Pancreatic Inflammation and Proenzyme Activation Are Associated With Clinically Relevant Postoperative Pancreatic Fistulas After Pancreas Resection

Abstract

Objective: We investigated the activation of pancreatic proenzymes and signs of peripancreatic inflammation in patients with clinically relevant postoperative pancreatic fistulas (POPFs). Summary Background Data: An increase of systemic amylase concentration was associated with POPFs. This suggested parallels in the pathomechanisms between the development of POPFs and pancreatitis. Methods: Trypsinogen, procathepsin B, and IL-6 concentrations as well as cathepsin B, myeloperoxidase and trypsin activities were determined throughout the first 7 postoperative days in drain fluids of 128 consecutive patients after pancreas resection. Histology and immunohistochemistry were performed in pancreatic specimens after total pancreatectomy due to complications and after placing experimental pancreatic sutures in the pancreatic tail of C57/Bl6 mice. Results: Trypsin activity, cathepsin B activity and myeloperoxidase activity on the first postoperative day were elevated and predictive for clinically relevant pancreatic fistulas. Drain fluid stabilized trypsin activity and prevented the activation of the cascade of digestive enzymes. Leukocytes were the source of cathepsin B in drain fluid. Findings differed between fistulas after distal pancreatectomy and pancreatoduodenectomy. Immunohistochemistry of the pancreatic remnant revealed an inflammatory infiltrate expressing cathepsin B, independent of the presence of pancreatic fistulas. The infiltrate could be reproduced experimentally by sutures placed in the pancreatic tail of C57/Bl6 mice. Conclusions: Trypsinogen activation, increased cathepsin B activity and inflammation around the pancreato-enteric anastomosis on post operative day 1 are associated with subsequent clinically relevant POPFs after pancreatoduodenectomy. The parenchymal damage seems to be induced by placing sutures in the pancreatic parenchyma during pancreatic surgery.

Postpancreatectomy Acute Pancreatitis (PPAP)

“…The presence of an ischemic/inflammatory process of the pancreatic remnant was suggested as the etiology in several pathologic reports, particularly in series considering operative revisions for Grade C POPF 11,20,37 . These patients indeed represent the most severe and rare scenarios of PPAP (Fig.…”

“…9,19 These pathophysiological events may trigger a series of cascading events causing acinar cell disruption, intracellular activation of proteolytic enzymes, pancreatic parenchymal edema, and peripancreatic inflammation, leading to local and/or systemic effects. 20 PPAP may impair the healing of the pancreatic remnant and/or anastomosis with the subsequent development of a postoperative pancreatic fistula (POPF). 21 However, even in the absence of POPF, it may also lead to other abdominal and systemic complications, such as organ space infection/intra-abdominal abscess, 22 hemorrhage, the systemic inflammatory response syndrome (SIRS), and systemic sepsis.…”

Increased postoperative pancreatic fistula rate after distal pancreatectomy compared with pancreatoduodenectomy is attributable to a difference in acinar scores

“…Previous work from our unit has shown that POPF risk is associated with the acinar content of remnant pancreata but not fat content 5 . Moreover, there is an increasing body of evidence supporting the link between postoperative pancreatitis and POPF 9,10 . As pancreatic digestive enzymes originate from the acinar cell, a higher density of acinar cells in the remnant pancreas likely leads to an increased risk of postoperative pancreatitis and POPF 5 .…”

“…5 Moreover, there is an increasing body of evidence supporting the link between postoperative pancreatitis and POPF. 9,10 As pancreatic digestive enzymes originate from the acinar cell, a higher density of acinar cells in the remnant pancreas likely leads to an increased risk of postoperative pancreatitis and POPF. 5 The multivariable model in this work therefore demonstrates that pancreatic consistency acts merely as an imperfect surrogate marker of the acinar content of the remnant pancreas, which is the key histological determinant of postoperative pancreatitis and POPF.…”

Establishment and Application of a Novel Difficulty Scoring System for da Vinci Robotic Pancreatoduodenectomy

“…The stimulation of pancreatic juice exudation on the surrounding tissues will cause inflammation and adhesion, which will affect the difficulty of operation. The phenomena of liquid residue and increased tissue density can be observed in imaging ( 30 , 31 ). All the image data defining these indicators have been saved for reference, if necessary.…”