Pelvic Plexus Block Versus Periprostatic Nerve Block for Ultrasound-Guided Prostate Biopsy: A Meta-Analysis.

BACKGROUND: To relieve prostate biopsy-related pain, various local anesthetic methods have been used. The best approach was periprostatic nerve block (PNB) in the past decade. Recently, pelvic plexus block (PPB) was employed to ultrasound-guided prostate biopsy. Compared with the PNB, the PPB may block a more extensive area. Therefore, PPB may be more effective in relieving prostate biopsy-related pain. However, several prospective randomized controlled trials (RCTs) comparing PPB and PNB drew conflicting conclusions, so we compared the difference of pain control between PPB and PNB for prostate biopsy. METHODS: The following databases were retrieved up to October 2020: PubMed, Chinese biomedicine literature database, the Cochrane Library, China National Knowledge Internet databases, Wan fang databases and Google Scholar. Only the RCTs were included. The main outcome measures were Visual Analog Scale (VAS) score and complications. The literature quality and extracted data were evaluated by two authors independently. The software Review Manager (version 5.3) was used to perform the data analysis that comparing the difference of VAS score and complications between PPB and PNB. RESULTS: After screening, six articles including 336 patients from PPB group and 337 patients from PNB group were performed meta-analysis in this study. The results showed that there were no significant difference of pain control in probe insertion and local anesthetic injection between PPB and PNB, while compared with PNB, patients with PPB experienced less pain during biopsy and 30 min after biopsy, respectively(MD = -0.57, 95% CI: -1.11 to -0.03, Z = 2.06, P = 0.04; MD = -0.21, 95% CI: -0.40 to -0.02, Z = 2.15, P = 0.03). In subgroup analysis, the pooled results showed that PPB was superior to PNB in 12-cores biopsy (pooled MD = -1.16, 95% CI: -1.61 to -0.71, P < 0.00001), and more than 40-ml prostate size, regardless of transrectal or transperineal prostate biopsy. The reported major complications were urinary retention, hematuria, infection and hemospermia. The pooled results showed that there were no obvious difference in complications between PPB group and PNB group. CONCLUSIONS: Overall, this meta-analysis suggests that PPB provides safe and effective pain control of ultrasound-guided prostate biopsy, and PPB is superior to PNB. In future, it also needs more high quality, large samples RCTs to verify.

Trimodal Therapy vs. Radical Cystectomy for Muscle-Invasive Bladder Cancer: A Meta-Analysis.

Background: To compare the difference between trimodal therapy (TMT) and radical cystectomy (RC) in treating muscle-invasive bladder cancer, we performed a meta-analysis for data from the following database. Methods: We searched PubMed, Chinese biomedicine literature database, the Cochrane Library, China National Knowledge Internet databases, Wanfang databases, and Google Scholar up to December 2019. The main outcome measures assessed were overall survival (OS), cancer-specific survival (CSS), mortality, and Charlson comorbidity score (CCS). Two authors independently evaluated the study quality and extracted data. All data were analyzed using Review Manager (version 5.3). Results: After database retrieval, article selection, data extraction, and quality assessment, nine articles comprising 5,721 cases from the TMT group and 48,262 cases from the RC group were included in this study. The data showed that there was no statistical difference between TMT and RC at <10 years OS [pooled hazard ratio (HR) = 1.26, 95% confidence interval (CI): 0.92-1.73, Z = 1.46, P = 0.14], while OS of the RC group was higher than that of the TMT group at more than 10 years (pooled HR = 1.34, 95% CI: 1.18-1.54, Z = 4.33, P < 0.0001). As for CSS, compared with the TMT group, the patients in the RC group had longer CSS (pooled HR = 1.50, 95% CI: 1.29-1.76, Z = 5.15, P < 0.00001). Compared with RC, TMT is linked to an obvious increase in all-cause mortality and bladder-specific cancer mortality (pooled HR = 1.30, 95% CI: 1.16-1.46, Z = 4.55, P < 0.00001; pooled HR = 1.32, 95% CI: 1.15-1.51, Z = 3.92, P < 0.0001). The bladder cancer patients belonging to CCS "0" score preferred RC [pooled relative risk (OR) = 0.94, 95% CI: 0.89-0.98, Z = 2.79, P = 0.005], while CCS "2" score's patients were prone to TMT (pooled OR = 1.40, 95% CI: 1.29-1.53, Z = 7.73, P < 0.00001). Conclusions: Overall, this meta-analysis suggests that the efficacy of TMT is non-inferior to that of RC at <10-year OS, and RC is superior to TMT at more than 10-year OS. Therefore, TMT may be a reasonable treatment option in well-selected patients who are unsuitable for surgery or are not willing to experience surgery. In the future, more high-quality, large-sample randomized controlled trials (RCTs) are needed to verify the results.

