trypsinogen and Pancreatic-Fistula

Pancreaticoduodenectomy is associated with considerable morbidity and mortality rates. Early recognition of patients likely to develop severe postoperative complications will allow the timely commencement of a tailored approach. This study aimed to predict postoperative complications using inflammatory and nutritional markers measured early in the postoperative period.. Patients who underwent pancreaticoduodenectomy between June 2019 and November 2020 were included in the study. Postoperative pancreatic fistula, delayed gastric emptying, and postoperative pancreatic hemorrhage were graded according to the International Study Group of Pancreatic Fistula and the International Study Group of Pancreatic Surgery. We also documented other complications such as wound infection, intra-abdominal collection, and nonsurgical complications. Nutritional and inflammatory markers were analyzed on postoperative days 1 and 3. Patients were followed up for 30 days or until discharge, depending on which was longer.. Of the 58 enrolled patients, 51 were included in the study. The incidence of postoperative pancreatic fistula was 51% (clinically relevant postoperative pancreatic fistula 27.4%), delayed gastric emptying was 80.4% (clinically relevant delayed gastric emptying 43%), postoperative pancreatic hemorrhage was 3.9%, intra-abdominal collection was 23.5%, and wound infection was 29.4%. The median drain fluid interlukin-6 levels on postoperative day 1 and postoperative day 3 were significantly higher in patients developing clinically relevant postoperative pancreatic fistula than in those who did not develop clinically relevant postoperative pancreatic fistula on postoperative day 1 (211 [125, 425] fg/dL vs 99 [15, 170] fg/dL, [P = .045]) and on postoperative day 3 (110 [22, 28] fg/dL vs 10 [1.8, 45] fg/dL [P = .002]). Patients who tested negative for urine trypsinogen-2 on postoperative day 3 had a significantly lower probability of developing clinically relevant postoperative pancreatic fistula than those who tested positive (1 vs 24 [P < .001]). A model comprising both drain fluid interlukin-6 and urine trypsinogen-2 on postoperative day 3 definitively ruled out the occurrence of clinically relevant postoperative pancreatic fistula.. Drain fluid interlukin-6 and urine trypsinogen-2 on postoperative day 3 ruled out the occurrence of clinically relevant postoperative pancreatic fistula.

Topics: Biomarkers; Gastroparesis; Humans; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Postoperative Hemorrhage; Trypsinogen

We investigated the activation of pancreatic proenzymes and signs of peripancreatic inflammation in patients with clinically relevant postoperative pancreatic fistulas (POPFs).. An increase of systemic amylase concentration was associated with POPFs. This suggested parallels in the pathomechanisms between the development of POPFs and pancreatitis.. 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.. 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.. 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.

Topics: Amylases; Animals; Cathepsin B; Enzyme Precursors; Female; Humans; Inflammation; Interleukin-6; Male; Mice; Pancreatectomy; Pancreatic Fistula; Peroxidase; Postoperative Complications; Prospective Studies; Trypsin; Trypsinogen

There has been recent evidence supporting post-pancreatectomy pancreatitis as a factor in the development of postoperative pancreatic fistula (POPF). The aims of this study were to evaluate: (i) the correlation of the acinar cell density at the pancreatic resection margin with the intra-operative amylase concentration (IOAC) of peri-pancreatic fluid, postoperative pancreatitis, and POPF; and (ii) the association between postoperative pancreatitis on the first postoperative day and POPF.. Consecutive patients who underwent pancreatic resection between June 2016 and July 2017 were included for analysis. Fluid for IOAC was collected, and amylase concentration was determined in drain fluid on postoperative days 1, 3, and 5. Serum amylase and lipase and urinary trypsinogen-2 concentrations were determined on the first postoperative day. Histology slides of the pancreatic resection margin were scored for acinar cell density.. Sixty-one patients were included in the analysis. Acinar cell density significantly correlated with IOAC (r = 0.566, p < 0.001), and was significantly associated with postoperative pancreatitis (p < 0.001), and POPF (p = 0.003). Postoperative pancreatitis was significantly associated with the development of POPF (OR 17.81, 95%CI 2.17-145.9, p = 0.001).. The development of POPF may involve a complex interaction between acinar cell density, immediate leakage of pancreatic fluid, and postoperative pancreatitis.

Topics: Acinar Cells; Adult; Aged; Aged, 80 and over; Amylases; Biomarkers; Biopsy; Female; Humans; Lipase; Male; Margins of Excision; Middle Aged; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Pancreatitis; Risk Factors; Time Factors; Treatment Outcome; Trypsin; Trypsinogen

Pancreatic fistula after pancreatoduodenectomy (PD) is associated with high mortality and morbidity. Trypsinogen activation and bacteria, although hypothesized to be interrelated etiopathogenetically, have not had their relationship and pathogenic mechanisms elucidated. This study investigated bacterial involvement in pancreatic juice activation perioperatively after PD at sites of pancreatic fistula formation.. Fifty patients underwent PD; postoperative pancreatic fistulae were graded based on the International Study Group for Pancreatic Fistula grading criteria. Bacteria were isolated from cultures of drainage fluid. Digested peptides from trypsinogen and bacterial culture supernatants underwent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separation and mass spectrometric analysis. Zymography was used to detect the trypsinogen activator.. Pseudomonas aeruginosa and Enterobacter cloacae isolated from drainage fluid in patients with grades B and C pancreatic fistulae could cause trypsinogen activation. Trypsinogen activation by P. aeruginosa and E. cloacae were preventable by the use of a serine protease inhibitor in vitro. A protease in the supernatant from P. aeruginosa-positive cultures acted as the trypsinogen activator.. Infection with P. aeruginosa perioperatively to PD entails secretion of a protease activator of trypsinogen to trypsin. Bacterial infection control in the perioperative PD period could be crucial to prevent development of pancreatic fistula.

