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Preventing Liver Metastasis by Resecting the Primary Pancreatic Carcinoma at an Early Stage of Intrapancreatic Transplantation in Hamsters

Eiji Uchida, Matsuo Inoue, Takayuki Aimoto, Yoshiharu Nakamura, Akira Katsuno and Takashi Tajiri

Department of Surgery, Division of Gastroenterology, General, Breast and Transplant, Nippon Medical School

Purpose: To determine whether early primary pancreatic tumor resection can prevent liver metastases of intrapancreatic transplantation in a hamster model.
Methods: Cells from the PGHAM-1 cell line were transplanted into the pancreases of 30 Syrian golden hamsters. A suspension of 5 × 10⁶ cells was injected into the splenic lobe of each pancreas. The primary pancreatic tumor was resected in 15 of the hamsters 10 days after transplantation (resection group). Fifteen other animals with transplantation but without resection served as controls (control group). All hamsters were killed 21 days after transplantation. The primary pancreatic tumors were measured for size and volume and examined histologically and immunohistologically for angiogenesis and tumor proliferation.
Results: In the resection group, small pancreatic tumors 4.7 ± 0.94 mm in diameter were found and resected 10 days after transplantation. Neither pancreatic tumors nor liver metastases were found in the resection group at the end of the experiment. All animals in the control group had pancreatic tumors 12.3 ± 3.29 mm in size, and 11 of 15 (73.3%) had liver metastases. The primary pancreatic tumors in the group with liver metastasis were significantly larger in diameter and volume than those in this group without liver metastasis (p<0.01). In the control group, proliferation of the primary pancreatic tumor, evaluated according to argyrophilic nucleolar organizer region, showed no differences within the pancreatic tumor group. On the other hand, the microvessel density of pancreatic tumors with liver metastases was significantly higher than that of tumors without liver metastases.
Conclusions: Our results suggest that 10 days after transplantation, the pancreatic tumors were small in size and volume and ready to proliferate but not yet ready to begin metastasizing through angiogenesis. This is one reason why early resection of the primary tumor prevents liver metastasis.

J Nippon Med Sch 2007; 74: 37-44

Keywords
pancreatic cancer, liver metastasis, prevention, angiogenesis, transplantation model

Correspondence to
Eiji Uchida, Department of Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
uchida@nms.ac.jp

Received, October 3, 2006
Accepted, December 14, 2006