A novel model of urosepsis in mice developed by ureteral ligation and injection of Escherichia coli into the renal pelvis.

Despite extensive investigations, urosepsis remains a life-threatening and high-mortality illness. The absence of widely acknowledged animal models for urosepsis prompted this investigation with the objective of formulating a replicable murine model. Eighty-four adult male C57BL/6J mice were arbitrarily distributed into three cohorts based on the concentration of the Escherichia coli (E. coli) solution administered into the renal pelvis: Sham, Low-grade sepsis (1.0 × 108 cfu/mL), and High-grade sepsis (1.0 × 109 cfu/mL). By fabricating a glass needle with a 100 µm outer diameter, bacterial leakage during renal pelvic injection was minimized. After the ureteral ligation, the mice were injected with this needle into the right renal pelvis (normal saline or E. coli solution, 1 ml/kg). Ten days post after E. coli injection, the mortality rates for the Low-grade sepsis and High-grade sepsis groups stood at 30 % and 100 %, respectively. Post-successful modeling, mice in the urosepsis cohort exhibited a noteworthy reduction in activity, body temperature, and white blood cell count within a 2-h timeframe. At the 24-h mark post-modeling, mice afflicted with urosepsis displayed compromised coagulation functionality. Concurrently, multiple organ dysfunction was confirmed as evidenced by markedly elevated levels of inflammatory factors (IL-6 and TNF-α) in four distinct organs (heart, lung, liver, and kidney). This study confirmed the feasibility of establishing a standardized mouse model of urosepsis by ureteral ligation and E. coli injection into the renal pelvis. A primary drawback of this model resides in the mice's diminished blood volume, rendering continuous blood extraction at multiple intervals challenging.

Prognostic variations between 'primary' and 'progressive' muscle-invasive bladder cancer following radical cystectomy: a novel propensity score-based multicenter cohort study.

OBJECTIVE: To assess prognostic differences between primary and progressive muscle-invasive bladder cancer (MIBC) following radical cystectomy. MATERIAL AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to abstract MIBC data following radical cystectomy from 2000 to 2019. Patients were classified as either 'Primary' MIBC (defined as the presentation of muscle-invasive disease at initial diagnosis) or 'Progressive' MIBC (defined as a non-muscle invasive disease that later progressed to MIBC). Baseline characteristics for the two groups were balanced using a propensity score overlap weight (PSOW) technique. Survival differences between the two groups were analyzed using Kaplan-Meier's plots and log-rank tests. Cox's proportional hazard regression was used to assess risk factors associated with overall survival (OS) and cancer-specific survival (CSS). RESULTS: Six thousand six hundred thirty-two MIBC patients were identified in the SEER database. Among them, 83.3% ( n =5658) were considered primary MIBC patients, and 16.7% ( n =974) were categorized as progressive MIBC patients. Distribution of baseline covariates, including age, sex, race, T stage, N stage, tumour grade, marital status, and chemotherapy, were well-balanced after PSOWs were applied. After stable PSOW adjustments, Kaplan-Meier survival analysis showed that the CSS for progressive MIBC [hazard ratio (HR)=1.25, 95% confidence interval (CI): 1.12-1.38, P <0.001) was poorer than the primary MIBC group. However, the difference in OS (HR=1.08, 95% CI: 0.99-1.18) was not significant ( P =0.073). Multivariate analysis also suggested that patients with progressive MIBC have significantly poorer CSS (HR=1.24, 95% CI: 1.19-1.38, P <0.001) but not OS (HR=1.08, 95% CI: 0.99-1.18, P =0.089). CONCLUSION: CSS for progressive MIBC patients appears worse than for those with primary MIBC. This highlights the need to direct more resources for this patient population and particularly for high-risk cases of non-MIBC, where timely radical surgery will improve patients prognoses.

Effect of subsequent bladder cancer on survival in upper tract urothelial carcinoma patients post-radical nephroureterectomy: a systematic review and meta-analysis.

