We aimed to examine the association between metabolic syndrome and the risk of kidney stone development in a large-scale community-based cohort. A total of 121,579 participants enrolled in the Taiwan Biobank were analyzed. They were divided into two groups on the basis of presence of metabolic syndrome. The presence of kidney stone disease was defined by self-reported history of kidney stones. The mean age of participants was 50 years old, and self-reported kidney stones were observed in 3446 (10%) and 4292 (5%) participants with metabolic syndrome and without metabolic syndrome, respectively. Higher prevalence of kidney stone disease was found in participants with metabolic syndrome compared to those without metabolic syndrome (odds ratio (OR), 1.32; 95% confidence interval (95% CI), 1.25 to 1.39). In addition, the risk of incident kidney stone development was analyzed in a longitudinal cohort of 25,263 participants without kidney stones at baseline during a mean follow-up of 47 months. Multivariable Cox regression analysis revealed that the risk for incident kidney stone disease was higher in participants with metabolic syndrome than those without metabolic syndrome (hazard ratio, 1.24; 95% CI, 1.04 to 1.49). Our study suggests that metabolic syndrome does increase the risk of kidney stones.
The importance of blood cell markers in patients with malignant tumors has been studied, but there are few studies on the prognostic value of hemoglobin-to-red cell distribution width ratio (HRR) in cancer. This is the first study to investigate the effect of preoperative HRR on patients with upper tract urothelial carcinoma (UTUC). Our retrospective cohort study included 730 UTUC patients who underwent nephroureterectomy from 2000 to 2019. Clinicopathological parameters were compared according to HRR levels, and the relationship between blood cell markers (HRR, white blood cell [WBC] count, platelet count) and prognosis was evaluated using Kaplan–Meier method and Cox regression model. We found that patients with HRR ≤ 1.05 tended to have worse renal function, higher pathological stages, and more high-grade tumors. In univariate analysis, HRR ≤ 1.05, WBC > 8.65 × 103 cells/μL and platelets >309 × 103 cells/μL were associated with poor progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Multivariate analysis demonstrated that HRR ≤ 1.05 and WBC > 8.65 × 103 cells/μL were independent prognostic factors for predicting deterioration of PFS, CSS, and OS. In conclusion, HRR and WBC are easy to obtain in clinical practice and are useful indicators to provide prognostic information before surgery for UTUC.
1 April 2019 in Urologic Oncology: Seminars and Original Investigations
Background and objectives: Bladder urothelial carcinoma is the most common type of genitourinary cancer. Patients with bladder cancer may have limited treatment efficacy related to drug toxicity, resistance or adverse effects, and novel therapeutic strategies to enhance treatment efficacy or increase sensitivity to drugs are of high clinical importance. Epigallocatechin gallate (EGCG) is a polyphenolic compound found in green tea leaves, and a potential anti-cancer agent in various cancer types through modulating and regulating multiple signaling pathways. The current study aimed to explore the role and novel therapeutic targets of EGCG on bladder urothelial carcinoma. Materials and Methods: The BFTC-905 cells, human urinary bladder transitional cell carcinoma (TCC) cell line, were treated with EGCG or water for 24 hours, and the expression profiles of mRNAs and microRNAs were analyzed using next generation sequencing (NGS). The enriched biological functions were determined using different bioinformatics databases. Results: A total of 108 differentially expressed genes in EGCG-treated bladder TCC cells were identified, which were mainly involved in nicotinamide adenine dinucleotide (NAD) biogenesis, inflammatory response and oxidation-reduction metabolism. Moreover, several microRNA-mRNA interactions that potentially participated in the response of bladder TCC to EGCG treatment, including miR-185-3p- ARRB1 (arrestin beta 1), miR-3116- MGAT5B (alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase B), miR-31-5p-TNS1 (tensin 1), miR-642a-5p-TNS1, miR-1226-3p- DLG2 (discs large homolog 2), miR-484-DLG2, and miR-22-3p- PPM1K (protein phosphatase 1K). Conclusions: The current findings provide insights into novel therapeutic targets and underlying mechanisms of action of EGCG treatment in bladder cancer.
To clarify if diagnostic ureteroscopy (URS) before radical nephroureterectomy for patients with upper tract urothelial carcinoma (UTUC) will increase the risk of intravesical recurrence. From retrospective review of cohort at our institution, 502 patients with UTUC who underwent radical nephroureterectomy with bladder cuff excision were enrolled from 1990 to 2013. Cox proportional hazards model was used to analyze the overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and intravesical recurrence-free survival (IVRFS). The log-rank test was used for comparing survival curves. All potential risk factors were included in the multivariate Cox proportional hazards model to recognize independent predictors. From NHI database, we included patients of UTUC without bladder cancer history using population-based database in Taiwan from 1996 to 2013. In total, 3079 URS and 2634 non-URS patients with UTUC were identified. Univariate and multivariate Cox proportional hazards regressions were performed to measure the risk of IVRFS and all-cause mortality. From our database, the comparison of clinicopathological characteristics in UTUC patients between with URS biopsy group (URS+) (n = 206, 41%) and without URS biopsy group (URS−) (n = 296, 59%) was insignificantly different excluding surgical method. URS biopsy is not associated with worse OS (p = 0.720), DFS (p = 0.294), MFS (p = 0.808), and IVRFS (p = 0.560) by multivariate analysis. Only bladder cancer history is an independent significant factor to predict IVR (p < 0.001). The same result from NHI database, URS before radical surgery will not increase the risk of IVRFS [adjusted HR 1.136, 95% CI 1.00–1.30; P = 0.059] and OS [adjusted HR 0.919, 95% CI 0.82–1.04; P = 0.164]. Preoperative URS manipulation is not associated with higher risk of IVRFS even in patients without bladder cancer history. Diagnostic URS is feasible to compensate the insufficient information of image in patients with UTUC.
ADP‐ribosylation factor 6 (ARF6) is a well‐studied protein that is involved in multiple biological functions including cell migration and invasion. The mechanism by which ARF6 regulates the migration and invasion of upper tract urothelial carcinoma (UTUC) is still unknown. MiR‐145‐5p is a tumor suppressor microRNA, which is downregulated in several cancer types. We aimed to elucidate the molecular mechanism underlying the regulation of ARF6 by miR‐145‐5p in UTUC. ARF6 expression was observed to be higher in UTUC tissues than paired adjacent normal tissues. A reverse correlation between ARF6 and miR‐145‐5p was found in UTUC tissues. MiR‐145‐5p inhibited ARF6 expression by directly targeting its 3′‐UTR. The functional studies indicated that ARF6 expression reversed the miR‐145‐5p‐reduced tumor cell migration and invasion. Notably, miR‐145‐5p reduced MMP2, N‐cadherin, FAK and MMP7, and elevated E‐cadherin protein levels in vitro; however, the above effects were reversed by ARF6. Further, the expression of epithelial‐to‐mesenchymal transition (EMT) markers and cell invasion was suppressed by knocking down MMP7 in UTUC cells. These findings suggest that miR‐145‐5p may suppress UTUC cell motility and invasion by targeting ARF6/MMP7 through EMT.