Okamoto and colleagues also reported a much lower complication rate in gastric cancer patients who received immunonutrition (13.3%) compared with that of those receiving an isoenergetic formula (40%).11 The group receiving immunonutrition in the Okamoto and colleagues study had 4 times fewer infectious complications than did the standard group (P = .039), and a contributing reason might be that they supplemented for 7 days preoperatively. Similar to the current study’s results, Giger-Pabst and colleagues and Hübner and colleagues did not find any significant difference in infectious complications.10,30 Important notes of comparison include a low adherence rate in the study conducted by Hübner and colleagues and the lower dose of immunonutrition used by Giger-Pabst andcolleagues who used 3 days of preoperative supplementation, which may not be long enough to promote the tissue benefits of immunonutrition.
Although, the current study did not find any statistically significant difference in infectious complications, the SNG experienced 1.8 times more infections than did the ING, which indicates that immunonutrition support may be clinically beneficial. Based on previous literature and the results of this study, the authors speculate that at least 5 days of intake of the study immunonutrition formula could positively affect outcomes.
The authors suspect that the added arginine and fish oil in the immunonutrition product act synergistically as therapeutic ingredients to shift toward a preoperative anti-inflammatory prostaglandin environment while providing exogenous arginine to possibly prevent or correct a conditionally essential need for arginine that would promote adequate nitric oxide production. Another crucial factor is that the a priori power analysis was looking at a 38% complication rate in the SNG and only 15% complication rate in the ING, which generated a sample size of 108 participants. The post hoc power analysis indicates that this study is underpowered based on the complication rates, which could be a reason for insignificant infectious complications.
The benefits of immunonutrients are still being studied. Future studies in a controlled surgical setting could determine whether immunonutrition has a clinical outcome effect on operative time and surgical blood loss. A challenge for the investigators was to decide whether the difference in operative time and blood loss was a surgical characteristic or a clinical outcome. The positive impact of immunonutrients on tissue perfusion and cell integrity have been shown in other studies to reduce tissue inflammation and alter gene expression, which could affect how tissues respond to surgical insults.10,11 Because JAHVH is a teaching institution and multiple surgeons are involved with the patients, this question will continue to be unresolved. Future research may want to consider controlling for variability in surgical technique and perioperative protocols to evaluate this as a clinical outcome.
Limitations
Several limitations of this trial need to be addressed. Although the design of the study was a randomized controlled trial, it was an unblinded, single-center study with a small sample size. Surgeons were not aware of which supplement each subject had received; however, researchers took no measures to ensure the surgeons were blinded. To minimize bias, 2 investigators evaluated the records for complication rates to confirm consistency, and any discrepancies were resolved by a third investigator. Although adherence was evaluated, it was patient-reported, and lab testing was not conducted to ensure that tissues were loaded with therapeutic amounts of immunonutrients or to determine baseline levels of nutrient intake, which could show a nutrient response curve.
The use of other nutritional supplements, such as vitamins, probiotics, or additional fatty acids were not monitored, and the study formulas differed in protein and fiber content, which could have impacted the overall nutrient intake and affected the primary outcomes. Another limitation includes the variety of surgeons used over the period of the study. At a teaching institution, it is not feasible to limit the number of surgeons performing surgery.
Additionally, the study period was 5 years, and there have been changes in fasting times, medications, and bowel preparation over the course of that period, which could not be accounted for. Postoperative immunonutrition was not provided in this study based on the limited evidence available when the protocol was initiated. However, since that time, evidence supports and encourages postoperative therapy and might have proven beneficial to the patients. Data were not collected on the need for additional surgery within the study period, which could significantly impact outcomes.
Future studies would benefit from a longer postoperative monitoring period because this study looked only at the 30-day postoperative period. Last, randomization did not account for equal allocation of surgical procedures, and a higher number of pancreatic surgeries in the SNG could account for the higher complication rate found in that group. Although the colorectal analysis is underpowered, the results continue to show beneficial results with the use of immunonutrition.
