Abstract
Objective: To study angiogenesis and microcirculation in experimental pancreatic carcinoma.
Design: Open experimental study.
Setting: 2 University hospitals, Germany and USA.
Animals: 16 male Lewis rats.
Interventions: Induction of a duct-like pancreatic cancer in the pancreas and peritoneum by interposition of fragments of tumour between 2 inert transparent polymethylmethacrylate plates.
Main outcome measures: Microcirculation in the tumour and interaction between leucocytes, tumour, and endothelium investigated by intravital microscopy.
Results: The density of vessels in the carcinoma was significantly less than in normal pancreatic tissue (p = 0.0004). The vasculature of the tumour was characterised by a lack of differentiation in architecture of vessels, formation of sinusoidal and lacunar vessels and sudden changes in diameter of vessels. Red blood cell velocity differed among tumour vessels, but mean values were similar to those of normal exocrine pancreas. The mixed lymphocyte culture test indicated that the cell line DSL6A was immunogenic. However, high-affinity leucocyte-endothelium-interaction was significantly reduced in the tumour's microcirculation after both orthotopic and heterotopic implantation (p = 0.002). Rates of apoptosis were suppressed in heterotopic tumours compared with orthotopic ones. Tumour growth was faster in heterotopic tumours.
Conclusions: Experimental duct-like pancreatic carcinoma can be differentiated from normal pancreas by: chaotic arrangement of vessels with loss of differentiation of architecture and heterogeneous distribution; the formation of sinusoidal or lacunar vessels; lower vascular density with similar erythrocyte velocity; increase in mean diameter of vessels; reduced leucocyte-endothelium interaction despite confirmed immunogeneity independent of wall shear rates. The site of implantation influences apoptosis and growth rates.