Objective parameters aid the prediction of fistulas in pancreatic surgery

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.

The effect of atrophied pancreas as shown in the preoperative imaging on the leakage rate after pancreaticoduodenectomy

“…In prior studies, the presence of a fibrotic pancreas has been shown to be protective against leaks. This may be explained by the fact that atrophic pancreas on imaging may reflect a fibrotic pancreas intraoperatively [ 10 ].…”

High Values of Drain Fluid Epidermal Growth Factor and Transforming Growth Factor-Beta Are Associated with the Development of Pancreatic Fistula after Pancreatoduodenectomy

“…If on one hand it seems that a proinflammatory environment could led to an increased risk of anastomotic disruption, there are several evidences demonstrating how a high degree of fibrosis, elevated inflammatory activity, and higher inflammatory infiltration, as well as an absence of lipomatous atrophy in the pancreatic tissue, correlate with a low incidence of POPF [18]. As for every process of wound healing, the environment of pancreatic anastomosis changes according to four basic steps: bleeding, inflammation, proliferation, and remodeling [47].…”

“…Samples were centrifuged at 3,000 g for 10 min at 4°C and then stored in aliquots at −80°C until determination of the respective biomarkers. According to the available evidence [15,17,18], we chose to measure transforming growth factor β (TGFβ), insulin-like growth factor 1 (IGF-1), epidermal growth factor (EGF), and interleukin 6 (IL-6). Cytokines were measured through an enzyme-linked immunosorbent assay according to the protocol provided by the manufacturer (R&D System ® , Minneapolis, MN, USA).…”

Lower geriatric nutritional risk index predicts postoperative pancreatic fistula in patients with distal pancreatectomy

“…A number of risk factors of POPF following pancreatic resection have been recognized, including a soft pancreas, obesity, blood transfusion, age, sex, diabetes mellitus history, preoperative serum albumin levels, extended lymphadenectomy, substantial intraoperative blood loss, and longer operative time (8). At the tissue level, substantial inflammatory activity, indicated by high levels of proinflammatory cytokines and matrix metalloproteinases, and marked chronic inflammatory infiltrates are reportedly associated with a lower incidence of fistula (9). A meta-analysis indicated that a soft pancreas, high BMI, blood transfusion, intraoperative blood loss, and operative time were clinical predictors of POPF (5).…”