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.

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.

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.

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.

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.

Risk factors for survival in patients with von Hippel-Lindau disease.

BACKGROUND: Historically, von Hippel-Lindau (VHL) disease is characterised by a poor survival. Although genotype-phenotype correlation has been described in many studies, the risk factors for VHL survival remain unclear. This study aims to evaluate the median survival of Chinese patients with VHL disease and explore whether VHL survival is influenced by genetic and clinical factors. METHODS: In this retrospective study, we recruited 340 patients from 127 VHL families. Kaplan-Meier plot and Cox regression model were used to evaluate the median survival and assess how survival was influenced by birth year, birth order, sex, family history, mutation type, onset age and first presenting symptom. RESULTS: The estimated median life expectancy for Chinese patients with VHL disease was 62 years. Patients with early-onset age, positive family history and truncating mutation types had poorer overall and VHL-related survival. Patients with haemangioblastoma as their first presenting symptom were related to a higher risk of death from central nervous system haemangioblastoma than those with abdominal lesions (HR 8.84, 95% CI 2.04 to 38.37, P=0.004). CONCLUSIONS: This largest VHL survival analysis indicates that onset age, family history, mutation type and first presenting symptom have an effect on the survival of patients with VHL disease, which is helpful to genetic counselling and clinical decision-making.

Impact of prostate cancer radiotherapy on the biological behavior and specific mortality of subsequent bladder cancer.

BACKGROUND: The impact of different radiotherapy modalities on the development and characteristics of second primary bladder cancers (BCa) and BCa-specific mortality (BCa-SM) remains unclear. Thus, we evaluated the incidence and biological behavior of subsequent BCa and related survival in patients who underwent radiation therapy for prostate cancer (PCa). METHODS: A total of 530,581 patients in the surveillance, epidemiology, and end results database with localized PCa between 1988 and 2013 were identified. PCa treatments included radical prostatectomy (RP), external beam radiotherapy (EBRT), radioactive implants (RI), and combined EBRT and RI (EBRI). A multivariable competing risk analysis based on a proportional sub distribution hazards model was used to determine the impact of different radiotherapy modalities on BCa incidence and specific mortality. RESULTS: Incidence of BCa was significantly high in patients treated with EBRT, RI, and EBRI vs. RP [sub distribution hazard ratio (SHR) 1.41, P < 0.001; SHR 1.58, P < 0.001; SHR 1.56, P < 0.001, respectively]. BCa following EBRT, RI, and EBRI were more commonly non-urothelial (3.3%, 2.9%, 3.3%, respectively, versus 1.2%) and T4 (3.5%, 6.1%, 5.0%, respectively, versus 1.6%) compared with RP. RI associated with a higher rate of BCa metastasis than RP (2.6% vs. 1.1%). Prior EBRT, RI, and EBRI increased BCa-SM (SHR 1.44, P = 0.001; SHR 1.21, P = 0.047; and SHR 1.42, P = 0.032, respectively). CONCLUSIONS: Patients receiving radiotherapy for PCa have a higher risk of BCa. BCa after EBRT, RI, and EBRI is more likely to be non-urothelial, stage T4, and with increased BCa-SM. Prior RI associated with a higher rate of BCa metastasis.

Genotype and phenotype correlation in von Hippel-Lindau disease based on alteration of the HIF-α binding site in VHL protein.

PURPOSE: Von Hippel-Lindau (VHL) disease is a rare hereditary cancer syndrome that reduces life expectancy. We aimed to construct a more valuable genotype-phenotype correlation based on alterations in VHL protein (pVHL). METHODS: VHL patients (n = 339) were recruited and grouped based on mutation types: HIF-α binding site missense (HM) mutations, non-HIF-α binding site missense (nHM) mutations, and truncating (TR) mutations. Age-related risks of VHL-associated tumors and patient survival were compared. RESULTS: Missense mutations conferred an increased risk of pheochromocytoma (HR = 1.854, p = 0.047) compared with truncating mutations. The risk of pheochromocytoma was lower in the HM group than in the nHM group (HR = 0.298, p = 0.003) but was similar between HM and TR groups (HR = 0.901, p = 0.810). Patients in the nHM group had a higher risk of pheochromocytoma (HR = 3.447, p < 0.001) and lower risks of central nervous system hemangioblastoma (CHB) (HR = 0.700, p = 0.045), renal cell carcinoma (HR = 0.610, p = 0.024), and pancreatic tumor (HR = 0.382, p < 0.001) than those in the combined HM and TR (HMTR) group. Moreover, nHM mutations were independently associated with better overall survival (HR = 0.345, p = 0.005) and CHB-specific survival (HR = 0.129, p = 0.005) than HMTR mutations. CONCLUSION: The modified genotype-phenotype correlation links VHL gene mutation, substrate binding site, and phenotypic diversity (penetrance and survival), and provides more accurate information for genetic counseling and pathogenesis studies.

