Microbiome Evidence of Digestive Reflux and Inflammation in the Pancreatic Stump with Pancreatic Fistula After Pancreaticoduodenectomy

Abstract Background In the past century, postoperative pancreatic fistula (POPF) has been the major complication and cause of mortality after pancreaticoduodenectomy (PD). No one knows what exactly happens in the pancreatic stump after POPF. The hypothesis of this manuscript was to investigate changes that occur in the pancreatic stump. Methods Two patients who had previously undergone PD for malignant tumors subsequently underwent complete pancreatectomy for life-threatening abdominal bleeding in the context of POPF. The pancreatic stumps were pathologically analyzed. It’s hard to prove digestive reflux directly. But we found that we can use 16s rRNA gene sequencing to detect the distribution of bacteria in the jejunum, pancreatic head, and pancreatic stump. Results Inflammation is widespread in both patients' pancreatic stumps, including hematoma, edema, infiltration of inflammatory cells, scattered necrosis, and acinar-duct metaplasia (ADM). The whole pancreatic stump shows a proliferative state. Apoptosis decreases significantly or even disappears. The inflammation of the pancreatic stump shows a descending trend from the anastomosis to the tail. Simultaneously, we found a universal phenomenon: chemotaxis in the ductal system. Inflammatory cells penetrate the ducts formed by ADM and gather in the ducts. The bacteria from duodena are also discovered in the major part of the pancreatic stump. The bacterial distribution shows the same trend as inflammation. Conclusions Inflammation and ADM widely exist in the pancreatic stump with POPF after PD and show a descending trend from the anastomosis to the pancreatic tail. Digestive reflux through the pancreatic ductal system does happen during the pancreatic fistula. We could stop POPF if we eliminate the digestive reflux and reduce the inflammation in the pancreatic stump.