BACKGROUND: Radical nephroureterectomy (RNU) is the primary treatment strategy for upper tract urothelial carcinoma (UTUC). However, the intravesical recurrence occurs in 20-50% of all patients. The specific effect of subsequent bladder cancer (SBCa) on survival remains unclear. Therefore, we investigated the effect of SBCa following RNU in patients with UTUC. METHODS: PubMed, EMBASE, and Cochrane Library were exhaustively searched for studies comparing oncological outcomes between SBCa and without SBCa. Standard cumulative analyses using hazard ratios (HR) with 95% confidence intervals (CI) were performed using Review Manager (version 5.3). RESULTS: Five studies involving 2057 patients were selected according to the predefined eligibility criteria. Meta-analysis of cancer-specific survival (CSS) and overall survival (OS) revealed no significant differences between the SBCa and non-SBCa groups. However, subgroup analysis of pT0-3N0M0 patients suggested that people with SBCa had worse CSS (HR = 5.13, 95%CI 2.39-10.98, p < 0.0001) and OS (HR = 4.00, 95%CI 2.19-7.31, p < 0.00001). CONCLUSIONS: SBCa appears to be associated with worse OS in patients with early stage UTUC. However, caution must be taken before recommendations are made because this interpretation is based on very few clinical studies and a small sample size. Research sharing more detailed surgical site descriptions, as well as enhanced outcome data collection and improved reporting, is required to further investigate these nuances.

Development and validation of a nomogram based on geriatric nutritional risk index for predicting prognosis and postoperative complications in surgical patients with upper urinary tract urothelial carcinoma.

BACKGROUND: This study aimed to evaluate the potential role of the Geriatric Nutritional Risk Index (GNRI) in predicting oncological outcomes and postoperative complications in UTUC patients undergoing radical nephroureterectomy (RNU) and to develop a nomogram incorporating GNRI to predict outcomes. METHODS: A retrospective analysis was performed on 458 consecutive patients who underwent RNU in our center. According to nutritional scores, patients were divided into the following groups: low GNRI (GNRI ≤ 98) and high GNRI (GNRI > 98). Univariable and multivariable logistic regression were performed to investigate the role of GNRI in predicting the perioperative complications. The survival was compared with Kaplan - Meier curve, and test by log-rank tests. Risk factors associated with cancer-specific survival (CSS) and overall survival (OS) were evaluated using Cox proportional hazards regression model and were integrated into a nomogram for individualized risk prediction. The calibration and discrimination ability of the model were evaluated by concordance index (C-index) and risk group stratification. RESULTS: When compared with high GNRI, low GNRI had significantly lower survival (CSS, p < 0.001; OS, p < 0.001). Across all patients, multivariable analyses revealed that low GNRI was an independent prognostic factor (CSS, p = 0.007; OS, p = 0.005). Nomograms for 1-, 3-, and 5 years of CSS and OS had good performance. Patients can be stratified into different groups based on the nomogram, with significant differences in OS and CSS. Further, GNRI was also found to be an independent risk factor for postoperative complications. The complication - prediction nomogram based on GNRI was also internally validated and showed good performance. CONCLUSIONS: The GNRI score is an independent predictor for the prognosis and postoperative complications of UTUC following RNU. This study presented a nomogram incorporating preoperative GNRI that might be used as a convenient tool to facilitate the preoperative individualized prediction of short- and long-term outcomes for patients with UTUC.

Systematic oxidative stress indices predicts prognosis in patients with urothelial carcinoma of the upper urinary tract after radical nephroureterectomy.

