Abstract
Objectives
To determine whether celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, can potentiate hepatic radiofrequency ablation (RFA)-induced local cellular infiltration and distant tumour growth.
Methods
First, COX-2 expression was evaluated using immunohistochemistry in the local periablational rim 24 h after hepatic RFA without/with intraperitoneal celecoxib in normal Fisher 344 rat liver. Next, local cellular infiltration of macrophages, stellate cells, and hepatocyte proliferation were quantified in C57BL6 mice 3–7d after RFA without/with celecoxib. c-Met, HGF, and VEGF levels after RFA were also measured. Finally, distant tumour growth and proliferation (Ki67 and CD34) were observed in subcutaneous R3230 tumours after hepatic RFA with/without celecoxib.
Results
Hepatic RFA-induced local activation of COX-2 was significantly suppressed using celecoxib. Celecoxib also reduced RFA-associated a) increased c-Met expression at 24 h, b) HGF and VEGF levels at 72 h, c) periablational macrophage and stellate cells at 3d, and d) hepatocyte proliferation at 7d. Similarly, celecoxib with RFA reduced distant tumour growth, tumour cell proliferation, and tumour microvascular density to sham levels, compared to increases observed with hepatic RFA alone.
Conclusions
Increased activation of COX-2 after hepatic RFA contributes to periablational cellular infiltration and inflammation-mediated distant tumour growth, which can be successfully suppressed with a COX-2 inhibitor.
Key Points
• Thermal ablation of liver tissue can increase local inflammation and COX-2 expression.
• Ablation-induced local inflammation can contribute to stimulation of distant tumour growth.
• Local COX-2 inhibition with celecoxib can block ablation-induced distant tumour growth.
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Acknowledgments
The scientific guarantor of this publication is Dr. Muneeb Ahmed. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.
This study has received funding from the National Cancer Institute, Bethesda, MD (CCNE 1U54CA151881-01), the Israeli Centers for Research Excellence (I-CORE), and the Israel Science Foundation. No complex statistical methods were necessary for this paper. Institutional review board approval was not required because as this is an animal study. Approval from the institutional animal care committee was obtained. Methodology: experimental/animal study.
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Kumar, G., Goldberg, S.N., Wang, Y. et al. Hepatic radiofrequency ablation: markedly reduced systemic effects by modulating periablational inflammation via cyclooxygenase-2 inhibition. Eur Radiol 27, 1238–1247 (2017). https://doi.org/10.1007/s00330-016-4405-4
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DOI: https://doi.org/10.1007/s00330-016-4405-4