Native Mass Spectrometry Quantitation of α2-3-Linked N-Acetylneuraminic Acid Content of Prostate-Specific Antigen: An Accurate Liquid Biopsy for Clinically Significant Prostate Cancer.

Application of the prostate-specific antigen (PSA) test, which measures PSA levels in blood, is standard in prostate cancer (PCa) screening. However, because PSA levels may be elevated for reasons other than PCa, it leads to high rates of misdiagnosis and overtreatment. Recently, alteration in the N-glycan sialylation of PSA, specifically increased levels of α2-3-linked N-acetylneuraminic acid (α2-3-Neu5Ac or α2-3-sialic acid), was identified as a potential biomarker for clinically significant PCa. Here, we introduce a robust top-down native mass spectrometry (MS) approach, performed using a combination of α2-3-Neu5Ac-specific and nonspecific neuraminidases and employing center-of-mass monitoring (CoMMon), for quantifying the levels of α2-3-Neu5Ac as a fraction of total N-linked Neu5Ac present on PSA extracted from blood serum. To illustrate the potential of the assay for clinical diagnosis and disease staging of PCa, the percentages of α2-3-Neu5Ac on PSA (%α23PSA) in the serum of low-grade (International Society of Urological Pathology Grade Group/GG1), intermediate-grade (GG2), and high-grade (GG3,4,5) PCa individuals were measured. We observed a high sensitivity (85.5%) and specificity (84.6%) for discrimination of GG1 from clinically significant GG2-5 patients when using a %α23PSA test cut-off of 28.0%. Our results establish that the %α23PSA in blood serum PSA, which can be precisely measured in a non-invasive manner with our dual neuraminidase native MS/CoMMon assay, can discriminate between clinically significant PCa (GG2-5) and low-grade PCa (GG1). Such discrimination has not been previously achieved and represents an important clinical need. This assay could greatly improve the standard PSA test and serve as a valuable PCa diagnostic tool.

Prognostic factors of non-muscle invasive bladder cancer: a study based on next-generation sequencing.

OBJECTIVE: To investigate the genetic prognostic factors for the recurrence of non-muscle invasive bladder cancer. MATERIALS AND METHODS: The patients underwent transurethral resection of bladder tumor and received bacillus Calmette-Guérin (BCG) or epirubicin. Next-generation sequencing was performed and alterations of genes, pathways, and tumor mutation burden were recorded. Associations between these clinicopathological and genetic variants were estimated, and prognostic factor identified. RESULTS: A total of 58 cases were included in our study, and 46 patients underwent treatment with BCG. FGFR3 was the most frequently altered gene (48%), and more commonly detected in intermediate-risk patients. Univariate Cox analysis demonstrated that 10 genes were significantly correlated with BCG failure, while NEB, FGFR1 and SDHC were independent recurrence predictors. Besides, epigenetic-related gene pathway mutations were negatively correlated with recurrence (hazard ratio: 0.198, P = 0.023). DNA damage response and repair gene alterations were positively correlated with tumor burden, while altered TP53 was most frequent among these genes and significant correlated with high tumor burden. CONCLUSION: BCG instillation significantly reduced the rate of recurrence compared with epirubicin in this population. Potential biomarkers and therapeutic targets were found with the help of next-generation sequencing; correlations between DDR genes alterations and high tumor mutation burden were also demonstrated.

[A Randomized Controlled Study of Intravesical Instillation Therapy of Bacillus Calmette-Guérin vs. Epirubicinin Treating Non-muscular Invasive Bladder Cancer].

