Pringle maneuver induces hepatic metastasis by stimulating the tumor vasculature.

Abstract

BACKGROUND/AIMS: The Pringle maneuver is traditionally used to avoid hemorrhage during hepatectomy for hepatic metastasis. However, metastasis can occur under ischemic conditions due to some unknown mechanism. METHODOLOGY: An orthotopic model of murine colon cancer was established in syngeneic BALB/c mice. Viable CT-26 cells were implanted into the spleen of these mice. The mice underwent a laparotomy 5 days after the implantation and the hepato-duodenal ligament was clamped for 0 or 10 minutes (Pringle maneuver). The mice were sacrificed 7 days after this maneuver and the number of hepatic metastasis were counted. RESULTS: The mice that underwent the maneuver developed a greater number of hepatic metastasis. An immunohistochemical analysis revealed that the expression of microvessel density, VEGF and KDR/Flk-1 were higher in the hepatic metastasis in the mice treated with the maneuver. In addition, the mice which were treated by the maneuver had a higher level VEGF in the serum. CONCLUSION: These data suggest that the Pringle maneuver induces hepatic metastasis by stimulating the overexpression of tumor vasculature.