Abstracts
1997 Digestive Disease Week

Reduced leukocyte adhesion in pancreatic cancer vasculature of the rat.

J Schmidt, E Ryschich, L Herzog, MM Gebhard*, Ch Herfarth, E Klar. Departments of General and Experimental* Surgery, University of Heidelberg, 69120 Heidelberg, Germany.

The interaction of immunocompetent cells and tumor endothelium represents an essential precondition during immunologic recognition and defense against malignant tumors. In the present study the degree of leucocyte-endothelium-interaction was assessed in a newly developed model for in vivo microscopy of the microcirculation of pancreatic cancer in the rat.

Methods: In 24 male Lewis rats (220-240g) tumor induction of a duct-like pancreatic cancer (DSL6A, Am J Pathol 1993;143:292) was achieved intraperitoneally by tumor fragment interposition (0.5x1mm) between 2 biologically inert transparent PMMA-plates. Tumor immunogeneity was proven by mixed lymphocyte culture test (MLC). After 6 weeks an intravital microscopic assessment of tumor microcirculation was performed in a temperature-controlled immersion chamber. Five non-tumor-bearing animals served as controls. Parameters were erythrocyte velocity, leucocyte-endothelium-interaction (Rhodamin 6G) and vascular diameter. The calculation of the wall shear rates was performed according to standard formulas. The observation was performed either in healthy collecting venules (20-40 µm) or in tumor vessels of the same diameter.

Results: Tumor diameter in the tumor-bearing animals at the time of observation was 3-4 mm. Erythrocyte velocity of normal pancreatic venules was 0.83 ±0.28 mm/sec (n=16) and in tumor vessels of equal diameter 1.06 ±0.62 mm/sec (n=52). Leucocyte-endothelium-interaction in healthy collecting pancreatic venules showed 4.56 ±1.96 Rollers/100µm. In comparison leucocyte-endothelium-interaction in pancreatic tumor vessels of equal diameter was significantly reduced to 2.26 ±3.21 Rollers/100µm, p=0.009, t-test). There was no correlation between leucocyte-endothelium-interaction and wall shear rates in tumor vessels.

Conclusion: In experimental pancreatic cancer low-affinity leucocyte-endothelium-interaction is substantially reduced despite similar wall shear rates. This is the likely consequence of reduced adhesion molecule expression and may represent a possible mechanism of host tumor immunotolerance.