OBJECTIVE: To explore the best treatment plan of intravesical instillation for patients with non-muscular invasive bladder cancer (NMIBC), to explore recurrence-related clinicopathological factors after intravesical instillation, and to evaluate the value of the prognosis and prediction models currently used for NMIBC patients. METHODS: Starting from 2016, patients who underwent transurethral resection of bladder tumor (TURBT) in our hospital and who received post-surgery diagnosis of having intermediate or high risks for NMIBC were enrolled in the study. They were randomly assigned to different group sat a ratio of 2∶2∶1 for receiving intravesical instillation therapy of Bacillus Calmette-Guérin (BCG) for 19 times, BCG for 15 times, and epirubicin (EPI) for 18 times. The clinicopathological data of the patients were recorded before, during and after instillation therapy, and survival curves were drawn to evaluate the effects of the three regimens, using recurrence-free survival as the endpoint. Clinicopathological data were analyzed to study the associations between various factors and post-instillation recurrence. The consistency index (c-index) was used to evaluate the predictive accuracy of the scoring model of the Spanish Urological Club for Oncological Treatment (CUETO) and the risk tables of European Organization for Research and Treatment of Cancer (EORTC). RESULTS: A total of 93 NMIBC patients (35 in the 19-time BCG group, 37 in the 15-time BCG group, and 21 in the EPI group) were included, with a median follow-up time of 33.46 months. Twenty-two patients experienced tumor recurrence and eight, tumor progression. The survival curve showed that the BCG group had better recurrence-free survival than the EPI group ( P=0.002), while the difference in recurrence-free survival between 19-time BCG and 15-time BCG groups was not statistically significant. Higher general complication rate was seen in the BCG groups compared with the EPI group (84.7% vs. 61.9%, P=0.022), but there was no grade 3-5 adverse events in any group. The c-index of CUETO scoring model and EORTC risk tables was higher than that of the prediction based solely on T stage, nuclear grade, or EAU risk stratification. In addition, the c-index in the BCG group was higher than that in the whole cohort. CONCLUSION: Among the subjects of this study, the recurrence rate of bladder cancer in the intravesical BCG instillation groups was lower than that of the epirubicin group. EORTC risk tables and CUETO scoring model exhibited higher predictive accuracies in BCG-treated patients than its performance for the whole NMIBC cohort.

Minimally Invasive Versus Open Adrenalectomy in Patients with Adrenocortical Carcinoma: A Meta-analysis.

BACKGROUND: Open surgery remains the preferred surgical treatment of adrenocortical carcinoma (ACC), while the role of minimally invasive adrenalectomy surgery (MIS) in ACC is still controversial. The present study was conducted to compare MIS with open adrenalectomy (OA) in ACC. METHODS: The Embase, PubMed, and Cochrane Library databases were comprehensively searched. The weighted mean difference (WMD), relative risk (RR), and hazard ratio (HR) were pooled. RESULTS: A total of 15 studies incorporating 2207 patients were included in the present study. MIS approaches were likely to have a comparable operation time (WMD - 17.77; p = 0.150) and postoperative complications (RR 0.74; p = 0.091) compared with OA, and were significantly associated with less blood loss (WMD - 1761.96; p = 0.016) and shorter length of stay (WMD - 2.96; p < 0.001). MIS approaches were also more likely to have an earlier recurrence (WMD - 8.42; p = 0.048) and more positive surgical margin (RR 1.56; p = 0.018) and peritoneal recurrence (RR 2.63; p < 0.001), while the overall recurrence (RR 1.07; p = 0.559) and local recurrence (RR 1.33; p = 0.160) were comparable between the two groups. Furthermore, surgical approaches did not differ in overall survival (HR 0.97; p = 0.801), cancer-specific survival (HR 1.04; p = 0.869), and recurrence/disease-free survival (HR 0.96; p = 0.791). CONCLUSIONS: In the present study, MIS approaches were likely to have a better recovery. Although MIS approaches were associated with earlier recurrence and more positive surgical margin and peritoneal recurrence, no significant differences in survival outcomes were found. OA should still be considered as the standard treatment, but MIS approaches could be offered for selected ACC cases, and performed by surgeons with appropriate laparoscopic expertise, ensuring an improved survival for patients.

Preoperative systemic immune-inflammation index predicts prognosis of patients with non-metastatic renal cell carcinoma: a propensity score-matched analysis.