BACKGROUND: Oxidative stress plays an important role in the occurrence and development of malignancy. However, the relationship between oxidative stress and upper urinary tract urothelial carcinoma (UTUC) prognosis remains elusive. This study aimed to evaluate the prognostic value of systematic oxidative stress indices as a predictor of patient outcomes in UTUC after radical nephroureterectomy. METHODS: Clinical data for 483 patients with UTUC who underwent radical nephroureterectomy were analyzed. Patients were categorized according to an optimal value of systematic oxidative stress indices (SOSIs), including fibrinogen (Fib), gamma-glutamyl transpeptidase (γ-GGT), creatinine (CRE), lactate dehydrogenase (LDH) and albumin (ALB). Kaplan-Meier analyses were used to investigate associations of SOSIs with overall survival (OS) and progression-free survival (PFS). Moreover, associations between SOSIs and OS and PFS were assessed with univariate and multivariate analyses. RESULTS: High values of Fib, γ-GGT, CRE, and LDH, and low values of ALB were associated with reduced OS. SOSIs status correlated with age, tumor site, surgical approach, hydronephrosis, tumor size, T stage, and lymph node status. The Kaplan-Meier survival analysis showed a significant discriminatory ability for death and progression risks in the two groups based on SOSIs. Multivariate Cox proportional hazards models showed that SOSIs were an independent prognostic indicator for OS (p = 0.007) and PFS (p = 0.021). SOSIs and clinical variables were selected to establish a nomogram for OS. The 1-, 3-, and 5-year AUC values were 0.77, 0.78, and 0.81, respectively. Calibration curves of the nomogram showed high consistencies between the predicted and observed survival probability. Decision curve analysis curves showed that the nomogram could well predict the 1-year, 3-year, and 5-year OS. CONCLUSIONS: SOSIs are an independent unfavorable predictor of OS and PFS in patients diagnosed with UTUC undergoing RNU. Therefore, incorporating SOSIs into currently available clinical parameters may improve clinical decision-making.

Identifying possible hub genes and biological mechanisms shared between bladder cancer and inflammatory bowel disease using machine learning and integrated bioinformatics.

BACKGROUND: Recent studies have shown that inflammatory bowel disease (IBD) is associated with bladder cancer (BC) incidence. But there is still a lack of understanding regarding its pathogenesis. Thus, this study aimed to identify potential hub genes and their important pathways and pathological mechanisms of interactions between IBD and BC using bioinformatics methods. METHODS: The data from Gene Expression Omnibus (GEO) and the cancer genome atlas (TCGA) were analyzed to screen common differentially expressed genes (DEGs) between IBD and BC. The "clusterProfiler" package was used to analyze GO term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment in DEGs. After that, we conducted a weighted gene co-expression network analysis (WGCNA) on these DEGs to determine the vital modules and genes significantly related to BC. Protein-protein interaction (PPI) networks was used to identify hub genes. Further, the hub genes were used to develop a prognostic signature by Cox analysis. The validity of the ten hub DEGs was tested using three classification algorithms. Finally, we analyzed the microRNAs (miRNA)-mRNA, transcription factors (TFs)-mRNA regulatory network. RESULTS: Positive regulation of organelle fission, chromosomal region, tubulin binding, and cell cycle signaling pathway were the major enriched pathways for the common DEGs. PPI networks identified three hub proteins (AURKB, CDK1, and CCNA2) with high connectivity. Three machine-learning classification algorithms based on ten hub genes performed well for IBD and BC (accuracy > 0.80). The robust predictive model based on the ten hub genes could accurately classify BC cases with various clinical outcomes. Based on the gene-TFs and gene-miRNAs network construction, 9 TFs and 6 miRNAs were identified as potential critical TFs and miRNAs. There are 13 drugs that interact with the hub gene based on gene-drug interaction analysis. CONCLUSIONS: This study explored common gene signatures and the potential pathogenesis of IBD and BC. We revealed that an unbalanced immune response, cell cycle pathway, and neutrophil infiltration might be the common pathogenesis of IBD and BC. Molecular mechanisms for the treatment of IBD and CC still require further investigation.

Impact of a novel immune and nutritional score on prognosis in patients with upper urinary tract urothelial carcinoma following radical nephroureterectomy.

