Hepatic radiofrequency ablation: markedly reduced systemic effects by modulating periablational inflammation via cyclooxygenase-2 inhibition.
OBJECTIVE
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.


CONCLUSIONS
• 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.
Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA.
Gaurav
G
Kumar
Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA.|Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Hospital, Jerusalem, Israel.|Division of Image-guided Therapy and Interventional Oncology, Department of Radiology, Hadassah Hebrew University Hospital, Jerusalem, Israel.
S Nahum
SN
Goldberg
Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA.
Yuanguo
Y
Wang
Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA.
Erik
E
Velez
Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Hospital, Jerusalem, Israel.
Svetlana
S
Gourevitch
Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Hospital, Jerusalem, Israel.
Eithan
E
Galun
Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA. mahmed@bidmc.harvard.edu.|Department of Radiology, WCC 308-B, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Boston, MA, 02215, USA. mahmed@bidmc.harvard.edu.
Muneeb
M
Ahmed
D000818:Animals; D017115:Catheter Ablation / Q000379:methods*; D000068579:Celecoxib / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000517:prevention & control*; D008099:Liver / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011916:Rats, Inbred F344
D052246:Cyclooxygenase 2 Inhibitors; D000068579:Celecoxib
Celecoxib; Cyclooxygenase-2 receptor; Liver; Radiofrequency ablation; Tumour growth