Interstitial laser thermotherapy (ILT) of an adenocarcinoma implanted into rat liver - methodology and effects

Abstract: Local treatment of a tumour is of interest from a number of perspectives. It is focused on reducing the tumour volume with minimal trauma, inducing tumour immunity and is a potential component of a combination therapy against tumours. Interstitial laser thermotherapy (ILT) has turned out to be a method well suited for selective local destruction of malignant tumours. This thesis is based on an experimental study on ILT and treatment of a tumour model with an adenocarcinoma implanted into rat liver. The aims were to improve the local treatment method and try to explain the favourable results with respect to tumour treatment. A new multi-fibre power feedback regulated laser system was tested in vitro. It was possible to maintain a stable temperature during the treatment with 1-4 laser fibres and the treatment volume was big enough to treat relatively large tumours. It was also possible to use computer simulated calculation for predicting the treatment volume. By using Linomide, an immunomodulating substance, it was possible to reduce the tumour growth both alone and in combination with ILT and to reduce the tumour spread after ILT. We found that the main effect of Linomide depends on the reduction of the neoangiogenesis. By comparing ILT with liver resection of an adenocarcinoma implanted into a rat liver, it was concluded that ILT was better because it decreases the risk of tumour spread. The results support the proposal that the favourable effect of ILT depends on some immunologic response. This response after ILT could be explained by the association of heat shock protein 70 (HSP70) in the tissue. In our tumour model there was a shift of HSP70 in tumour cells from the cytoplasm to the nucleus and at the same time there was HSP70 in tumour associated macrophages (TAM). This indicates that HSP70 can be involved in the immunologic process seen after ILT. By implantation of a new tumour after treatment of the first we tested if there was any immunologic response against the tumour. The result showed that after ILT the challenged tumour did not grow and disappeared and there was a reduced tumour spread. There was also an increased number of ED1 macrophages and CD8 lymphocytes in the viable tumour and tumour capsule. This was significant compared to liver resection or ILT of normal liver tissue. In these groups there was an aggressive growth and spread of new tumour. This thesis demonstrates that ILT can give a well-defined tissue damage big enough for the clinical treatment of tumours and it is possible to plan the treatment by computer simulation. ILT can be enhanced by antiangiogenetic drugs and compared to liver resection, ILT is better in the decrease of tumour spread which can depend on an immunologic mechanism where HSP70 is involved. This immunological effect can mean that ILT can vaccinate against a tumour in situ.