Elsevier

Surgery

Volume 139, Issue 1, January 2006, Pages 73-81
Surgery

Altered growth patterns of colorectal liver metastases after thermal ablation

https://doi.org/10.1016/j.surg.2005.07.030Get rights and content

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 β, 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.

Section snippets

Animals

Male inbred CBA-strain mice, 6 to 8 weeks of age, were used. Animals were housed in standard cages with access to irradiated food and water ad libitum and exposed to a 12-hour light/dark cycle. All procedures were performed according to the guidelines of the Austin Hospital Animal Ethics Committee.

Liver metastases model

A dimethyl hydrazine–derived primary murine colon cancer cell line was used for the induction of colorectal liver metastases by methods described previously.10 The histology, vasculature, and growth

Extrahepatic metastases

All animals killed at 21 days after induction of metastases in treatment and control groups had liver metastases without evidence of extrahepatic spread.

Control animals

Macroscopically, there was homogenous spread of neoplasms throughout the liver in the control group. There were no differences in the percentage of metastases between the anterior and posterior lobes in the control group (36% ± 3% vs 29% ± 4%; P = .451) (Fig 1). The absolute number of metastases in the left posterior liver lobe in controls was

Discussion

Cancer recurrence after operative resection of colorectal liver metastases is remarkably high despite preoperative staging using several techniques to identify all metastatic disease.1, 4, 15 The liver is the predominant site of recurrent disease in approximately 50% of patients.1, 4, 15 More recently, thermal ablation by radiofrequency and laser ablation have been used for the treatment of liver neoplasms, with data suggesting similar survival rates to operative resection in selected patients.1

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