Hepatic Ischemia-reperfusion Injury Clinical Trial
Official title:
In Situ Hypothermic Perfusion During Right Hemihepatectomy
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).
| Status | Completed |
| Enrollment | 22 |
| Est. completion date | August 2015 |
| Est. primary completion date | May 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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 |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Netherlands | Academic Medical Center (AMC) | Amsterdam | Noord-Holland |
| Lead Sponsor | Collaborator |
|---|---|
| Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) |
Netherlands,
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. — View 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. — View 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 — View 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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Postoperative hepatocellular damage | Hepatocellular damage expressed as an postoperative increase in transaminases (i.e., AST and ALT). | 5 days postoperatively | No |
| Secondary | Intraoperative blood loss | Blood loss during surgery | 2-3 hours | No |
| Secondary | Postoperative complications | Incidence of surgery-related complications | 5 days postoperatively | No |
| Secondary | Regeneration of liver function and volume | Regeneration of liver function (measured via hepatobiliary scintigraphy) and -volume (measured via CT volumetry). | 3 days | No |