Renal Arterial Pseudoaneurysm and Renal Arteriovenous Fistula Following Partial Nephrectomy.

INTRODUCTION: Renal arterial pseudoaneurysm (RAP) and renal arteriovenous fistula (RAVF) are rare but can cause fatal bleeding. MATERIALS AND METHODS: A retrospective review was conducted for patients undergoing partial nephrectomy (PN) in our department. The clinical features and treatment methods were analysed, and the relationships between RAP/RAVF and the surgical methods and R.E.N.A.L. score were investigated. RESULTS: Eleven patients were diagnosed with RAP/RAVF (9 with RAP and 2 with RAVF). The incidence of RAP/RAVF after laparoscopic PN showed no significant difference compared to that after open PN (p = 0.47). A low R.E.N.A.L. score was present in 6 patients, while an intermediate/high score was present in the other 5 patients. The major clinical manifestations included haematuria and haemorrhagic shock, and the median time of occurrence was 8 days after the operation. Six patients underwent an ultrasound examination. Of the 4 patients who underwent enhanced CT, 2 patients were diagnosed with RAP. All 11 patients were diagnosed by renal angiography and were cured after super-selective arterial embolization. The serum creatinine levels before and after embolization showed no significant differences (p = 0.14). CONCLUSIONS: RAP/RAVF may not have any relationship with the surgical procedure or R.E.N.A.L. score. Renal angiography and super-selective arterial embolization are the preferred methods for diagnosing and treating RAP/RAVF.

Cytoreductive nephrectomy with thrombectomy before targeted therapy improves survival for metastatic renal cell carcinoma with venous tumor thrombus: a single-center experience.

BACKGROUND: The aim of the study is to evaluate the role of cytoreductive nephrectomy (CN) with thrombectomy before targeted molecular therapy (TMT) on survival in metastatic renal cell carcinoma (mRCC) with venous tumor thrombus. METHODS: We performed a retrospective analysis of 47 patients treated in our center from April 2008 to October 2014. In the study, 20 patients underwent CN with thrombectomy followed by targeted therapy (group 1); 15 patients received targeted therapy alone (group 2); and 12 patients underwent CN with thrombectomy alone (group 3). The overall survival (OS) and cancer-specific survival (CSS) were calculated according to the Kaplan-Meier survival curve method, and prognostic variables were assessed by Cox regression analyses. RESULTS: The median follow-up times of group 1, group 2, and group 3 were 24.5, 12, and 6.5 months, respectively. During follow-up, in both group 1 and group 3, 12 patients died. In group 2, 14 patients died. The median OS of group 1, group 2, and group 3 was 22, 12, and 6 months, respectively (P < 0.001). Compared with surgery alone and targeted therapy alone, patients with cytoreductive surgery before targeted therapy had statistically better survival benefits (P < 0.001, P = 0.009, respectively). On univariate analysis, the number of metastatic sites (P = 0.004) was a statistically significant prognostic factor influencing OS. CONCLUSIONS: Our single-center experience showed that CN with thrombectomy before targeted therapy improved the survival of patients with mRCC with venous tumor thrombus. The number of metastatic sites was an independent prognostic factor influencing OS.

MiR-139-5p is Increased in the Peripheral Blood of Patients with Prostate Cancer.

BACKGROUND: Emerging evidence suggested that microRNAs (miRNAs) play a causal role in cancer tumorigenesis. Aberrant expression of miRNA (miR)-139-5p has been observed in various types of cancers. The present study evaluated the relationship between miR-139-5p expression levels and prostate cancer (PCa), to assess the feasibility of using peripheral blood miR-139-5p as a potential non-invasive biomarker for PCa. METHODS: Total RNA was extracted from peripheral whole blood samples from 45 PCa patients, 45 benign prostatic hyperplasia (BPH) patients and 50 healthy controls (HC). The expression of miR-139-5p was assessed by reverse transcription quantitative polymerase chain reaction. RESULTS: MiR-139-5p in peripheral blood was significantly higher in PCa patients than in patients with BPH and HC individuals (P<0.001). Higher miR-139-5p expression was observed to be associated with certain clinicopathological parameters, including PSA>20ng/ml (P<0.05), pathological tumor stage 3/4 (P<0.05) and Gleason score >7 (P<0.01). A receiver operating characteristic (ROC) curve analysis revealed that miR-139-5p distinguished PCa patients from BPH patients [area under the curve (AUC), 0.936; 95% CI, 0.878-0.993; P<0.001]. CONCLUSIONS: Peripheral blood miR-139-5p may be utilized as a potential novel non-invasive biomarker for PCa screening.

