Effects of major liver resection, with or without recombinant bactericidal/permeability-increasing protein (rBPI21), on the angiogenic profile of patients with metastatic colorectal carcinoma.
BACKGROUND
Surgery induces a process of wound healing, which has immunological and angiogenic aspects. Bactericidal/permeability-increasing protein (BPI) is found in azurophilic granules of human neutrophils, which is bactericidal and neutralizes lipo-polysaccharide (LPS). This may reduce postoperative infectious complications. In addition, BPI has been shown to be an inhibitor of angiogenesis.


METHODS
A total of 18 patients with metastasized colorectal carcinoma to the liver were double blind randomized. The levels of the pro-angiogenic factors interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) and the angiogenesis inhibitor endostatin were investigated after liver surgery with perioperative administration of either rBPI(21) or placebo.


RESULTS
The highest IL-6 levels were found during the first 24 hr and reached peak levels already at 2 hr postoperatively in both groups. In both groups VEGF levels decreased sharply in the postoperative hours, returning to baseline levels in the days afterwards. In both groups, an immediate decrease in endostatin levels was observed which remained significantly low. RBPI(21) transiently influenced IL-6 and VEGF.


CONCLUSIONS
RBPI(21) only marginally affected IL-6 and VEGF levels. Surgery per se induced an immediate immune response (IL-6) and an immediate angiogenic response, reflected in an initial VEGF decrease and a longer lasting decrease of endostatin. These findings demonstrate the dynamics of tissue responses in the first phase of wound healing.
Department of Surgery, VU Medical Center, Amsterdam, The Netherlands.
Francis P K
FP
Wu
Petra G
PG
Boelens
Paul A M
PA
van Leeuwen
Klaas
K
Hoekman
Annemarie H G
AH
Hansma
Marinus J
MJ
Wiezer
Catharina
C
Meijer
Sybren
S
Meijer
Michel
M
Scotté
Miguel A
MA
Cuesta
D000293:Adolescent; D000328:Adult; D000368:Aged; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000008:administration & dosage* / Q000032:analysis / Q000502:physiology; D015179:Colorectal Neoplasms / Q000097:blood / Q000098:blood supply* / Q000473:pathology; D004311:Double-Blind Method; D043169:Endostatins / Q000097:blood*; D005260:Female; D006498:Hepatectomy; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008113:Liver Neoplasms / Q000097:blood / Q000556:secondary* / Q000601:surgery; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology; D009504:Neutrophils / Q000737:chemistry; D011994:Recombinant Proteins / Q000008:administration & dosage; D042442:Vascular Endothelial Growth Factors / Q000097:blood*
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D043169:Endostatins; D015850:Interleukin-6; D008565:Membrane Proteins; D011994:Recombinant Proteins; D042442:Vascular Endothelial Growth Factors; C021623:bactericidal permeability increasing protein; C025357:endotoxin binding proteins