Progreat

All TACE procedures were performed by two experienced interventional radiologists (with 15 and 5 years of TACE experience) in a consistent way. After local anaesthesia, the right femoral artery was punctured with the modified Seldinger technique. A 4-Fr arterial catheter (RH, Terumo, Japan) was inserted for selective HA and SMA, and then a 3-Fr microcatheter (Progreat, Terumo, Japan) was superselectively inserted into the supply artery of the tumour. An oil-in-water-based emulsion comprising chemotherapy drugs epirubicin (30–50 mg), oxaliplatin (100–150 mg), 5-fluorouracil (5-FU) (500–750 mg) and leucovorin (200–300 mg) mixed with lipiodol (8 ml) at a proportion of 1:1 were injected through a microcatheter, and then 0.1 g polyvinyl alcohol (PVA) particles (300–500 μm) and gelatine sponge particles were injected successively. The treatment endpoint was determined by the interventional radiologist, and the main manifestation was the complete coverage of the tumour site by lipiodol deposition and feeding artery shown as a “dry-branch”, which means there were no blood supply absolutely.

The operators (XK, GZ, BX, BL, FP, and CZ) of the TACE procedures had at least 8 years of experience in performing TACE procedures. Initially, the tip of a 3-French microcatheter (Progreat, Terumo, Tokyo, Japan) or a 5-French catheter (Cook, Bloomington, IN, USA) was introduced into the tumor-feeding arteries. Then, 10–20 ml of lipiodol (Lipiodol Ultrafluido, Guerbet, France) was mixed with 20–40 mg of doxorubicin hydrochloride (Hisun Pharmaceutical Co. Ltd., Zhejiang, China) to create an emulsion. Based on the tumor size and the liver function, 5–20 ml of the emulsion was injected into the tumor-feeding arteries through a 5-French catheter or a 3-French microcatheter. Lastly, gelatin sponge particles (300–700 um, Cook, USA) were used to supplement embolization until the stagnation of artery flow appeared. For patients with arterioportal shunt, polyvinyl alcohol particles (300–1,000 um, Cook, USA) were used for blocking the shunt before infusion of the emulsion of lipiodol and doxorubicin.

The embolization procedure has been described previously [23 (link),25 (link),26 (link),27 (link)]. The procedures were performed under aseptic conditions with prophylactic antibiotics. The animals were maintained under general anesthesia. A C-arm unit (Pulsera BV, Philips Medical Systems Inc., Best, The Netherlands) was used for angiography. The femoral artery was accessed through a surgical cut-down and catheterized with a 3 F vascular sheath, after which a 2.4 F microcatheter (Progreat, Terumo, Irvine, CA, USA) and microwire (Transcend 0.018”, Stryker Inc., Kalamazoo, MI, USA) were advanced into the common hepatic artery. Angiography was performed. The tumor was visualized as a region of hypervascular blush in the liver. The hepatic artery supplying the tumor was catheterized as selectively as possible and embolized using the DEE loaded with liposomal sorafenib or regorafenib under fluoroscopic visualization until vascular stasis was achieved. Post TACE, the femoral artery was ligated. Post procedure, the animals were monitored daily for signs of discomfort. Doses of Buprenorphine ranging from 0.01 to 0.05 mg/Kg and a 5 mg/Kg dose of Enrofloxacin were administered intramuscularly or subcutaneously if needed.