Percutaneous Ablation Versus Nephrectomy for Small Renal Masses: Clinical Outcomes in a Single-Center Cohort.

PURPOSE: To compare the outcomes of percutaneous ablation (PA) versus nephrectomy (NE) for small renal masses (SRMs) in patients with T1 renal cell carcinoma and evaluate the role of pre-procedural biopsy in the treatment of SRM. MATERIALS AND METHODS: Retrospective cohort analysis of patients subjected to PA or NE for SRM (< 5 cm) from January 2006 to August 2016. A total of 231 patients with T1 SRM were included in the main analysis. Patient demographics, tumor characteristics, biopsy and procedural details, clinical outcomes, complication rates, and changes in renal function were compared in patients with malignant SRMs. Survival rates were compared using log-rank test. RESULTS: A total of 142 patients underwent PA and 89 patients underwent NE, with a respective mean follow-up period of 2.50 (SD 1.77) and 1.85 (SD 0.97) years (P = 0.029). Rate of intervention for benign tumors was similar in PA (n = 21, 15%) and NE (n = 16, 18%; P = 0.520) without routine pre-procedural biopsy. Routine pre-procedural biopsy resulted in zero benign tumors treated in the PA cohort. Tumor recurrence was similar and cumulative survival was similar in both groups (P = 0.287). Residual tumor was observed in 18 PA patients. Complication rates were lower for PA than for NE (9 vs 30%, P < 0.001). A significant reduction in eGFR was observed after NE (12.1 mL/min/1.73 m2; P = 0.009) relative to PA (5.9 mL/min/1.73 m2; P = 0.060). CONCLUSION: PA is a safe alternative to NE in the treatment of SRM, with similar overall survival and decreased complication rates. Pre-procedural biopsy decreases the rate of intervention for benign tumors and should be routinely performed.

Clearance of beta-amyloid is facilitated by apolipoprotein E and circulating high-density lipoproteins in bioengineered human vessels.

Amyloid plaques, consisting of deposited beta-amyloid (Aß), are a neuropathological hallmark of Alzheimer's Disease (AD). Cerebral vessels play a major role in AD, as Aß is cleared from the brain by pathways involving the cerebrovasculature, most AD patients have cerebrovascular amyloid (cerebral amyloid angiopathy (CAA), and cardiovascular risk factors increase dementia risk. Here we present a notable advance in vascular tissue engineering by generating the first functional 3-dimensioinal model of CAA in bioengineered human vessels. We show that lipoproteins including brain (apoE) and circulating (high-density lipoprotein, HDL) synergize to facilitate Aß transport across bioengineered human cerebral vessels. These lipoproteins facilitate Aß42 transport more efficiently than Aß40, consistent with Aß40 being the primary species that accumulates in CAA. Moreover, apoE4 is less effective than apoE2 in promoting Aß transport, also consistent with the well-established role of apoE4 in Aß deposition in AD.

High-density lipoproteins suppress Aß-induced PBMC adhesion to human endothelial cells in bioengineered vessels and in monoculture.

BACKGROUND: Alzheimer's Disease (AD), characterized by accumulation of beta-amyloid (Aß) plaques in the brain, can be caused by age-related failures to clear Aß from the brain through pathways that involve the cerebrovasculature. Vascular risk factors are known to increase AD risk, but less is known about potential protective factors. We hypothesize that high-density lipoproteins (HDL) may protect against AD, as HDL have vasoprotective properties that are well described for peripheral vessels. Epidemiological studies suggest that HDL is associated with reduced AD risk, and animal model studies support a beneficial role for HDL in selectively reducing cerebrovascular amyloid deposition and neuroinflammation. However, the mechanism by which HDL may protect the cerebrovascular endothelium in the context of AD is not understood. METHODS: We used peripheral blood mononuclear cell adhesion assays in both a highly novel three dimensional (3D) biomimetic model of the human vasculature composed of primary human endothelial cells (EC) and smooth muscle cells cultured under flow conditions, as well as in monolayer cultures of ECs, to study how HDL protects ECs from the detrimental effects of Aß. RESULTS: Following Aß addition to the abluminal (brain) side of the vessel, we demonstrate that HDL circulated within the lumen attenuates monocyte adhesion to ECs in this biofidelic vascular model. The mechanism by which HDL suppresses Aß-mediated monocyte adhesion to ECs was investigated using monotypic EC cultures. We show that HDL reduces Aß-induced PBMC adhesion to ECs independent of nitric oxide (NO) production, miR-233 and changes in adhesion molecule expression. Rather, HDL acts through scavenger receptor (SR)-BI to block Aß uptake into ECs and, in cell-free assays, can maintain Aß in a soluble state. We confirm the role of SR-BI in our bioengineered human vessel. CONCLUSION: Our results define a novel activity of HDL that suppresses Aß-mediated monocyte adhesion to the cerebrovascular endothelium.