Influence of a Paclitaxel-Eluting Covered Metallic Stent On Tissue Hyperplasia: An Experimental Study in a Canine Biliary Model

Abstract

Aim: The aim was to evaluate safety of a paclitaxel-eluting covered metallic stent in a canine biliary model by comparing histologic tissue reaction. Methods: Six paclitaxel-eluting covered metallic stents were endoscopically placed in the bile ducts of six mongrel dogs, and five covered metallic stents were placed in five dogs as controls. The dogs were sacrificed at six weeks after stent placement and gross and histopathologic examinations were done. Degree of inflammation was graded as follows: 0, none; 1, mild; 2, moderate; 3, severe. Results: All 11 dogs survived until the sacrifice without evidence of jaundice. All the stents except for two drug-eluting stents were placed within the canine bile duct successfully. Two malpositioned stents were excluded from histologic analysis. There was no migration or perforation. In the control stent group, there was no tissue ingrowth. Both proximal and distal ends of all the control stents showed minimal tissue overgrowth except for distal end obstruction in one and 20% narrowing of proximal end in another. In the drug-eluting stent group, tissue ingrowth was found in three animals. Two were malpositioned stents. Minimal tissue overgrowth was noted in both ends of three animals. One dog without malpositioned stent showed ingrowth at both ends. Microscopic examination demonstrated increased thickness of epithelial layers in middle and distal ends of canine bile ducts in contact with drug-eluting stents (575.00 ± 301.39 μm vs. 180.00 ± 109.55 μm, P = 0.022; 1150.00 ± 100.00 μm vs. 430.00 ± 323.27 μm, P = 0.012, respectively). Proximal ends of bile ducts showed no significant difference in thickness of epithelial layers, but there was tendency for increased thickness in the drug-eluting stent group (800.00 ± 282.84 μm vs. 530.00 ± 272.95 μm, P = 0.260). Canine bile duct in contact with drug-eluting stents showed less severe inflammatory reaction in the proximal and distal ends (2 vs. 2.80 ± 0.45, P = 0.024; 1.50 ± 0.58 vs. 2.60 ± 0.55, P = 0.036, respectively). In the middle of canine bile duct in contact with drug-eluting stents, there was tendency for less severe inflammation although not statistically significant (1.50 ± 1.00 vs. 1.80 ± 0.84, P = 0.498). Conclusion: Placement of paclitaxel-eluting covered metallic stents in normal canine bile duct was without significant complications despite significant histologic changes from local drug delivery. The results provide a basis for extending the use of a paclitaxel-eluting covered metallic stent in clinical trials. Further studies in patients with malignant biliary obstruction are needed to establish the role of this stent in the palliation of obstructive jaundice.