Local Heat Treatment for Suppressing Gastroduodenal Stent-Induced Tissue Hyperplasia Using Nanofunctionalized Self-Expandable Metallic Stent in Rat Gastric Outlet Model.

ABSTRACT

Despite the promising results from the placement of covered or uncovered self-expandable metallic stent (SEMS) as a nonsurgical therapeutic option for the malignant gastric outlet obstruction (GOO), the long patency of the stent is still limited because of stent-induced tissue hyperplasia. Here, a local heat treatment using a nanofunctionalized SEMS is proposed for suppressing stent-induced tissue hyperplasia during GOO treatment. Highly efficient photothermal gold nanoparticle (GNP) transducer-coated SEMSs (GNP-SEMSs) were prepared for local heat treatment in rat gastric outlet. The in vivo heating temperature in rat gastric outlet model was evaluated and compared with in vitro heating temperature. Three groups of our developed 45 rat gastric outlet models were used group A, noncoated SEMS only; group B, GNP-SEMS plus local heating; and group C, GNP-SEMS only to investigate in vivo efficacy of GNP-SEMS mediated local heating. Ten rats per group were sacrificed for 4 weeks, and five rats per group were sacrificed immediately after local heat treatment. The in vivo heating temperature was found to be 10.8% lower than the in vitro heating temperatures. GNP-SEMSs were successfully placed through a percutaneous approach into the rat gastric outlet (n = 45). The therapeutic effects of GNP-SEMS were assessed by histologic examination including hematoxylin-eosin, Masson trichrome, immunohistochemistry (TUNEL and CD31), and immunofluorescence (Ki67), and the results showed significant prevention of tissue hyperplasia following stent placement without adjacent gastrointestinal tissue damage. GNP-SEMS-mediated local heating could be an alternative therapeutic option for the suppression of tissue hyperplasia following stent placement in benign and malignant GOOs.