Impact of Perioperative Immunonutrition on Postoperative Outcomes in Patients with Upper Gastrointestinal Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There is no consensus on the efficacy of perioperative immunonutrition in patients with upper gastrointestinal (GI) cancer surgery. We clarified the impact of perioperative immunonutrition on postoperative outcomes in patients with upper GI cancers. We searched MEDLINE (PubMed), MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trials, Web of Science Core Selection, and Emcare from 1981-2022 using search terms related to immunonutrition and upper GI cancer. We included randomized controlled trials. Intervention was defined as immunonutritional therapy, including arginine, n-3 omega fatty acids, or glutamine during the perioperative period. The control was defined as standard nutritional therapy. The primary outcomes were infectious complications, defined as events with a Clavien-Dindo classification grade ≥ II that occurred within 30 days after surgery. After screening, 23 studies were included in the qualitative synthesis and in the quantitative synthesis. The meta-analysis showed that immunonutrition reduced infectious complications (relative risk ratio: 0.72; 95% confidence interval: 0.57-0.92; certainty of evidence: Moderate) compared with standard nutritional therapy. In conclusion, nutritional intervention with perioperative immunonutrition in patients with upper GI cancers significantly reduced infectious complications. The effect of immunonutrition for upper GI cancers in reducing the risk of infectious complications was about 30%.

Effect of ω-3 polyunsaturated fatty acid-supplemented parenteral nutrition on inflammatory and immune function in postoperative patients with gastrointestinal malignancy: A meta-analysis of randomized control trials in China.

BACKGROUND: There are no consensus regarding the efficacy of omega-3polyunsaturated fatty acids (PUFAs) on inflammatory and immune function in postoperative patients with gastrointestinal malignancy. METHODS: The literatures published randomized control trials (RCT) were searched in PubMed, Embase, Scopus, Cochrane Library, CNKI, Weipu, and Wanfang Databases. The immune efficacy outcomes of ω-3 polyunsaturated fatty acid-supplemented parenteral nutrition in patients with gastrointestinal malignancy were compared. RESULTS: Sixteen RCTs involving 1008 patients (506 in the omega-3 group, 502 in the control group) were enrolled into the analysis. The results of meta-analysis: the cell immunity: The proportions of CD3, CD4, CD4/CD8 in the omega-3 group were significantly higher than those in the control group (CD3: WMD = 4.48; 95% CI, 3.34-5.62; P < .00001; I = 0%; CD4: WMD = 5.55; 95% CI, 4.75-6.34; P < .00001; I = 0%; CD4/CD8: WMD = .28; 95% CI, 0.13-0.44; P = .0004; I = 81%). In the humoral immunity: The levels of IgA, IgM and IgG in the omega-3 group were significantly higher than those in the control group (IgA: WMD = 0.31; 95% CI, 0.25-0.37; P < .00001; I = 0%; IgM: WMD = 0.12; 95% CI, 0.06-1.81; P < .00001; I = 0%; IgG: WMD = 1.19; 95% CI, 0.80-1.58; P < .00001; I = 0%). The count of lymphocyte in the omega-3 group was significantly higher than that in the control group (WMD = 0.22; 95% CI, 0.12-0.33; P < .0001; I = 40%). In the postoperative inflammatory cytokine: The levels of interleukin-6, tumor necrosis factor (TNF)-α and C-reactive protein in the omega-3 group were significantly lower than those in the control group (IL-6: WMD = -3.09; 95% CI, -3.91 to 2.27; P < .00001; I = 45%; TNF-α: WMD = -1.65; 95% CI, -2.05 to 1.25; P < .00001; I = 28%; CRP: WMD = -4.28; 95% CI, -5.26 to 3.30; P < .00001; I = 37%). The rate of postoperative infective complications in the omega-3 group was significantly lower than that in the control group (OR = 0.36; 95% CI, 0.20-0.66; P = .0008; I = 0%). CONCLUSION: This meta-kanalysis confirmed that early intervention with Omega -3 fatty acid emulsion in gastrointestinal cancer can not only improve the postoperative indicators of immune function, reduce inflammatory reaction, and improve the postoperative curative effect but also improve the immune suppression induced by conventional PN or tumor. Therefore, postoperative patients with gastrointestinal cancer should add omega-3 unsaturated fatty acids in their PN formula. Further high-quality RCTs are needed to verify its efficacy.

