Connexin43 is associated with the progression of clear cell renal carcinoma and is regulated by tangeretin to sygergize with tyrosine kinase inhibitors.

BACKGROUND: The roles of Connexin43 (Cx43) in clear cell renal cell carcinoma (ccRCC) microenviroment remains to be poorly defined. METHODS: The expression profile, prognosis and immune analysis of Cx43 in various cancers, particularly in ccRCC were performed using TCGA database, and various biological function assays were applied to explore the physiological role of Cx43 and tangeretin in ccRCC. Western blot were applied to examine the protein expression and Kunming mice were used to evaluate preliminary safety or anti-tumor activity of tangeretin and sunitinib. RESULTS: Compared with the normal group, higher expression levels of Cx43 in ccRCC, and distinct associations between Cx43 expression and ccRCC prognosis or immune infiltration, were found. Notably, the expression of Cx43 was found to be highly correlated with that of receptor tyrosine kinases (RTKs), particularly with VEGFR1, VEGFR2 and VEGFR3. The expression of Cx43 and EGFR was also found to be higher in ccRCC than that in the para-cancerous specimens. Knocking down Cx43 expression decreased RCC cell viability, cell migration, p-EGFR, MMP-9 and survivin expression. Using 14 Chinese medicine monomers, tangeretin was screened and found to inhibit tumor cell viability and Cx43 expression. Tangeretin also enhanced the sensitivity of RCC cells to tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib. However, the same concentration of tangeretin exerted a less prominent effect on normal renal cell viability. CONCLUSIONS: Cx43 is strongly associated with RTK expression and ccRCC progression, while tangeretin can inhibit RCC cell malignancy by inhibiting Cx43 expression and enhance the sensitivity of RCC cells to TKIs.

Safety of Surgery in benign Prostatic Hyperplasia Patients on Antiplatelet or Anticoagulant Therapy: A Systematic Review and Meta-Analysis.

PURPOSE: The management strategies of anticoagulant (AC) or antiplatelet (AP) therapy in the preoperative period of benign prostatic hyperplasia (BPH) is still controversial. Therefore, a meta-analysis to systematically evaluate the surgical safety for BPH patients on AC or AP therapy was performed. MATERIALS AND METHODS: The protocol for the review is available on PROSPERO (CRD42018105800). A literature search was performed by using MEDLINE, Web of Science, PubMed, Cochrane library, and Embase. Summarized odds ratios (OR), mean difference (MD) and 95% confidence intervals (CI) were used to assess the difference in outcomes. RESULTS: We identified 13 trials with a total of 3767 patients. An intragroup significant difference was found in bleeding complications and blood transfusions when undergoing transurethral resection of the prostate (TURP). For laser surgery, the intragroup significant difference was found in the result of blood transfusion. Bridging therapy would not cause a higher risk of bleeding complications and blood transfusion during the perioperative period. Besides, no difference existed in operation time, catheterization time, hospitalization, and thromboembolic events. CONCLUSION: Patients with BPH on perioperative AC/AP therapy would have a risk of postoperative hemorrhage after TURP or laser treatments. To reduce the risk of hemorrhage, bridging therapy could be a good choice.

Cell death-related molecules and biomarkers for renal cell carcinoma targeted therapy.

Renal cell carcinoma (RCC) is not sensitive to conventional radio- and chemotherapies and is at least partially resistant to impairments in cell death-related signaling pathways. The hallmarks of RCC formation include diverse signaling pathways, such as maintenance of proliferation, cell death resistance, angiogenesis induction, immune destruction avoidance, and DNA repair. RCC diagnosed during the early stage has the possibility of cure with surgery. For metastatic RCC (mRCC), molecular targeted therapy, especially antiangiogenic therapy (e.g., tyrosine kinase inhibitors, TKIs, such as sunitinib), is one of the main partially effective therapeutics. Various forms of cell death that may be associated with the resistance to targeted therapy because of the crosstalk between targeted therapy and cell death resistance pathways were originally defined and differentiated into apoptosis, necroptosis, pyroptosis, ferroptosis and autophagic cell death based on cellular morphology. Particularly, as a new form of cell death, T cell-induced cell death by immune checkpoint inhibitors expands the treatment options beyond the current targeted therapy. Here, we provide an overview of cell death-related molecules and biomarkers for the progression, prognosis and treatment of mRCC by targeted therapy, with a focus on apoptosis and T cell-induced cell death, as well as other forms of cell death.

Early and rapid prediction of postoperative infections following percutaneous nephrolithotomy in patients with complex kidney stones.

OBJECTIVES: To obtain more accurate and rapid predictors of postoperative infections following percutaneous nephrolithotomy (PCNL) in patients with complex kidney stones, and provide evidence for early prevention and treatment of postoperative infections. PATIENTS AND METHODS: A total of 802 patients with complex kidney stones who underwent PCNL, from September 2016 to September 2017, were recruited. Urine tests, urine cultures (UCs) and stone cultures (SCs) were performed, and the perioperative data were prospectively recorded. RESULTS: In all, 19 (2.4%) patients developed postoperative urosepsis. A multivariate logistic regression analysis revealed that an operating time of ≥100 min, urine test results with both positive urine white blood cells (WBC+) and positive urine nitrite (WBC+NIT+), positive UCs (UC+), and positive SCs (SC+) were independent risk factors of urosepsis. The incidence of postoperative urosepsis was higher in patients with WBC+NIT+ (10%) or patients with both UC+ and SC+ (UC+SC+; 8.3%) than in patients with negative urine test results or negative cultures (P < 0.01). Preoperative WBC+NIT+ was predictive of UC+SC+, with an accuracy of >90%. The main pathogens found in kidney stones were Escherichia coli (44%), Proteus mirabilis (14%) and Staphylococcus (7.4%); whilst the main pathogens found in urine were E. coli (54%), Enterococcus (9.4%) and P. mirabilis (7.6%). The incidence of E. coli was more frequent in the group with urosepsis than in the group without urosepsis (P < 0.05). CONCLUSIONS: WBC+NIT+ in preoperative urine tests could be considered as an early and rapid predictor of UC+SC+ and postoperative urosepsis. Urosepsis following PCNL was strongly associated with E. coli infections in patients with complex kidney stones.