Low-level Ki-67 expression as an independent predictor of bladder tumour recurrence in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy.

OBJECTIVE: To evaluate the association of molecular markers and conventional clinicopathological factors with bladder tumour recurrence in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy. METHODS: The expressions of Ki-67 and P53 were measured by immunohistochemical staining prospectively in 115 consecutive patients with primary upper tract urothelial carcinoma from March 2004 to February 2014. The Cox proportional hazards regression model was used to identify independent predictors. The association between Ki-67 expression and clinicopathological variables was assessed by the χ(2) test. RESULTS: Intravesical recurrence occurred in 13 out of 115 (11.3%) patients with a mean follow-up of 54.2 months (range: 7-130). Low-level Ki-67 expression (P = 0.010), older age (>65, P = 0.040) and lower ureter tumour (P = 0.001) were independent predictors of bladder tumour recurrence in Cox regression analysis. Ki-67 expression was elevated with the progression of tumour grade (P = 0.004) but not with stage (P = 0.186). Ki-67 overexpression was also significantly higher in aggressive pathological types (P = 0.008), but only shows an inclination towards poor oncologic outcomes in the cancer-specific survival rate (P = 0.107) and the overall survival rate (P = 0.063). CONCLUSIONS: Low-level Ki-67 expression was an independent predictor for bladder tumour recurrence, while Ki-67 overexpression was associated with adverse clinicopathological parameters and poor prognosis in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy.

Prophylactic intravesical chemotherapy decreases bladder tumor recurrence after nephroureterectomy for primary upper tract urothelial carcinoma: A systematic review and meta-analysis.

PURPOSE: A high incidence of bladder tumor (BT) occurs after radical nephroureterectomy (NU) for primary upper tract urothelial carcinoma (UTUC). Although some studies have shown that prophylactic intravesical chemotherapy could prevent BT recurrence, it has not become standard practice at this stage. The purpose of this study was to evaluate the effect of intravesical instillation chemotherapy in preventing BT recurrence in patients with primary UTUC after nephroureterectomy. METHODS: A comprehensive literature search was performed in July 2014 using the Medline, Embase, and Cochrane Library databases, as well as the China National Knowledge Infrastructure and Wanfang Data. All clinical trials compared the effect of prophylactic intravesical chemotherapy after radical NU for primary UTUC. Analysis was performed using the Stata 12.0 SE software. RESULTS: Eight trials were analyzed with a total of 979 patients including 521 patients receiving intravesical chemotherapy instillation and 458 without instillation. The BT incidence rate was 125 out of 521 patients (24.0%) with intravesical instillation chemotherapy after NU, and 169 out of 458 patients (36.9%) without intravesical chemotherapy after NU. Compared with those who didn't receive instillation, the pooled odds ratio (OR) of BT recurrence was 0.45 (95% confidence interval/CI 0.34-0.61, p<0.0001) in instillation patients. In the sub-analyses, the OR of single instillation was similar to repeated instillations (0.48 and 0.42). The OR of beginning the first instillation within 24 hrs, 48 hrs and 2 weeks was 0.34, 0.48 and 0.46, respectively. CONCLUSIONS: This systematic review demonstrates that prophylactic intravesical instillation chemotherapy can prevent BT recurrence in primary UTUC patients after NU. It also suggests that single instillation may have a similar effect to repeated instillations. The first instillation beginning within 24 hrs seems to show lower BT recurrence than at 48 hrs or 2 weeks. However, given that some limitations exist, well-designed randomized controlled trials are needed to further evaluate these results.

[Use of abiraterone acetate in the treatment of patients with metastatic castration resistant prostate cancer and no prior chemotherapy: 3 case reports and literature review].