Effects of parenteral ω-3 fatty acid supplementation in postoperative gastrointestinal cancer on immune function and length of hospital stay: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Omega-3 fatty acids are widely used in nutritional support. However, whether parenteral supplementation with ω-3 fatty acids is effective for gastrointestinal cancer patients remains uncertain. This study assessed the effects of this form of parenteral nutrition on immune function and clinical outcomes in postoperative gastrointestinal cancer patients. METHODS AND STUDY DESIGN: We searched Medline, Embase, Scopus, and the reference lists of selected studies to identify randomized controlled trials that compared ω-3 fatty acids with a control, and that included immune indices, infectious complications, or length of hospital stay in the final outcomes. The odds ratio and weighted mean difference with 95% confidence intervals were calculated and the I2 statistic was used to assess heterogeneity. RESULTS: Seven trials with a total of 457 participants were included in the meta-analysis. Five pooled trials with 373 participants indicated that the incidence of infectious complications was significantly different between the intervention and control groups (odds ratio: 0.36; 95% confidence interval: 0.18, 0.74, p<0.05). Five trials involving 385 participants indicated that parenteral ω-3 fatty acid supplementation significantly shortened the length of hospital stay (weighted mean difference: -2.29, 95% confidence interval: -3.64, -0.93; p<0.05). Meta-analysis also indicated that ω-3 fatty acids increased the level of CD4+ and CD4+/CD8+ ratio. CONCLUSIONS: The results of this study suggest that parenteral ω-3 fatty acid supplementation is beneficial for gastrointestinal cancer patients, and is accompanied by improved postoperative immune function and satisfactory clinical outcomes.

Impact of allogenic and autologous transfusion on immune function in patients with tumors.

OBJECTIVE: To observe the effects of allogeneic and autologous transfusion on cellular immunity, humoral immunity and secretion of serum inflammatory factors and perforin during the perioperative period in patients with malignant tumors. METHODS: A total of 80 patients (age: 38-69 years; body weight: 40-78 kg; ASA I - II) receiving radical operation for gastro-intestinal cancer under general anesthesia were selected. All the patients were divided into four groups based on the methods of infusion and blood transfusion: blank control group (Group C), allogeneic transfusion group (group A), hemodiluted autotransfusion Group (Group H) and hemodiluted autotransfusion + allogenic transfusion Group (A+H group). Venous blood was collected when entering into the surgery room (T0), immediately after surgery (T1) and 24h (T2), 3d (T3) and 7d (T4) after surgery, respectively. Moreover, flow cytometry was applied to assess changes of peripheral blood T cell subpopulations and NK cells. Enzyme linked immunosorbent assays were performed to determine levels of IL-2, IL-10, TNF-α and perforin. Immune turbidimetry was employed to determine the changes in serum immunoglobulin. RESULTS: Both CD3+ and NK cells showed a decrease at T1 and T2 in each group, among which, in group A, CD3+ decreased significantly at T2 (P<0.05) compared with other groups, and CD3+ and NK cell reduced obviously only in group A at T3 and T4 (P<0.05). CD4+ cells and the ratio of D4+/CD8+ were decreased in groups A, C and A+H at T1 and T2 (P<0.05). No significant intra- and inter-group differences were observed in CD8+ of the four groups (P<0.05). IL-2 declined in group C at T1 and T2 (P<0.05) and showed a decrease in group A at each time point (P<0.05). Moreover, IL-2 decreased in group A + H only at T1. No significant difference was found in each group at T1 (P<0.05). More significant decrease in group C at T2, T3 and T4 compared with group A (P<0.05), and there were no significant differences among other groups (P>0.05). IL-10 increased at T1 and T2 in each group (P<0.05), in which it had an obvious increase in group A, and increase of IL-10 occurred only in group A at T3 and T4 (P<0.05). TNF-α level rose at T1 (P<0.05), no inter- and intra-group difference was found in perforin in all groups (P<0.05). Compared with the preoperation, both IgG and IgA level decreased at T1 in each group (P<0.05), and they declined only in Group A at T2 and T3 (P<0.05), and these parameters were back to the preoperative levels in other groups. No significant differences were observed between preoperative and postoperative IgG and IgA levels in each group at T4 (P>0.05). No obvious inter- and intra-group changes were found in IgM in the four groups (P>0.05). CONCLUSIONS: Allogeneic transfusion during the perioperative period could obviously decrease the number of T cell subpopulations and NK cells and the secretion of stimulating cytokines and increase the secretion of inhibiting cytokines in patients with malignant tumors, thus causing a Th1/Th2 imbalance and transient decreasing in the content of plasma immune globulin. Autologous transfusion has little impact and may even bring about some improvement of postoperative immune function in patients with tumors. Therefore, cancer patients should receive active autologous transfusion during the perioperative period in place of allogeneic transfusion.

