Hypothermic Perfusion During Hemihepatectomy

NCT ID: NCT01499979

Last Updated: 2016-01-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2015-08-31

Brief Summary

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).

Conditions

Hepatic Ischemia-reperfusion Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Vascular inflow occlusion

Patients that will receive intermittent vascular inflow occlusion, the standard method for vascular occlusion at our institution, during liver resection.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Hypothermic perfusion

Patients will receive in situ hypothermic perfusion of the future remnant liver during liver resection.

Group Type: EXPERIMENTAL

In situ hypothermic perfusion

Intervention Type: PROCEDURE

In situ perfusion of the future remnant liver with chilled lactated Ringer's solution during liver resection.

Interventions

In situ hypothermic perfusion

In situ perfusion of the future remnant liver with chilled lactated Ringer's solution during liver resection.

Intervention Type: PROCEDURE

Other Intervention Names

In situ hypothermic preservation

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER

Sponsor Role: lead

Responsible Party

Megan J. Reiniers

PhD student

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Prof. Thomas M. van Gulik, MD, PhD

Role: STUDY_CHAIR

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

Megan J. Reiniers, MSc

Role: PRINCIPAL_INVESTIGATOR

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

Rowan F. van Golen, MSc

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Academic Medical Center (AMC)

Amsterdam, North Holland, Netherlands

Countries

Netherlands

References

Azoulay D, Eshkenazy R, Andreani P, Castaing D, Adam R, Ichai P, Naili S, Vinet E, Saliba F, Lemoine A, Gillon MC, Bismuth H. In situ hypothermic perfusion of the liver versus standard total vascular exclusion for complex liver resection. Ann Surg. 2005 Feb;241(2):277-85. doi: 10.1097/01.sla.0000152017.62778.2f.

Reference Type: BACKGROUND

PMID: 15650638 (View on PubMed)

Dinant S, van Veen SQ, Roseboom HJ, van Vliet AK, van Gulik TM. Liver protection by hypothermic perfusion at different temperatures during total vascular exclusion. Liver Int. 2006 May;26(4):486-93. doi: 10.1111/j.1478-3231.2006.01248.x.

Reference Type: BACKGROUND

PMID: 16629653 (View on PubMed)

Verhoef C, de Wilt JH, Brunstein F, Marinelli AW, van Etten B, Vermaas M, Guetens G, de Boeck G, de Bruijn EA, Eggermont AM. Isolated hypoxic hepatic perfusion with retrograde outflow in patients with irresectable liver metastases; a new simplified technique in isolated hepatic perfusion. Ann Surg Oncol. 2008 May;15(5):1367-74. doi: 10.1245/s10434-007-9714-z. Epub 2008 Feb 1.

Reference Type: BACKGROUND

PMID: 18239976 (View on PubMed)

Reiniers MJ, van Golen RF, Heger M, Mearadji B, Bennink RJ, Verheij J, van Gulik TM. In situ hypothermic perfusion with retrograde outflow during right hemihepatectomy: first experiences with a new technique. J Am Coll Surg. 2014 Jan;218(1):e7-16. doi: 10.1016/j.jamcollsurg.2013.09.013. Epub 2013 Nov 6. No abstract available.

Reference Type: RESULT

PMID: 24210146 (View on PubMed)

Other Identifiers

NL37241.018.11

Identifier Type: OTHER

Identifier Source: secondary_id

2011_214

Identifier Type: -

Identifier Source: org_study_id