Biocompatibility, Inflammatory Response, and Recannalization Characteristics of Nonradioactive Resin Microspheres: Histological Findings

Abstract

Intra-arterial radiotherapy with yttrium-90 microspheres (radioembolization) is a therapeutic procedure exclusively applied to the liver that allows the direct delivery of high-dose radiation to liver tumors, by means of endovascular catheters, selectively placed within the tumor vasculature. The aim of the study was to describe the distribution of spheres within the precapillaries, inflammatory response, and recannalization characteristics after embolization with nonradioactive resin microspheres in the kidney and liver. We performed a partial embolization of the liver and kidney vessels in nine white pigs. The left renal and left hepatic arteries were catheterized and filled with nonradioactive resin microspheres. Embolization was defined as the initiation of near-stasis of blood flow, rather than total occlusion of the vessels. The hepatic circulation was not isolated so that the effects of reflux of microspheres into stomach could be observed. Animals were sacrificed at 48 h, 4 weeks, and 8 weeks, and tissue samples from 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 the kidney (the arciform arteries, vasa recti, and glomerular afferent vessels) and liver. Aggregates were associated with focal ischemia and mild vascular wall damage. Occlusion of the small vessels was associated with a mild perivascular inflammatory reaction. After filling of the left hepatic artery with microspheres, there was some evidence of arteriovenous shunting into the lungs, and one case of cholecystitis and one case of marked gastritis and ulceration at the site of arterial occlusion due to the presence of clusters of microspheres. Beyond 48 h, microspheres were progressively integrated into the vascular wall by phagocytosis and the lumen recannalized. Eight-week evaluation found that the perivascular inflammatory reaction was mild. Liver cell damage, bile duct injury, and portal space fibrosis were not observed. In conclusion, resin microspheres (15-30 lm diameter) trigger virtually no inflammatory response in target tissues (liver and kidney). Clusters rather than individual microspheres were associated with a mild to moderate perivascular inflammatory reaction. There was no evidence of either a prolonged inflammatory reaction or fibrosis in the liver parenchyma following recannalization.

Safety of a Scout Dose Preceding Hepatic Radioembolization with 166Ho Microspheres

“…We investigated only the latter. An animal study in 9 pigs by Bilbao et al (2) showed that nonradioactive microspheres only induce ulceration when aggregated, and embolization of small distal vessels alone does not cause ulceration. Blood flow was regenerated by the appearance of new vessels or recanalization of occluded vessels.…”

“…Millions of radioactive microspheres are injected in the hepatic artery to radiate and embolize malignancies (1). Deposition of microspheres in gastrointestinal organs can result in ulceration or inflammation of tissue by a combination of embolization and radiation damage (2)(3)(4). To prevent this, vessels leading to gastrointestinal organs may be coil-embolized in patients scheduled for radioembolization treatment, during a pretreatment session using contrastenhanced images (i.e., digital subtraction angiography complemented by C-arm CT) to identify the culprit vessel (5).…”

The dosimetric importance of the number of 90Y microspheres in liver transarterial radioembolization (TARE)

“…The paper by Lewandowski et al also mentions the embolic role of an augmented number of microspheres, although previous results are controversial in this respect: a trend toward improved survival of patients with the stasis phenomenon [29], in contrast to only mild inflammation of animal tissues embolized with nonradioactive resin microspheres [30]. Some caveats should be raised about the new idea.…”

Radioembolization Treatment for Liver Cancer

“…This situation is a general indication of extensive intrahepatic tumor growth, extrahepatic spread, progressive functional impairment, and progressive disease and often considered to be a contraindication for TACE (28). However, because RE has no macroembolic effect, it can be applied to patients with portal vein thrombosis (29,30). Al- though the width of portal thrombosis influences the survival time, no significant difference was found in terms of toxicity in the groups with and without portal vein thrombosis (29,31).…”