Human leukocyte death after a preoperative infusion of medium/long-chain triglyceride and fish oil parenteral emulsions: a randomized study in gastrointestinal cancer patients.

BACKGROUND: Parenteral lipid emulsions (LEs) can influence leukocyte functions. The authors investigated the effect of 2 LEs on leukocyte death in surgical patients with gastrointestinal cancer. MATERIAL AND METHODS: Twenty-five patients from a randomized, double-blind clinical trial (ID: NCT01218841) were randomly included to evaluate leukocyte death after 3 days of preoperative infusion (0.2 g fat/kg/d) of an LE composed equally of medium/long-chain triglycerides and soybean oil (MCTs/LCTs) or pure fish oil (FO). Blood samples were collected before (t0) and after LE infusion (t1) and on the third postoperative day (t2). RESULTS: After LE infusion (t1 vs t0), MCTs/LCTs did not influence cell death; FO slightly increased the proportion of necrotic lymphocytes (5%). At the postoperative period (t2 vs t0), MCTs/LCTs tripled the proportion of apoptotic lymphocytes; FO maintained the slightly increased proportion of necrotic lymphocytes (7%) and reduced the percentage of apoptotic lymphocytes by 74%. In the postoperative period, MCT/LCT emulsion increased the proportion of apoptotic neutrophils, and FO emulsion did not change any parameter of apoptosis in the neutrophil population. There were no differences in lymphocyte or neutrophil death when MCT/LCT and FO treatments were compared during either preoperative or postoperative periods. MCT/LCTs altered the expression of 12 of 108 genes related to cell death, with both pro- and antiapoptotic effects; FO modulated the expression of 7 genes, demonstrating an antiapoptotic effect. CONCLUSION: In patients with gastrointestinal cancer, preoperative MCT/LCT infusion was associated with postoperative lymphocyte and neutrophil apoptosis. FO has a protective effect on postoperative lymphocyte apoptosis.

[The effect of protein metabolism and immunologic function of glutamine after operation in elder gastrointestinal tumor].

AIM: To explore the effect of protein metabolism and immunologic function of glutamine after operation in elder gastrointestinal tumor. METHODS: Form march 2007 to 2010, 87 cases of elder gastrointestinal tumor were given parenteral nutrition and glutamine 0.6 g/( Kg x d).The period of treatment were 8 days. IgA, IgG, IgM were CD4, measured by single immunodiffusion, CD3(+), CD4(+), CD8(+), CD4(+) /CD8(+) were measured by immunohistochemical method, and the index(Alb, PAB, TF, nitrogen equilibrium) were monitored the proteid catabolism distribution. RESULTS: After the treatment, CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), IgG, IgA, IgM were evidently declined( P <0.05). Alb, PAB, TF were evidently declined in 4 days postoperatively (P < 0.05), the restore were more obvious in 8 days postoperatively (P < 0. 05). Nitrogen equilibrium was worse in the early postoperative and the restore were more obvious in 8 days postoperatively (P < 0.05). CONCLUSION: Glutamine can improve patient's nutrition, enhance their immunologic function.

Efficacy and safety of orally administered Lentinula edodes mycelia extract for patients undergoing cancer chemotherapy: a pilot study.

Lentinula edodes mycelia extract (L.E.M.) is extensively utilized as an herbal medicine. However, its safety and effectiveness have not yet been scientifically verified. In this study, we investigated its safety and its influence on quality of life (QOL) and the immune response in patients undergoing cancer chemotherapy. Seven patients were studied in total. The patients were undergoing postoperative adjuvant chemotherapy for breast cancer (n = 3) or gastrointestinal cancer (n = 2), or were receiving chemotherapy to prevent recurrence of gastrointestinal cancer (n = 2). The first course of treatment was chemotherapy alone and the second was chemotherapy plus concomitant administration of L.E.M. Adverse events and changes in the QOL score, lymphocyte subpopulations, lymphocyte activity and serum immune indices were evaluated during the study period. No adverse events attributable to L.E.M. were observed. Compared to the pre-chemotherapy state, no changes in QOL or immune parameters were noted after the first chemotherapy course. In contrast, following the second course of combined therapy, improvements were noted in QOL (p < 0.05), NK cell activity (p < 0.05) and immunosuppressive acidic protein (IAP) (p < 0.01) levels. Although a future large-scale investigation is necessary to confirm these results, these data suggest that the concomitant of L.E.M. with chemotherapy is safe and improves the QOL and immune function of patients undergoing chemotherapy.