BACKGROUND: A novel systemic immune-inflammation index (SII), based on the neutrophils, lymphocytes and platelet counts, is associated with the prognosis of several cancers. The present study evaluates the prognostic significance of SII in non-metastatic renal cell carcinoma (RCC). METHOD: The present study retrospectively reviewed the medical record of patients with non-metastatic RCC who underwent nephrectomy between 2010 and 2013. Receiver operating characteristic (ROC) curve analysis was performed to identify the optimal cut-off value. In addition, the propensity score matching (PSM) was performed with a matching ratio of 1:1. Univariate and multivariate Cox proportional hazards models were used to identify the prognostic factors. The results were reported by hazard ratio (HR) with 95% confidence interval (95% CI). RESULTS: A total of 646 patients were included in the final analysis. High SII group (> 529) was significantly associated with older age (P = 0.014), larger tumor (P < 0.001), higher pathological T stage (P < 0.001), higher tumor grade (P < 0.001) and more tumor necrosis (P < 0.001). Multivariate Cox regression analysis demonstrated that the higher preoperative SII was significantly associated with worse overall survival (OS) (HR = 2.26; 95% CI 1.44-3.54; P < 0.001) and cancer-specific survival (CSS) (HR = 2.17; 95% CI 1.33-3.55; P = 0.002). After PSM, elevated preoperative SII was an independent predictor of poor OS (HR = 1.78; 95% CI 1.1-2.87; P = 0.018) and CSS (HR = 1.8; 95% CI 1.07-3.03; P = 0.027). CONCLUSION: In conclusion, preoperative SII is associated with adverse factors for RCC. Furthermore, higher preoperative SII is an independent predictor of poor OS and CSS in surgically treated patients with non-metastatic RCC. More prospective and large scale studies are warranted to validate our findings.

The prognostic value of De Ritis (AST/ALT) ratio in patients after surgery for urothelial carcinoma: a systematic review and meta-analysis.

BACKGROUND: Recently, the De Ritis (AST/ALT) ratio has been considered as a prognostic biomarker for various malignancies. We conducted this systematic review and meta-analysis to explore the prognostic value of preoperative De Ritis ratio in patients after surgery for urothelial carcinoma. METHODS: We searched the online database Embase, PubMed and Cochrane Library up to October 2019. The hazard ratio (HR) and 95% confidence interval (CI) were extracted from the studies. RESULTS: A total of 8 studies incorporating 3949 patients were included in the quantitative synthesis. We observed that elevated preoperative De Ritis ratio is associated with inferior OS (HR = 1.97; 95% CI 1.70-2.28; P < 0.001), CSS (HR = 2.40; 95% CI 2.02-2.86; P < 0.001), RFS (HR = 1.31; 95% CI 1.11-1.54; P = 0.001), PFS (HR = 2.07; 95% CI 1.68-2.56; P < 0.001) and MFS (HR = 2.39; 95% CI 1.16-4.91; P = 0.018). Stratified by diseases, the elevated De Ritis ratio also served as an unfavorable factor. CONCLUSION: The elevated preoperative De Ritis ratio is an unfavorable factor for patients with urothelial carcinoma. In patients with BC and UTUC, the elevated preoperative De Ritis ratio is also associated with poor prognosis. But De Ritis ratio must be validated in large, independent cohorts before it can be applied widely.

[Cytoreductive Partial Nephrectomy versus Cytoreductive Radical Nephrectomy for Locally T 1 Stage Metastatic Renal Rell Carcinoma (mRCC)].

OBJECTIVE: To explore whether cytoreductive partial nephrectomy (cPN) or cytoreductive radical nephrectomy (cRN), is more beneficial for patients with locally T 1 stage metastatic renal cell carcinoma (mRCC). METHODS: We retrospectively collected the data ofthe patients with locally T 1 stage mRCC ( n=934) from the Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was conducted to identify the determinants of cPN. Propensity-score match (PSM) was used to diminish the confounder. Kaplan-Meier survival analyses was performed and multivariable Cox proportional hazards model was used to evaluate the effect of cPN and cRN on overall survival (OS) and cancer specific survival (CSS). RESULTS: Among the 934 patients, 142 (15.2%) received cPN and 792 (84.8%) received cRN. Before PSM, both OS and CSS in cPN group were better in Kaplan-Meier analysis (log rank test, each P< 0.01). In a survival analysis of propensity-score matched 141 pairs of patients, cPN was still associated with improved OS and CSS compared with cRN (log rank test, each P< 0.01). After PSM, the 2-year OS were 61.7% and 74.4%, and 5-year OS were 35.6% and 59.2% in the cRN and cPN cohorts respectively. Cox proportional hazards model confirmed cPN the independent risk factor of both OS and CSS. CONCLUSION: For mRCC patients with locally T 1 stage, cPN may gain an OS and CSS benefit compared with cRN.