BACKGROUND: This study aimed to evaluate the clinical significance of a novel immune and nutritional score combining prognostic values of the controlling nutritional status (CONUT) score and prognostic immune and nutritional index (PINI) on long-term outcomes in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). METHODS: This study analyzed 437 consecutive patients with UTUC treated by RNU. Restricted cubic splines were used to visualize the relation of PINI with Survival in patients with UTUC. The PINI was stratified into low- (1) and high-PINI (0) categories. The CONUT score was divided into three groups: Normal (1), Light (2), and Moderate/severe (3). Subsequently, patients were grouped according to CONUT-PINI score (CPS) (CPS group 1; CPS group 2; CPS group 3; and CPS group 4). Survival curves were plotted using the Kaplan-Meier method and log-rank test. The Cox proportional hazards regression model was used to determine the risk factors associated with overall Survival (OS) and cancer-specific Survival (CSS). By comprising independent prognostic factors, a predictive nomogram was constructed. RESULTS: PINI and CONUT score were identified as independent prognostic factors for OS and CSS. Kaplan-Meier survival analysis showed that the high CPS group was associated with worse OS and CSS than the low CPS group. Multivariate Cox regression and competing risk analyses showed that CPS, LVI, T stage, margin, and pN were independent factors associated with OS and CSS. Based on these five significant factors, we constructed a prognostic model for predicting clinical outcomes. The receiver operating characteristic curve indicated that the model had excellent predictive abilities for survival. The C-index of this model for OS and CSS were 0.773, and 0.789, respectively. The nomogram for OS and CSS showed good discrimination and calibration. Decision curve analysis (DCA) showed that this nomogram has a higher net benefit. CONCLUSION: The CPS combined the prognostic capacity of PINI and CONUT score and was able to predict patient outcomes in our cohort of UTUC patients. We have developed a nomogram to facilitate the clinical use of the CPS and provide accurate estimates of survival for individuals.

Prognostic models for upper urinary tract urothelial carcinoma patients after radical nephroureterectomy based on a novel systemic immune-inflammation score with machine learning.

PURPOSE: This study aimed to evaluate the clinical significance of a novel systemic immune-inflammation score (SIIS) to predict oncological outcomes in upper urinary tract urothelial carcinoma(UTUC) after radical nephroureterectomy(RNU). METHOD: The clinical data of 483 patients with nonmetastatic UTUC underwent surgery in our center were analyzed. Five inflammation-related biomarkers were screened in the Lasso-Cox model and then aggregated to generate the SIIS based on the regression coefficients. Overall survival (OS) was assessed using Kaplan-Meier analyses. The Cox proportional hazards regression and random survival forest model were adopted to build the prognostic model. Then we established an effective nomogram for UTUC after RNU based on SIIS. The discrimination and calibration of the nomogram were evaluated using the concordance index (C-index), area under the time-dependent receiver operating characteristic curve (time-dependent AUC), and calibration curves. Decision curve analysis (DCA) was used to assess the net benefits of the nomogram at different threshold probabilities. RESULT: According to the median value SIIS computed by the lasso Cox model, the high-risk group had worse OS (p<0.0001) than low risk-group. Variables with a minimum depth greater than the depth threshold or negative variable importance were excluded, and the remaining six variables were included in the model. The area under the ROC curve (AUROC) of the Cox and random survival forest models were 0.801 and 0.872 for OS at five years, respectively. Multivariate Cox analysis showed that elevated SIIS was significantly associated with poorer OS (p<0.001). In terms of predicting overall survival, a nomogram that considered the SIIS and clinical prognostic factors performed better than the AJCC staging. CONCLUSION: The pretreatment levels of SIIS were an independent predictor of prognosis in upper urinary tract urothelial carcinoma after RNU. Therefore, incorporating SIIS into currently available clinical parameters helps predict the long-term survival of UTUC.

Empagliflozin improves renal ischemia-reperfusion injury by reducing inflammation and enhancing mitochondrial fusion through AMPK-OPA1 pathway promotion.