Randomized clinical trial of intravenous soybean oil alone versus soybean oil plus fish oil emulsion after gastrointestinal cancer surgery.

BACKGROUND: Specific immunonutrients may reduce the incidence of postoperative complications and shorten recovery time. This randomized trial evaluated the clinical efficacy of a fish oil emulsion on outcome and immune function after gastrointestinal cancer surgery. METHODS: A total of 206 patients with gastrointestinal or colonic cancer were randomized to receive isocaloric and isonitrogenous intravenous infusions of either soybean oil alone (1.2 g per kg bodyweight per day; control group, 103 analysed) or soybean plus fish oil emulsion (1.0 and 0.2 g per kg per day respectively; treatment group, 100 analysed) over 20-24 h daily for 7 days after surgery. RESULTS: Baseline data were comparable in the two groups. There were fewer infectious complications (four versus 12 on day 8; P = 0.066), systemic inflammatory response syndrome (SIRS) was significantly less common (four versus 13; P = 0.039) and hospital stay was significantly shorter (mean(s.d.) 15(5) versus 17(8) days; P = 0.041) in the treatment group. Total postoperative medical costs were comparable in the two groups (mean(s.d.) US $ 1269(254) and 1302(324) in treatment and control groups respectively; P = 0.424). The median (interquartile range) difference in CD4/CD8 between days 1 and 8 after surgery was + 0.30 (0.06 to 0.79) in patients receiving fish oil and + 0.20 (-0.19 to 0.55) in controls (P = 0.021). No severe adverse events occurred in either group. CONCLUSION: Fish oil emulsion-supplemented parenteral nutrition significantly reduced SIRS and length of hospital stay. These clinical benefits may be related to normalization of cellular immune functions and modulation of the inflammatory response.

Neuroimmunomodulation in medical oncology: application of psychoneuroimmunology with subcutaneous low-dose IL-2 and the pineal hormone melatonin in patients with untreatable metastatic solid tumors.

BACKGROUND: Anticancer immunity is under psychoneuroendocrine regulation, mainly via the pineal gland and brain opioid system, which may stimulate and inhibit antitumor immunity respectively. Cancer-related immuno-suppression does not depend only on functional damage of immune cells, but also on alterations of systems responsible for the neuroimmunomodulation, the most frequent of wich is a decline in blood levels of the pineal hormone melatonin (MLT). PATIENTS AND METHODS: A study was performed to evaluate the influence of an exogenous administration of MLT alone or MLT plus subcutaneous (SC) low-dose interleukin-2 on tumor progression and survival time in patients with untreatable metastatic solid tumors. The study included 846 patients with metastatic solid tumor (non-small cell lung cancer or gastrointestinal tract tumors) randomized to receive the best supportive care only, supportive care plus MLT (20 mg/day, orally in the evening), or MLT plus SC low-dose IL-2 (3 MIU/day for 5 days/week, for 4 consecutive weeks). RESULTS: The MLT alone was able to induce a significant increase of disease stabilization and survival time with respect to supportive care alone. The association of lL-2 with MLT provided a further improvement in the percentage of tumor regressions and of 3-year survival with respect to MLT alone. CONCLUSION: The administration of IL-2 and the pineal hormone MLT may induce control of neolplastic growth and a prolonged survival time in patients with metastatic solid tumors, for whom no other conventional anticancer therapy is available.

Application of perioperative immunonutrition for gastrointestinal surgery: a meta-analysis of randomized controlled trials.

