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. 2010 Jul 29:8:73.
doi: 10.1186/1479-5876-8-73.

Low temperature of radiofrequency ablation at the target sites can facilitate rapid progression of residual hepatic VX2 carcinoma

Shan Ke  1 , Xue-mei Ding, Jian Kong, Jun Gao, Shao-hong Wang, Yan Cheng, Wen-bing Sun
Affiliations

Low temperature of radiofrequency ablation at the target sites can facilitate rapid progression of residual hepatic VX2 carcinoma

Shan Ke et al. J Transl Med. .

Abstract

Background: Rapid progression of residual tumor after radiofrequency ablation (RFA) of hepatocellular carcinoma has been observed increasingly. However, its underlying mechanisms remain to be clarified. The present study was designed to determine whether low temperature of RFA at the target sites facilitates rapid progression of residual hepatic VX2 carcinoma and to clarify the possible underlying mechanisms.

Methods: The residual VX2 hepatoma model in rabbits was established by using RFA at 55, 70 and 85 degrees C. Rabbits that were implanted with VX2 hepatoma but did not receive RFA acted as a control group. The relationship between rapid progression of residual hepatic VX2 carcinoma and low temperature of RFA at the target sites was carefully evaluated. A number of potential contributing molecular factors, such as proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and Interleukin-6 (IL-6) were measured.

Results: The focal tumor volume and lung metastases of RFA-treated rabbits increased significantly compared with the control group (P < 0.05), and the greatest changes were seen in the 55 degrees C group (P < 0.05). Expression of PCNA, MMP-9, VEGF, HGF and IL-6 in tumor tissues increased significantly in the RFA-treated groups compared with the control group, and of the increases were greatest in the 55 degrees C group (P < 0.05). These results were consistent with gross pathological observation. Tumor re-inoculation experiments confirmed that low temperature of RFA at the target sites facilitated rapid progression of residual hepatic VX2 carcinoma.

Conclusions: Insufficient RFA that is caused by low temperature at the target sites could be an important cause of rapid progression of residual hepatic VX2 carcinoma. Residual hepatic VX2 carcinoma could facilitate its rapid progression through inducing overexpression of several molecular factors, such as PCNA, MMP-9, VEGF, HGF and IL-6.

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Figures

Figure 1
Figure 1
Schematic diagram of the whole experimental plan.
Figure 2
Figure 2
Sketch of residual hepatic VX2 carcinoma following RFA. The oval-shaped area of "adbe" represents the whole tumor. The line "ab" is the minor axis of the tumor and the line "de" is the major axis. The tumor center was also designated as the RFA center. The measured minor axis of the tumor was used to guide the release of the RFA needle electrode. Thus, residual tumor was left on both sides of the measured major tumor axis (shadowed area).
Figure 3
Figure 3
Growth of hepatic VX2 carcinoma after insufficient RFA due to low temperature at the target sites. Data were expressed as means ± SD of three independent experiments. (*P < 0.05, groups I, II and III vs. control group. #P < 0.05, group I vs. groups II and III, by one-way ANOVA and Newman-Keuls test).
Figure 4
Figure 4
Macroscopic characteristics of pulmonary metastatic nodules. A. Macroscopic view of the lung. B. Fractionated view of the lung, which has been magnified to show the details of the metastatic nodules.
Figure 5
Figure 5
Frequency of pulmonary metastatic nodules in the control group and groups treated with RFA at different low target temperatures. Data were expressed as means ± SD of three independent experiments. (*P < 0.05, groups I, II and III vs. control group. #P < 0.05, group I vs. groups II and III by one-way ANOVA and Newman-Keuls test).
Figure 6
Figure 6
Immunohistochemical staining for MMP-9, VEGF and PCNA in residual hepatic VX2 carcinoma tissues. Original magnifications: MMP-9 and VEGF, ×400; PCNA, ×200. A, control group; B, group I; C, group II; D, group III.
Figure 7
Figure 7
MMP-9, VEGF and PCNA expression in residual hepatic VX2 carcinoma tissues. A, MMP-9; B, VEGF; C, PCNA. 1, control group; 2, group III; 3, group II; 4, group I.
Figure 8
Figure 8
RFA might affect the expression of HGF and IL-6 in liver and tumor tissues. A, Concentration of HGF; B, Concentration of IL-6. Liver tissues represented the normal tissues from the same liver which was treated with RFA. Data were expressed as means ± SD of three independent experiments. (*P < 0.05, groups I, II and III vs. control group. #P < 0.05, group I vs. groups II and III, by one-way ANOVA and Newman-Keuls test).
Figure 9
Figure 9
Volumes of hepatic VX2 carcinoma 21 days after reinoculation. A, Photographs of the hepatic VX2 carcinoma of five rabbits selected from the control group and five from group I. 1, Group I, RFA at 55°C; 2, control group. The top row shows hepatic VX2 carcinoma of rabbits treated with RFA, and large tumors were seen. The bottom row shows hepatic VX2 carcinoma of control rabbits with smaller tumors. B, 1, group I, RFA at 55°C; 2, control group. Data are expressed as means ± SD of three independent experiments. (*P < 0.05, by Student's t test)
Figure 10
Figure 10
Lung metastasis of hepatic VX2 carcinoma 21 days after reinoculation. A, Photographs of the lungs of five rabbits selected from the control group and five from group I. 1, group I, RFA at 55°C; 2, control group. The top row shows lungs of rabbits treated with RFA, and numerous, large, white-grey tumors were seen. The bottom row shows lungs of control rabbits with fewer and smaller tumors. B, 1, group I, RFA at 55°C; 2, control group. Data are expressed as means ± SD of three independent experiments. (*P < 0.05, by Student's t test)
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