BACKGROUND: Renal ischemia-reperfusion injury (IRI) is one reason for renal transplantation failure. Recent studies have shown that mitochondrial dynamics is closely related to IRI, and that inhibition or reversal of mitochondrial division protects organs against IRI. Optic atrophy protein 1 (OPA1), an important factor in mitochondrial fusion, has been shown to be upregulated by sodium-glucose cotransporter 2 inhibitor (SGLT2i). Also, the antiinflammatory effects of SGLT2i have been demonstrated in renal cells. Thus, we hypothesized that empagliflozin could prevent IRI through inhibiting mitochondrial division and reducing inflammation. METHODS: Using hematoxylin-eosin staining, enzyme linked immunosorbent assay (ELISA), flow cytometry, immunofluorescent staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining, real-time PCR, RNA-sequencing, and western blot, we analyzed renal tubular tissue from in vivo and in vitro experiments. RESULTS: Through animal experiments and sequencing analysis, we first confirmed the protection against IRI and the regulation of mitochondrial dynamics-related factors and inflammatory factors by empagliflozin pretreatment. Then, through hypoxia/reoxygenation (H/R) cellular experiments, we confirmed that empagliflozin could inhibit mitochondrial shortening and division and upregulate OPA1 in human renal tubular epithelial cell line (HK-2) cells. Subsequently, we knocked down OPA1, and mitochondrial division and shortening were observed, which could be alleviated by empagliflozin treatment. Combined with the previous results, we concluded that OPA1 downregulation leads to mitochondrial division and shortening, and empagliflozin can alleviate the condition by upregulating OPA1. We further explored the pathway through which empagliflozin functions. Related studies have shown the activation of AMPK pathway by empagliflozin and the close correlation between the AMPK pathway and OPA1. In our study, we blocked the AMPK pathway, and OPA1 upregulation by empagliflozin was not observed, thus demonstrating the dependence of empagliflozin on the AMPK pathway. CONCLUSION: The results indicated that empagliflozin could prevent or alleviate renal IRI through antiinflammatory effects and the AMPK-OPA1 pathway. Ischemia-reperfusion injury is an inevitable challenge in organ transplantation. It is necessary to develop a new therapeutic strategy for IRI prevention in addition to refining the transplantation process. In this study, we confirmed the preventive and protective effects of empagliflozin in renal ischemia-reperfusion injury. Based on these findings, empagliflozin is promising to be a preventive agent for renal ischemia-reperfusion injury and can be applied for preemptive administration in kidney transplantation.

Decision regret related to urinary diversion choices after cystectomy among Chinese bladder cancer patients.

AIM: To explore factors associated with decision regret after cystectomy among Chinese bladder cancer patients. METHODS: This cross-sectional study involved 112 patients, who had received radical bladder cancer resection. Participants were recruited from August 2021 until January 2022. The decision regret scale (DRS), decision conflict scale (DCS), and the Functional Assessment of Cancer Therapy-Bladder cancer (FACT-BL) form were used to measure decision regret, decision conflict, and quality of life. Investigator-designed items further explored perceptions involved in decision-making participation and outcomes. RESULTS: The average score for decision regret was 26.21 (SD 15.886), while decision conflict was 20.27 (SD 13.375) and quality of life was 94.74 (SD 20.873). 57.1% of our participants had a little knowledge about the quality of life of patients who chose an alternate urinary diversion method; however, only 13.4% reported having a clear understanding. In addition, 8.9%, 26.8%, and 36.6% thought that quality of life related to alternate decisions was poor, average, or good, respectively. Multiple regression analysis suggested that decision regret is associated with decision conflict, quality of life, and the perceptions that others (who took alternate urinary diversion decisions) had a better quality of life. CONCLUSION: Decision regret is common among Chinese bladder cancer patients, after cystectomy. The prevalence of regret appears to be much higher in Chinese bladder cancer patients compared to similar studies from other regions. Decisions in mainland China are often made by the treating physician or by family members which may cause more profound regret. However, education and economic status are positively related to higher levels of regret which creates questions around knowing, participation, and expectations, which must be explored.

Presence of secondary bladder cancer following radical nephroureterectomy for upper tract urothelial carcinoma: characteristics, risk factors, and predictive value.

BACKGROUND: To assess the characteristics, predictive risk factors, and prognostic effect of secondary bladder cancer (SBCa) following radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). METHODS: Using the Surveillance, Epidemiology, and End Results database, the authors analyzed clinicopathologic characteristics and survival data from 472 UTUC patients with SBCa after RNU, between 2004 and 2017. Cox's proportional hazard regression model was implemented to identify independent predictors associated with post-recurrence outcomes. The threshold for statistical significance was p < 0.05. RESULTS: In total, 200 Ta-3N0M0 localized UTUC patients with complete data were finally included. With a median follow-up of 71.0 months (interquartile ranges [IQR] 36.0 -103.8 months), 52.5% (n = 105) had died, with 30.5% (n = 61) dying of UTUC. The median time interval from UTUC to SBCa was 13.5 months (IQR 6.0-40.8 months). According to multivariable Cox regression analysis, patients with SBCa located at multiple sites, advanced SBCa stage, higher SBCa grade, elderly age and a shorter recurrence time, encountered worse cancer-specific survival (CSS), all p < 0.05. CONCLUSION: For primary UTUC patients with SBCa after radical surgery, advanced age, multiple SBCa sites, shorter recurrence time, higher SBCa stage, and grade proved to be significant independent prognostic factors of CSS. We ought to pay more attention to SBCa prevention as well as to earlier signs which may increase the likelihood of early detection. Having the ability to manage what may be seen as the superficial SBCa signs may enable us to improve survival but further research is required.

