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.
OBJECTIVE
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.


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+/-8 mm(3) in group I (laser), 39 +/- 7 mm(3) in group II (resection), and 42 +/- 12 mm(3) in group III (control) and did not differ significantly (P > 0.05). Fourteen days after the intervention the mean tumor+/-SEM volume of untreated tumor in group I (laser) [223 +/- 36] was smaller than in group II (resection) [1233.28 +/- 181.52; P < 0.001], and in group III (control) [978.92 +/- 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 +/- 1.0 c/mf vs. 3.9 +/- 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 +/- 0.77 c/mf vs. 9.09 +/- 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.
Isbert
Christoph
C
Department of Surgery, Klinikum Nuernberg Nord, D-90419 Nuernberg, Germany. isbert@klinikum-nuernberg.de
Ritz
Jörg-Peter
JP
Roggan
André
A
Schuppan
Detlef
D
Ajubi
Navid
N
Buhr
Heinz Johannes
HJ
Hohenberger
Werner
W
Germer
Christoph-Thomas
CT
D000818:Animals; D055513:Connective Tissue Growth Factor; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000528:radiation effects; D017874:Immediate-Early Proteins / Q000235:genetics / Q000528:radiation effects*; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000528:radiation effects*; D053685:Laser Therapy; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D008297:Male; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D018365:Neoplasm, Residual / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000528:radiation effects*; D051381:Rats
C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; D017228:Hepatocyte Growth Factor