Hepatoprotective Effect of Remote vs Local Preconditioning of Liver

Comparison of Hepatoprotective Effect From Ischemia-reperfusion Injury of Remote Ischemic Preconditioning of the Liver vs. Local Ischemic Preconditioning of the Liver During Human Liver Resections

The aim of this study is to evaluate hepatoprotective effect from ischemia-reperfusion injury of remote ischemic preconditioning of the liver against local ischemic preconditioning of the liver during human liver resections.

Study Overview

• Status: Completed
• Conditions: Liver Metastases
• Intervention / Treatment: Procedure: Preconditioning

Detailed Description

In this randomized control study, a total of 60 patients were randomized into 3 groups: remote ischemic precondition group - RIPC (3 intervals of 5 minute right upper limb ischemia with 3 intervals of 5 minute reperfusion), local ischemic precondition group - LIPC (15 minutes of inflow liver occlusion followed by 10 minutes of reperfusion before liver transection), control group - CG (group without ischemic preconditioning before liver transection). Patients were also stratified according to the extent of the hepatectomy. Hepatoprotective effect was evaluated by comparing serum transaminase levels, bilirubin levels, albumin, and protein levels, coagulograms and pathohistological exams. We also measured flow rate by Doppler ultrasound of hepatic artery and portal vein before and after preconditioning.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Croatia
  • Zagreb, Croatia, 10000
    • University Hospital Dubrava

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients with colorectal cancer liver metastasis all of which signed an informed consent

Exclusion Criteria:

• having any other underlying liver disease, or preoperative increased liver transaminase, bilirubin
• patients with chronic cardiac, pulmonary or renal disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control
Active Comparator: Remote ischemic preconditioning	Procedure: Preconditioning; Local ischemic preconditioning (LIPC) is process during which a short period of ischemia is followed by a period of reperfusion prior to the prolonged ischemia which seems to render organs more tolerant to the IR(ischemic-reperfusion) injury. Remote ischemic preconditioning (RIPC) involves the protection of an organ from prolonged ischemia by brief periods of ischemia and reperfusion to a remote organ.
Active Comparator: Local ischemic preconditioning	Procedure: Preconditioning; Local ischemic preconditioning (LIPC) is process during which a short period of ischemia is followed by a period of reperfusion prior to the prolonged ischemia which seems to render organs more tolerant to the IR(ischemic-reperfusion) injury. Remote ischemic preconditioning (RIPC) involves the protection of an organ from prolonged ischemia by brief periods of ischemia and reperfusion to a remote organ.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in synthetic liver function	We measured residual synthetic liver function and liver ischemic-reperfusion injury by value level of bilirubin, total proteins, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamic aminotransferase (ƴGT), cholinesterase, alkaline phosphatase (AP), coagulogram.	Preoperatively, first, third and seventh postoperative day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow through the hepatic artery and portal vein	During operation we preformed Doppler ultrasonography of hepatic artery and portal vein.	Before and after preconditioning
Liver histology evaluation	Liver paraffin-embedded, standard haematoxylin-eosin stained sections were analysed postoperatively to evaluate the ischemic reperfusion injury . According to Rodriguez et al. four elements of the liver histology were analysed: steatosis (micro vesicular and macro vesicular) in 4 grades, degree of sinusoidal congestion and dilatation in 3 grades, leukocyte infiltration in 3 grades and necrosis (focal, confluent, or zonal) in 3 grades.26 Each biopsy was evaluated by a single pathologist blinded to the treatment allocation.	Up to 10 days after operation

Collaborators and Investigators

• Sponsor: University Hospital Dubrava
• Investigators: Study Chair: Leonardo Patrlj, Clinical Hospital Dubrava

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2017
• Primary Completion (Actual): July 4, 2017
• Study Completion (Actual): April 20, 2018

Study Registration Dates

• First Submitted: April 1, 2017
• First Submitted That Met QC Criteria: April 23, 2017
• First Posted (Actual): April 27, 2017

Study Record Updates

• Last Update Posted (Actual): October 11, 2018
• Last Update Submitted That Met QC Criteria: October 10, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: preconditioning, resection
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: UHDubrava

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No