Intravesical recurrence factors and outcome after radical nephroureterectomy for upper tract urothelial carcinoma: Multivariate analysis with propensity score matching.

Objective: The risk factors for intravesical recurrence (IVR) after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) remain inconsistent and unclear. Thus, the risk factors of IVR after RNU and the prognostic significance of the risk indicators were explored herein. Methods: We retrospectively analyzed UTUC patients upon RNU in our center from January 2009 to December 2019. After propensity score matching, 139 patients were included in this study. Univariate and multivariate Cox proportional hazard regressions were used to estimate the hazard ratio and 95% confidence intervals. Overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) were measured using the Kaplan-Meier curve with a log-rank test. A P-value < 0.05 was considered statistically significant. Results: We included 139 patients with a median follow-up of 42 months, of which 48 patients had an intravesical recurrence. Multivariate Cox regression analysis showed cytological abnormalities in urine (HR=3.101, P=0.002), hydronephrosis (HR=1.852, P=0.042), adjuvant chemotherapy (HR=0.242, P<0.001), and previous history of bladder cancer (HR=5.51, P<0.001) were independent risk factors for IVR. As for clinical outcomes, OS and CSS suggested disadvantages in patients with IVR compared with patients without recurrence (P=0.042 for OS, P<0.0001 for CSS), OS of patients with abnormal urine cytology and OS and CSS of patients receiving adjuvant chemotherapy did not present clinical significance, and other risk factors all affected the clinical outcome. Conclusion: In this propensity-score matching study, cytological abnormality of urine, hydronephrosis, adjuvant chemotherapy and previous history of bladder cancer were shown to be independent risk factors for IVR. Moreover, risk factors also influence clinical outcomes, thereby rendering it necessary to adopt more active postoperative surveillance and treatment strategies for these patients, which may help improve treatment outcomes.

Could Metabolic Syndrome Be a Predictor of Survival Outcomes in Upper Tract Urothelial Carcinoma? A Propensity Score Matching Study in a Large Chinese Center.

Purpose: To evaluate the prognostic value of metabolic syndrome (MetS) in upper tract urothelial carcinoma (UTUC) patients based on propensity score matching (PSM) analysis. Patients and Methods: A total of 573 patients with UTUC after radical nephroureterectomy were included at Peking University People's Hospital from January 2007 to April 2021. MetS was diagnosed according to the criteria of Chinese Diabetes Society and was defined as the presence of 3 or more of the following 4 conditions (obesity, hyperglycemia, hypertension, high triglycerides and/or low high-density lipoprotein-cholesterol). Patients were divided into two groups based on whether they had MetS, whose variables were adjusted using 1:1 PSM analysis with a caliber of 0.02 to minimize selection bias. Univariate and multivariate Cox regression analysis were used to evaluate the association of MetS and its components with pathological outcomes after adjusting preoperative confounders by propensity score matching. The Kaplan-Meier method was used to estimate overall survival (OS), cancer-specific survival (CSS), and intravesical recurrence-free survival (IVRFS) after surgery. Results: MetS was significantly correlated with older age, a history of coronary heart disease, high Charlson Comorbidity Index, low estimated Glomerular filtration rate, and low aspartate/alanine aminotransferase ratio (all P<0.05). Multivariate Cox regression analysis and Kaplan-Meier curves demonstrated that MetS showed no statistical correlation with lower OS or IVRFS and approaching significance with lower CSS (P=0.063) before PSM. After PSM, the 5-year OS, CSS, and IVRFS were 64.1%, 74.7%, and 77.2%, respectively, in the MetS group, compared with 67.4%, 78.8%, and 77.2%, respectively, in non-MetS group. Univariate Cox regression analyses showed that MetS and its components were not associated with decreased OS, CSS, or IVRFS (all P>0.05). Conclusion: In our study, no statistical difference was found between MetS and survival outcomes in UTUC, except a marginal association with lower CSS. Further studies are needed to evaluate the role of MetS and its each single component on UTUC.

