Vascular structure and microcirculation of experimental pancreatic carcinoma in rats

Objective: To study angiogenesis and microcirculation in experimental pancr eatic carcinoma. Designs: 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 a nd peritoneum by interposition of fragments of tumour between 2 inert trans parent polymethylmethacrylate plates. Main outcome measures: Microcirculation in the tumour and interaction betwe en leucocytes, tumour, and endothelium investigated by intravital microscop y. Results: The density of vessels in the carcinoma was significantly less tha n in normal pancreatic tissue (p = 0.0004). The vasculature of the tumour w as characterised by a lack of differentiation in architecture of vessels, f ormation of sinusoidal and lacunar vessels and sudden changes in diameter o f vessels. Red blood cell velocity differed among tumour vessels, but. mean values were similar to those of normal exocrine pancreas. The mixed lympho cyte culture test indicated that the cell line DSL6A was immunogenic. Howev er, high-affinity leucocyte-endothelium-interaction was significantly reduc ed in the tumour's microcirculation after both orthotopic and heterotopic i mplantation (p = 0.002). Rates of apoptosis were suppressed in heterotopic tumours compared with orthotopic ones. Tumour growth was faster in heteroto pic rumours. Conclusions: Experimental duct-like pancreatic carcinoma can be differentia ted from normal pancreas by: chaotic arrangement of vessels with loss of di fferentiation of architecture and heterogeneous distribution; the formation ai: sinusoidal or lacunar vessels; lower vascular density with similar ery throcyte 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 rate s.