Reperfusion-induced Self-antigen Excretion Following Major Liver Surgery

NCT01700660 | Completed

• 2 other identifiers: 2012_238NL41737.018.12
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Major liver surgery often requires the surgeon to temporarily halt the afferent blood flow in order to prevent excessive blood loss. However, this predisposes the liver to a detrimental inflammatory response once the circulation is restored. Altogether, the effects that result from this temporary withdrawal of blood are known as ischemia and reperfusion (I/R) injury, and the extent to which this occurs determines the functional outcome of the liver after surgery. Recently, it has become clear that (over)activation of the immune system forms the mainstay of I/R injury in the liver. More importantly, it has been shown in animal models that self-antigens, which are normal cellular constituents that become immunogenic mediators following their release from dying cells, are involved in the earliest stages of I/R injury of the liver. Clinical data on the release self-antigens in I/R injury are however scarce to date. Therefore, the aim of this study is to investigate the release of self-antigens in patients that undergo a major liver resection with or without withdrawal of the liver's blood flow. Also, the results will be correlated to genes involved in the inflammatory response as well as clinical parameters for liver damage and function.

Conditions

Warm Hepatic Ischemia-reperfusion Injury

Outcome Measures

Primary Outcomes (1)

• DAMPs in systemic circulation

  Plasma DAMP levels will be determined perioperatively.

  8 hours

Secondary Outcomes (3)

• Up regulation of acute inflammatory response genes

  1 hour

• Parenchymal damage

  8 hours

• Liver function

  8 hours

Study Arms (2)

VIO

Patients operated under VIO.

Control

Patients operated without VIO.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with a malignant or benign hepatic tumor that are scheduled for a liver resection.

You may qualify if:

• Patients scheduled to undergo a major liver resection for a benign or malignant hepatic tumor
• Signed informed consent obtained prior to any study-specific procedure
• ASA classification I-III

You may not qualify if:

• VIO \<20 min
• ASA classification IV/V
• Emergency operations
• Pregnancy or breast feeding

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Academic Medical Center

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Related Publications (1)

• van Golen RF, van Gulik TM, Heger M. The sterile immune response during hepatic ischemia/reperfusion. Cytokine Growth Factor Rev. 2012 Jun;23(3):69-84. doi: 10.1016/j.cytogfr.2012.04.006. Epub 2012 May 17.

  PMID: 22609105 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

2 liver biopsies

Study Officials

• Thomas M. van Gulik, MD, PhD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  STUDY DIRECTOR

• Megan J. Reiniers, MSc

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD student at the Department of Surgery

Study Record Dates

• First Submitted: October 3, 2012
• First Posted: October 4, 2012
• Study Start: October 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 26, 2016

Record last verified: 2016-01

Locations

NL (1)