Morphological and molecular characterization of Ceratomyxa batam n. sp. (Myxozoa: Ceratomyxidae) infecting the gallbladder of the cultured Trachinotus ovatus (Perciformes: Carangidae) in Batam Island, Indonesia.

A new coelozoic myxozoan species, Ceratomyxa batam n. sp., was identified in cultured carangid fish, Trachinotus ovatus (Perciformes: Carangidae), in waters off Batam Island of Indonesia. The bi- and trivalved spores were observed in the gallbladder of T. ovatus. Mature bivalved spores of C. batam n. sp. were transversely elongated and narrowly crescent in shape, 3.8 ± 0.36 (2.7-4.6) µm long and 19.2 ± 1.75 (16.2-22.0) µm thick. Two sub-spherical polar capsules were 2.3 ± 0.18 (2.0-2.8) µm long and 2.6 ± 0.16 (2.3-2.9) µm wide. Prevalence was 72.2% in 72 examined T. ovatus according to evaluations dating from November 2016. The maximum likelihood phylogenetic tree based on small subunit rDNA sequence showed similarity with Ceratomyxa robertsthomsoni and Ceratomyxa thalassomae found in Australia. This is the first report of Ceratomyxa species identified in a seawater fish at Batam Island, Indonesia.

[Application of Prognostic Predication Model in Clinical Non-metastatic Renal Cell Carcinoma].

OBJECTIVE: To study and compare the practical use of three prognostic predication models in clinical non-metastatic renal cell carcinoma (RCC). METHODS: We retrospectively collected the data of 1 202 clinical non-metastatic RCC patients operated on between 1999 and 2012 at West China Hospital of Sichuan University. Survival analysis method was used to establish three prognostic prediction models including SSIGN, Leibovich and UISS based on different clinical and pathological indicators. The predictive ability was evaluated by the area under receiver operating characteristic curve (AUC). RESULTS: Of the 1 202 clinical non-metastatic RCC patients, 1 030 cases were limited RCC patients, and 172 cases were locally advanced RCC patients. The median follow-up time of the patients was 63.02 months. The 2-year and 5-year overall survival rate were 94.7% and 87.6%, respectively. The 5-year overall survival rates of patients with different clinical stages and grades were significantly different. The predictive accuracies for limited RCC of UISS, SSIGN and Leibovich model were 0.667, 0.785 and 0.758, respectively. For locally advanced RCC, the predictive accuracies of the three models were all lower than 0.6. CONCLUSIONS: SSIGN has certain predictive value in clinical non-metastatic RCC. However, for the advanced RCC, all the prognostic models demonstrate limited predictive value.

Validation and comparison of prognostic value of different preoperative systemic inflammation indices in non-metastatic renal cell carcinoma.

BACKGROUND: Several preoperative systemic inflammation indices have been proven to be correlated with the prognosis of patients diagnosed with non-metastatic renal cell carcinoma (RCC). However, these indices are currently not included in the main prognostic models, and few studies have compared the prognostic efficacy of different preoperative systemic inflammation indices. PATIENTS AND METHODS: This retrospective study reviewed patients diagnosed with non-metastatic RCC who underwent nephrectomy at West China Hospital of Sichuan University from 2011 to 2013. Different preoperative systemic inflammation indices (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], monocyte-to-lymphocyte ratio [MLR], systemic immune-inflammation index [SII], and systemic inflammation response index [SIRI]) were calculated. Logistic regression was used to explore the relationship between systemic inflammation indices and clinical characteristics, and Cox regression was used to identify independent prognostic factors of overall survival (OS). The concordance index (c-index) was also calculated. RESULTS: A total of 820 patients were included in the study, with a median follow-up of 78 months. Higher levels of NLR (> 3.04), PLR (> 147), MLR (> 0.32), SII (> 700), and SIRI (> 1.27) were found to be associated with more advanced tumor stage, higher Furman grade, and larger tumor size. In multivariate Cox regression, NLR, PLR, MLR, SII, and SIRI were identified as independent prognostic factors, and SII had the highest and most significant hazard ratio and the largest c-index. CONCLUSION: In conclusion, various systemic inflammation indices were found to be associated with poorer OS. Among them, SII exhibited the highest predictive efficacy, suggesting its potential inclusion as a component in future prognostic models.

