Total pancreatectomy with islet autotransplantation outcomes in patients with pancreatitis of genetic etiology: A single-center experience with a large cohort of patients.

PURPOSE: Total pancreatectomy with islet autotransplantation (TPIAT) is an effective treatment for patients with chronic pancreatitis (CP) when other interventions are unsuccessful. CP has many etiologies including heredity. Metabolic and pain relief outcomes after TPIAT are presented among patients with a genetic CP etiology compared with those with a nongenetic etiology in a large cohort of patients who underwent this procedure at our center. METHODS: A retrospective analysis was performed of 237 patients undergoing TPIAT between 2006 and 2023. We analyzed the differences in patients with genetic (n = 56) vs nongenetic CP etiologies (n = 181) in terms of pre-TPIAT factors including patient characteristics and disease state, results from the isolation process, and outcomes such as long-term glycemic and pain control. RESULTS: Patients with genetic CP underwent TPIAT at a significantly younger age (32.3 vs 41.3 years nongenetic; P < .0001) and endured symptoms for a significantly longer period (10 vs 6 years; P < .01). A significantly lower mass of islets was isolated from patients with genetic CP (P < .01), which increased with body mass index in both groups. Despite lower yields, patients with genetic CP maintained metabolic function similar to patients with nongenetic CP, as indicated by insulin independence and C-peptide, blood glucose, and hemoglobin A1C levels after TPIAT. Post-transplant narcotic usage and pain scores significantly decreased compared with those before TPIAT, and more patients with genetic CP were pain free and narcotic free after TPIAT. CONCLUSION: Our data validate TPIAT as a beneficial procedure for patients enduring CP of genetic etiology. Pain that is inevitably recurrent after minor interventions owing to the nature of the disease and favorable TPIAT outcomes should be considered in the decision to perform early TPIAT in cases of genetic CP.

Toll-like receptor 4 in pancreatic damage and immune infiltration in acute pancreatitis.

Acute pancreatitis is a complex inflammatory disease resulting in extreme pain and can result in significant morbidity and mortality. It can be caused by several factors ranging from genetics, alcohol use, gall stones, and ductal obstruction caused by calcification or neutrophil extracellular traps. Acute pancreatitis is also characterized by immune cell infiltration of neutrophils and M1 macrophages. Toll-like receptor 4 (TLR4) is a pattern recognition receptor that has been noted to respond to endogenous ligands such as high mobility group box 1 (HMGB1) protein and or exogenous ligands such as lipopolysaccharide both of which can be present during the progression of acute pancreatitis. This receptor can be found on a variety of cell types from endothelial cells to resident and infiltrating immune cells leading to production of pro-inflammatory cytokines as well as immune cell activation and maturation resulting in the furthering of pancreatic damage during acute pancreatitis. In this review we will address the various mechanisms mediated by TLR4 in the advancement of acute pancreatitis and how targeting this receptor could lead to improved outcomes for patients suffering from this condition.