Pancreatic fistulae secondary to trypsinogen activation by <i>Pseudomonas aeruginosa</i> infection after pancreatoduodenectomy

Yamashita, Kanefumi; Sasaki, Takuma; Itoh, Roichi; Kato, Daisuke; Hatano, Naoya; Soejima, Toshinori; Ishii, Kazuya; Takenawa, Tadaomi; Hiromatsu, Kenji; Yamashita, Yuichi

doi:10.1002/jhbp.223

Cited by 34 publications

(27 citation statements)

References 40 publications

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“…Previous studies found that Enterococcus, Pseudomonas, and Candida were associated with POPF after PD [9,10,48]. Due to the small sample size of these studies, fewer other bacteria were isolated.…”

Section: Discussionmentioning

confidence: 90%

Clinical significance of drain fluid culture after pancreaticoduodenectomy

Yang

Jin

et al. 2018

J Hepato Biliary Pancreat

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Background The mechanism of infected postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy (PD) is undefined. Drain amylase has been used to predict POPF, whereas little data are available about the value of drain fluid culture. The aim was to investigate the incidence, risk factors and association with surgical outcomes of positive drainage culture (PDC) after PD. Methods A single‐center retrospective analysis was conducted of prospectively collected data from patients who underwent PD between January 2005 and December 2015. Drain fluid samples were obtained for microbiological analysis after surgery. Risk factors for PDC were evaluated, and its influence on surgical outcomes was explored. Results Of 768 patients, 261 (34%) had PDC during the postoperative period. Among them, a total of 434 isolates were yielded. One hundred and seven (24.7%) were Gram‐positive, 283 (65.2%) Gram‐negative, and 44 (10.1%) fungi. Multivariate analysis revealed that body mass index (BMI) ≥25 kg/m2, preoperative chemoradiation and intra‐operative red blood cell transfusion were independent risk factors for PDC. PDC was associated with higher incidences of complications including POPF, major complications and reoperation, but with no correlation between the day of PDC and complications. BMI ≥25 kg/m2, early PDC (≤3 days), main pancreatic duct <3 mm, and soft pancreas were revealed as independent predictors for POPF. There was a correlation between type of microorganisms and complications. Conclusion Considering the correlation between PDC and postoperative complications, preventive measures are crucial to improve outcomes after PD. Whether antibiotic treatment for early PDC will alter the clinical course of POPF needs further evaluation.

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Section: Discussionmentioning

confidence: 90%

Clinical significance of drain fluid culture after pancreaticoduodenectomy

Yang

Jin

et al. 2018

J Hepato Biliary Pancreat

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“…However, a clinical study in patients who underwent resection and developed postoperative pancreatic fistulae (POPF) found that Pseudomonas aeruginosa and Enterobacter cloacae isolated from drainage fluid in patients with clinically relevant (grade B/C) POPF could cause trypsinogen activation. 70 The investigators further found that trypsinogen activation by P. aeruginosa and E. cloacae were preventable by the use of a serine protease inhibitor in vitro and that a protease in the supernatant from P. aeruginosa-positive cultures acted as the trypsinogen activator. 70 Again, this is extrapolation from data from a different setting, but serves to show that certain bacteria have the ability to activate trypsinogen into trypsin and thereby eliciting effects that may have clinical relevance (Figs.…”

Section: Why Has Trypsin Yet To Be Investigated As a Major Player Befmentioning

confidence: 99%

“…70 The investigators further found that trypsinogen activation by P. aeruginosa and E. cloacae were preventable by the use of a serine protease inhibitor in vitro and that a protease in the supernatant from P. aeruginosa-positive cultures acted as the trypsinogen activator. 70 Again, this is extrapolation from data from a different setting, but serves to show that certain bacteria have the ability to activate trypsinogen into trypsin and thereby eliciting effects that may have clinical relevance (Figs. 1 and 2).…”

Section: Why Has Trypsin Yet To Be Investigated As a Major Player Befmentioning

confidence: 99%

Is There a Trojan Horse to Aggressive Pancreatic Cancer Biology? A Review of the Trypsin-PAR2 Axis to Proliferation, Early Invasion, and Metastasis

Søreide

Roalsø

Aunan

2020

Journal of Pancreatic Cancer

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Purpose: Pancreatic cancer is one of the most lethal of solid tumors and is associated with aggressive cancer biology. The purpose is to review the role of trypsin and effect on molecular and cellular processes potentially explaining the aggressive biology in pancreatic cancer. Methods: A narrative literature review of studies investigating trypsin and its effect on protease systems in cancer, with special reference to pancreatic cancer biology. Results: Proteases, such as trypsin, provides a significant advantage to developing tumors through the ability to remodel the extracellular matrix, promote cell invasion and migration, and facilitate angiogenesis. Trypsin is a digestive enzyme produced by the exocrine pancreas that is also related to mechanisms of proliferation, invasion and metastasis. Several of these mechanisms may be co-regulated or influenced by activation of proteinaseactivated receptor 2 (PAR-2). The current role in pancreatic cancer is not clear but emerging data suggest several potential mechanisms. Trypsin may act as a Trojan horse in the pancreatic gland, facilitating several molecular pathways from the onset, which leads to rapid progression of the disease. Pancreatic cancer cell lines containing PAR-2 proliferate upon exposure to trypsin, whereas cancer cell lines not containing PAR-2 fail to proliferate upon trypsin expression. Several mechanisms of action include a proinflammatory environment, signals inducing proliferation and migration, and direct and indirect evidence for mechanisms promoting invasion and metastasis. Novel techniques (such as organoid models) and increased understanding of mechanisms (such as the microbiome) may yield improved understanding into the role of trypsin in pancreatic carcinogenesis. Conclusion: Trypsin is naturally present in the pancreatic gland and may experience pathological activation intracellularly and in the neoplastic environment, which speeds up molecular mechanisms of proliferation, invasion, and metastasis. Further investigation of these processes will provide important insights into how pancreatic cancer evolves, and suggest new ways for treatment.

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“…Previous studies have shown that serum presepsin is useful for the early detection of bacterial infection and sepsis (11,12). POPF is considered to be closely associated with bacterial infection (8,14). Indeed, surgical site bacterial infection involves the secretion of certain protease activators in the pancreatic juice that convert trypsinogen to trypsin, subsequently inducing CR-POPF (14).…”

Section: Introductionmentioning

confidence: 99%

“…POPF is considered to be closely associated with bacterial infection (8,14). Indeed, surgical site bacterial infection involves the secretion of certain protease activators in the pancreatic juice that convert trypsinogen to trypsin, subsequently inducing CR-POPF (14). However, no study has focused on the utility of presepsin as a predictive marker for CR-POPF.…”

Section: Introductionmentioning

confidence: 99%

The novel early predictive marker presepsin for postoperative pancreatic fistula: A pilot study

et al. 2020

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Pancreatic fistulae secondary to trypsinogen activation by Pseudomonas aeruginosa infection after pancreatoduodenectomy

Abstract: 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.

Cited by 34 publications

References 40 publications

Clinical significance of drain fluid culture after pancreaticoduodenectomy

Clinical significance of drain fluid culture after pancreaticoduodenectomy

Is There a Trojan Horse to Aggressive Pancreatic Cancer Biology? A Review of the Trypsin-PAR2 Axis to Proliferation, Early Invasion, and Metastasis

The novel early predictive marker presepsin for postoperative pancreatic fistula: A pilot study

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