Pancreatic fistulae secondary to trypsinogen activation by Pseudomonas aeruginosa infection after pancreatoduodenectomy
Pancreatic fistulae secondary to trypsinogen activation by Pseudomonas aeruginosa infection after pancreatoduodenectomy
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DOI：
10.1002/jhbp.223
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发表时间：
2015-06-01
影响因子：
3
通讯作者：
Yamashita, Yuichi
中科院分区：
文献类型：
--
作者：
Yamashita, Kanefumi;Sasaki, Takamitsu;Yamashita, Yuichi
背景胰十二指肠切除术（PD）后的胰瘘与高死亡率和发病率相关。尽管假设胰蛋白酶原激活和细菌在发病机制上相互关联，但尚未阐明它们的关系和致病机制。本研究调查了腹膜透析后胰瘘形成部位的细菌参与围手术期胰液激活的情况。方法 50 名患者接受了腹膜透析；术后胰瘘根据国际胰瘘研究组分级标准进行分级。从引流液培养物中分离出细菌。对胰蛋白酶原和细菌培养上清液中的消化肽进行十二烷基硫酸钠-聚丙烯酰胺凝胶电泳 (SDS-PAGE) 分离和质谱分析。采用酶谱法检测胰蛋白酶原激活剂。结果B、C级胰瘘患者引流液中分离到的铜绿假单胞菌和阴沟肠杆菌可引起胰蛋白酶原激活。体外使用丝氨酸蛋白酶抑制剂可以防止铜绿假单胞菌和阴沟肠杆菌激活胰蛋白酶原。铜绿假单胞菌阳性培养物上清液中的蛋白酶充当胰蛋白酶原激活剂。结论PD围手术期铜绿假单胞菌感染需要将胰蛋白酶原的蛋白酶激活剂分泌到胰蛋白酶。围手术期腹膜透析期间的细菌感染控制对于预防胰瘘的发生至关重要。
BackgroundPancreatic 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.MethodsFifty 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.ResultsPseudomonas 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.ConclusionsInfection 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.