Combination of C-Reactive Protein and Neutrophil-to-Lymphocyte Ratio as a Novel Prognostic Index in Patients With Bladder Cancer After Radical Cystectomy.

BACKGROUND: Inflammation is widely considered an important hallmark of cancer and associated with poor postoperative survival. The objective of this study is to assess the significance of preoperative C-NLR, a new inflammation-based index that includes preoperative C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), on therapeutic outcomes for bladder cancer (BC) patients after radical cystectomy (RC). MATERIALS AND METHODS: BC patients who underwent RC between 2010 and 2019 were retrospectively analyzed from our medical center. The predictive effect of CRP, NLR, and C-NLR on the survival of BC patients were analyzed by the receiver operating characteristic (ROC) curves. The relationship between C-NLR and postoperative survival was investigated by Cox regression. The corresponding nomograms were built based on the Cox regression results of overall survival (OS) and disease-free survival (DFS), which were further validated by ROC curves, decision curve analysis (DCA) curves, and calibration curves. RESULTS: Of the 199 eligible patients, 83 (41.70%) were classified as high C-NLR group and the remaining 116 (58.30%) were classified as low C-NLR group. ROC analysis showed that C-NLR had the largest area under curve (AUC) compared to CRP and NLR. Multivariate analysis revealed that T-stage and C-NLR [high C-NLR vs. low C-NLR, hazard ratio (HR) = 2.478, 95% confidence interval (CI), 1.538-3.993, p < 0.001] were independent predictors of OS, whereas T-stage, M-stage, and C-NLR (high C-NLR vs. low C-NLR, HR = 2.817, 95% CI, 1.667-4.762, p < 0.001) were independent predictors of DFS. ROC and DCA analysis demonstrated better accuracy and discrimination of 3- and 5-year OS and DFS with C-NLR-based nomogram compared to TNM stage. The calibration curve reconfirmed the accurate predicting performance of nomograms. CONCLUSION: C-NLR is a reliable predictor of long-term prognosis of BC patients after RC and will contribute to the optimization of individual therapy for BC patients.

Perioperative outcomes of intracorporeal robot-assisted radical cystectomy versus open radical cystectomy: A systematic review and meta-analysis of comparative studies.

PURPOSE: To systematically review studies comparing the perioperative outcomes of intracorporeal robot-assisted radical cystectomy (iRARC) and open radical cystectomy (ORC). METHODS: Systematic searches of PubMed, Web of Science and the Cochrane Library were performed in June 2020. Studies with data comparing iRARC and ORC were included in our review, and a pooled meta-analysis was completed. RESULTS: In total, 8 studies (7 prospective studies, 1 retrospective study) comparing 1193 patients were included for our review and meta-analysis. Compared with ORC, iRARC demonstrated lower estimated blood loss (weighted mean difference (WMD): -449.25; 95% CI -566.47 - -332.03; p < 0.01), lower blood transfusion rates (OR: 0.31; 95% CI 0.22 - 0.46; p < 0.01), and lower postoperative complication rates with Clavien-Dindo grades III-IV (30 days: OR: 0.65; 95% CI 0.47 - 0.90; p = 0.01; 90 days: OR: 0.72; 95% CI 0.53 - 0.98; p = 0.04), but a longer operative time (WMD: 78.82; 95% CI 52.77 - 104.87; P < 0.01). Furthermore, there was no significant difference between iRARC and ORC in terms of postoperative complication rates with Clavien-Dindo grades Ⅰ-Ⅱ (30 days: OR: 0.71; 95% CI 0.36 - 1.40; p = 0.32; 90 days: OR: 0.98; 95% CI 0.74 - 1.30; p = 0.89), length of stay (WMD: -1.18; 95% CI -3.33 - -2.07; p = 0.06) and positive surgical margins (OR: 0.78; 95% CI 0.0.45 - 1.36; p = 0.38). CONCLUSION: iRARC was associated with a significantly lower estimated blood loss and a lower blood transfusion rate and major postoperative complication rate than ORC.

Effects of radical cystectomy combined with GC chemotherapy in the treatment of invasive bladder cancer and its influence on the incidence of adverse reactions.