The aim of this study was to evaluate clinical and economic validity of perioperative immunonutrition and effect on postoperative immunity in patients with gastrointestinal cancers. Immunonutrition diet supplemented two or more of nutrients including glutamine, arginine, omega-3 polyunsaturated fatty acids and ribonucleic acids. A meta-analysis of all relevant clinical randomized controlled trials (RCTs) was performed. The trials compared perioperative immunonutrition diet with standard diet. We extracted RCTs from electronic databases: Cochrane Library, MEDLINE, EMBASE, SCI and assessed methodological quality of them according handbook for Cochrane reviewer in June 2006. Statistical analysis was performed by RevMan4.2 software. Thirteen RCTs involving 1269 patients were included. The combined results showed that immunonutrition had no significant effect on postoperative mortality (OR =0.91, p= 0.84). But it had positive effect on postoperative infection rate (OR =0.41, p<0.00001), length of hospital stay (WMD=-3.48, p<0.00001). Furthermore, it improved immune function by increasing total lymphocytes (WMD=0.40, p<0.00001), CD4 levels (WMD=11.39, p<0.00001), IgG levels (WMD=1.07, p=0.0005) and decreasing IL6 levels (WMD=-201.83, p<0.00001). At the same time, we did not found significant difference in CD8, IL2 and CRP levels . There were no serious side effects and two trials found low hospital cost. In conclusion, perioperative diet adding immunonutrition is effective and safe to decrease postoperative infection and reduce length of hospital stay through improving immunity of postoperative patients as compared with the control group. Further prospective study is required in children or critical patients with gastrointestinal surgery.

Nutrition and infections.

BACKGROUND: Patients with cancer suffer alterations of their metabolic state and nutritional depletion. This review was designed to evaluate the effect of different nutritional regimens on surgical outcomes. METHOD: Review of the literature on parenteral and enteral nutrition and immunonutrition in patients with gastrointestinal cancer undergoing major surgery. The outcome measures were postoperative complication rate and length of hospital stay. RESULTS: Postoperative enteral nutrition reduced significantly the rate of postoperative complications compared with parenteral feeding only in malnourished subjects. Several metaanalyses and randomized trials showed that preoperative and perioperative use of an enteral formula containing arginine and omega-3 fatty acids has a significant beneficial effect on surgical outcome in both well-nourished and malnourished patients. CONCLUSIONS: Enteral immunonutrition should represent the first choice to nourish surgical subjects.

Dendritic cells: tools and targets for antitumor vaccination.

Dendritic cells are the most potent antigen-presenting cells of the immune system and represent a promising tool in therapeutic vaccination against cancer. Immunotherapy applying ex vivo-generated and tumor antigen-loaded dentritic cells has been successfully introduced in clinical vaccination protocols and has proven to be feasible and effective in some patients. A better understanding of how dentritic cells succeed to induce and modulate immunity is necessary to optimally exploit dentritic cells in anticancer vaccines. The authors will review novel insights in antigen loading, activation and migration of dentritic cells and their impact on the application of ex vivo-generated dentritic cell vaccines. In addition, novel means to exploit dentritic cells in cancer vaccines by loading and activation of dentritic cells directly in situ and possible obstacles that should be overcome to induce long-lasting immunity in therapeutic settings will be discussed.

[Effects of early intestinal application of sijunzi decoction on immune function in post-operational patients of gastrointestinal tumor].

OBJECTIVE: To assess the effects of early intestinal application of sijunzi decoction (SJZD) on the immune function in post-operational patients of gastrointestinal tumor. METHODS: Ninety-two patients with malignant gastrointestinal tumor were randomly divided into two groups. Patients in both groups were given the isocaloric and isonitrogenous enteral nutritional support starting from the first day after operation for 1 week, but to the tested group, SJZD was given additionally. The concentration of serum cytokines such as interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), the peripheral blood cell counts of total lymphocyte, T-lymphocyte, B lymphocyte, and T lymphocyte subsets (CD3, CD4, CD8, CD4/CD8) as well as the levels of IgA, IgG, IGM and C-reactive protein (CRP) were measured on the day before operation, the first morning after operation and at the end of study. RESULTS: At the end of the study, the concentration of IgA, IgG, 1gM, number of total lymphocyte, CD3, CD4 and CD4 lCD8, and serum IL-2 were obviously higher (P < 0.05), and levels of IL-6, TNF-alpha and CRP were obviously lower in the tested group than those in the control group (P < 0.05). CONCLUSION: Early application of SJZD on the base of enteral nutritional therapy can lessen the degree of post-operational stress and inflammatory response, and enhance the immune function of patients.

Perioperative immunonutrition ameliorates the postoperative immune depression in patients with gastrointestinal system cancer (prospective clinical study in 42 patients).

