Molecular basis of chronic pancreatitis

Morphological studies have clearly established the distinction between obstructive chronic pancreatitis in which the occlusion of pancreatic ducts, mainly by tumors, precedes the onset of pancreatitis and chronic calcifying pancreatitis (CCP), the most frequent form of chronic pancreatitis which is characterized by the presence of calcite stones in pancreatic ducts. So many causes (alcoholic, hypercalcemic, tropical, hereditary, idiopathic) could explain CCP that it is logical to assume the existence of several pathophysiological pathways involved in the disease. Two hypotheses, not mutually exclusive, were advanced to explain the role of alcohol in CCP. A direct cytotoxic and/or metabolic effect of alcohol on acinar cell could injure the pancreas and lead to necrosis and fibrosis; by another way, alcohol could favour the precipitation of both proteins and calcium in pancreatic ducts in which the secretion of lithostathine, the calcium crystallization inhibitor, is decreased. The fibrosis is the ultimate process leading to exocrine and endocrine insufficiency. The fibrogenesis is in part triggered by local inflammatory processes including a significant increase of growth factors biosynthesis. Finally 1996 was the year of the molecular characterization of the genetical abnormality responsible for the hereditary chronic pancreatitis; this significant progress which has enriched our knowledge of the pathophysiology of this inherited disease could optimize the future therapeutic approaches.