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Enhanced polymorphonuclear neutrophil-mediated endothelial cell injury and its relation to high surgical mortality
1First Department of Surgery, School of Medicine, Chiba University, Japan.
Objective:
A high incidence of complications has been documented in patients with cirrhosis after operations. Recently, polymorphonuclear neutrophils (PMN) have been revealed to have the capacity to injure vascular endothelium and to cause organ damage. Furthermore, the altered function of PMN has been shown in patients with cirrhosis. However, there are few reports investigating the interaction between PMN and endothelial cells and its relation to a high incidence of postoperative complications in cirrhosis. The aim of this study was to evaluate PMN-mediated endothelial cell injury in patients with cirrhosis.
Methods:
Patients were divided into two groups: those who had normal liver with metastatic liver carcinoma and those who had cirrhosis with hepatocellular carcinoma. All patients in both groups underwent hepatic resection. PMN were isolated from patients before operation. Human umbilical vein endothelial cells and PMN were cocultured after addition of phorbol myristate acetate. The release of lactate dehydrogenase (LDH) and thrombomodulin in the cocultured medium and the elastase activity in PMN suspension were measured.
Results:
The release of both LDH and thrombomodulin in the group with cirrhosis was significantly higher than in the group with normal liver. The elastase activity was similarly higher in the group with cirrhosis than in the group with normal liver. The surgical morbidity rate was remarkably higher in the group with cirrhosis (50%) than in the group with normal liver (0%).
Conclusions:
This study shows that PMN have an enhanced potential to cause endothelial cell injury in patients with cirrhosis. This PMN "priming" may be responsible for the occurrence of postoperative complications in patients with cirrhosis after hepatectomy.
Insights
Polymorphonuclear neutrophils (PMN) show increased injury potential in cirrhosis patients, contributing to higher postoperative complications after liver surgery. This PMN "priming" highlights a key factor in surgical outcomes for liver disease.
Area of Science:
- Hepatology
- Immunology
- Vascular Biology
Background:
- Patients with cirrhosis exhibit a high incidence of postoperative complications after surgery.
- Polymorphonuclear neutrophils (PMN) can injure vascular endothelium and cause organ damage.
- Altered PMN function is observed in cirrhosis, but their role in post-hepatectomy complications is under-investigated.
Purpose of the Study:
- To evaluate the potential of PMN to cause endothelial cell injury in patients with cirrhosis.
- To investigate the link between PMN-mediated endothelial damage and postoperative complications in cirrhosis.
Main Methods:
- Hepatic resection was performed on patients with normal liver and metastatic liver carcinoma, and patients with cirrhosis and hepatocellular carcinoma.
- PMN were isolated from patients pre-operation and co-cultured with human umbilical vein endothelial cells.
- Lactate dehydrogenase (LDH), thrombomodulin release, and PMN elastase activity were measured.
Main Results:
- Cirrhosis patients showed significantly higher release of LDH and thrombomodulin compared to normal liver patients.
- PMN elastase activity was also significantly elevated in the cirrhosis group.
- Surgical morbidity was 50% in cirrhosis patients versus 0% in normal liver patients.
Conclusions:
- PMN possess an enhanced capacity for endothelial cell injury in patients with cirrhosis.
- This PMN "priming" is a likely contributor to the increased postoperative complications observed after hepatectomy in cirrhosis patients.