gms | German Medical Science

Introduction: Over the last few years, multimodal treatment approaches has led to an increase of the median survival time of patients with colorectal liver metastases. This is particularly attributed to new perioperative chemotherapy regimens and so-called biologicals like Bevacizumab (Anti-VEGF), which can also pose risks. 20-60% of the patients treated with Oxaliplatin (OX) develop a sinusoidal obstruction syndrome (SOS) implying a higher peri- and postoperative morbidity and mortality.

Some clinical trials report about a less frequent appearance 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 (MCT), 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.

Results: 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 (Figure 1 [Fig. 1]). The production of MMP9 has been described as one of the first steps in SOS development and is made responsible for the characteristic damage of liver parenchyma.

The MMP9 concentration measured in liver tissue in animals developing an SOS was significantly higher than in the control. Additional treatment with Anti-rat-VEGF increased the MMP9 concentration significantly.

Conclusion: From the results can be concluded, that Anti-VEGF exacerbates SOS most likely by MMP9 induction. The application of both, Oxaliplatin and Bevacizumab, should be therefore carefully considered, especially if liver parenchyma damage is apparent.