"Involvement of Platelets and Platelet Derived Growth Factors in Postoperative Liver Regeneration, Liver Dysfunktion and Morbidity in Patients Undergoing Hepatectomy"
试验速览
- 阶段
- 不适用
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Validation of the role of platelets in the process of early liver regeneration in humans
研究概览
简要总结
The most relevant factor predicting morbidity and mortality after liver resections is the ability of the remnant liver to regenerate. The investigators recently demonstrated that serotonin and thrombospondin-1, two growth factors abundantly stored in platelets, seem to play a critical role in liver regeneration of patients after liver resection. The investigators now aim to gain more precise insight concerning the relevance of platelets and platelet derived growth factors in liver regeneration in humans. The investigators will focus on specific alpha-granula release as a key regulator of postoperative LR. Using peri- and intraoperative blood and tissue samples, platelet adhesion, granula release and induction of gene expression known to be involved in liver regeneration form experimental studies will be analyzed. This study should allow the investigators to verify observations from preclinical models and evaluate their relevance in the human setting. Furthermore, this might enable the investigators to identify new therapeutic targets.
详细描述
The investigators could previously show that platelet derived growth factors like TSP-1 and 5-HT are of relevance in human liver regeneration. In this project the investigators aim to elucidate how platelets specifically release their granules. Indeed, while dense granules stored 5-HT induces proliferation of hepatocytes, alpha-granules stored TSP-1 reduces their proliferative potential. More importantly, various pro-proliferative growth factors as VEGF are also stored in alpha-granules. Therefore, a systemic reduction in platelet counts would reduce both, pro and anti-proliferative factors. A highly regulated granula release has been postulated to allow platelets to exert specific functions. In 2008, Italiano et al. presented convincing in vitro evidence that platelets store molecules in separate granules, which they are able to specifically release upon platelet activation. Furthermore, results by other groups support this finding.
It is the aim of this project to characterize platelet activation in patients with liver resection and determine if specific platelet activation profiles correlate with clinical outcome.
Project plan
Included patients:
A total of 40 patients undergoing hemihepatectomy will be included. Patients will be closely monitored perioperatively. Plasma, serum, platelet and tissue preparation will be performed as outlined below.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patients undergoing elective hemihepatectomy
排除标准
- •peroperative portal vein thrombosis
- •age > 85
结局指标
主要结局
Validation of the role of platelets in the process of early liver regeneration in humans
时间窗: 2 years
Preclinical studies have identified multiple platelet associated candidate molecules in the highly regulated process of liver regeneration. Using a complex peri and intraoperative sampling schedule, we will try to validate the relevance of these molecules in the human setting.
次要结局
- Postoperative liver dysfunction(2 years)
- Postoperative morbidity(2 years)
研究者
Patrick Starlinger
MD, PhD
Medical University of Vienna