Prognostic value of preoperative microscopic hematuria in patients with non-metastatic renal cell carcinoma who underwent nephrectomy.

BACKGROUND: Microscopic hematuria is associated with various urinary system diseases and is commonly used for the diagnosis of these conditions. Its prognostic role in non-metastatic renal cell carcinoma (RCC) patients who underwent nephrectomy remains unclear. PATIENTS AND METHODS: A retrospective analysis of non-metastatic RCC patients who underwent nephrectomy in West China Hospital of Sichuan University from 2011 to 2013 was performed. Significant microscopic hematuria (SMH), defined as a threshold with a significant impact on disease-free survival (DFS) and overall survival (OS), was determined by Kaplan-Meier curves and the Maximally Selected Log-Rank Statistic. Kaplan-Meier curves were then used to estimate patients' DFS and OS, and the log-rank test was used to examine statistical significance. Logistic regression was utilized to identify clinical-pathological factors associated with SMH, while Cox regression was employed to determine independent factors of survival. RESULTS: A total of 773 patients were included, and 20 red blood cells per high-power field was identified as the cutoff of SMH, of which 90 patients had preoperative SMH (11.6%) and 683 patients (88.4%) did not. Larger tumor size (OR = 1.10 [per cm], 95% CI 1.01-1.19, p = 0.036) and higher Fuhrman grade (grade 3 vs. grade 1-2, OR = 1.76, 95% CI 1.09-2.83, p = 0.02; grade 4 vs. grade 1-2, OR = 2.15, 95% CI 0.73-6.31, p = 0.164) were predictors of SMH. Compared to non-SMH patients, SMH patients had poorer DFS (HR = 3.16, 95% CI 2.07-4.83, p < 0.001) and OS (HR = 2.11, 95% CI 1.34-3.32, p = 0.001). CONCLUSION: In summary, preoperative SMH is associated with larger tumor size and higher Fuhrman grade, and it is also independently correlated with poorer DFS and OS in non-metastatic RCC patients who underwent nephrectomy.

Relationship between weight-adjusted-waist index and erectile dysfunction in the United State: results from NHANES 2001-2004.

Objective: The purpose of this study is to examine the association between a novel adiposity parameter, the weight-adjusted-waist index (WWI), and erectile dysfunction (ED). Methods: According to National Health and Nutrition Examination Survey (NHANES) 2001-2004, a total of 3884 participants were categorized as ED and non-ED individuals. WWI was calculated as waist circumference (WC, cm) divided by the square root of weight (kg). Weighted univariable and multivariable logistic regression models were conducted to assess the correlation between WWI and ED. Smooth curve fitting was utilized to examine the linear association. The receiver operating characteristic (ROC) curve and DeLong et al.'s test were applied to compare the area under curve (AUC) value and predictive power among WWI, body mass index (BMI), and WC for ED. Results: WWI was positively related to ED with the full adjustment [odds ratio (OR)=1.75, 95% confidence interval (95% CI): 1.32-2.32, p=0.002]. After converting WWI to a categorical variable by quartiles (Q1-Q4), compared to Q1 the highest WWI quartile was linked to an obviously increased likelihood of ED (OR=2.78, 95% CI: 1.39-5.59. p=0.010). Subgroup analysis revealed the stability of the independent positive relationship between WWI and ED. It was shown that WWI had a stronger prediction for ED (AUC=0.745) than BMI (AUC=0.528) and WC (AUC=0.609). Sensitivity analysis was performed to verify the significantly positive connection between WWI and stricter ED (OR=2.00, 95% CI: 1.36-2.94, p=0.003). Conclusion: An elevated WWI was related to higher risks of ED in the United State adults, and a stronger predictive power of WWI for ED was observed than BMI and WC.

