review of literature on clinical pancreatology - The Pancreapedia

were validated in another series <strong>of</strong> patients with autoimmune pancreatitis or pancreaticcancer: 14 <strong>of</strong> 15 patients with autoimmune pancreatitis (93 %) and 1 <strong>of</strong> 70 patients withpancreatic cancer (1 %) had a positive test for anti-PBP peptide antibodies. When thetraining and validation groups were combined, the test was positive in 33 <strong>of</strong> 35 patients withautoimmune pancreatitis (94 %) and in 5 <strong>of</strong> 110 patients with pancreatic cancer (5 %). It wasconcluded that the antibody that was identified was detected in most patients withautoimmune pancreatitis but also in a few patients with pancreatic cancer, making it animperfect test to distinguish between these two conditions [305].Possible etiological factorsK-rasTo assess the relationship between autoimmune pancreatitis (AIP) and pancreatic cancer, itwas analyzed K-ras mutation in the pancreatobiliary tissues <strong>of</strong> patients with AIP. An analysis<strong>of</strong> K-ras mutation and an immunohistochemical study were performed on the pancreas <strong>of</strong> 8patients with autoimmune pancreatitis and 10 patients with chronic alcoholic pancreatitis andon the common bile duct and the gallbladder <strong>of</strong> 9 patients with AIP. K-ras mutation wasanalyzed in the pure pancreatic juice from 3 patients with AIP. High-frequency K-ras mutation(2+ or 3+) was detected in the pancreas <strong>of</strong> all the 8 patients and in the pancreatic juice <strong>of</strong> theother 2 patients. The mutation in codon 12 <strong>of</strong> the ras gene was GAT in all the 10 patients.High-frequency K-ras mutation was detected in the common bile duct <strong>of</strong> 5 patients withautoimmune pancreatitis and in the gallbladder epithelium <strong>of</strong> 4 patients with AIP. The K-rasmutation was detected in the fibroinflammatory pancreas, the bile duct, and the gallbladder,with abundant infiltrating IgG4-positive plasma and Foxp3-positive cells <strong>of</strong> patients with AIPwith elevated serum IgG4 levels. It was concluded that significant K-ras mutation occursmost frequently in the pancreatobiliary regions <strong>of</strong> patients with AIP. Autoimmune pancreatitismay be a risk factor <strong>of</strong> pancreatobiliary cancer [306].TGF-beta1Tumor growth factor-beta (TGF-beta) is an immunosuppressive cytokine and has beenimplicated in a variety <strong>of</strong> disease processes, including those in autoimmune disease. Tumorgrowth factor [beta] is also involved in fibrosis by regulating matrix metalloproteinases(MMPs) and the tissue inhibitor <strong>of</strong> MP (TIMP). The purpose <strong>of</strong> one study was to compare theexpression patterns <strong>of</strong> TGF-beta1, MMP-2, and TIMP-2 between autoimmune chronicpancreatitis (AIP) and alcoholic chronic pancreatitis (ACP) by immunohistochemical staining<strong>of</strong> pancreatic tissue specimens. Pancreatic tissue specimens were obtained from 16 <strong>of</strong> 57patients who had a diagnosis <strong>of</strong> AIP. Pancreatic tissue specimens <strong>of</strong> alcoholic chronicpancreatitis were obtained from 10 patients who were surgically treated. The degree <strong>of</strong>immunohistochemical staining for TGF-beta1 was significantly weaker in AIP than inalcoholic chronic pancreatitis in the pancreatic ductal epithelial and mononuclear cells. Thisfinding suggests that there may be a defect in the function <strong>of</strong> regulatory T (Treg) cells, whichnormally prevents autoimmune disease progression via a suppressor mechanism. Furtherstudies are needed to identify the type <strong>of</strong> regulatory T cell involved in this process [307].Extrapancreatic manifestationsThe frequency and clinical characteristics <strong>of</strong> extrapancreatic lesions during the clinical course<strong>of</strong> autoimmune pancreatitis were investigated retrospectively in 64 patients with autoimmunepancreatitis. The predictive factors for relapse <strong>of</strong> autoimmune pancreatitis at clinical onset