The Consequences of Surgical Trauma on Intra-Peritoneal Tumour Recurrence and/or Adhesion Formation

textabstractPeritoneal carcinomatosis and postoperative intra-abdominal adhesion formation still are genuine problems after potentially curative intra-abdominal surgery. The inflammatory reaction triggered by surgical trauma to the peritoneum not only promotes adhesion formation but also stimulates tumour recurrence. Implicating a common denominator. The exact mechanisms involved are only partly clarified. To be able to prevent or reduce these surgical “complications” a thorough knowledge of the underlying process is necessary. Animal experimental models as well as cell culture models were used to unravel this process. For tumour recurrence this thesis showed that the (post) surgical intra-peritoneal microenvironment enhances successful implantation of spilled tumour cells, whereas growth of adhered tumour cell clusters is not affected. Further analysis of the microenvironment showed that an important role in this process is played by PMN and their products, reactive oxygen species. Tempering the post-operative inflammatory reaction proved to be a successful measure in reducing peritoneal tumour recurrence (eg scavengers, selective COX-2 inhibition). The mechanism by which post-operative intra-abdominal adhesions are triggered is closely associated to the mechanism by which surgery stimulates tumourcell implantation. PMN showed to stimulate adhesion formation as well. Moreover tempering the post-operative inflammatory reaction by reducing the influx of PMN or treatment with anti-oxidants could reduce post-operative adhesion formation. Icodextrin is an immerging agent in the prevention of postoperative adhesions. An analysis to the mechanism of action of this agent is performed and its influence on different parts of the postoperative inflammatory reaction