Liver Dysfunction, Liver Metastasis Colon Cancer, Liver Regeneration
Conditions
Keywords
Hyperinsulinemic-Normoglycemic Clamp, High Dose Insulin Therapy, 99mTc-Mebrofenin Hepatobiliary Scintigraphy, Colorectal Cancer Liver Metastasis, Liver Resection
Brief summary
The primary objective of this interventional study is determine if the future liver remnant can be optimized by improving liver function pre-operatively in patients who are scheduled for major hepatectomy. The main questions it aims to answer are: 1. Does high-dose insulin therapy improve liver function in the pre-operative setting? 2. What is the effect of high-dose insulin therapy on liver function and liver regeneration after a liver venous deprivation (LVD) procedure? 3. What is the relationship between volume hypertrophy and function in the regenerating liver? Participants will receive a 6-hour infusion of insulin and dextrose to maintain a hyperinsulinemic-normoglycemic state in the weeks prior to planned liver surgery to assess its effect on liver function measured by 99m-Tc-Mebrofenin hepatobiliary scintigraphy.
Interventions
DRUGHigh-Dose Insulin Therapy
A baseline blood glucose value will be obtained. Two units of insulin will be administered IV if the blood glucose is \> mmol/L. An insulin infusion of 0.12 units/kg/hr will be started. Ten minutes after starting the insulin, and when the blood glucose is \< 6 mmol/L, dextrose 20% supplemented with phosphate (30 mmol/L) will be infused. Blood glucose levels will be measured every 15 minutes, and the dextrose infusion rate adjusted to maintain glycemic levels between 4 and 6 mmol/L for a duration of 6 hours. At the end of the 6 hour period, the insulin will be stopped and the dextrose will be weaned off.
Sponsors
McGill University Health Centre/Research Institute of the McGill University Health Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Group 1 will consist of participants scheduled for liver resection and will undergo high-dose insulin therapy preoperatively to determine if baseline liver function can be optimized/improved, as measured by 99mTc-Mebrofenin HBS. Cytokine profiling will also be collected and analyzed pre- and post-insulin infusion. Group 2 will consist of participants scheduled for liver resection that require LVD. They will then be randomized to two different arms -- control vs high-dose insulin therapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years old * Candidate for major liver resection * Resectable colorectal liver metastasis
Exclusion criteria
* Inability to give consent * Type 1 diabetes mellitus * Uncontrolled blood glucose levels (fasting level \> 10 mmol/L) * Unresectable colorectal liver metastasis * Extrahepatic metastatic disease that is unresectable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Liver function improvement after high-dose insulin therapy measured with 99mTc-Mebrofenin Hepatobiliary Scintigraphy (HBS). | Baseline to 24-hours post treatment | 99mTc-Mebrofenin HBS is a diagnostic nuclear medicine imaging procedure used to evaluate liver function by measuring radiotracer uptake and excretion. The outcome will be evaluating a measurable increase in 99mTc-Mebrofenin (measured %/min/meter\^2) from baseline scan to post-treatment scan. |
| Liver function improvement after high-dose insulin therapy after LVD measured with 99mTc-Mebrofenin Hepatobiliary Scintigraphy (HBS). | Baseline to 7 days post treatment | 99mTc-Mebrofenin HBS is a diagnostic nuclear medicine imaging procedure used to evaluate liver function by measuring radiotracer uptake and excretion. The outcome will be evaluating a measurable increase in 99mTc-Mebrofenin (measured %/min/meter\^2) from baseline scan to post-treatment scan. |
| Liver regeneration improvement after high-dose insulin therapy after LVD measured CT volumetry | Baseline to 7 days post treatment | The volume of the liver can be measured from liver protocoled CT scans |
Countries
Canada
Contacts
Primary ContactJennifer Kalil, MD
Outcome results
None listed