Inflammation and digestive reflux in the pancreatic stump after pancreaticoduodenectomy subtitle: Mechanisms of pancreatic fistula

Abstract Background and Objectives: Postoperative pancreatic fistula (POPF) contributes to significant morbidity and mortality after pancreaticoduodenectomy (PD). However, the underlying mechanisms of POPF remain unclear. This study is to explore the pathology in the pancreatic stump and elucidates the mechanisms of POPF following PD. Methods: Pathological analysis and 16S rRNA gene sequencing were performed on the specimens obtained from the two patients who accepted complete pancreatectomy for grade C POPF after PD. In addition, a retrospective radiological analysis was conducted on a cohort of 125 consecutive patients who underwent PD to evaluate the inflammatory response in the pancreatic stump. Results: The presence of gradient inflammation and acinar-duct metaplasia (ADM) in the pancreatic stumps is ubiquitous. The incidence of apoptosis is markedly reduced in the pancreatic stump. Moreover, a significant accumulation of neutrophil-dominated inflammatory cells is detected in the ductal system. Notably, the ADM-formed duct is the site where the neutrophils transmigrate through the ductal wall. Additionally, the microbial evidence indicates that gut microbes migrate from the digestive tract. Radiological analysis proves that a gradient of pancreatitis exists in all cases after PD and reaches peak on the fourth postoperative day. Conclusions: Inflammation and digestive reflux exist in the pancreatic stump after PD. The underlying mechanisms of POPF are the high biochemical activity of the pancreas, mechanical injury, and digestive reflux.