2'­Hydroxyflavanone inhibits epithelial­mesenchymal transition, and cell migration and invasion via suppression of the Wnt/ß­catenin signaling pathway in prostate cancer.

Despite the availability of a number of treatment options, certain cases of primary prostate cancer (PCa) will develop into metastatic PCa, in which epithelial­mesenchymal transition (EMT) serves an important role. Recently, a natural flavonoid known as 2'­hydroxyflavanone (2HF) exerts remarkable anticancer activity on various types of cancer. Our previous study demonstrated that 2HF could promote apoptosis and inhibit the proliferation of PCa cells, but whether 2HF is involved in the regulation of EMT, and cell migration and invasion in metastatic PCa remains unknown. The present study used two different metastatic PCa cell lines (PC­3 and DU145) to investigate the effects of 2HF on EMT, and cell migration and invasion. The results demonstrated that 2HF could inhibit EMT, and cell migration and invasion through the Wnt/ß­catenin signaling pathway by suppressing GSK­3ß phosphorylation, ß­catenin expression and transactivation. In conclusion, the present study revealed a novel function of 2HF, which may be used to prevent or treat PCa metastasis.

The role of Silodosin as a new medical expulsive therapy for ureteral stones: a meta-analysis.

To evaluate the efficacy of Silodosin as a medical expulsive therapy of ureteral stones, we searched PubMed, EMBASE, the Cochrane Library, and CBM up to June 2015. All randomized controlled trials (RCTs) were identified in which patients were randomized to receive Silodosin versus placebo or other therapies for ureteral stones. Outcome measures assessed were overall stone expulsion rate (primary) and expulsion time, analgesics times, and the incidence of additional treatment and regarding treatment complications (secondary). Two authors independently assessed study quality and extracted data. All data were analyzed using RevMan 5.3. Seven RCTs with a total of 1035 patients met the inclusion criteria. The pooled meta-analysis showed a significant improvement in stone clearance with Silodosin (Silodosin versus placebo, OR =1.69, 95% CI [1.19-2.40], p = 0.003; Silodosin versus tamsulosin, OR =2.82, 95% CI [1.79-4.44], p < 0.00001). According to the size and location of ureteral stone, the pooling effects of Silodosin were analyzed, with a meaningful expulsion rate in distal ureteral stone when the size was 5-10 mm. In addition, a shorter expulsion time, fewer analgesics times, and additional treatments were observed. The common side effect was retrograde ejaculation. In summary, Silodosin appears to be more effective than either placebo or tamsulosin. Within the limits of available data, high-quality multicenter RCTs are needed to thoroughly evaluate the outcome in the future.

Murine Double Minute 2 SNP T309G Polymorphism and Urinary Tract Cancer Risk: A Meta-Analysis.

Urinary tract cancer is a common cause of cancer-related death. The etiology and pathogenesis of urinary tract cancer remain unclear, with genetic and epigenetic factors playing an important role. Studies of the polymorphism of murine double minute 2 (MDM2) have shown inconclusive trends in the risk of urinary tract cancer.To clarify this inconsistency, we conducted updated meta-analyses to evaluate the role of MDM2 T309G polymorphism in urinary tract cancer susceptibility.Data sources were Pubmed (1966-May 2015), Chinese biomedicine literature database (1978-May 2015), and hand searching of the reference lists of included studies:(1) research categories case-control study or a nested case-control study; (2) information evaluating the association between the MDM2 SNP309 and urinary tract cancer risk; (3) studies with sufficient data to perform a meta-analysis.It included the use of odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) give a sense of the precision of the estimate. We used I for the assessment of between-study heterogeneity, and publication bias was assessed using the funnel plot and the Egger test. Statistical analyses were performed by Review Manage, version 5.0 and Stata 11.0.A total of 18 studies met the eligibility criteria and were included in our analyses. Overall, there was no statistical association between MDM2 SNP309 and prostate cancer risk for the allele contrast, the GG genotype, the recessive genetic model, the dominant genetic model, and prostate cancer risk in all subjects (OR = 0.96, 95% CI 0.87-1.05, P = 0.36; OR = 0.93, 95% CI 0.75-1.15, P = 0.50; OR = 1.00, 95% CI 0.87-1.15, P = 0.99; OR = 0.93, 95% CI 0.80-1.07, P = 0.30), and between MDM2 SNP309 and bladder cancer risk (the allele contrast: OR = 1.06, 95% CI 0.89-1.27, P = 0.50; the GG genotype: OR = 1.12, 95% CI 0.79-1.61, P = 0.52; the dominant genetic model: OR = 1.03, 95% CI 0.83-1.28, P = 0.78; the recessive genetic model: OR = 1.12, 95% CI 0.84-1.49, P = 0.45). However, there was positive association between MDM2 SNP309 and kidney cancer risk for the allele contrast (OR = 1.24, 95% CI 1.05-1.46, P = 0.01), the GG genotype (OR = 1.57, 95% CI 1.11-2.20, P = 0.01), dominant model contrast (OR = 1.30, 95% CI 1.00-1.68, P = 0.05), the recessive genetic model (OR = 1.37, 95% CI 1.02-1.83, P = 0.04).First, only the data of published studies were included in this meta-analysis. Unpublished studies tend to show more negative results; therefore, publication bias may be present. Second, because of the lack of the original data, we did not perform stratification analysis by age, hormone levels, dietary habit, or other variables. This might have caused confounding bias. Third, because the number of studies was relatively small for kidney cancer, the results might not have enough statistical power for us to investigate the association of the polymorphism with kidney cancer susceptibility, and we could not perform subgroup analyses. Finally, there were no studies about Africans in this meta-analysis.In summary, the results of our meta-analysis suggest an increased risk role of the MDM2 SNP T309G in renal cancer. However, there was no association between the MDM2 SNP T309G and prostate cancer risk or between the MDM2 SNP T309G and bladder cancer risk. Moreover, well-designed studies should estimate different ethnicities, degree of malignancy and clinical progression on the association between MDM2 SNP309 and urinary cancer risk in the future.

