Tumour growth following portal branch ligation in an experimental model of liver metastases.
BACKGROUND
Portal branch ligation (PBL) is being used increasingly before hepatectomy for colorectal metastases. This study evaluated the effect of PBL on angiogenesis, growth factor expression and tumour growth in a mouse model of hepatic colorectal metastases.


METHODS
CT26.WT cells were implanted into the left liver lobe of BALB/c mice. Animals underwent PBL of the left liver lobe or sham treatment. Angiogenesis, microcirculation, growth factor expression, cell proliferation and tumour growth were studied over 14 and 21 days by intravital multifluorescence microscopy, laser Doppler flowmetry, immunohistochemistry and western blotting.


RESULTS
Left hilar blood flow and tumour microcirculation were significantly diminished during the first 7 days after PBL. This resulted in tumour volume being 20 per cent less than in sham controls by day 14. Subsequently, PBL-treated animals demonstrated recovery of left hilar blood flow and increased expression of hepatocyte growth factor and transforming growth factor alpha, associated with increased cell proliferation and acceleration of growth by day 21.


CONCLUSIONS
PBL initially reduced vascular perfusion and tumour growth, but this was followed by increased growth factor expression and cell proliferation. This resulted in delayed acceleration of tumour growth, which might explain the stimulated tumour growth observed occasionally after PBL.
Kollmar
O
O
Department of General, Visceral, Vascular and Paediatric Surgery, University of Saarland, Homburg/Saar, Germany. otto.kollmar@uks.eu
Corsten
M
M
Scheuer
C
C
Vollmar
B
B
Schilling
M K
MK
Menger
M D
MD
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006133:Growth Substances / Q000378:metabolism; D007150:Immunohistochemistry; D017078:Laser-Doppler Flowmetry; D008026:Ligation; D008099:Liver / Q000098:blood supply*; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology
D016207:Cytokines; D006133:Growth Substances