Radical versus partial nephrectomy for T1 non-clear cell renal cell carcinoma.

INTRODUCTION: Nephron-sparing surgery is the recommended surgical management of T1 renal cell carcinoma (RCC). However, non-clear cell RCC (nccRCC) is heterogeneous and included many histological types. Therefore, the present study was performed to compare radical nephrectomy (RN) versus partial nephrectomy (PN) in nccRCC. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results registry (2000-2019), the patients with nccRCC were identified. Kaplan-Meier survival curve and the log-rank test were conducted. Univariate analysis and multivariate Cox regression analysis were performed to explore the prognostic factors. RESULTS: A total of 7575 patients with nccRCC were included, of which papillary RCC (n = 5219) is the major histology. Kaplan-Meier plots and log-rank tests showed that nccRCC patients who underwent RN had significantly worse overall survival (OS) and cancer-specific survival (CSS) than those who received PN (all P < 0.05). Multivariate analysis also revealed that RN was significantly associated with poor OS and CSS in nccRCC patients. Stratified by histological types, the multivariate analysis also revealed that RN was significantly associated with poor OS in papillary and chromophobe (all P < 0.05). Besides, the multivariable analysis indicated that RN was associated with poor CSS in papillary RCC (P < 0.05). For other histology, the patients who received RN had a comparable survival to those who received PN. CONCLUSION: For patients with T1 nccRCC, our findings revealed that PN was not inferior to RN in OS and CSS. PN may be also the preferred option for T1 nccRCC, but more prospective studies are required to validate this finding.

The biological role and immunotherapy of gangliosides and GD3 synthase in cancers.

Gangliosides are a large subfamily of glycosphingolipids that broadly exist in the nervous system and interact with signaling molecules in the lipid rafts. GD3 and GD2 are two types of disialogangliosides (GDs) that include two sialic acid residues. The expression of GD3 and GD2 in various cancers is mostly upregulated and is involved in tumor proliferation, invasion, metastasis, and immune responses. GD3 synthase (GD3S, ST8SiaI), a subclass of sialyltransferases, regulates the biosynthesis of GD3 and GD2. GD3S is also upregulated in most tumors and plays an important role in the development and progression of tumors. Many clinical trials targeting GD2 are ongoing and various immunotherapy studies targeting gangliosides and GD3S are gradually attracting much interest and attention. This review summarizes the function, molecular mechanisms, and ongoing clinical applications of GD3, GD2, and GD3S in abundant types of tumors, which aims to provide novel targets for future cancer therapy.

Development and validation of pyroptosis-related lncRNAs prediction model for bladder cancer.

Bladder cancer (BLCA) is one of the highly heterogeneous disorders accompanied by a poor prognosis. The present study aimed to construct a model based on pyroptosis-related long-stranded non-coding RNA (lncRNA) to evaluate the potential prognostic application in bladder cancer. The mRNA expression profiles of bladder cancer patients and corresponding clinical data were downloaded from the public database from The Cancer Genome Atlas (TCGA). Pyroptosis-related lncRNAs were identified by utilizing a co-expression network of pyroptosis-related genes and lncRNAs. The lncRNA was further screened by univariate Cox regression analysis. Finally, eight pyroptosis-related lncRNA markers were established using least absolute shrinkage and selection operator (Lasso) regression and multivariate Cox regression analyses. Patients were separated into high- and low-risk groups based on the performance value of the median risk score. Patients in the high-risk group had significantly poorer overall survival (OS) than those in the low-risk group (P<0.001). In multivariate Cox regression analysis, the risk score was an independent predictive factor of OS (HR > 1, P<0.01). The areas under the curve (AUCs) of the 3- and 5-year OS in the receiver operating characteristic (ROC) curve were 0.742 and 0.739, respectively. In conclusion, these eight pyroptosis-related lncRNA and their markers may be potential molecular markers and therapeutic targets for bladder cancer patients.

