Hypothermic Perfusion During Hemihepatectomy

Study Overview
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Brief Summary
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Rationale Currently, hepatic resection is often the only curative treatment for primary or secondary hepatic malignancies and is also frequently performed in patients with benign liver tumors to prevent malignant transformation and/or alleviate symptoms. Liver resections are nowadays associated with low mortality and acceptable morbidity. As result of that, an increasing number of patients is currently under consideration for resection of more complex or large tumors, thus requiring extensive resection procedures. Application of vascular exclusion (i.e., clamping of the portal vein and hepatic artery) during such procedures reduces blood loss, which is one of the most important factors affecting peri-operative outcomes. However, vascular exclusion leads to ischemia-reperfusion (I/R) injury as an inevitable side-effect, which adversely impacts postoperative liver function and regeneration. Additional cooling of the liver by means of hypothermic perfusion is expected to further reduce intraoperative blood loss, as well as to protect the liver from I/R injury. Therefore, the aim of this pilot study is to cool the future remnant liver (FRL) in situ during right hemihepatectomy under vascular exclusion. Consequently, an overall improvement in postoperative outcomes is expected due to a decrease in intraoperative blood loss, reduced parenchymal damage, and a better ability of the liver remnant to regenerate. Objective To reduce intraoperative blood loss and enhance tolerance of the FRL to I/R injury during right hemihepatectomy under vascular exclusion by means of in situ hypothermic perfusion with retrograde outflow (R-IHP) of the FRL. Study design The study is designed as a prospective randomized pilot study in 18 patients (9 interventions and 9 controls) to assess the effects of the proposed intervention. Additionally, 4 patients will be included separately for assessment of the intervention's feasibility prior to randomized inclusion. Study population Eligible patients for participation in this study are those planned to undergo right hemihepatectomy under vascular inflow occlusion because of a malignant or benign liver tumor, and who do not suffer from any hepatic co-morbidity that might influence postoperative outcomes (i.e., severe steatosis, cholestasis, cirrhosis, or hepatitis B/C infection). Intervention During right hemihepatectomy, the FRL of patients allocated to the intervention group will be perfused with a chilled perfusion solution (i.e., lactated Ringer's solution).

Official Title
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In Situ Hypothermic Perfusion During Right Hemihepatectomy

Conditions
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Hepatic Ischemia-reperfusion Injury

Intervention / Treatment
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* Procedure: In situ hypothermic perfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients scheduled for right hemihepatectomy under vascular inflow occlusion for a malignant or benign hepatic tumor Diagnostic exclusion of hepatic co-morbidity, that is: Cirrhosis, Severe steatosis (≥ 30%), Cholestasis, and Hepatitis B/C infection Age ≥ 18 years Signed informed consent obtained prior to any study-specific procedure ASA classification I-III Exclusion Criteria: Patients diagnosed with any of the hepatic co-morbidities listed under point 2 of the inclusion criteria Age < 18 years BMI > 35 kg/m2 ASA classification IV/V Patient is scheduled for a combined surgical procedure (e.g., bile duct resection, gastrointestinal procedures) Patient underwent liver resection ≤ 1 year prior to scheduled surgery Emergency operations Pregnancy or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Vascular inflow occlusion<br>Patients that will receive intermittent vascular inflow occlusion, the standard method for vascular occlusion at our institution, during liver resection. | |
| Experimental: Hypothermic perfusion<br>Patients will receive in situ hypothermic perfusion of the future remnant liver during liver resection. | Procedure: In situ hypothermic perfusion<br>* In situ perfusion of the future remnant liver with chilled lactated Ringer's solution during liver resection.<br>* Other names: In situ hypothermic preservation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative hepatocellular damage | Hepatocellular damage expressed as an postoperative increase in transaminases (i.e., AST and ALT). | 5 days postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoperative blood loss | Blood loss during surgery | 2-3 hours | 
| Postoperative complications | Incidence of surgery-related complications | 5 days postoperatively | 
| Regeneration of liver function and volume | Regeneration of liver function (measured via hepatobiliary scintigraphy) and -volume (measured via CT volumetry). | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ischemia-reperfusion injury, In situ hypothermic perfusion, In situ hypothermic preservation