Tumour growth stimulation after partial hepatectomy can be reduced by treatment with tumour necrosis factor alpha

This study investigated whether partial hepatectomy enhances the growth of experimental liver metastases of colonic carcinoma in rats and whether treatment with recombinant human tumour necrosis factor (TNF) alpha can reduce this increased growth. Resection of 35 or 70 per cent of the liver was performed in inbred WAG rats, with sham-operated controls (five to eight animals per group). Immediately after surgery 5 x 10(5) CC531 colonic tumour cells were injected into the portal vein. After 28 days the animals were killed and the number of liver metastases counted. A 35 per cent hepatectomy induced a significant increase in the median number of liver metastases (28 versus 3 in controls), whereas a 70 per cent resection provoked excessive growth, consistently leading to more than 100 liver metastases and a significantly increased wet liver weight in all animals. TNF-alpha was given intravenously to rats following 70 per cent hepatectomy or sham operation in a dose of 160 micrograms/kg three times per week. This had only a marginal effect on tumour development in sham-operated rats but was very effective following partial hepatectomy (median 45 liver metastases). These observations confirm previous findings that surgical metastasectomy may act as a 'double-edged sword' by provoking outgrowth of dormant tumour cells and suggest that adjuvant treatment with TNF-alpha may be of benefit in patients undergoing resection of metastases.