Prognostic significance of Naples prognostic score in operable renal cell carcinoma.

Background: Naples prognostic score (NPS), a novel scoring system based on nutritional and inflammatory status, is associated with prognosis in several cancers. This study aimed to evaluate the prognostic significance of preoperative NPS in patients undergoing nephrectomy. Patients and Methods: This study retrospectively analyzed patients with renal cell carcinoma (RCC) who underwent radical or partial nephrectomy between 2010 and 2013. The clinicopathological characteristics of patients stratified by preoperative NPS were compared. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox proportional hazards models were used to identify independent prognostic factors. Receiver operating characteristic curves were used to evaluate prediction efficiency. Results: A total of 638 patients with operable RCC were included. The high-NPS group (NPS group 2) was significantly associated with older age (P < 0.001), larger tumor size (P < 0.001), worse pathological T stage (P < 0.001), positive lymph node pathology (P = 0.002), higher tumor grade (P < 0.001), and greater tumor necrosis (P < 0.001). Multivariable analysis demonstrated that the high-NPS subgroup had significantly worse overall survival (OS) [hazard ratio (HR): 2.25, 95% confidence interval (CI): 1.45-3.50, P < 0.001] and progression-free survival (PFS) (HR: 2.26, 95% CI: 1.48-3.44, P < 0.001). Among several preoperative scoring systems, NPS had the strongest discriminatory power for predicting OS and PFS. Conclusion: Preoperative NPS can serve as a simple novel risk stratification tool to optimize the prognosis of patients with operable RCC. Further prospective and large-scale studies are needed to validate our findings.

Comparison of different surgical methods and strategies for inguinal lymph node dissection in patients with penile cancer.

To compare the clinical feasibility and oncological outcome of different surgical techniques for inguinal lymphadenectomy (ILND) in patients suffering from penile cancer. This study included data from 109 cN0-2 patients diagnosed with penile cancer who received ILND. 80 laparoscopic ILND were performed on 40 patients, while 138 open surgeries were performed on 69 patients. Perioperative complications and prognosis were compared between different surgical techniques. Compared with the open surgery group, the laparoscopy group had a shorter hospital stay (8.88 ± 7.86 days vs. 13.94 ± 10.09 days, P = 0.004), and a lower wound healing delay rate (8.75% vs. 22.46%, P = 0.017), but also had longer drainage time (10.91 ± 9.66 vs. 8.70 ± 4.62, P = 0.002). There were no significant differences in terms of other intraoperative parameters, complications, and survival between open and laparoscopic group. Compared with saphenous vein ligated subgroup, preserved subgroup showed no significant reducing of complication rate. There was no significant difference among complication between different open surgery subgroup. Immediate ILND showed no prognostic advantage over delayed ILND regardless of clinical lymph node status. Compared with open surgery, the minimally invasive ILND technique has similar oncological efficiency and a lower complication rate. Saphenous vein preservation has limited value in reducing complications. Delayed lymphadenectomy might be a more reasonable option for ILND.

Nomogram predicting survival to assist decision-making of radical prostatectomy in patients with metastatic prostate cancer.

