Abstracts
1997 Digestive Disease Week

Pancreatitis confers a survival benefit in an orthotopic model of pancreatic cancer.

D Denham, M Zervos, M Franz, A Rosemurgy, J Norman. University of South Florida, Tampa, FL.

It has been suggested that the onset of acute pancreatitis in the setting of pancreatic cancer imparts a worse prognosis. Since pancreatitis is a known inducer of cytokines, we hypothesized that this detrimental effect was mediated through production of intrapancreatic TNF in an already compromised host. Methods: An established orthotopic model was used to implant 10⁶ human pancreatic cancer cells (HPAC) in nude mice. Once tumor implantation was established (20% weight loss; 49±2.6 days), 30 animals were randomized to pancreatitis (caerulein 50 mg/kg/hr x 4) or vehicle (IP saline). To determine pancreatitis-induced intrapancreatic production of TNF, another group received caerulein or vehicle with pancreatic tissue levels of TNF assayed at 0,2,4,6,8 and 24 hours by ELISA. To assess the effect of TNF on pancreatic cancer in vitro, HPAC cells were incubated with rh-TNF (20ng/ml) and growth determined for 4 days by MTT assay. Results: Contrary to our hypothesis, the induction of moderate pancreatitis conferred a significant survival benefit to animals harboring pancreatic cancer (Fig 1 [not available], mean survival p=0.03 vs vehicle). Animals with pancreatitis showed a rapid rise in pancreatic tissue TNF levels (Fig 2 [not available]). When exposed to TNF in vitro, HPAC cell growth was arrested (Fig 3 [not available]).

Conclusion: Survival during pancreatic cancer may be prolonged rather than shortened when complicated by moderate pancreatitis. The mechanism appears to be the production of high levels of TNF within the pancreatic parenchyma which inhibits cancer cell growth.