Background: Hepatocellular carcinoma (HCC) frequently recurs after curative resection. In the present study, we assessed the survival of HCC patients with or without preoperative transarterial immunoembolization (TIE) in relation to changes in serum cytokine levels and histological characteristics of resected specimens.
Methods: After confirmation of the safety and feasibility of preoperative TIE in a preliminary study of 9 patients, 15 pa-tients who planned to undergo curative resection of HCC were randomized to the TIE group (n=8) or the control group (n=7). TIE was performed with a mixture of OK-432, fibrinogen, thrombin, and lipiodol. Hepatic resection was planned 2 weeks after TIE.
Results: In the preliminary study, none of 9 patients with TIE developed complications that were severe enough to postpone the scheduled operation. Retrospectively, the 3-year disease-free and overall survival rate in the 9 patients who received preoperative TIE were both 100%; in contrast, the disease-free survival and overall survival were 27% and 64%, respectively, in 22 patients who received a hepatectomy around the same period without TIE. Furthermore, the prospective study revealed that the 3-year disease-free survival and overall survival in the TIE group were 88% and 100%, which were significantly higher than the corresponding rates in the control group (17% and 57%, respectively, both: p<0.05). Serum levels of interleukin-12 and interferon gamma were increased after TIE. Histologically, significant infiltrations of dendritic cells were observed in embolized areas, but the infiltration of FOXP3-positive cells was significantly suppressed after TIE.
Conclusion: Preoperative TIE suppresses recurrences of HCC after surgery. The suppressive effect might be caused by increased levels of helper T-cell 1 cytokines, the accumulation and maturation of dendritic cells, and the suppression of T-regulatory lymphocytes.