To obtain a homogenous population, we selected patients with colorectal cancer staging TNM I-III to undergo radical resection. Patients were enrolled consecutively and randomly assigned to receive TPN supplemented with either SO or SO + FO emulsion. There were no statistically significant differences between the two groups at entry.
It was reported that reduction in platelet aggregation can be modified by increasing omega-3 long-chain fatty acid content of platelet phospholipids in humans[18
]. In a randomized, controlled double-blind study, Heller AR and colleagues[19,20
] demonstrated that no coagulation and platelet abnormalities are evoked by fish oil supplementation as high as 0.2 g/kg per day for five postoperative days. In the present study, the change in platelet counts showed no statistical difference between the two groups. Neither bleeding complication nor other adverse events were observed. This is in line with the notion that a short-term parenteral administration of omega-3 fish oil is safe[9,21
]. In addition, our results demonstrate that the serum level of γ-GT on POD+8 in the FO group was lower than that in the SO group. Heller AR et al[20
] found that after a major abdominal tumor surgery, fish oil supplementation could improve liver and pancreas function. Animal experiments have demonstrated improved perfusion and fewer translocations of viable bacteria from the gut into the mesenteric lymph nodes and liver after omega-3 fatty acid infusion in rats[22,23
]. Therefore, our results suggest that parenteral nutrition supplemented with omega-3 fish oil might protect liver function after a major abdominal operation in colorectal cancer patients.
Omega-3 and -6 PUFAs are essential for humans and must be nutritionally provided. Recently, omega-3 PUFA deficiency has been recognized and appreciated[2
]. After intravenous administration, EPA and docosahexaenoic acid (DHA) promptly incorporate into the cell membrane, compete with arachidonic acid (AA) in the cyclooxygenase and 5-lipoxygenase pathways, resulting in a reduced generation of diene prostanoids (e.g. PGE2
) and tetraene leukotrienes (e.g. LTB4
), derived from AA in favor of the corresponding triene prostanoids (e.g. PGE3
) and pentaene leukotriene (LTB5
) derived from EPA[13,24
]. In a randomized controlled trial, Köller et al[17
] demonstrated that release of 5-series leukotrienes from isolated leukocytes stimulated with Ca-ionophore is increased in patients receiving fish oil. Leukotrienes have numerous effects on inflammatory and immune functions, such as leucocyte-endothelial interaction, lymphocyte proliferation, and induction of cytokine gene expression (e.g. IL-1, IL-6, or TNF-α)[25,26
]. In a randomized controlled study, Wachtler et al[25
] showed that the systemic levels of IL-10, IL-6 and TNF-α are significantly decreased in surgical patients 5 d after administration of TPN enriched with omega-3 fatty acids. In another clinical trial, Weiss et al[27
] also found that IL-6 levels are significantly decreased and TNF-α release from monocytes is also decreased in patients receiving fish oil perioperatively. In addition, HLA-DR expression induced by monocytes, an indicator of compensatory potential required to balance immune response, is significantly decreased[28,29
]. Mayer et al[13
] displayed that neutrophil function is significantly improved in patients receiving omega-3 fatty acids, including leukotriene generation and respiratory burst. In our study, serum IL-6 levels were significantly lower in the FO group than t in the reference group. This is in agreement with the previous reports[25,27,30
]. Simultaneously, the ratios of CD4+
were significantly increased in the FO group. In addition, depression of serum TNF-α levels and elevation of CD3+
lymphocyte percentage were noted in the FO group. In an experimental animal model, administration of parental fish oil during sepsis could prevent sepsis-induced suppression of lymphocyte proliferation and IL-2 release[31
]. These findings suggest that supplementation of omega-3 PUFA may restrain inflammatory response, modulate lymphocyte proliferation, and maintain the function of immunocompetent cells under inflammatory conditions such as surgical trauma.
The lower magnitude of postoperative inflammatory response to administration of omega-3 fatty acids may have a favorable impact on clinical outcomes of patients with CRC. A shorter postoperative hospital stay was noted in our study. No statistically significant difference was found when stratified to death and occurrence of infectious complications. In a cohort of elective postoperative patients, mortality is such a rare event that changes in mortality is underpowered to be detected. Various factors may influence the outcomes of surgical patients. A short single nutritional intervention is unlikely to produce extensive effects on the outcomes of postoperative patients. Recently, in a randomized controlled trial, Weiss et al[27
] have demonstrated a shorter postoperative ICU and hospital stay, and a lower rate of severe infections in patients administrating omega-3 fish oil perioperatively beginning on POD-1. These results suggest that supplementation with with omega-3 fatty acids may have a more favorable effect on the outcomes of CRC patients after a major surgery.
In conclusion, postoperative supplementation of omega-3 fatty acids may have a favorable effect on the outcome of colorectal cancer patients by lowering the magnitude of inflammatory responses and modulating the immune response. Perioperative administration of omega-3 fish oil may have a more favorable effect on the outcome of CRC patients after a major surgery. Further prospective, randomized controlled trials are required to delineate this effect in a larger number of patients.