This is a randomized controlled blinded superiority trial to evaluate the impact of perioperative immunosupplementation on immune function following resection for hepatopancreaticobiliary (HPB) malignancy.
This is a 1:1:1 randomized controlled blinded superiority trial to evaluate the impact of perioperative immunosupplementation on immune function following resection for hepatopancreaticobiliary (HPB) malignancy. Two variations of immunosupplementation will be compared to control nutritional supplement containing whey protein with an additional teaspoon (tsp) of placebo oil. These variations will be 1) a powdered formula containing whey protein and arginine (Active A) with an additional tsp of lipid bolus containing omega-3 fatty acids, and 2) a powdered formula containing whey protein and arginine (Active A) with an additional tsp of placebo oil which does not contain omega-3 fatty acids. The control nutritional supplement will be a powdered formula containing whey protein with an additional tsp of placebo oil.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
45
Powdered formula containing whey protein and arginine
Powdered formula containing whey protein
Omega-3 fatty acids
The Ottawa Hospital - General Campus
Ottawa, Ontario, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Natural killer (NK) cell killing
Reduction in NK cell killing as measured on post-operative day one (POD1) as compared to baseline (pre-operative) between the control and experimental cohorts. Nutritional supplementation will be considered effective at reducing postoperative NK cell dysfunction if there is a 50% or greater improvement in postoperative suppression of NK cell cytotoxicity (reduction of 27% from baseline).
Time frame: Post-operative day 1 (Day 1) as compared to baseline (pre-operative)
Secondary immune function outcomes: Immune cell subsets
Flow cytometric analysis of different immune cell subsets to compare their proportions at all time points.
Time frame: Day of surgery to 30-days after surgery
Secondary immune function outcomes: NK cell activating and inhibitory receptors
Flow cytometric characterization of NK cell activating and inhibitory receptors to assess whether they are affected by immunosupplementation.
Time frame: Day of surgery to 30-days after surgery
Secondary immune function outcomes: amino acid levels
Systemic blood levels of amino acids will be measured via liquid chromatography-mass spectrometry protein card analysis.
Time frame: Day of surgery to 30-days after surgery
Incidence of pancreatic fistula
Pancreatic fistula of International Study Group on Pancreatic Fistula (ISGPF) Grade B \& C (i.e. clinically significant) will be diagnosed clinically.
Time frame: Day of surgery to 90-days after surgery
Postoperative wound complication and surgical site infection
Wound complications including dehiscence and infection will be diagnosed clinically.
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Control placebo oil that does not contain omega-3 fatty acids
Time frame: Day of surgery to 90-days after surgery
Length of stay
Length of stay will be measured as number of days from admission to discharge.
Time frame: Day of surgery to day of discharge after surgery, assessed until day of discharge after surgery occurs
90-day postoperative complications (Clavien-Dindo 3-5)
Postoperative complications with Clavien-Dindo Grades 3-5 (i.e. requiring procedural intervention or ICU admission, or causing death) will be recorded.
Time frame: Day of surgery to 90-days after surgery
90-day postoperative mortality
The incidence of readmission within 90 days of surgery will be recorded as the number of days associated with each re-admission. Death within 90 days of surgery will be considered complications of the surgery.
Time frame: Day of surgery to 90-days after surgery
Incidence of liver insufficiency
Posthepatectomy liver failure of International Study Group of Liver Surgery (ISGLS) Grade B \& C (i.e. clinically significant) will be diagnosed clinically
Time frame: Day of surgery to 90-days after surgery