Pancreatic fistulae secondary to trypsinogen activation by Pseudomonas aeruginosa infection after pancreatoduodenectomy
Kanefumi Yamashita
Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan
Search for more papers by this authorCorresponding Author
Takamitsu Sasaki
Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan
Search for more papers by this authorRyota Itoh
Department of Microbiology and Immunology, Fukuoka University School of Medicine, Jonan-ku, Fukuoka, Japan
Search for more papers by this authorDaisuke Kato
Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan
Search for more papers by this authorNaoya Hatano
Integrated Center for Mass Spectrometry, Kobe University, Kobe, Hyogo, Japan
Search for more papers by this authorToshinori Soejima
Department of Microbiology and Immunology, Fukuoka University School of Medicine, Jonan-ku, Fukuoka, Japan
Search for more papers by this authorKazunari Ishii
Department of Microbiology and Immunology, Fukuoka University School of Medicine, Jonan-ku, Fukuoka, Japan
Search for more papers by this authorTadaomi Takenawa
Integrated Center for Mass Spectrometry, Kobe University, Kobe, Hyogo, Japan
Search for more papers by this authorKenji Hiromatsu
Department of Microbiology and Immunology, Fukuoka University School of Medicine, Jonan-ku, Fukuoka, Japan
Search for more papers by this authorYuichi Yamashita
Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan
Search for more papers by this authorKanefumi Yamashita
Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan
Search for more papers by this authorCorresponding Author
Takamitsu Sasaki
Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan
Search for more papers by this authorRyota Itoh
Department of Microbiology and Immunology, Fukuoka University School of Medicine, Jonan-ku, Fukuoka, Japan
Search for more papers by this authorDaisuke Kato
Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan
Search for more papers by this authorNaoya Hatano
Integrated Center for Mass Spectrometry, Kobe University, Kobe, Hyogo, Japan
Search for more papers by this authorToshinori Soejima
Department of Microbiology and Immunology, Fukuoka University School of Medicine, Jonan-ku, Fukuoka, Japan
Search for more papers by this authorKazunari Ishii
Department of Microbiology and Immunology, Fukuoka University School of Medicine, Jonan-ku, Fukuoka, Japan
Search for more papers by this authorTadaomi Takenawa
Integrated Center for Mass Spectrometry, Kobe University, Kobe, Hyogo, Japan
Search for more papers by this authorKenji Hiromatsu
Department of Microbiology and Immunology, Fukuoka University School of Medicine, Jonan-ku, Fukuoka, Japan
Search for more papers by this authorYuichi Yamashita
Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan
Search for more papers by this authorAbstract
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.
Supporting Information
Fig. S1 Analysis of trypsinogen-decomposed products using mass spectrometry. Mass spectrometry was conducted using a MS/MS analysis following the decomposition of the 13- and 10-kDa bands (Fig. 1), as detected on SDS-PAGE with chymotrypsin and porcine trypsin. This figure shows the amino acids detected based on the mass spectral peak
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| jhbp223-sup-0001-FigureS1.tifTIFF image, 1.5 MB | Supporting info item |
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