Background: Aggressive local and systemic spread is characteristic for ductal pancreatic cancer. Even after curative resection, most patients will succumb to local and systemic tumor recurrence. This study aimed to create a nude mouse resection model of pancreatic cancer that reflects the situation after curative surgical treatment and allows the evaluation of novel adjuvant treatment strategies. Methods: Two fragments (1 cmm) of subcutaneous donor tumors (derived from the human pancreatic cancer cell line AsPC-1) were orthotopically implanted into the pancreatic tail of 30 nude mice. Animals were randomly allocated into 5 groups and sacrificed after 2, 4, 6, 8, and 10 weeks. Primary tumor growth was determined at autopsy, as well as local infiltration and systemic metastasis (dissemination score). In a second set of experiments, orthotopic tumors were induced in 21 other mice. Either the primary tumor with the spleen (resection group), or the spleen alone (splenectomy group) was resected after two weeks. A third group of mice served as control and was only observed after tumor induction. The mice were autopsied after 14 weeks or after death, and local and systemic tumor spread was quantified. H&E stained sections were analyzed from all resected specimens to confirm complete tumor resection. Results: Donor tumor implants were grown to small primary tumors (28 ± 18 cmm) two weeks after implantation, without local or systemic spread. In contrast, animals developed already large tumors and metastasis after 4 weeks. Tumors and metastasis grew continuously until 10 weeks of observation. Second set of experiments: table. Conclusions: 1) A histologically confirmed curative resection is feasible two weeks after tumor induction in this model. Later on, local and distant spread is already present. 2) Despite a seemingly curative tumor resection, there were no significant differences with regard to metastasis and survival in comparison to untreated controls or splenectomized animals (table). 3) As in human beings, early tumor recurrence and aggressive spread develops in this model after resection of the primary. This nude mouse model may be suitable to evaluate novel adjuvant therapies for pancreatic cancer.
Second set of experiments: