Advances in acute and chronic pancreatitis

Abstract

Acute pancreatitis (AP) and chronic pancreatitis are the third leading gastrointestinal causes for admissions and readmissions to hospitals in the United States. This review of articles published between 2019-2022 (December) from international sources identified four categories of crucial new findings: The report includes (1) New genetic pathogenic mutations (TRPV6); expected genetic outcomes in a Northern European population; (2) a new serum diagnostic marker for AP-fatty acid ethyl esters-distinguishing acute pancreatitis associated with alcohol; explanations of the impact of monocytes/macrophages on the inflammatory process that defines their future in diagnosis, staging, and treatment; (3) innovations in timing of per os low-fat, solid food intake immediately on admission; resolution of concepts of aggressive parenteral fluid intake; dramatic shifts to non-operative from operative treatment of infected pancreatic necrosis. Each modification reduced interventions, complications, and lengths-of-stay; and (4) authoritarian recommendations for medical treatment of chronic pain. These advances offer opportunities to initiate newly proven treatments to enhance outcomes, alter the natural history, and envision the future of two diseases that have no known cure.

Keywords: Fluid management; Genetics; Macrophage regulation; New approaches to early feeding; New diagnostics.

Figure 1

Diagrammatic depiction of fundamental events contributing to the complex molecular pathways resulting in pancreatitis. Although a unifying concept is not available for all events, recent literature has provided a clearer description of the complexity of pathologic events which is briefly summarized. A proposed first step is injury to cytoplasmic organelles from external stressors, including prolonged, high intake of ethanol and smoking. These injuries result in endoplasmic reticulum stress, mitochondrial depolarization, inadequate ATP production, vacuole accumulation, protein misfolding, and disordered autophagy leading to activation of trypsinogen and inflammatory pathways. Disruption of the normal pathways may be augmented by genetic mutations at key functional sites responsible for trypsinogen activation, trypsin inhibition, Ca⁺⁺ concentrations, and HCO3^- and H₂O movement[4-9,20,21]. CTRC: Chymotrypsin C; CFTR: Cystic fibrosis transmembrane conductance receptor; NF-Κb: Noncanonical nuclear factor-kappaB; TNF-α: Tumour necrosis factor alpha; IL: Interleukin.