Chronic pancreatitis is best described as a relentless, continuous inflammatory destruction of the pancreas parenchyma, characterized by irreversible destruction of the exocrine tissues, fibrosis, and at the late stag...Chronic pancreatitis is best described as a relentless, continuous inflammatory destruction of the pancreas parenchyma, characterized by irreversible destruction of the exocrine tissues, fibrosis, and at the late stage, the destruction of endocrine cells. Current therapies for chronic pancreatitis patients focus on pain relief by medical and minimally invasive endoscopic treatment as well as surgical management with resection of diseased parenchyma and drainage of obstructed ducts. Radical treatment of chronic pancreatitis has been successful with total pancreatictomy and islet autotransplantation (TP-IAT) that may prevent maladaptive intractable pain pathways and also avoid pancreatogenic diabetes in the well-selected patient. Distinct loss of pancreatic islet cells occurs in about 30%-50% of patients during the progression of chronic pancreatitis when severe fibrosis develops at the late stage of the disease. Profound β cell apoptosis induced by stresses encountered during islet isolation and transplantation further compromises β cell survival and function after TP-IAT. The molecular mechanisms that lead to β cell dysfunction in chronic pancreatitis remain largely undelineated. In this review, we summarize factors that may contribute β cell apoptosis during the disease progress and after TP-IAT and discuss potential interventional approaches that may prevent islet cell death during these processes. Such information is critical to the development of therapeutic protocols that can preserve the viability and function of β cell in patients with chronic pancreatitis.展开更多
文摘Chronic pancreatitis is best described as a relentless, continuous inflammatory destruction of the pancreas parenchyma, characterized by irreversible destruction of the exocrine tissues, fibrosis, and at the late stage, the destruction of endocrine cells. Current therapies for chronic pancreatitis patients focus on pain relief by medical and minimally invasive endoscopic treatment as well as surgical management with resection of diseased parenchyma and drainage of obstructed ducts. Radical treatment of chronic pancreatitis has been successful with total pancreatictomy and islet autotransplantation (TP-IAT) that may prevent maladaptive intractable pain pathways and also avoid pancreatogenic diabetes in the well-selected patient. Distinct loss of pancreatic islet cells occurs in about 30%-50% of patients during the progression of chronic pancreatitis when severe fibrosis develops at the late stage of the disease. Profound β cell apoptosis induced by stresses encountered during islet isolation and transplantation further compromises β cell survival and function after TP-IAT. The molecular mechanisms that lead to β cell dysfunction in chronic pancreatitis remain largely undelineated. In this review, we summarize factors that may contribute β cell apoptosis during the disease progress and after TP-IAT and discuss potential interventional approaches that may prevent islet cell death during these processes. Such information is critical to the development of therapeutic protocols that can preserve the viability and function of β cell in patients with chronic pancreatitis.
