Patterns of growth and metastases of induced pancreatic cancer in relation to the prognosis and its clinical implications

Abstract

To understand high malignancy of pancreatic cancer, the growth and metastatic patterns of pancreatic cancer induced in Syrian hamsters were examined. In this model, induced tumors resemble the human disease morphologically, clinically, biologically, and immunologically. In the current study, primary-induced cancer and transplants of pancreatic cancer cell line (PC-1) into the SC tissue or pancreas of homologous hosts were used. In the primary-induced pancreatic cancer, perineural invasion was the most common path (88%), followed by lymphogenic (31%) or vascular (2%) metastases. Inoculation of PC-1 cells into the pancreas resulted in 100% tumor take within 3 weeks. Of 19 intrapancreatic allografts, all showed peritoneal invasion, 5 (26%) liver metastases, 3 (16%) lymph node metastases, 17 (89%) perineural invasion, and none vascular invasion. Even microscopic tumors were found to metastasize primarily via perineural spaces. It was also demonstrated, for the first time, that cancer cells take this route to reach distant tissues, including the lymph nodes. Intraductal spreading occurred in both primary cancers and intrapancreatic allografts either continuously or discontinuously. The patterns of discontinuous intraductal tumor expansion imitated tumor multicentricity. Although perineural invasion was the most common feature of primary cancer and intrapancreatic allografts, lymphatic, hepatic, and vascular invasion and metastases usually occurred in advanced cases. Environmental factors seem to influence expansion and metastases, as evidenced by differences in growth and in metastatic patterns between SC and intrapancreatic allografts.