Clinicopathological and Prognostic Significance of Preoperative Prognostic Nutritional Index in Patients with Upper Urinary Tract Urothelial Carcinoma.

To investigate the prognostic value of preoperative prognostic nutritional index (PNI) to predict oncological outcome and intravesical recurrence (IVR) in upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU).This study involved the clinical data of 255 patients with UTUC who had undergone RNU from 2004 to 2019 at our institution. Patients were grouped according to an optimal value of preoperative PNI. Kaplan-Meier analyses and Cox proportional hazards models were used to analyze the associations of preoperative PNI with progression-free survival (PFS), cancer-specific survival (CSS), overall survival (OS), and IVR.Patients with low PNI were more likely to be older, have higher tumor stage, higher eGFR, and multifocal lesions. No significant association was found between PNI and CSS, IVR. In subgroup analysis according to the risk stratification, low PNI was associated with worse PFS, CSS, and OS for patients with higher risk. Multivariate analyses showed that elevated PNI was an independent prognostic indicator for PFS (P = 0.014) and OS (P = 0.048).A low PNI is an independent predictor of PFS and OS in patients with UTUC after RNU. By subgroup analysis, the prognostic value of PNI was limited to patients with higher risk. PNI may become a useful biomarker to predict oncological outcomes in patients with UTUC after RNU.

N6-Methyladenosine-Related Long Non-coding RNA Signature Associated With Prognosis and Immunotherapeutic Efficacy of Clear-Cell Renal Cell Carcinoma.

Increasing evidence suggests that N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play important roles in cancer progression and immunotherapeutic efficacy in clear-cell renal cell carcinoma (ccRCC). In this study, we conducted a comprehensive ccRCC RNA-seq analysis using The Cancer Genome Atlas data to establish an m6A-related lncRNA prognostic signature (m6A-RLPS) for ccRCC. Forty-four prognostic m6A-related lncRNAs (m6A-RLs) were screened using Pearson correlation analysis (|R| > 0.7, p < 0.001) and univariable Cox regression analysis (p < 0.01). Using consensus clustering, the patients were divided into two clusters with different overall survival (OS) rates and immune status according to the differential expression of the lncRNAs. Gene set enrichment analysis corroborated that the clusters were enriched in immune-related activities. Twelve prognostic m6A-RLs were selected and used to construct the m6A-RLPS through least absolute shrinkage and selection operator Cox regression. We validated the differential expression of the 12 lncRNAs between tumor and non-cancerous samples, and the expression levels of four m6A-RLs were further validated using Gene Expression Omnibus data and Lnc2Cancer 3.0 database. The m6A-RLPS was verified to be an independent and robust predictor of ccRCC prognosis using univariable and multivariable Cox regression analyses. A nomogram based on age, tumor grade, clinical stage, and m6A-RLPS was generated and showed high accuracy and reliability at predicting the OS of patients with ccRCC. The prognostic signature was found to be strongly correlated to tumor-infiltrating immune cells and immune checkpoint expression. In conclusion, we established a novel m6A-RLPS with a favorable prognostic value for patients with ccRCC. The 12 m6A-RLs included in the signature may provide new insights into the tumorigenesis and allow the prediction of the treatment response of ccRCC.

Developing a nomogram for predicting intravesical recurrence after radical nephroureterectomy: a retrospective cohort study of mainland Chinese patients.

OBJECTIVE: To evaluate the role of Ki-67 in predicting subsequent intravesical recurrence following radical nephroureterectomy and to develop a predictive nomogram for upper tract urothelial carcinoma patients. METHODS: This retrospective analysis involved 489 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision. The data set was randomly split into a training cohort of 293 patients and a validation cohort of 196 patients. Immunohistochemical analysis was used to assess the immunoreactivity of the biomarker Ki-67 in the tumor tissues. A multivariable Cox regression model was utilized to identify independent intravesical recurrence predictors after radical nephroureterectomy before constructing a nomographic model. Predictive accuracy was quantified using time-dependent receiver operating characteristic curve. Decision curve analysis was performed to evaluate the clinical benefit of models. RESULTS: With a median follow-up of 54 months, intravesical recurrence developed in 28.2% of this sample (n = 137). Tumor location, multifocality, pathological T stage, surgical approach, bladder cancer history and Ki-67 expression levels were independently associated with intravesical recurrence (all P < 0.05). The full model, which intercalated Ki-67 with traditional clinicopathological parameters, outperformed both the basic model and Xylinas' model in terms of discriminative capacity (all P < 0.05). Decision-making analysis suggests that the more comprehensive model can also improve patients' net benefit. CONCLUSIONS: This new model, which intercalates the Ki-67 biomarker with traditional clinicopathological factors, appears to be more sensitive than nomograms previously tested across mainland Chinese populations. The findings suggest that Ki-67 could be useful for determining risk-stratified surveillance protocols following radical nephroureterectomy and in generating an individualized strategy based around intravesical recurrence predictions.

Does Xylinas' nomogram accurately predict intravesical recurrence risk after radical nephroureterectomy for primary upper urinary tract urothelial carcinoma when applied to Asian populations?

OBJECTIVE: To validate a prognostic nomogram (Xylinas' nomogram) for intravesical recurrence after radical nephroureterectomy for primary upper urinary tract urothelial carcinoma patients of Asian descent. METHODS: Clinicopathological and survival data from 243 primary urinary tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision between January 2004 and May 2017 were collated. Univariate and multivariable Cox regression analyses were performed to identify independent risk factors associated with intravesical recurrence-free survival. External validation was determined using regression coefficients abstracted from previously published data. Performance was then quantified through calibration and discrimination, according to concordance indexes (c-index) in receiver operating characteristic curves. RESULTS: 163 patients met our eligibility criteria and were finally included in this study. At a median follow-up of 60 months, intravesical recurrence occurred in 29.4% (n = 48). Multivariable analysis revealed that being male, ureteral tumor location, tumor multifocality and previous bladder cancer were independent prognostic factors of intravesical recurrence-free survival. When Xylinas' nomogram was applied to our cohort, the discriminatory power was found to be roughly equivalent with a c-index of 68.3% for the reduced model and 68.4% for the full model. Calibration plots also revealed intravesical recurrence predictions at 3, 6, 12, 18, 24 and 36 months had relative concordance. Contrasting the respective performances of the reduced and full model suggests there is no significant difference between the two (all P > 0.05). CONCLUSIONS: This nomogram appears accurate at predicting intravesical recurrence after radical nephroureterectomy for primary urinary tract urothelial carcinoma in Asian populations. However, it remains necessary to data mine for unknown prognostic factors for optimization. Further external validation is required across larger, ethically diverse populations before applying this nomogram in clinical practice.

Preoperative Monocyte-to-lymphocyte Ratio Predicts for Intravesical Recurrence in Patients With Urothelial Carcinoma of the Upper Urinary Tract After Radical Nephroureterectomy Without a History of Bladder Cancer.

BACKGROUND: This study aimed to investigate the preoperative monocyte-to-lymphocyte ratio (MLR) as a biomarker for intravesical recurrence (IVR) in upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU) for the first time. PATIENTS AND METHODS: This study involved the clinical data of 255 patients with UTUC without a history of bladder cancer who had undergone RNU from March 2004 to February 2019 at an academic institution. The associations between MLR and IVR were assessed with Kaplan-Meier method and Cox regression analysis. RESULTS: The median follow-up was 43.93 months. Of the 255 patients, 37 developed IVR during the follow-up period. Kaplan-Meier analysis revealed that patients with high MLR (> 0.22) had poor IVR-free survival (P = .001); this prognostic value was in accordance with patients with high grade and more advanced stage UTUC. Cox regression preoperative models showed that ureteral tumor site (hazard ratio [HR], 2.784; P = .005), surgical approach (HR, 2.745; P = .008), and high MLR (HR, 4.085; P < .001) were an independent risk factor for IVR. These factors were used as a signature to establish a prognostic risk model, which revealed significant differences among the 3 subgroups of patients with low, intermediate, and high risk (P < .001). CONCLUSION: Ureteral tumor site, surgical approach, and preoperative MLR are significant predictors for IVR in patients with UTUC after RNU. MLR may become a useful biomarker to predict IVR in patients with UTUC after RNU.