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

Kanefumi Yamashita, Takamitsu Sasaki, Ryota Itoh, Daisuke Kato, Naoya Hatano, Toshinori Soejima, Kazunari Ishii, Tadaomi Takenawa, Kenji Hiromatsu, Yuichi Yamashita

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Background 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. Methods 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. Results 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. Conclusions 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.

Original languageEnglish
Pages (from-to)454-462
Number of pages9
JournalJournal of Hepato-Biliary-Pancreatic Sciences
Issue number6
Publication statusPublished - Jun 1 2015
Externally publishedYes


  • Bacteria
  • Pancreatic fistula
  • Pancreatoduodenectomy
  • Pseudomonas aeruginosa
  • Trypsinogen

ASJC Scopus subject areas

  • Medicine(all)


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