title: Pancreatic fistulae secondary to trypsinogen activation by Pseudomonas aeruginosa infection after pancreatoduodenectomy.
abstract: 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.
authors: Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan.
authors: Kanefumi
authors: K
authors: Yamashita
authors: Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan. takamitu@fc4.so-net.ne.jp.
authors: Takamitsu
authors: T
authors: Sasaki
authors: Department of Microbiology and Immunology, Fukuoka University School of Medicine, Jonan-ku, Fukuoka, Japan.
authors: Ryota
authors: R
authors: Itoh
authors: Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan.
authors: Daisuke
authors: D
authors: Kato
authors: Integrated Center for Mass Spectrometry, Kobe University, Kobe, Hyogo, Japan.
authors: Naoya
authors: N
authors: Hatano
authors: Department of Microbiology and Immunology, Fukuoka University School of Medicine, Jonan-ku, Fukuoka, Japan.
authors: Toshinori
authors: T
authors: Soejima
authors: Department of Microbiology and Immunology, Fukuoka University School of Medicine, Jonan-ku, Fukuoka, Japan.
authors: Kazunari
authors: K
authors: Ishii
authors: Integrated Center for Mass Spectrometry, Kobe University, Kobe, Hyogo, Japan.
authors: Tadaomi
authors: T
authors: Takenawa
authors: Department of Microbiology and Immunology, Fukuoka University School of Medicine, Jonan-ku, Fukuoka, Japan.
authors: Kenji
authors: K
authors: Hiromatsu
authors: Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan.
authors: Yuichi
authors: Y
authors: Yamashita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004789:Enzyme Activation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010185:Pancreatic Fistula / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D016577:Pancreaticoduodenectomy / Q000009:adverse effects*; D011552:Pseudomonas Infections / Q000150:complications* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*; D012189:Retrospective Studies; D013530:Surgical Wound Infection / Q000150:complications* / Q000382:microbiology; D014362:Trypsinogen / Q000378:metabolism*
chemical_list: D014362:Trypsinogen
keywords: Bacteria; Pancreatic fistula; Pancreatoduodenectomy; Pseudomonas aeruginosa; Trypsinogen