OBJECTIVE: To explore the efficiency of radical cystectomy combined with GC chemotherapy in the treatment of invasive bladder cancer and its influence on the incidence of adverse reactions. METHODS: The clinical data of 120 patients with invasive bladder cancer admitted to our hospital from February 2015 to February 2016 were retrospectively analyzed. According to different treatment methods, they were equally divided into two groups. The experimental group (n=60) was treated with radical cystectomy combined with GC chemotherapy. The control group (n=60) was treated with bladder-preserving comprehensive treatment (transurethral bladder tumor resection + internal iliac artery infusion chemotherapy + intravesical infusion chemotherapy). The short-term efficiency, adverse reactions, long-term treatment indicators, survival, surgical indicators, and quality of life were compared between the two groups. RESULTS: The two groups showed similar objective remission rate and disease control rate (P>0.05). Both groups of patients had different degrees of hematological toxicity and non-hematological toxicity, but no severe systemic organ toxicity. Fewer patients in the experimental group experienced anemia and fever compared with the control group (P<0.05). The incidence of recurrence, hydronephrosis, and metastasis in the experimental group was significantly lower than that in the control group (P<0.05). The experimental group showed a higher 3-year survival rate than the control group (86.7% vs 75.0%), with no statistical difference between the two groups (P>0.05). The experimental group obtained a significantly higher 5-year survival rate than that of the control group (70.0% vs 51.7%) (P<0.05). The experimental group outperformed the control group in terms of surgical indicators (P<0.001). The two groups had similar quality of life scores after the 5-year follow-up (P>0.05). CONCLUSION: Radical cystectomy combined with GC for the treatment of invasive bladder cancer reduces the incidence of adverse reactions and enhances the 5-year survival of patients, with a promising long-term efficiency.

UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis.

Emerging evidences have demonstrated that ubiquitin-associated domain-containing protein 2 (UBAC2) is closely related to the occurrence and development of malignant tumors. However, the functions and underlying molecular mechanisms of UBAC2 in bladder cancer (BC) development have not been defined. In this study, we found that both UBAC2 mRNA and protein levels were upregulated in BC tissues and cell lines, and knockdown of UBAC2 inhibited BC cells proliferation both in vitro and in vivo. Meanwhile, Kaplan-Meier survival plots of 406 BC cases from TCGA database showed that higher expression of UBAC2 in BC patients was associated with lower survival rate. Mechanistic studies revealed that knockdown of UBAC2 increased the expression of p27 by posttranscriptional regulation. Our previous study indicated that circular RNA BCRC-3 (BCRC-3) promoted the expression of p27 through interacting with miR-182-5p, and reversed miR-182-5p-induced inhibition of p27 3'UTR activity. In the present study, we found that UBAC2 could bind to BCRC-3, and subsequently affected the interaction of BCRC-3 with miR-182-5p to inhibit the expression of p27. Furthermore, knockdown of BCRC-3 partly reversed the upregulation of p27 expression induced by knockdown of UBAC2. Our findings highlight a novel mechanism of UBAC2 in regulating p27 through affecting the function of BCRC-3, and provide a research basis for the diagnostic and therapeutic application of BC.

Lasers versus bipolar technology in the transurethral treatment of benign prostatic enlargement: a systematic review and meta-analysis of comparative studies.

PURPOSE: To systematically review studies comparing the overall efficacy and safety of lasers and bipolar technology for the transurethral treatment of benign prostatic enlargement (BPE). METHODS: A systematic review of the literature was completed in February 2018. Studies with comparative data between different lasers and bipolar technologies (enucleation or resection) were included in this review. A meta-analysis was performed using STATA 14.0, and subgroup analyses were also performed regarding the type of laser (holmium, thulium, green light and diode). RESULTS: 27 studies with 31 published articles (4382 patients) were selected for the meta-analysis. Compared with bipolar technology, lasers demonstrated shorter catheterization duration (standardized mean difference (SMD): 1.44; 95% CI 1.07-1.81; p < 0.001) and shorter hospital stay (SMD: 1.16; 95% CI 0.83-1.49; p < 0.001), and a smaller drop in hemoglobin (Hb) level (SMD: 0.86; 95% CI 0.47-1.26; p < 0.001). However, significant heterogeneity was detected in the studies and statistical significance was lost on sub-analyses. Furthermore, there were no significant differences between lasers and bipolar technology in the maximum flow rate (Qmax) and international prostate symptom score (IPSS) at a minimum of 3 months after treatment. Complications, including urethral stricture, urinary incontinence, urinary tract infection, re-catheterization and blood transfusion, did not significantly differ between lasers and bipolar technology. CONCLUSION: Early efficacy and safety profiles were comparable between bipolar and laser treatments. Differences were observed in terms of smaller reduction in Hb, shorter catheterization duration and shorter hospital stay in favor of lasers. However, the smaller reduction in Hb, with lasers, did not translate into reduced transfusion requirements. Furthermore, there was significant heterogeneity in the studies and, in subgroup analyses, the differences were not statistically significant.

Mettl14 inhibits bladder TIC self-renewal and bladder tumorigenesis through N6-methyladenosine of Notch1.

