INTRODUCTION: Proliferation and synthesis of hepatocellular tissue and the extracellular matrix (ECM) are mediated by growth factors (HGF/CTGF=hepatic/connective tissue growth factor). Laser-induced thermotherapy (LITT) is an in situ ablation procedure without parenchymal loss. The aim of this study was to compare the impact of surgical resection (SR) and LITT on residual tumor tissue, metastatic spread and HGF and CTGF expression.
METHODS: 2 liver tumors/animal were induced in WAG rats. One tumor (therapy tumor) was treated either by LITT (group I, n=25) or by left hepatectomy (group II, n=25); the other tumor was left untreated (control tumor). In group III (n=25) both tumors were left untreated. Animals were sacrificed after 24, 48, 72, 96 h and 14 d. Peritoneal tumor spread was quantified, and the control tumors were measured and cryostored. In situ hybridization was used to detect mRNA HGF and CTGF. Tumor proliferation was determined by BrdU.
RESULTS: In gr. I and II, the therapy tumor was completely eradicated in all cases. Pre-interventional control tumor volumes did not differ between the groups (p>0.01). After 14 days, tumor volume in gr. I (232±40 mm3) was smaller than that in gr. II (1233±118 mm3) and III (978±87 mm3) (p<0.001). Peritoneal tumor spread was 20% in gr. I, 100% in II and 80% in III. Already after 96 h, mRNA expression of CTGF was higher in gr. I with 6.76±0.9 cells/mf than in group II with 4.1±0.3 cells/mf (p<0.05) and remained clearly higher even after 14 d with 13.89±0.8 vs. 8.09±0.8 cells/mf (p<0.001). After 48 h, mRNA expression of HGF was considerably higher in gr. II with 7.2±1.0 cells/mf than in gr. I with 3.9±0.4 cells/mf (p<0.01). Proliferation in control tumors did not differ.
CONCLUSIONS: LITT resulted in a decrease of residual tumor growth in comparison to SR with similar tumor cell proliferation. Accelerated growth after SR is associated with higher HGF expression and reduced tumor growth after LITT with higher CTGF expression. The increased CTGF-mediated regulation of ECM may cause reduced residual tumor growth after LITT.
