Pancreatic Cancer in Chronic Pancreatitis: Pathogenesis and Diagnostic Approach

SIMPLE SUMMARY: Chronic alcoholic pancreatitis displays a cumulative risk of pancreatic cancer estimated at 4% after 15 to 20 years, this risk being higher for hereditary pancreatitis with 19% and 12% in the case of PRSS1 and SPINK1 mutations, respectively, and at an age of 60 years. Oncogene and tumor suppressor gene mutations associated with chronic inflammation are key promoters of this complication, tobacco being an additional co-factor. This event underlines two practical problems from a clinical point of view: diagnosis is difficult due clinical symptoms and radiological features shared by the two diseases; and screening of cancer in chronic pancreatitis patients. Endoscopic ultrasound-guided fine-needle biopsy can be contributive with the help of molecular biology by next generation sequencing, including for KRAS, TP53, CDKN2A, and DPC4 mutation assays. A short-term follow-up of patients is necessary in cases with clinical and/or radiological suspicion of cancer. Pancreatic surgery is sometimes necessary if there is any doubt. ABSTRACT: Chronic pancreatitis is one of the main risk factors for pancreatic cancer, but it is a rare event. Inflammation and oncogenes work hand in hand as key promoters of this disease. Tobacco is another co-factor. During alcoholic chronic pancreatitis, the cumulative risk of cancer is estimated at 4% after 15 to 20 years. This cumulative risk is higher in hereditary pancreatitis: 19 and 12% in the case of PRSS1 and SPINK1 mutations, respectively, at an age of 60 years. The diagnosis is difficult due to: (i) clinical symptoms of cancer shared with those of chronic pancreatitis; (ii) the parenchymal and ductal remodeling of chronic pancreatitis rendering imaging analysis difficult; and (iii) differential diagnoses, such as pseudo-tumorous chronic pancreatitis and paraduodenal pancreatitis. Nevertheless, the occurrence of cancer during chronic pancreatitis must be suspected in the case of back pain, weight loss, unbalanced diabetes, and jaundice, despite alcohol withdrawal. Imaging must be systematically reviewed. Endoscopic ultrasound-guided fine-needle biopsy can contribute by targeting suspicious tissue areas with the help of molecular biology (search for KRAS, TP53, CDKN2A, DPC4 mutations). Short-term follow-up of patients is necessary at the clinical and paraclinical levels to try to diagnose cancer at a surgically curable stage. Pancreatic surgery is sometimes necessary if there is any doubt.