OBJECTIVE: To evaluate the safety and efficiency of using abiraterone and prednisone in the treatment of patient with metastatic castration resistant prostate cancer (mCRPC) no prior chemotherapy. METHODS: Three mCRPC no prior chemotherapy patients accepted abiraterone and prednisone treatment. The clinical data were analyzed retrospectively and the safety and efficiency of this treatment option were discussed. The Gleason scores of the three mCRPC patients were 5, 9, and 9. The clinical stages were T3aNxM0, T3aNxM1b, and T3aNxM1b. The patients received abiraterone 1 000 mg daily and prednisone 5 mg twice daily and androgen deprivation therapy in the treatment. Their blood pressure, complete blood count, prostate specific antigen (PSA), biochemical parameters, whole body CT scan and bone scan were done regularly to monitor the progression of the diseases. RESULTS: In this study, the general condition improved in two patients. Two of the three patients experienced decrease of PSA and no progression. One patient experienced disease progression. Generally, abiraterone and prednisone resulted in prolonged radiographic progression-free survival and delayed in PSA progression in mCRPC no prior chemotherapy. There were no severe side effects, such as hypokalemia, hypertension, and water-sodium retention. The patient's tolerance was good. CONCLUSION: Abiraterone and prednisone are safe and can improve mCRPC no prior chemotherapy patient's life quality and may prolong the overall survival.

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.

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.

A simplified frailty index and nomogram to predict the postoperative complications and survival in older patients with upper urinary tract urothelial carcinoma.

Purpose: This study was designed to investigate the clinical value of a simplified five-item frailty index (sFI) for predicting short- and long-term outcomes in older patients with upper urinary tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). Method: This retrospective study included 333 patients (aged ≥65 years) with UTUC. Patients were classified into five groups: 0, 1, 2, 3, and 3+, according to sFI score. The variable importance and minimum depth methods were used to screen for significant variables, and univariable and multivariable logistic regression models applied to investigated the relationships between significant variables and postoperative complications. Survival differences between groups were analyzed using Kaplan-Meier plots and log-rank tests. Cox proportional hazards regression was used to evaluate risk factors associated with overall survival (OS) and cancer-specific survival (CSS). Further, we developed a nomogram based on clinicopathological features and the sFI. The area under the curve (AUC), Harrel's concordance index (C-index), calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram. Result: Of 333 cases identified, 31.2% experienced a Clavien-Dindo grade of 2 or greater complication. Random forest-logistic regression modeling showed that sFI significantly influenced the incidence of postoperative complications in older patients (AUC= 0.756). Compared with patients with low sFI score, those with high sFI scores had significantly lower OS and CSS (p < 0.001). Across all patients, the random survival forest-Cox regression model revealed that sFI score was an independent prognostic factor for OS and CSS, with AUC values of 0.815 and 0.823 for predicting 3-year OS and CSS, respectively. The nomogram developed was clinically valuable and had good ability to discriminate abilities for high-risk patients. Further, we developed a survival risk classification system that divided all patients into high-, moderate-, and low-risk groups based on total nomogram points for each patient. Conclusion: A simple five-item frailty index may be considered a prognostic factor for the prognosis and postoperative complications of UTUC following RNU. By using this predictive model, clinicians may increase their accuracy in predicting complications and prognosis and improve preoperative decision-making.

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.

FOXP2 confers oncogenic effects in prostate cancer.

Identification oncogenes is fundamental to revealing the molecular basis of cancer. Here, we found that FOXP2 is overexpressed in human prostate cancer cells and prostate tumors, but its expression is absent in normal prostate epithelial cells and low in benign prostatic hyperplasia. FOXP2 is a FOX transcription factor family member and tightly associated with vocal development. To date, little is known regarding the link of FOXP2 to prostate cancer. We observed that high FOXP2 expression and frequent amplification are significantly associated with high Gleason score. Ectopic expression of FOXP2 induces malignant transformation of mouse NIH3T3 fibroblasts and human prostate epithelial cell RWPE-1. Conversely, FOXP2 knockdown suppresses the proliferation of prostate cancer cells. Transgenic overexpression of FOXP2 in the mouse prostate causes prostatic intraepithelial neoplasia. Overexpression of FOXP2 aberrantly activates oncogenic MET signaling and inhibition of MET signaling effectively reverts the FOXP2-induced oncogenic phenotype. CUT&Tag assay identified FOXP2-binding sites located in MET and its associated gene HGF. Additionally, the novel recurrent FOXP2-CPED1 fusion identified in prostate tumors results in high expression of truncated FOXP2, which exhibit a similar capacity for malignant transformation. Together, our data indicate that FOXP2 is involved in tumorigenicity of prostate.