Biocompatibility, inflammatory response, and recannalization characteristics of nonradioactive resin microspheres: histological findings

摘要

Abstract Intra-arterial radiotherapy with yttrium-90microspheres (radioembolization) is a therapeutic procedureexclusively applied to the liver that allows the directdelivery of high-dose radiation to liver tumors, by means ofendovascular catheters, selectively placed within the tumorvasculature. The aim of the study was to describe thedistribution of spheres within the precapillaries, inflammatoryresponse, and recannalization characteristics afterembolization with nonradioactive resin microspheres in thekidney and liver. We performed a partial embolization ofthe liver and kidney vessels in nine white pigs. The leftrenal and left hepatic arteries were catheterized and filledwith nonradioactive resin microspheres. Embolization wasdefined as the initiation of near-stasis of blood flow, ratherthan total occlusion of the vessels. The hepatic circulationwas not isolated so that the effects of reflux of microspheresinto stomach could be observed. Animals weresacrificed at 48 h, 4 weeks, and 8 weeks, and tissue samplesfrom the kidney, liver, lung, and stomach evaluated.Microscopic evaluation revealed clusters of 10–30 microspheres(15–30 lm in diameter) in the small vessels of thekidney (the arciform arteries, vasa recti, and glomerularafferent vessels) and liver. Aggregates were associatedwith focal ischemia and mild vascular wall damage.Occlusion of the small vessels was associated with a mildperivascular inflammatory reaction. After filling of the lefthepatic artery with microspheres, there was some evidenceof arteriovenous shunting into the lungs, and one case ofcholecystitis and one case of marked gastritis and ulcerationat the site of arterial occlusion due to the presence ofclusters of microspheres. Beyond 48 h, microspheres wereprogressively integrated into the vascular wall by phagocytosisand the lumen recannalized. Eight-week evaluationfound that the perivascular inflammatory reaction wasmild. Liver cell damage, bile duct injury, and portal spacefibrosis were not observed. In conclusion, resin microspheres(15–30 lm diameter) trigger virtually no inflammatoryresponse in target tissues (liver and kidney).Clusters rather than individual microspheres were associatedwith a mild to moderate perivascular inflammatoryreaction. There was no evidence of either a prolongedinflammatory reaction or fibrosis in the liver parenchymafollowing recannalization.