BACKGROUND: N6-methyladenosine (m6A) emerges as one of the most important modification of RNA. Bladder cancer is a common cancer type in developed countries, and hundreds of thousands of bladder cancer patients die every year. MATERIALS AND METHODS: There are various cells in bladder tumor bulk, and a small population cells defined as tumor initiating cells (TIC) have self-renewal and differentiation capacities. Bladder TICs drive bladder tumorigenesis and metastasis, and their activities are fine regulated. However, the role of N6-methyladenosine in bladder TIC self-renewal is unknown. RESULTS: Here, we found a decrease of N6-methyladenosine in bladder tumors and bladder TICs. N6-methyladenosine levels are related to clinical severity and outcome. Mettl14 is lowly expressed in bladder cancer and bladder TICs. Mettl14 knockout promotes the proliferation, self-renewal, metastasis and tumor initiating capacity of bladder TICs, and Mettl14 overexpression exerts an opposite role. Mettl14 and m6A modification participate in the RNA stability of Notch1 mRNA. Notch1 m6A modification inhibits its RNA stability. Notch1 plays an essential role in bladder tumorigenesis and bladder TIC self-renewal. CONCLUSION: This work reveals a novel role of Mettl14 and N6-methyladenosine in bladder tumorigenesis and bladder TICs, adding new layers for bladder TIC regulation and N6-methyladenosine function.

[Clinical characterization of testicular yolk sac tumor in children and adults].

OBJECTIVE: To compare the clinical characteristics of simple testicular yolk sac tumor (YST) in children with those in adults so as to improve the diagnosis and treatment of the malignance. METHODS: This study included 75 cases of simple testicular YST pathologically confirmed between May 2008 and July 2018, which were divided into groups A (aged <18 years, n = 64) and B (aged ≥18 years, n = 11). We analyzed the clinical data on all the cases and compared the clinical manifestations, laboratory results, pathological findings, clinical stages, treatment methods and prognostic outcomes between the two groups of patients. RESULTS: The patients of group A ranged in age from 6 months to 5 years (ï¼»1.38 ± 0.89ï¼½ yr), with the tumor diameter of 0.9－6.0 (2.48 ± 1.12) cm, while those of group B from 25 to 49 years (median 34 years), with the tumor diameter of 3.5－6.3 (5.16 ± 1.32) cm, most presenting with a painless scrotal mass, 4 (6.2%) in group A and 5 (45.5%) in group B with testis pain. There were statistically significant differences between the two groups in the tumor diameter and initial manifestations (P < 0.05). All the patients were treated by radical high-level spermatectomy and orchiectomy and, in addition, 1 in group A and 3 in group B by retroperitoneal lymph node dissection (RPLND), 24 in the former and 5 in the latter group followed by chemotherapy. Elevated levels of serum alpha-fetoprotein (AFP) were observed in all the cases. Sixty-five of the patients were followed up for 10－78 (52.00 ± 23.78) months, during which 2 cases of simple metastasis, 3 cases of simple relapse, 3 cases of relapse with metastasis and 5 cases of death were found in group A, and 5 cases of simple metastasis, 1 case of simple relapse, 1 case of relapse with metastasis and 4 cases of death in group B. CONCLUSIONS: There are significant differences in the clinical manifestation, biological behavior, treatment and prognosis of testicular YST between children and adults. In children, most of the testicular YST cases are at clinical stage I and preferably treated by radical high-level spermatectomy and orchiectomy with favorable prognosis. In adults, however, the tumor is highly malignant, with high incidences of recurrence and metastasis and poor prognosis, for the treatment of which the first choice is radical high-level spermatectomy and orchiectomy combined with RPLND and chemotherapy.

circGprc5a Promoted Bladder Oncogenesis and Metastasis through Gprc5a-Targeting Peptide.

Bladder cancer is a serious cancer in the world, especially in advanced countries. Bladder cancer stem cells (CSCs) drive bladder tumorigenesis and metastasis. Circular RNAs (circRNAs) are involved in many biological processes, but their roles in bladder oncogenesis and bladder CSCs are unclear. Here, we identified that circGprc5a is upregulated in bladder tumors and CSCs. circGpr5a knockdown impairs the self-renewal and metastasis of bladder CSCs, and its overexpression exerts an opposite role. circGpr5a has peptide-coding potential and functions through a peptide-dependent manner. circGprc5a-peptide binds to Gprc5a, a surface protein highly expressed in bladder CSCs. Gprc5a knockout inhibits the bladder CSC self-renewal and metastasis. circGprc5a-peptide-Gprc5a can be utilized to target bladder cancer and bladder CSCs.