BACKGROUND: Radical prostatectomy (RP) has heterogeneous effects on survival of patients with metastatic prostate cancer (mPCa). A reliable model to predict risk of cancer-specific mortality (CSM) and the potential benefit derived from RP is needed. METHODS: Patients diagnosed with mPCa were identified using the Surveillance, Epidemiology, and End Results database (2004-2015) and categorized in RP versus nonlocal treatment (NLT). Based on the Fine and Gray competing risks model in 8,463 NLT patients, a nomogram was created to predict CSM in mPCa patients. Decision tree analysis was then utilized for patient stratification. The effect of RP was evaluated among 3 different subgroups. RESULTS: A total of 8,863 patients were identified for analysis. Four hundred (4.5%) patients received RP. The 5-year cumulative incidence of CSM was 52.4% for the entire patients. Based on nomogram scores, patients were sorted into three risk groups using decision tree analysis. In the low- and intermediate-risk group, RP was found to be significantly correlated with a 21.7% risk reduction of 5-year CSM, and 25.0% risk reduction of 5-year CSM, respectively, whereas RP was not associated with CSM in high-risk group (hazard ratio =0.748, 95% confidence interval 0.485-1.150; P=0.190). CONCLUSIONS: We developed a novel nomogram and corresponding patient stratification predicting CSM in mPCa patients. A newly identified patient subgroup with low-, and intermediate-risk of CSM might benefit more from RP. These results should be further validated and improved by ongoing prospective trials.

Effectiveness and safety of tibial nerve stimulation versus anticholinergic drugs for the treatment of overactive bladder syndrome: a meta-analysis.

BACKGROUND: This meta-analysis aimed to evaluate the efficacy and safety of tibial nerve stimulation (TNS) and anticholinergic drugs (ACDs) for the treatment of overactive bladder syndrome (OAB). METHODS: Qualified studies up to November 3, 2020 were retrieved from PubMed, Embase, the Cochrane Library and Web of Science. Pooled mean differences (MDs) were calculated to evaluate the improvement of micturition frequency per day, nocturia per night, urinary urgency episodes per day, incontinence episodes per day, and voided volume each time. Odd ratios (ORs) were used to assess the discontinuation rate. RESULTS: A total of 6 RCTs including 291 patients were included. Comparing with those receiving ACDs, patients receiving TNS had a significantly better improvement of urge incontinence episodes (MD =-1.11; 95% CI: -1.66, -0.55; P<0.001), but had comparable effect on micturition (MD =-0.75; 95% CI: -1.78, 0.28; P=0.16), nocturia (MD =-1.11; 95% CI: -2.93, 0.72; P=0.23), urgency (MD =-0.57; 95% CI: -1.93, 0.79; P=0.41) and voided volume (MD =11.61; 95% CI: -3.95, 27.18; P=0.14). Moreover, TNS group had a significantly lower discontinuation rate (OR =0.13; 95% CI: 0.03, 0.51; P=0.003) during the trials. DISCUSSION: TNS is as effective as ACDs for treating OAB, but with better performance on the decrease of urge incontinence episodes. Besides, TNS appears to be more tolerable than ACDs.

Evaluation of the Efficacy of PARP Inhibitors in Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis.

Background: Poly(ADP-ribose) polymerase (PARP) inhibitors have breakthrough designations for metastatic castration-resistant prostate cancer (mCRPC). We performed a meta-analysis of current clinical trials to evaluate the efficacy of PARP inhibitors in mCRPC patients based on their genetic status. Methods: On August 2020, PubMed, Scopus, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched for phase II/III clinical studies on PARP inhibitors in mCRPC patients. Data were extracted independently by two investigators and analyzed using Review Manager software version 5.3. Primary endpoints included overall response rate (ORR) and progression-free survival (PFS). Results: Nine clinical trials were identified and analyzed for the clinical benefit of PARP inhibitors in mCRPC patients (n = 1,219). Pooled analyses demonstrated that PARP inhibitors could provide a significant improvement of ORR and PFS in patients with homologous recombination deficiency (HRD) when compared with non-HRD patients. Within the HRD subgroup, BRCA mutation patients achieved significantly higher ORR [odds ratio (OR): 9.97, 95% confidence interval (CI): 6.08-16.35] and PFS rates at 12 months (OR: 3.23, 95% CI: 1.71-6.10) when compared with BRCA wild-type patients. Furthermore, patients harboring HRD without BRCA mutations have a higher objective response after PARP inhibitor treatment compared with non-HRD patients. Conclusion: PARP inhibitor is an effective treatment option for mCRPC patients with mutations in genes related to the HR DNA repair pathway when compared with non-HRD patients. In addition to BRCA mutations, other HRD-related gene aberrations may also be used as novel biomarkers to predict the efficacy of PARP inhibitors.