Abstract

Lymphatic vessels provide a critical pathway to drain interstitial fluid and participate immune cell response. We sought to investigate the effects of TAE on lymphatic vessel density in a preclinical model of HCC. Twenty-four adult male buffalo rats were randomly assigned to receive a fixed dose unloaded beads (70-150 μm) or sham hepatic artery saline infusion. After 7 or 14 days, 6 animals per group were euthanized. Five hotspots located in the tumor were assessed after double immunostaining with podoplanin and Lyve-1, specific markers for lymphatic endothelium. The number of lymphatic vessels per field, area occupied by the vessels, and lumen area were recorded. The data was expressed as median and range of absolute number of lymphatic vessels or area in pixels. Higher lymphatic microvascular density was observed in the group of rats treated with TAE after 14 days with a median vessel number per field of 27 (4-126), followed by bland embolization at 7 days 10 (1-69). In contrast, a similar number of lymphatic vessels was observed in the control group at seven days or at 14 days 8.5 (0-28) versus 8 (1-25) vessels per field; p<0.0001. The largest area occupied by the lymphatic vessels was observed in the group of animals treated with TAE after 14 days 1168.4 (144.92-62598.4), followed by the TAE group at 7 days 1055.5 (358.6-15329.1) and sham control after 14 days 647.25 (90.8-13094.1); p<0.0001. Lymphatic vessels in the group treated with TAE displayed a more dilated lumen compared with controls. Larger lumens were more frequently observed at 14 days after TAE 373.025 (8.422-14247.7) followed by TAE at 7 days 333.385 (37.72-11966.7) when compared with controls after 14 days 132.615 (13.53-9144.7); P = 0.001. Higher lymphatic microvascular density was significantly associated with hepatic artery embolization. Structural and numerical changes were observed in lymphatic vessels after treatment.

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