Chronic Pancreatitis: Mechanisms of Inflammation, Pathways of Progression and Emerging Therapeutic Strategies

Chronic pancreatitis is a progressive fibroinflammatory disease of the pancreas that causes recurrent or chronic abdominal pain and functional insufficiency. Chronic pancreatitis follows the conceptual model of acinar cell injury, which leads to inflammation and finally fibrosis, resulting in progressively worsening morphologic and functional changes in the pancreas. The diagnosis is generally made in the presence of pancreatic duct dilatation or calcification, or both, which represents an advanced form of the disease. The diagnosis of the early stage of the disease remains challenging due to a lack of validated biomarkers and limited access to histopathologic assessment. Thus, the current treatment strategy primarily focuses on relieving pancreatic ductal obstruction via endoscopic or surgical intervention in advanced chronic pancreatitis. Our understanding of the early pathophysiological events, particularly the mechanisms of inflammation, is limited. This has hampered progress in developing disease-modifying therapies to prevent and retard disease progression. This review focuses on mechanisms of inflammation, pathways of progression from early- to late-stage disease, and current and emerging therapies with the potential to modify the clinical trajectory of chronic pancreatitis. A patient-tailored approach to therapy that limits inflammation and preserves organ function should be developed in the future.