Histone deacetylase inhibitor valproic acid suppresses the growth and increases the androgen responsiveness of prostate cancer cells.

We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and methylation increased and cyclin proteins decreased. In PAcP shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C-81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments increase androgen responsiveness

Postoperative Discharge Destination Impacts 30-Day Outcomes: A National Surgical Quality Improvement Program Multi-Specialty Surgical Cohort Analysis

Surgical patients can be discharged to a variety of facilities which vary widely in intensity of care. Postoperative readmissions have been found to be more strongly associated with post-discharge events than pre-discharge complications, indicating the importance of discharge destination. We sought to evaluate the association between discharge destination and 30-day outcomes. A retrospective cohort study was conducted using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Patients were dichotomized based on discharge destination: home versus non-home. The main outcome of interest was 30-day unplanned readmission. The secondary outcomes included post-discharge pulmonary, infectious, thromboembolic, and bleeding complications, as well as death. In this cohort study of over 1.5 million patients undergoing common surgical procedures across eight surgical specialties, we found non-home discharge to be associated with adverse 30-day post-operative outcomes, namely, unplanned readmissions, post-discharge pulmonary, infectious, thromboembolic, and bleeding complications, as well as death. Non-home discharge is associated with worse 30-day outcomes among patients undergoing common surgical procedures. Patients and caregivers should be counseled regarding discharge destination, as non-home discharge is associated with adverse post-operative outcomes

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Modifiable risk factors to reduce renal cell carcinoma incidence: Insight from the PLCO trial.

INTRODUCTION: Identify modifiable factors contributing to renal cell carcinoma in the PCLO to target disease prevention and reduce health care costs. METHODS: The prostate, lung, colorectal, and ovarian database were queried for the primary outcome of kidney cancer. Demographics were investigated, specifically focusing on modifiable risk factors. Statistical analysis includes the Student t-test for continuous variables, chi-squared or Fisher\u27s exact tests for dichotomous and categorical variables for bivariate analysis. The Cox proportional hazards model was used in a multivariate time-to-event analysis. RESULTS: We investigate existing data relating specifically to renal cancer. After missing data were excluded, we analyzed 149,683 subjects enrolled in the prostate, lung, colorectal, and ovarian trial and noted 0.5% (n = 748) subjects developed renal cancer. Age, male gender, body mass index, diabetes, and hypertension were all significant associated with renal cancer in bivariate analysis (P CONCLUSIONS: Obesity, hypertension, and smoking are the 3 modifiable risk factors that could aggressively be targeted to reduce renal cell carcinoma

Radiologic indicators prior to renal cell cancer thrombectomy: Implications for vascular reconstruction and mortality

Background: Renal cancer may invade the inferior vena cava (IVC) creating more complex surgical intervention. We investigate radiologic findings that may predict vascular reconstruction prior to surgery and future renal cancer-specific mortality. Materials and Methods: Radiologic findings included Mayo Clinic risk factors for vascular reconstruction: Right-sided tumor, anteroposterior diameter of the IVC at the ostium of the renal vein ≥24.0 mm, and radiologic identification of complete occlusion of the IVC. Additional factors included thrombus in the lumen of the hepatic veins and metastasis. Along with other demographic factors, analysis included Chi-squared analysis for vascular reconstruction and logistic regression for mortality. A Kaplan–Meier curve was created for the most significant radiologic factor. Results: Thirty-seven patients underwent IVC tumor thrombectomy at two institutions from April 2007 to February 2015. We found that Mayo risk factors of 0, 1, 2, and 3 and the proportions of vascular reconstruction of 0%, 0%, 12.5%, and 13.6%, respectively (P = 0.788). Hepatic vein involvement was the most significant determinate of renal cell carcinoma-specific mortality in multivariable analysis, controlling for the size of IVC at the hepatic veins, pulmonary metastasis, and Fuhrman grade (P = 0.02, Log-rank P = 0.002). Conclusion: Mayo risk factors did not predict vascular reconstruction in our small cohort of Level II–Level IV IVC thrombus undergoing IVC thrombectomy. Tumor thrombus traveling into the lumen of the hepatic veins was a significant risk factor for accelerated mortality

Clinical and Prognostic Effect of Plasma Fibrinogen in Renal Cell Carcinoma: A Meta-Analysis

Background. Although numerous studies have shown that plasma fibrinogen is linked to renal cell carcinoma (RCC) risk, the consistency and magnitude of the effect of plasma fibrinogen are unclear. The aim of the study was to explore the association between plasma fibrinogen and RCC prognosis. Methods. An electronic search of Embase, PubMed/MEDLINE, and the Cochrane databases was performed to identify relevant studies published prior to June 1, 2016. Results. A total of 3744 patients with RCC from 7 published studies were included in the meta-analysis. The prognostic and clinical relevance of plasma fibrinogen are evaluated in RCC patients. Statistical significance of the combined hazard ratio (HR) was detected for overall survival, cancer-specific survival, and disease-free survival. Our pooled results showed that elevated plasma fibrinogen was significantly associated with clinical stage and Fuhrman grading. The level of plasma fibrinogen was not found to be associated with tumor type and gender. Conclusions. Elevated plasma fibrinogen is a strong indicator of poorer prognosis of patients with RCC, whereas the plasma fibrinogen is not significantly associated with tumor type. Therefore, plasma fibrinogen could be used in patients with RCC for risk stratification and decision providing a proper therapeutic strategy

Microbiome within Primary Tumor Tissue from Renal Cell Carcinoma May Be Associated with PD-L1 Expression of the Venous Tumor Thrombus

Objective. To perform a proof of concept microbiome evaluation and PD-L1 expression profiling in clear-cell renal cell carcinoma (cc-RCC) with associated tumor thrombus (TT). Methods. After IRB approval, six patients underwent radical nephrectomy (RN) with venous tumor thrombectomy (VTT). We collected fresh tissue specimens from normal adjacent, tumor, and thrombus tissues. We utilized RNA sequencing to obtain PD-L1 expression profiles and perform microbiome analysis. Statistical assessment was performed using Student’s t-test, chi-square, and spearman rank correlations using SPSS v25. Results. We noted the tumor thrombus to be mostly devoid of diverse microbiota. A large proportion of Staphylococcus epidermidus was detected and unknown if this is a surgical or postsurgical contaminant; however, it was noted more in the thrombus than other tissues. Microbiome diversity profiles were most abundant in the primary tumor compared to the thrombus or normal adjacent tissue. Differential expression of PD-L1 was examined in the tumor thrombus to the normal background tissue and noted three of the six subjects had a threshold above 2-fold. These three similar subjects had foreign microbiota that are typical residents of the oral microbiome. Conclusion. Renal tumors have more diverse microbiomes than normal adjacent tissue. Identification of resident oral microbiome profiles in clear-cell renal cancer with tumor thrombus provides a potential biomarker for thrombus response to PD-L1 inhibition