Different radiogenic effects on microcirculation in healthy pancreas and in pancreatic carcinoma of the rat.
OBJECTIVE
To compare the radiogenic effects on microcirculation in healthy and malignant pancreatic tissue.


BACKGROUND
Vascular injury is an important effect of radiotherapy, which has been suggested for antiangiogenic tumor therapy.


METHODS
An established model of duct-like pancreatic cancer (DSL6A) was used. Investigation was performed in 12 healthy and 24 tumor-bearing Lewis rats. The tumors were locally irradiated with 15 Gy in 12 animals 4 weeks after intraperitoneal inoculation. Additionally, local radiation of the normal pancreas was performed in six healthy animals. Intravital microscopy of tumor and normal pancreatic microcirculation was performed 5 days after radiation. Relevant parameters were erythrocyte velocity and functional vessel density. Tumor apoptosis and the fraction of vital tumor cells were estimated histologically 5 and 12 days after radiation.


RESULTS
Local radiation with 15 Gy caused a pronounced impairment of blood flow and functional capillary density in the normal pancreas 5 days after radiation, while the tumor blood flow was not significantly changed. A significant reduction in the fraction of vital tumor cells and a significant increase in tumor apoptosis were observed 12 days after radiation.


CONCLUSIONS
Local radiation impairs blood flow in healthy pancreas but not in pancreatic cancer tissue. Tumor cell death is the leading consequence of radiation injury in malignant pancreatic tissue without affecting the vascular system of the tumor. The authors conclude that external beam radiation does not appear to be a useful adjunct for a vascular-targeted therapy in pancreatic carcinoma but causes distinct hypoperfusion in the healthy pancreas.
Ryschich
Eduard
E
Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. eduard_ryschich@med.uni-heidelberg.de
Schmidt
Jan
J
Loeffler
Thorsten
T
Eble
Michel
M
Gebhard
Martha Maria
MM
Harms
Wolfgang
W
Klar
Ernst
E
D000818:Animals; D008833:Microcirculation; D010179:Pancreas / Q000098:blood supply* / Q000528:radiation effects*; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000532:radiotherapy*; D011829:Radiation Dosage; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors