Clinical trial NCT01499979: Hypothermic Perfusion During Hemihepatectomy
Official title: In Situ Hypothermic Perfusion During Right Hemihepatectomy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hepatic Ischemia-reperfusion Injury
Keywords: Ischemia-reperfusion injury
In situ hypothermic perfusion
In situ hypothermic preservation
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2011-12-26
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

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

Primary outcomes:
measure: Postoperative hepatocellular damage
timeFrame: 5 days postoperatively
Secondary outcomes:
measure: Intraoperative blood loss
timeFrame: 2-3 hours
measure: Postoperative complications
timeFrame: 5 days postoperatively
measure: Regeneration of liver function and volume
timeFrame: 3 days
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center (AMC)
state: Noord-Holland
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Prof. Thomas M. van Gulik, MD, PhD
role: STUDY_CHAIR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Megan J. Reiniers, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Rowan F. van Golen, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.