24 research outputs found

    Experimentally induced liver metastases from colorectal cancer can be prevented by mononuclear phagocyte-mediated monoclonal antibody therapy

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    Background 82 Aims: Development of liver metastases is a frequent complication in patients with colorectal cancer (CRC), even after successful resection of the primary tumor. As such, postoperative adjuvant therapies that aim to eliminate residual disease after surgery may improve patient outcome. Methods: We used a colon carcinoma liver metastases model, in which CC531s colon carcinoma cells are injected into the portal circulation by a surgical procedure. As injected tumor cells are arrested in the liver, this model is suitable for investigating the interaction of tumor cells with the liver microenvironment. By administering tumor specific monoclonal antibodies (mAb) directly post-operatively, we were able to determine the effect of antibody therapy on eradication of arrested tumor cells and subsequent liver metastases outgrowth. Results: We showed that post-operative treatment with tumor specific monoclonal antibodies (mAb) prevents liver metastases outgrowth. Antibody-dependent phagocytosis (ADPh) was the main mechanism involved, as enhanced uptake of tumor cells by innate mononuclear phagocytes in the liver was observed after mAb therapy. Furthermore, Kupffer cells (KC) were identified as the most prominent effector cells, as depletion of KC abolished therapeutic efficacy. This was partly compensated by monocytes when animals were treated with a high mAb dose, but monocytes were unable to phagocytose tumor cells when rats were treated with low mAb doses. Conclusions: The finding that KC and monocytes can eliminate tumor cells through ADPh has important and promising clinical implications for designing new adjuvant therapies for patients undergoing CRC resection. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.Surgical oncolog

    An experimental minimally invasive perfusion technique for the treatment of liver metastases.

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    Item does not contain fulltextAIM: Isolated hepatic perfusion (IHP) is an invasive, technically difficult, non-repeatable and demanding operation. In this study we report the development of a less invasive alternative for the surgical IHP in a pig model. METHODS: Our technique was tested in 8 Yorkshire pigs (60 kg). The liver was isolated from the systemic circuit using minimally invasive techniques: an occlusion stent-graft and balloon catheters, with reversal of the blood flow through the liver during IHP. RESULTS: Tests with varying pressures applied at the PV revealed a clear relation between the suction pressure at the outflow site (PV), intrahepatic pressure and systemic leakage of 99mTc. A leakage-free IHP could be obtained in seven separate experiments. CONCLUSION: Isolated hepatic perfusion using minimally invasive techniques is feasible in pigs when the intrahepatic pressure is controlled. This technique has yet to be tested in patients
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