Major liver resection stimulates stromal recruitment and metastasis compared with repeated minor resection

• Published in: The Journal of surgical research Vol. 178; no. 1; pp. 280 - 287
• Main Authors: Momiyama, Masashi, MD, Kumamoto, Takafumi, MD, PhD, Suetsugu, Atsushi, MD, PhD, Kishimoto, Hiroyuki, MD, PhD, Chishima, Takashi, MD, PhD, Tanaka, Kuniya, MD, PhD, Akiyama, Hirotoshi, MD, PhD, Ichikawa, Yasushi, MD, Bouvet, Michael, MD, Endo, Itaru, MD, PhD, Hoffman, Robert M., PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2012
• Subjects: Adenocarcinoma - secondary; Adenocarcinoma - surgery; Animals; Cell Line, Tumor; Color-coded imaging; Green fluorescent protein; Green Fluorescent Proteins - genetics; Hepatectomy - adverse effects; Hepatectomy - methods; Hepatocyte Growth Factor - blood; Liver metastasis; Liver Neoplasms - secondary; Liver Neoplasms - surgery; Liver resection; Luminescent Proteins - genetics; Lung metastasis; Lung Neoplasms - secondary; Mice; Mice, Inbred C57BL; Mice, Nude; Mice, Transgenic; Neoplasm Transplantation; Nude mice; Red Fluorescent Protein; Spleen - pathology; Stroma; Stromal Cells - pathology; Surgery; Transforming Growth Factor beta - blood; Vascular Endothelial Growth Factor A - blood; Liver resection; Nude mice; Lung metastasis; Green fluorescent protein; Red fluorescent protein; Stroma; Liver metastasis; Color-coded imaging
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2012.03.020

Abstract Background The present study examined the effects of types of liver resection on the growth of liver and lung metastases. Methods Experimental liver metastases were established by spleen injection of the Colon 26 murine adenocarcinoma cell line expressing green fluorescent protein (GFP) into transgenic nude mice expressing red fluorescent protein. Experimental lung metastases were established by tail-vein injection with Colon 26-GFP. Three days after cell injection, groups of mice underwent (35% + 35% repeated minor resection versus 70% major resection versus 35% minor resection). Metastatic tumor growth was measured by color-coded fluorescence imaging of the GFP-expressing cancer cells and red fluorescent protein-expressing stroma. Results Although major and repeated minor resection removed the same total volume of liver parenchyma, the 2 procedures had very different effects on metastatic tumor growth. Major resection stimulated liver and lung metastatic growth and recruitment of host-derived stroma compared with repeated minor resection. Repeated minor resection did not stimulate metastasis or stromal recruitment. No significant difference was found in liver regeneration between the 2 groups. Host-derived stroma density, which was stimulated by major resection compared with repeated minor resection, might stimulate growth in the liver-metastatic tumor. Transforming growth factor-β is also preferentially stimulated by major resection and might play a role in stromal and metastasis stimulation. Conclusions The results of the present study indicate that when liver resection is necessary, repeated minor liver resection will be superior to major liver resection, because major resection, unlike repeated minor resection, stimulates metastasis. This should be taken into consideration in clinical situations that require liver resection.