Associated medical or surgical factors

Diabetes Mellitus

Diabetes mellitus has been long associated with pancreatic cancer, however, the precise relationship has yet to be defined. Diabetes mellitus has been implicated as both an early manifestation of pancreatic carcinoma and a predisposing factor. It is known that pancreatic cancer can induce peripheral insulin resistance, and the argument that long-standing diabetes mellitus is also a risk factor for pancreatic cancer is supported by a recent cohort study showing that after an initial hospitalization for diabetes, patients had an increased risk of developing pancreatic cancer and that this risk persisted for more than a decade. In addition, a metaanalysis of studies published between 1975 and 1994 showed that pancreatic cancer occurred with increased frequency in patients with long-standing diabetes. The specific type of diabetes mellitus is also a factor; the cohort study described above agreed with other studies that suggested that the increased risk was limited to patients with noninsulin-dependent diabetes or patients whose diabetes was diagnosed before age 40. The mechanisms underlying the association between pancreatic cancer and diabetes are obscure; however, the diabetic state seems to enhance the growth of pancreatic cancer in animal models.

Chronic Pancreatitis

An association between pancreatitis and an increased risk of pancreatic cancer has long been suspected, although the magnitude of the risk remains uncertain. Older clinical studies suggested that chronic forms of pancreatitis, particularly those accompanied by pancreatic calcifications, were most closely associated with the subsequent development of pancreatic cancer. A series of recent reports have validated the epidemiologic association between chronic pancreatitis and pancreatic cancer, but the magnitude of the risk of pancreatic cancer attributable to pancreatitis remains unclear. Calculation of a general estimate of population-attributable risk has suggested that chronic pancreatitis may explain as many as 5% of pancreatic cancer cases.

Recent pathologic and molecular biologic studies have begun to explore the relationship between chronic pancreatitis and pancreatic cancer. Chronic inflammatory processes have long been associated with increased cancer risk. Pathologic examination of lesions along the pancreatic duct has revealed the spectrum of mucous cell hyperplasias (papillary and nonpapillary hyperplastic lesions and atypical hyperplastic lesions) in patients with chronic pancreatitis and patients with pancreatic cancer. The recent report of the identification of mutations in the K- ras oncogene, a mutation found almost universally in established pancreatic cancers, in regions of mucous cell hyperplasia in patients with chronic pancreatitis provides the first molecular link between chronic inflammation and the initiation of multistep pancreatic carcinogenesis. However, additional research is needed because other recent reports failed to identify K- ras mutations in pathologically similar lesions.

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