Background: Accelerated progression of residual hepatocellular carcinoma (HCC) after incomplete radiofrequency ablation (RFA) has been reported more frequently. Recent data have redefined the concept of inflammation as a critical component of tumor progression. However, there has been little understanding regarding the relationship between progression of residual HCC and the inflammation induced by thermal destruction of the tumor after RFA. The present study was designed to determine whether inflammation facilitates rapid progression of residual hepatic VX2 carcinoma and to clarify the possible underlying mechanisms.
Methods: Forty-eight rabbits were each implanted with two VX2 hepatic tumors via supraumbilical median laparotomy. One of the tumors in two different lobes was ablated by RFA. All the rabbits were then randomly divided into four groups (12 rabbits in each group) receiving anti-inflammatory treatment with different doses of aspirin: control group, AS-L group (aspirin, 5 mg/kg/d), AS-M group (aspirin, 20 mg/kg/d), and AS-H group (aspirin, 100 mg/kg/d). The levels of serum interleukin-6 (IL-6), high sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor-α (TNF-α) were detected to evaluate the effect of the anti-inflammation. Tumor growth, lung and kidney metastasis, and survival were assessed. The expression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), and cysteinyl aspartate specific proteinase 3 (caspase-3) in residual tumor was examined by immunohistochemistry and Western-blotting.
Results: The levels of serum IL-6, hs-CRP, and TNF-α in the AS-H group decreased significantly in comparison with those of the control group (P<0.05). The focal tumor volume and lung and kidney metastases of rabbits in the AS-H group were less significant compared with those of the control group (P<0.05). The expression of PCNA, MMP-9, and VEGF in the AS-H group decreased significantly compared with the control group (P<0.05). Finally, the survival time of the AS-H group was longer than that of the control group (P<0.05).
Conclusions: Inflammation induced by thermal destruction of the tumor following RFA could be an important cause of rapid progression of residual hepatic VX2 carcinoma. The anti-inflammation effect of aspirin can inhibit proliferation, invasion, and metastasis of residual tumor cells, and aspirin may be a good candidate drug as an adjuvant therapy with RFA for treating HCC.
Keywords: Hepatocellular carcinoma; IL-6; RFA; interleukin-6; radiofrequency ablation.