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Purpose: We aimed to establish and validate a nomogram for extraurothelial recurrence (EUR) after radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC). Methods: The data of 521 patients with UTUC after RNU from 2 medical centers were retrospectively studied and were used as training cohort (n = 301) and external validation cohort (n = 220). We used the least absolute shrinkage and selection operator (LASSO) to select variables for multivariable Cox regression, and included independent risk factors into nomogram models predicting EUR-free survival (EURFS). Multiple parameters were used to validate the nomogram, including the concordance index (C-index), the calibration plots, the time-dependent receiver-operator characteristics curve (ROC), and the decision curve analysis (DCA). Patients were stratified into three risk groups according to total points calculated by nomograms. The differences of EURFS in each group were analyzed by the Kaplan–Meier analysis. Results: Four variables were screened through LASSO regression. Bladder cancer history, Ki-67, lymphovascular invasion (LVI), and pathological T stage were shown to be independent predictive factors for EUR. The C-indexes of the model were 0.793 and 0.793 in training and validation cohorts, respectively. In comparison with prediction based on categorized pathological T stage, the DCA curves for 5-year EUR exhibited better performance. The 5-year EURFS rates were 92.2%, 63.8%, and 36.2% in patients stratified to the low-, medium-, and high-risk group. Conclusion: Our study provided a new nomogram to predict the probability of EUR in UTUC patients underwent RNU, with perfect performance in discrimination ability and clinical net benefit. The application of the model may help urologists to choose proper treatment and monitoring. [ABSTRACT FROM AUTHOR]

Background: To investigate the prognostic significance of the systemic immune-inflammation index (SII) for patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU) and develop nomogram models for predicting overall survival (OS), intravesical recurrence (IVR), and extra-urothelial recurrence (EUR). Methods: We retrospectively studied the clinical and pathological features of 195 patients who underwent RNU for UTUC. All patients were randomly divided into a training cohort (99 cases) and a validation cohort (96 cases). The training cohort was used to develop nomogram models, and the models were validated by the validation cohort. The least absolute shrinkage and selection operator (LASSO) regression and Cox regression were performed to identify independent predictors. The concordance index (C-index), receiver operator characteristics (ROC) analysis, and calibration plot were used to evaluate the reliability of the models. The clinical utility compared with the pathological T stage was assessed using the net reclassification index (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). Results: SII was an independent risk factor in predicting OS and EUR. The C-index values of the nomogram predicting OS, IVR, and EUR were 0.675, 0.702, and 0.756 in the training cohort and 0.715, 0.756, and 0.713 in the validation cohort. A high level of SII was correlated with the invasion of the mucosa, muscle layer of the ureter, nerves, vessels, and fat tissues. Conclusion: We developed nomogram models to predict the OS, IVR, and EUR of UTUC patients. The efficacy of these models was substantiated through internal validation, demonstrating favorable discrimination, calibration, and clinical utility. A high level of SII was associated with both worse OS and shorter EUR-free survival. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to establish and validate nomograms to predict the probability of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper urinary tract epithelial carcinoma (UTUC). Methods: Clinical data of 528 patients with UTUC after RNU were collected from two medical centers between 2009 and 2020. We used the least absolute shrinkage and selection operator (LASSO) regression to select variables for multivariable Cox regression analysis in the training cohort and included independent risk factors into nomogram models predicting IVR-free survival (IVRFS). Another center was applied as the external cohort to validate the predictive accuracy and discriminative ability of the nomogram by performing area under the receiver operating curve (AUC), consistency index (C-index), and calibration curve. Results: History of bladder cancer, tumor size, preoperative urine cytology, postoperative instillation, Ki-67, and platelet-to-lymphocyte ratio (PLR) were identified as independent risk factors for IVR. The prognosis model including these predictors demonstrated excellent discriminatory performance in both the training cohort (C-index, 0.814) and external validation cohort (C-index, 0.748). The calibration plots of the nomogram revealed good consistency in both cohorts. Finally, patients could be classified into two risk groups based on scores obtained from the nomogram, with significant differences in IVRFS. Conclusion: Our study provided a reliable nomogram for predicting the probability of IVR in patients with UTUC after RNU. Risk stratification based on this model may assist urologists make optimal clinical decisions on the management of UTUC. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the value of cytoreductive nephrectomy (CN) and develop nomograms to predict the prognosis of metastatic renal cell carcinoma (mRCC) patients with receiving radiology therapy or/and chemotherapy (RT/&CT). Methods: Clinical data of patients with mRCC between 2010 and 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Prognostic nomograms were constructed to predict the overall survival (OS) and cancer-specific survival (CSS) probability for 1-, 3-, and 5- years in patients with mRCC. A series of validation methods were used to validate the accuracy and reliability of the model, including area under the receiver operating curve (AUC), consistency index (C-index), calibration curve, and decision curve analysis (DCA). Results: 1394 patients were enrolled in this study. All patients were randomly divided into the training cohort (n = 976) and the validation cohort (n = 418). In the training cohort, multivariate Cox regression analysis suggested that pathology grade, histology type, T stage, N stage, surgery, and distant metastasis were independent risk factors for OS and CSS. The AUC and C-index were both over 0.65 in both cohorts, indicating that the nomograms for OS and CSS had satisfactory discriminative power. The calibration curves revealed that the predictive nomograms had a good consistency between the observed and the predicted survival. Conclusion: This study provided evidence that mRCC patients underwent RT/&CT could gain survival benefits from CN. The prognostic nomogram constructed in our study is reliable and practical, may help guide clinical strategies in the treatment of mRCC. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the current evidence on the effectiveness and safety of ureteric stent removal using strings compared to conventional methods. Materials and Methods. The electronic databases PubMed, Embase, China National Knowledge Infrastructure (CNKI), and the Cochrane Library were systematically searched up to March 2020. Two reviewers searched the literature, independently extracted the data, and evaluated the quality of the studies according to the inclusion and exclusion criteria. The data analysis was performed with the software program Review Manager 5.3. Results. Eleven studies with a total of 1809 patients were included in the analysis based on the inclusion criteria. Our meta-analysis showed that visual analogue scale (VAS) scores were significantly lower in the string group than in the conventional group (weighted mean difference (WMD) -2.63; 95% confidence interval (CI) -3.68, -1.58; P < 0.00001). In terms of stent dwell time, the string group had an advantage (WMD -9.53; 95% CI -14.20, -4.86; P < 0.0001). In addition, no significant differences in the occurrence of urinary tract infection (UTI) (odds ratio (OR) 1.03; 95% CI 0.62, 1.72; P = 0.92), emergency room visits (OR 0.99; 95% CI 0.59, 1.67; P = 0.97), or other complications (P > 0.05) were observed between the two groups. Conclusion. Our findings suggest that an extraction string is an effective and safe method for the removal of ureteric stents. This method gives patients the benefits of reduced pain and shortened stent dwell time without increasing the risk of UTI. Nevertheless, these findings should be further confirmed through large-volume, well-designed prospective randomized controlled trials (RCTs). [ABSTRACT FROM AUTHOR]

