Altered growth patterns of colorectal liver metastases after thermal ablation.
BACKGROUND
Thermal ablation by radiofrequency or laser is used increasingly for the treatment of colorectal liver metastases. Recurrence after thermal ablation is common and occurs both locally and at distant sites. One possible cause of this recurrence may be a result of growth stimulation of micrometastases in the remaining liver. This study examined the impact of thermal ablation on growth patterns of hepatic micrometastases.


METHODS
Colorectal liver metastases were induced in male CBA-strain mice via an intrasplenic injection of a murine-derived cancer cell line. Subtotal thermal ablation of the left posterior lobe of the liver (30% of total liver volume) was performed by neodymium yttrium-aluminum-garnet laser 7 days after induction of metastases. The distribution, number, cross-sectional diameter, volume, and proliferation rate of established neoplasms were compared with controls at 21 days after tumor induction. The effect of thermal ablation of 7% of the total liver volume by laser on the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor 2 (FGF-2), transforming growth factor beta, and cellular proliferation (Ki-67 antigen) adjacent to the ablated site was assessed by immunohistochemistry in separate groups of animals at specific time points after therapy.


RESULTS
Thermal ablation did not alter the overall volume, number, size, and proliferation rate of neoplasms 21 days after laser ablation. There were no extrahepatic metastases after therapy. The number of neoplasms in the regenerated posterior lobe was equivalent to control despite subtotal ablation (29 +/- 2 vs 27 +/- 2; P = NS). A greater amount of metastases occupied the regenerated thermal-ablated lobe compared with controls (55% +/- 4% vs 29% +/- 3%; P < .04). Thermal ablation stimulated liver proliferation adjacent to the treatment site at 12 hours compared with untreated controls. Stimulation peaked at 72 hours (20% +/- 1% vs 1% +/- 1%; P < .001) and persisted to 21 days after therapy. FGF-2 and VEGF expression increased in liver tissue adjacent to the ablation site compared with baseline, peaking at 12 hours (112% +/- 2% vs 102% +/- 1%; P < .001) and 72 hours (114% +/- 2% vs 101% +/- 1%; P < .001), respectively.


CONCLUSIONS
Thermal ablation promotes the progression of micrometastases to form macroscopically detectable neoplasms in treated regenerating liver. This effect may relate to an increased expression of VEGF and FGF-2 adjacent to the treatment site.
Nikfarjam
Mehrdad
M
Department of Surgery, University of Melbourne, Austin Hospital, Lance Townsend Building Level 8, Studley Road, Heldelberg, Melbourne, Victoria 3084, Australia. surgery-armc@unimelb.edu.au
Muralidharan
Vigayaragavan
V
Christophi
Christopher
C
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000473:pathology*; D018450:Disease Progression; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006979:Hyperthermia, Induced / Q000009:adverse effects*; D053685:Laser Therapy; D007834:Lasers / Q000009:adverse effects*; D008099:Liver / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011184:Postoperative Period; D013997:Time Factors; D015291:Transforming Growth Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors; D015291:Transforming Growth Factors