Background-Chronic pancreatitis is a significant cause of morbidity and a known risk factor for pancreatic adenocarcinoma. Interleukin-1β is a proinflammatory cytokine involved in pancreatic inflammation. We sought to determine whether targeted overexpression of interleukin-1β in the pancreas could elicit localized inflammatory responses and chronic pancreatitis.

BMDCs contribute to the pancreatic stellate cell population, suggesting a role in pancreatic tissue repair. In the absence of preneoplastic lesions, BMDCs contribute at a very low level to the ductal epithelium of the chronically inflamed pancreas. The role of BMDCs in pancreatic carcinogenesis remains to be defined.

The risk of pancreatic cancer is increased in both Snus (the Swedish variant of oral smokeless tobacco) users and, to a greater extent, in cigarette smokers. Concurrent chronic pancreatitis further increases the risk in cigarette smokers. Little is known about the mechanism by which cigarette smoke or Snus increase the risk of pancreatic cancer in individuals with chronic pancreatitis. This study examined the carcinogenic effects of an aqueous extract of cigarette smoke (tobacco smoke, TS) or Snus in an Elastase-IL-1b transgenic mouse model of chronic pancreatitis. Both transgenic and wild-type (WT) mice were fed diluted TS water or Snus-containing diet for up to 15 months, and monitored for phenotypic and molecular changes in the pancreas. Both TS-and Snus-treated Elastase-IL-1b mice, but not WT mice, developed significant pancreatic ductal epithelial flattening and severe glandular atrophy compared with untreated transgenic mice. Ductal epithelial cells displayed a high proliferative index, minimal apoptosis, and induction of COX-2 in the setting of chronic inflammation. Up-regulation of TNF-a correlated with the onset of severe glandular atrophy. In comparison with Snustreated mice, TS-Elastase-IL-1b mice had an earlier onset and a greater extent of phenotypic changes, which were associated with up-regulation of TNF-a and increased expression of IL-6, TGF-b, and SDF-1. Collectively, these findings provide new insights into the mechanism by which tobacco products are likely to promote carcinogenesis in the setting of chronic pancreatitis.

Three patients developed dacryoadenitis (DA) or lymphocytic pneumonitis before the diagnosis of lymphocytic hypophysitis (LyH). There were two previous reports of concurrence of DA and LyH. Our patients add support to the idea that DA and LyH are manifestations of a systemic autoimmune disease. We suggest that the discovery of DA should prompt imaging and endocrine investigation of LyH.

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