The present study aimed to assess current evidence on the effectiveness and safety of minimally invasive vs. standard percutaneous nephrolithotomy (PCNL) in the management of renal stones. A systematic search of electronic databases, which included PubMed, EMBASE and the Cochrane Library up to May 2019 was performed. Using Review Manager statistical software (version 5.3), primary outcomes, including stone-free rates (SFRs), were evaluated. Meanwhile, analysis was also performed to compare secondary outcomes, such as peri- and postoperative complications and operative data. Fourteen studies involving 1,611 patients with renal stones were analyzed based on the inclusion criteria. On the basis of the present analysis, mini percutaneous nephrolithotomy (MPCNL) was proven to have non-inferior clinical efficacy with respect to the SFR compared with PCNL [odds ratio (OR)=1.10; 95% confidence interval (CI), 0.84-1.44; P=0.48]. In addition, the meta-analysis showed that MPCNL had a significantly lower hemoglobin decrease [mean difference (MD)=-0.68; 95% CI, -1.05 to -0.31; P=0.0003] and fewer blood transfusions (OR=0.36; 95% CI, 0.18-0.71; P=0.003) compared with PCNL. Moreover, the MPCNL group had a shorter inpatient stay (MD=-0.81; 95% CI, -1.55 to -0.08; P=0.03) compared with the PCNL group. However, the overall evidence was insufficient to suggest a statistically significant difference in the adverse event profile for MPCNL compared with PCNL. The present meta-analysis indicates that MPCNL is an effective method for treating renal stones. Compared with PCNL, MPCNL not only has similarly high SFRs but is also associated with less blood loss, fewer blood transfusions, more favorable recovery time and shorter inpatient stays. However, the findings of the present study should be further confirmed by well-designed prospective randomized controlled trials with a larger patient series. [ABSTRACT FROM AUTHOR]

Objective. To assess current evidence on the effectiveness and safety of single- versus multiple-tract percutaneous nephrolithotomy in the surgical management of complex caliceal calculi or staghorn stones through a comprehensive literature review. Methods. A comprehensive literature review of articles investigating the clinical efficacy and safety of single- versus multiple-tract percutaneous nephrolithotomy was performed. Relevant literature was obtained by systematically searching PubMed, EMBASE, and the Cochrane Library through May 2020. We followed the search strategy based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The primary outcomes, including the stone-free rate (SFR), and secondary outcomes (peri- and postoperative complications and operative data) were evaluated using RevMan 5.3 statistical software. Results. Ten studies involving 1844 patients with complex caliceal calculi or staghorn stones met the inclusion criteria. Single-tract percutaneous nephrolithotomy (STPCNL) had noninferior clinical efficacy with respect to the immediate SFR (odds ratio OR = 0.80 , 95% confidence interval (CI) (0.46 to 1.38), p = 0.42) and 3-month SFR (OR = 1.22 , 95% CI (0.38 to 3.92), p = 0.74) compared with multiple-tract percutaneous nephrolithotomy (MTPCNL). In addition, pooled analyses showed that STPCNL resulted in significantly lower hemoglobin decreases (MD = − 0.46 , 95% CI (-0.68 to -0.25), p < 0.0001), fewer blood transfusions (OR = 0.48 , 95% CI (0.34 to 0.67), p < 0.0001), and fewer pulmonary complications (OR = 0.28 , 95% CI (0.09 to 0.83), p = 0.02) than MTPCNL. However, the overall evidence was insufficient to suggest a statistically significant difference for other adverse events. Conclusion. This meta-analysis indicated that STPCNL is an effective method for treating complex caliceal calculi or staghorn stones. Compared with MTPCNL, STPCNL not only yields similarly high SFRs but also is associated with many advantages, less blood loss, fewer blood transfusions, and fewer pulmonary complications without an increase in other complications. However, the findings of this study should be further confirmed by well-designed prospective randomized controlled trials (RCTs) with a larger patient series. [ABSTRACT FROM AUTHOR]

Background: In previous observational studies, food-derived antioxidant vitamins have been suggested to be associated with breast cancer. However, the findings were inconsistent and the causal relationship could not be clearly elucidated. To confirm the potential causal relationship between food-derived antioxidants (retinol, carotene, vitamin C and vitamin E) and the risk of breast cancer, we conducted a two-sample Mendelian randomization (MR) study. Methods: The instrumental variables (IVs) as proxies of genetic liability to food-derived antioxidant vitamins were obtained from the UK Biobank Database. We extracted breast cancer data (122,977 cases and 105,974 controls) from the Breast Cancer Consortium (BCAC). In addition, we studied estrogen expression status categorically, including estrogen receptor positive (ER+) breast cancer (69,501 cases and 105,974 controls) and versus estrogen receptor (ER−) negative breast cancer (21,468 cases and 105,974 controls). We performed two-sample Mendelian randomization study, and inverse variance–weighted (IVW) test was regarded as main analysis. Sensitivity analyses were further conducted to assess heterogeneity and horizontal pleiotropy. Results: The results of IVW showed that among the four food-derived antioxidants, only vitamin E had protective effect on the risk of overall breast cancer (OR = 0.837, 95% CI 0.757–0.926, P = 0.001) and ER+ breast cancer (OR = 0.823, 95% CI 0.693–0.977, P = 0.026). However, we found no association between food-derived vitamin E and ER− breast cancer. Conclusions: Our study suggested food-derived vitamin E can decrease the risk of breast cancer overall and ER+ breast cancer, and the robustness of our results was confirmed by sensitivity analyses. [ABSTRACT FROM AUTHOR]

Activating Transcription Factor 2 (ATF2) is a member of the ATF/CREB bZIP family of transcription factors and an oncogene in prostate cancer. ATF2 has been reported to be a critical substrate of the CUL3-SPOP-RBX1 E3 ubiquitin ligase complex and the recurrent somatic mutation of SPOP has been believed to be a key feature of prostate cancer. However, the deubiquitinating enzyme required for ATF2 stabilization is still unknown. Here, we show that ATF2 is associated with ubiquitin-specific protease 14 (USP14), which increased the protein abundance and transcriptional activity of ATF2. Pharmacologic inhibition or siRNA-mediated depletion of USP14 resulted in the decline and inactivation of ATF2. USP14 deubiquitinates and activates ATF2, resulting in enhanced prostate cancer cells proliferation both in vitro and in vivo. Importantly, silencing of ATF2 largely attuned USP14-mediated prostate cancer cells proliferation. Thus, our data revealed a critical role of USP1-ATF2 axis in the progress of prostate cancer and the inhibition of USP14 might be a promising strategy against prostate cancer. • USP14 is associated with ATF2. • USP14 deubiquitinates and stabilizes ATF2. • USP14 regulates the transcriptional activity of ATF2. • USP14 promotes prostate cancer cells proliferation partially dependent on ATF2. [ABSTRACT FROM AUTHOR]