Abstract
Insufficiency of pancreatic anastomosis with leakage from the pancreatic stump and the development of fistulas account for the majority of surgical complications following pancreatic resection, which are often life threatening. The cause of pancreatic fistulas of the remnant tissue on a molecular level remains unclear. Thus, the aim of the present study was to investigate risk factors associated with postoperative pancreatic fistula (POPF) formation and to define parameters that may predict the resection outcome. Pancreatic resection margins were selected from 31 patients, including 16 individuals without and 15 patients with POPF, to analyze the degree of fibrosis, lipomatous atrophy, inflammatory activity and infiltration. Wound healing factors were assessed by luminex technology using tissue homogenates, while the distribution in situ was assessed using immunohistochemistry. Increased chronic inflammatory infiltration, a higher degree of fibrosis and a reduction in lipomatous atrophy were observed in the samples without anastomotic fistulas. Multiplex analysis of 38 wound healing factors demonstrated significantly higher levels of interleukin (IL)-6, -8 and -12, glucagon-like peptide-1 and matrix metalloproteinase (MMP)-1, -2, -3 and -12 in the group without fistulas, while lower concentrations of IL-10, IL-17 and gastric inhibitory polypeptide were observed. Therefore, the observations of the present study indicated that increased inflammatory infiltration and inflammatory activity, as well as higher concentrations of proinflammatory cytokines and higher MMP levels at the resection margins, predisposed individuals to a lower fistula incidence rate following pancreatic resection.
Highlights
Pancreatic fistula and anastomotic leakage are major complications following pancreatic head resection or distal pancreatectomy [1,2], which are often associated with subsequent dangerous infectious complications, including peritonitis and sepsis [3]
Impaired healing of chronic wounds is known to be mediated by the dysregulation of numerous factors [10,11], including pro‐ and anti‐inflammatory cytokines, angiogenesis‐associated proteins, proteins associated with diabetic conditions and matrix metalloproteinases (MMPs) that remodel damaged tissue
postoperative pancreatic fistula (POPF) is the failure of healing/sealing a pancreatic‐enteric anastomosis or a parenchymal leak not directly associated with an anastomosis, and was defined as a drain output of any measurable volume on or following day three postoperatively, with an amylase content greater than three times the serum amylase activity
Summary
Pancreatic fistula and anastomotic leakage are major complications following pancreatic head resection or distal pancreatectomy [1,2], which are often associated with subsequent dangerous infectious complications, including peritonitis and sepsis [3]. These complications represent the leading cause of mortality following pancreatic resection. Wound healing is a complex process involving a coordinated interplay of cells, extracellular matrix and numerous regulatory mediators. It includes an organized stimulation of angiogenesis, fibroblast proliferation with stimulation of extracellular matrix and the growth of epithelial tissue. Impaired healing of chronic wounds is known to be mediated by the dysregulation of numerous factors [10,11], including pro‐ and anti‐inflammatory cytokines, angiogenesis‐associated proteins, proteins associated with diabetic conditions and matrix metalloproteinases (MMPs) that remodel damaged tissue
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