Topics: Adult; Aged; Aged, 80 and over; Enzyme Activation; Female; Follow-Up Studies; Humans; Incidence; Japan; Male; Middle Aged; Pancreatic Fistula; Pancreaticoduodenectomy; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Surgical Wound Infection; Trypsinogen

Ischaemia and local protease activation close to the pancreaticojejunal anastomosis (PJA) are potential mechanisms of postoperative pancreatic fistula (POPF) formation. To provide information on the pathophysiology of POPF, intraperitoneal microdialysis was used to monitor metabolic changes and protease activation close to the PJA after pancreaticoduodenectomy (PD).. In patients who underwent PD, intraperitoneal metabolites (glycerol, lactate, pyruvate and glucose) were measured by microdialysis, and lactate and glucose in blood were monitored, every 4 h for 5 days, starting at 12.00 hours on the day after surgery. Trypsinogen activation peptide (TAP) was measured in microdialysates as a marker of protease activation.. Intraperitoneal glycerol levels and the ratio of lactate to pyruvate were higher after PD and glucose levels were lower in seven patients who later developed symptomatic POPF than in eight patients with other surgical complications (OSC) and 33 with no surgical complications (NSC) (all P < 0·050). TAP was detected at a concentration greater than 0·1 µg/l in six of seven patients with POPF, two of eight with OSC and two of 33 with NSC. Intraperitoneal lactate concentrations were higher than systemic levels in all patients on days 1 to 5 after surgery (P < 0·001). In patients with POPF, high intraperitoneal lactate concentrations were observed without systemic hyperlactataemia.. Early in the postoperative phase, patients who later developed clinically significant POPF had higher intraperitoneal glycerol concentrations and lactate/pyruvate ratios, and lower glucose concentrations in combination with a TAP level exceeding 0·1 µg/l close to the PJA, than patients who did not develop POPF.

Topics: Adult; Aged; Aged, 80 and over; Amylases; Biomarkers; Blood Glucose; Enzyme Activation; Female; Glucose; Glycerol; Humans; Lactic Acid; Male; Microdialysis; Middle Aged; Pancreatic Fistula; Pancreaticoduodenectomy; Peptide Hydrolases; Peritoneal Cavity; Postoperative Period; Pyruvic Acid; Time Factors; Trypsinogen

Previous reports suggested that the urine trypsinogen 2 (U-TRP2) test might be a valuable method for the diagnosis of postoperative pancreatitis after pancreatic surgery. We hypothesize that the elevation of U-TRP2 level after pancreaticoduodenectomy (PD) could be associated with the occurrence of postoperative pancreatic fistula (POPF).. A total of 130 consecutive patients undergoing PD with duct-to-mucosa pancreaticogastrostomy were included. Urine samples for evaluation of U-TRP2 levels were collected prospectively. Risk factors for POPF were evaluated using univariate and multivariate analyses.. Of 130 patients, 19 developed POPF; grade A in 14 (11%), grade B in 3 (2%), and grade C in 1 (1%). Univariate analysis demonstrated that a nonobstructed main pancreatic duct, a pancreatic duct less than 3 mm, soft texture of the pancreatic gland, a PD with antrectomy, PD with hepatic resection, hyperamylasemia, and elevation of U-TRP2 levels (>50 μg/L) were significantly associated with POPF (P < 0.05). By multivariate analysis, elevation of U-TRP2 levels (odds ratio = 4.544, P = 0.029) was the only independent risk factor that correlated with POPF.. Elevation of U-TRP2 level is an independent risk factor for POPF after PD. Elevated U-TRP2 level might be the consequence of the postoperative pancreatitis, and postoperative pancreatitis may play an important role in the pathogenic mechanism of POPF after PD.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chi-Square Distribution; Female; Humans; Japan; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Pancreatic Fistula; Pancreaticoduodenectomy; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; Trypsin; Trypsinogen; Up-Regulation; Young Adult

Topics: Acute Disease; Adult; Aged; Catheterization; Chymotrypsin; Chymotrypsinogen; Enzyme Activation; Enzyme Precursors; Female; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Pancreatic Ducts; Pancreatic Elastase; Pancreatic Fistula; Pancreatic Juice; Pancreatitis; Proteins; Temperature; Thrombin; Time Factors; Trypsin; Trypsinogen

Topics: Atropine; Chymotrypsin; Gastrointestinal Hormones; Humans; Methionine; Pancreas; Pancreatic Fistula; Pancreatic Function Tests; Pancreatic Juice; Pharmacology; Physiology; Secretin; Trypsin; Trypsinogen