Background:
Multimodal treatment approaches has led to an increase of the median survival time of patients with colorectal liver metastases, particularly due to perioperative chemotherapy regimens and biologicals like Bevacizumab (Anti-VEGF). 20-60% of patients treated with Oxaliplatin develop an SOS implying a higher peri- and postoperative morbidity and mortality.Some clinical trials report about a less frequent occurence of SOS in patients treated with Bevacizumab assuming, that this drug has a preventive effect. So far, there are no experimental data available to support this assumption

Material and Methods:
Male Sprague-Dawley rats were gavaged with 90mg/kg/KG Monocrotaline, after 12h fasting, to induce SOS. Gr.A received immediately, Gr.B after 24h 0,2μg/kg/BW Anti-rat-VEGF into the tail vein. Gr. C and D received analogous NaCl. After 96h blood and liver tissue samples were taken.

Result:
After MCT administration 67% of the animals developed an SOS, with additional application of Anti-rat-VEGF 100% developed an SOS. To reveal the pathomechanism, the MMP-9 concentration was measured by ELISA. The production of MMP9 has been described as the first steps in SOS development and is made responsible for the characteristic damage of liver parenchyma. The MMP9 concentration in liver tissue in animals with an SOS was significantly higher than in the control. Additional treatment with Anti-rat-VEGF increased the MMP9 concentration significantly.

Conclusion:
We conclude, that Anti-VEGF exacerbates SOS by MMP9 induction. The application of Oxaliplatin and Bevacizumab should be therefore carefully considered, especially if liver parenchyma damage is apparent