Laser‐induced thermotherapy (LITT) elevates mRNA expression of connective tissue growth factor (CTGF) associated with reduced tumor growth of liver metastases compared to hepatic resection

Abstract

Background and Objectives: Proliferation and synthesis of hepatocellular tissue after tissue damage are promoted by specific growth factors such as hepatic tissue growth factor (HGF) and connective growth factor (CTGF). Laser-induced thermotherapy (LITT) for the treatment of liver metastases is deemed to be a parenchyma-saving procedure compared to hepatic resection. The aim of this study was to compare the impact of LITT and hepatic resection on intrahepatic residual tumor tissue and expression levels of mRNA HGF/CTGF within liver and tumor tissue. Study Design/Materials and Methods: Two independent adenocarcinomas (CC531) were implanted into 75 WAG rats, one in the right (untreated tumor) and one in the left liver lobe (treated tumor). The left lobe tumor was treated either by LITT or partial hepatectomy. The control tumor was submitted to in-situ hybridization of HGF and CTGF 24-96 hours and 14 days after intervention. Results: Volumes of the untreated tumors prior to intervention were 38 AE 8 mm 3 in group I (laser), 39 AE 7 mm 3 in group II (resection), and 42 AE 12 mm 3 in group III (control) and did not differ significantly (P > 0.05). Fourteen days after the intervention the mean tumor AE SEM volume of untreated tumor in group I (laser) [223 AE 36] was smaller than in group II (resection) [1233.28 AE 181.52; P < 0.001], and in group III (control) [978.92 AE 87.57; P < 0.003]. Forty-eight hours after the intervention intrahepatic mRNA expression level of HGF in group II (resection) was almost twofold higher than in group I (laser) [7.2 AE 1.0 c/mf vs. 3.9 AE 0.4 c/mf; P < 0.01]. Fourteen days after the intervention intrahepatic mRNA expression level of CTGF in group I (laser) was higher than in group II (resection) [13.89 AE 0.77 c/mf vs. 9.09 AE 0.78 c/mf; P < 0.003]. Conclusions: LITT leads to a decrease of residual tumor growth in comparison to hepatic resection. Accelerated tumor growth after hepatic resection is associated with higher mRNA level of HGF and reduced tumor growth after LITT with higher mRNA level of CTGF. The increased CTGF-mediated regulation of ECM may cause reduced residual tumor growth after LITT.

Changes in growth factor levels after thermal ablation in a murine model of colorectal liver metastases

“…did not present baseline GF levels (day 0) that may also have shown a temporal decrease, as in our study. In agreement with our study, these two studies 26,27 reported decreased expression of particular GFs following TA, with an increase in HGF common to all three studies. We demonstrated a similar decrease in GF expression in the sham‐ablated controls, suggesting that the decrease most likely reflects a general effect of laparotomy rather than TA.…”

“…By contrast, no difference emerged between TA‐treated animals and sham‐ablated controls at this time‐point, which is in agreement with our findings. Isbert et al 27 . did not present baseline GF levels (day 0) that may also have shown a temporal decrease, as in our study.…”

“…In light of this, it is important to note that no sham group was included in the study reported by Meredith et al 26 . In another study, Isbert et al 27 . compared the effects of TA or resection on HGF mRNA levels using an implanted CRC rat tumour model.…”

“…compared the effects of TA or resection on HGF mRNA levels using an implanted CRC rat tumour model. In this study, 27 two tumours were implanted, but only one was ablated, resembling the design of our experiment. Isbert et al 27 .…”

“…In this study, 27 two tumours were implanted, but only one was ablated, resembling the design of our experiment. Isbert et al 27 . reported that HGF mRNA levels at 48 h were significantly lower in distant tumours in animals undergoing TA compared with those undergoing resection.…”