Use of the ureteral access sheath during ureteroscopy: A systematic review and meta-analysis.

The debate still rages on for the usefulness of ureteral access sheath (UAS). Therefore, a meta-analysis to discuss the effects of applying UAS during ureteroscopy was performed. The protocol for the review is available on PROSPERO (CRD42017052327). A literature search was conducted up to November, 2017 using the Web of science, PUBMED, EMBASE and Cochrane Library. The quality of articles was assessed by the Jadad scale and Newcastle Ottawa Scale (NOS). Egger's test and the trim-and-fill method were used to evaluate publication bias. Effect sizes were calculated by pooled odds ratio (ORs) and mean differences (MDs). Sensitivity analyses and subgroup analyses were performed to explore the origin of heterogeneity. Eight trials with a total of 3099 patients and 3127 procedures were identified. Results showed no significant difference in stone-free rate (SFR) (OR = 0.83, 95% CI 0.52-1.33, P = 0.45), intraoperative complications (OR = 1.16, 95% CI 0.81-7.69, P = 0.88), operative time (MD = 4.09, 95% CI -15.08-23.26, P = 0.68) and hospitalization duration (MD = -0.13, 95% CI -0.32-0.06, P = 0.18). However, the incidence of postoperative complications was higher in UAS group (OR = 1.46, 95% CI 1.06-2.00, P = 0.02). Evidence from meta-analysis indicated that the use of UAS during ureteroscopy did not manifest advantages. However, given the intrinsic restrictions of the quality of selected articles, more randomized controlled trials (RCTs) are warranted to update the findings of this analysis.

Endourologic strategies for a minimally invasive management of urinary tract stones in patients with urinary diversion

ABSTRACT Objective To present our experience in minimally invasive management of urinary tract stones in patients with urinary diversion. Materials and Methods We retrospectively reviewed 26 patients with urinary tract stones after cystectomy and urinary diversion. The types of urinary diversion were ileal conduit, colon conduit, ileal orthotopic neobladder in 19, 4, and 3 patients, respectively. At postoperative days 2, a plain KUB and urinary ultrasonography were performed in order to assess stone fragmentation or hydronephrosis. According to postoperative imaging, stone free rate (SFR) was defined as complete absence of fragments or residual stones less than 4mm. Results 19 patients were treated with minimally invasive percutaneous lithotripsy (MPCNL) and 2 patients required second-look MPCNL. Anterograde flexible ureteroscopy was performed in 2 patients, while in 2 patients a combined anterograde and retrograde approach was required. Three reservoir stones were treated by transurethral neo-bladder lithotripsy. Postoperative significant complications occurred in 2 patients (7.7%). The highest percentage of stone composition was struvite, as a result of chronic urinary tract infection (UTI). SFR was 88.5% (23 of 26). Conclusions Our experience showed that MPCNL is a safe and effective treatment modality with little morbidity for renal and upper ureteral stones in patients with urinary diversion. For middle and lower ureteral stones, an anterograde approach could be also considered as a first line treatment, but a combined anterograde and retrograde approach was required when the anterograde access alone cannot provide acceptable results.

Endourologic strategies for a minimally invasive management of urinary tract stones in patients with urinary diversion.

OBJECTIVE: To present our experience in minimally invasive management of urinary tract stones in patients with urinary diversion. MATERIALS AND METHODS: We retrospectively reviewed 26 patients with urinary tract stones after cystectomy and urinary diversion. The types of urinary diversion were ileal conduit, colon conduit, ileal orthotopic neobladder in 19, 4, and 3 patients, respectively. At postoperative days 2, a plain KUB and urinary ultrasonography were performed in order to assess stone fragmentation or hydronephrosis. According to postoperative imaging, stone free rate (SFR) was defined as complete absence of fragments or residual stones less than 4mm. RESULTS: 19 patients were treated with minimally invasive percutaneous lithotripsy (MPCNL) and 2 patients required second-look MPCNL. Anterograde flexible ureteroscopy was performed in 2 patients, while in 2 patients a combined anterograde and retrograde approach was required. Three reservoir stones were treated by transurethral neo-bladder lithotripsy. Postoperative significant complications occurred in 2 patients (7.7%). The highest percentage of stone composition was struvite, as a result of chronic urinary tract infection (UTI). SFR was 88.5% (23 of 26). CONCLUSIONS: Our experience showed that MPCNL is a safe and effective treatment modality with little morbidity for renal and upper ureteral stones in patients with urinary diversion. For middle and lower ureteral stones, an anterograde approach could be also considered as a first line treatment, but a combined anterograde and retrograde approach was required when the anterograde access alone cannot provide acceptable results.