[Aberrant expressions of ß-catenin and ZEB1 in bladder cancer and their significance].

OBJECTIVE: To detect the expressions of ß-catenin and zinc finger E-box binding homeobox 1 (ZEB1) in bladder cancer tissues, and analyze their correlation and significance in bladder cancer occurrence and progression. METHODS: The study collected 79 specimens of bladder cancer. EnVision immunohistochemical staining was used to detect the expressions and distribution of ß-catenin and ZEB1 protein. Their correlation was analyzed and their relationship with clinicopathological characteristics was investigated. RESULTS: There was a significant heterogeneity in the expression of ß-catenin in bladder cancer tissues. It might be distributed in the cell membrane, cytoplasm or nucleus. In low-grade clinical and pathological urothelial carcinoma, ß-catenin was mainly expressed in cell membrane and cytoplasm, but in high-grade clinical pathological bladder cancer tissues, it was mostly located in cell cytoplasm and nucleus. ZEB1 in bladder cancer tissues was mainly expressed in cell nucleus, and its expression was elevated with the increased tumor pathological grade and clinical stage. The expressions of the above two proteins were significantly correlated. CONCLUSION: Aberrant expressions of ß-catenin and ZEB1 in bladder cancer tissues are relevant to bladder tumor differentiation and metastasis, and the two expressions are evidently correlated. The two proteins can be simultaneously used as candidate targets for early diagnosis and prognosis prediction.

[DAB2IP expression in bladder transitional cell carcinoma and its correlation with clinical outcome].

OBJECTIVE: To investigate the expression of DAB2IP in bladder transitional cell carcinoma (BTCC) and its correlation with clinical characteristics and prognosis of BTCC patients. METHODS: Immunohistochemical staining was applied to detect DAB2IP protein level in 79 cases of TCCB tissues and 11 cases of normal bladder tissues, and the relationships of the staining results with pathological grade, stage, lymph node metastasis, gender, age and the 3-year survival rate of the patients were analyzed. RESULTS: The expression of DAB2IP in BTCC tissues was significantly lower than that in normal bladder epithelium, and the expression score and rate of DAB2IP in the high-grade, invasive and metastatic BTCC were significantly lower than those in low-grade, superficial and non-metastatic BTCC (P < 0.05). The 3-year survival rate of the patients with high DAB2IP expression was significantly higher than that of the patients with low DAB2IP expression. CONCLUSION: DAB2IP may be one of the important inhibitory factors during the occurrence and progression of BTCC.

2'-hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis.

Although there have been advances in therapeutic regimes for metastatic castration-resistant prostate cancer (CRPC), these recent developments have not led to improved cure rates. Thus, more novel agents to prolong patient survival are desired. 2'-Hydroxyflavanone (2HF), a nontoxic natural flavonoid, has been shown to exhibit pleiotropic anticancer effects in many cancer types, including prostate cancer (PCa). However, the therapeutic effects of 2HF on tumor growth and its potential mechanisms in CRPC have not been completely elucidated. In the present study, utilizing three different metastatic and androgen-independent PCa cell models (PC-3, DU145 and C4-2), we found that 2HF treatment not only resulted in inhibition of cell proliferation and colony formation in vitro, but also delayed subcutaneous tumor growth in vivo. Mechanistically, besides its known inhibitory effects on aldo­keto reductase activity and de novo androgen synthesis, 2HF also markedly suppressed AKT phosphorylation, signal transducer and activator of transcription-3 (STAT3) phosphorylation and transactivation subsequently regulating the expression of members of the BCL-2 family (i.e., Mcl-1, Bcl-2 and Bax) and modulating caspase-mediated cell apoptosis. Overall, this study revealed a novel mechanism for 2HF targeting metastatic CRPC, in which inactivation of AKT/STAT3 signaling led to cell apoptosis and growth inhibition.

[Inhibitory effect of 2'-hydroxyflavanone on proliferation, invasion and migration of bladder cancer cells in vitro via blocking AKT/STAT3 signaling pathway].

OBJECTIVE: To study the effect of 2'-hydroxyflavanone on proliferation, invasion and migration of bladder cancer cells and its mechanism. METHODS: MTT assay was used to detect the effect of 2'-hydroxyflavanone on proliferation of bladdercancer cells, and the proliferation inhibition rate was calculated. Wound healing assay and Transwell (TM); assay were conducted to study the effect of 2'-hydroxyflavanone on migration and invasion of bladder cancer cells, respectively. Western blotting was performed to investigate the change of migration-associated proteins after 2'-hydroxyflavanone treatment. RESULTS: 2'-hydroxyflavanone inhibited the proliferation of bladder cancer cells (5637, T24, UMUC-3, 253J) in a time- and dose- dependent manner. The migration and invasion abilities of T24 cells were significantly reduced by 2'-hydroxyflavanone treatment (P<0.05), which was accompanied by the down-regulation of MMP-2, MMP-9, p-AKT and p-STAT3 protein expressions. CONCLUSION: 2'-hydroxyflavanone can effectively inhibit bladder cancer cell proliferation, invasion and migration, in which the inhibition of AKT/STAT3 signaling pathway may play an important role.

Silibinin inhibits ß-catenin/ZEB1 signaling and suppresses bladder cancer metastasis via dual-blocking epithelial-mesenchymal transition and stemness.

Muscle-invasive bladder cancer is associated with a high frequency of metastasis, and fewer therapies substantially prolong survival. Silibinin, a nontoxic natural flavonoid, has been shown to exhibit pleiotropic anticancer effects in many cancer types, including bladder cancer. Our and other previous studies have demonstrated that silibinin induced apoptosis and inhibited proliferation of bladder cancer cells, whether silibinin could suppress bladder cancer metastasis has not been elucidated. In the present study, we utilized a novel highly metastatic T24-L cell model, and found that silibinin treatment not only resulted in the suppression of cell migration and invasion in vitro, but also decreased bladder cancer lung metastasis and prolonged animal survival in vivo. Mechanistically, silibinin could inhibit glycogen synthase kinase-3ß (GSK3ß) phosphorylation, ß-catenin nuclear translocation and transactivation, and ZEB1 gene transcription that subsequently regulated the expression of cytokeratins, vimentin and matrix metalloproteinase-2 (MMP2) to reverse epithelial-mesenchymal transition (EMT). On the other hand, silibinin inhibited ZEB1 expression and then suppressed the properties of cancer stem cells (CSCs), which were evidenced as decreased spheroid colony formation, side population, and the expression of stem cell factor CD44. Overall, this study reveals a novel mechanism for silibinin targeting bladder cancer metastasis, in which inactivation of ß-catenin/ZEB1 signaling by silibinin leads to dual-block of EMT and stemness.

PI3K/Akt to GSK3ß/ß-catenin signaling cascade coordinates cell colonization for bladder cancer bone metastasis through regulating ZEB1 transcription.

Muscle-invasive bladder cancer is associated with a high frequency of metastasis, and bone is the most common metastatic site outside the pelvis. To clarify its organ-specific characteristics, we generated a successive bone metastatic T24-B bladder cancer subline following tail vein injection of metastatic T24-L cells. Compared with parental T24-L cells, epithelial-like T24-B cells displayed increased adhesion but decreased migration or invasion abilities as well as up-regulation of cytokeratins and down-regulation of vimentin, N-cadherin and MMP2. Mechanically, phosphatidylinositol 3-kinase (PI3K)/Akt targets glycogen synthase kinase-3ß (GSK3ß)/ß-catenin to control ZEB1 gene transcription, and then subsequently regulates the expression of cytokeratins, vimentin and MMP2. Importantly, ZEB1 is essential for bladder cancer invasion in vitro and distant metastasis in vivo, and ZEB1 overexpression was highly correlated with the expression of those downstream markers in clinical tumor samples. Overall, this study reveals a novel mechanism facilitating metastatic bladder cancer cell re-colonization into bone, and confirms the significance of mesenchymal-to-epithelial transition (MET) in formation of bone metastasis.