Cancer surgery is a major challenge for patients to develop immune depression in postoperative period. Several cytokines can depress immune cell subpopulations. Increased cytokine response after surgery is assumed to arise mainly from lipooxygenase pathway acting on membrane arachidonic acid. Therefore; investigators focused their efforts to alter the membrane fatty acid profile by changing the nutritional regimen with epsilon-3 fatty acid supplementation and encouraging results were obtained after surgery. Despite the theoretical and clinical advantage of enteral nutrition many surgeons remain committed to parenteral nutrition for feeding of patients due to maintain bowel rest and fear of anastomosis leakage at the postoperative period. Several studies investigating role of the postoperative immunonutrition reported that beneficial immunological changes were associated with reduction of infectious complications. Interestingly; these findings were observed at least five days after the surgery in which the highest incidence of complications was seen. In this prospective study including 42 patients eligible for curative gastric or colon cancer surgery; we investigated the beneficial effect of enteral immunonutrition (EEN) compared to total parenteral hyperalimentation (TPN) beginning from the preoperative period. Cortisol and CRP levels as stress parameters significantly increased one day after surgery in both groups but they rapidly returned to (on POD1) preoperative baseline level in EEN group whereas these values remained high in the TPN group. Additionally a significant decrease in natural killer (NK) cells and CD8+ levels were observed in both groups. However they recovered on POD3 in EEN group and on POD6 in TPN group. CD4+ subset remained almost same as preoperative value in the TPN group whereas it increased from (%) 40.14 to 46.40, 51.29 and 54.7 on PO 6th hr, POD3 and POD6 in the EEN group. Our findings suggest that preoperative nutrition via the enteral route provided better regulation of postoperative immune system restoration than parenteral nutrition. On the basis of our findings we recommend enteral immunonutrition to be started at the preoperative period rather than postoperatively before a major operation whenever the enteral route is feasible.

Effects of electro-acupuncture on immune function after chemotherapy in 28 cases.

PURPOSE: To observe the effects of electroacupuncture therapy on T cells and activity of NK cell in the patient of Chemotherapy. METHOD: Electro-acupuncture therapy was simultaneously applied during chemotherapy, T cells and activity of NK cell of patients were determined before electroacupuncture treatment (before chemotherapy) and after 4-course electro-acupuncture treatments. RESULTS: Before chemotherapy, CD3 was low within the normal range, CD4 was much lower than the normal range, and CD8, CD4/CD8 and activity of NK cell were within the normal range. After one month of chemotherapy combined with electro-acupuncture, no decline of all the indices was found (P > 0.05). CONCLUSION: Electro-acupuncture can really increase the immune function of patients of chemotherapy.

Modulation of postoperative immune and inflammatory response by immune-enhancing enteral diet in gastrointestinal cancer patients.

AIM: To evaluate if the administration of an enteral diet supplemented with glutamine, arginine and omega-3-fatty acids modulates inflammatory and immune responses after surgery. METHODS: A prospective randomized double-blind, clinical trial was performed. Forty-eight patients with gastrointestinal cancer were randomized into two groups, one group was given an isocaloric and isonitrogenous standard diet and the other was fed with the supplemented diet with glutamine, arginine and omega-3-fatty acids. Feedings were started within 48 hours after operation, and continued until day 8. All variables were measured before operation and on postoperative day 1 and 8. Immune responses were determined by phagocytosis ability, respiratory burst of polymorphonuclear cells, total lymphocytes lymphocyte subsets, nitric oxide, cytokines concentration, and inflammatory responses by plasma levels of C-reactive protein, prostaglandin E2 level. RESULTS: Tolerance of both formula diets was excellent. There were significant differences in the immunological and inflammatory responses between the two groups. In supplemented group, phagocytosis and respiratory burst after surgery was higher and C-reactive protein level was lower (P<0.01) than in the standard group. The supplemented group had higher levels of nitric oxide, total lymphocytes, T lymphocytes, T-helper cells, and NK cells. Postoperative levels of IL-6 and TNF-alpha were lower in the supplemented group (P <0.05). CONCLUSION: It was clearly established in this trial that early postoperative enteral feeding is safe in patients who have undergone major operations for gastrointestinal cancer. Supplementation of enteral nutrition with glutamine, arginine, and omega-3-fatty acids positively modulated postsurgical immunosuppressive and inflammatory responses.

A prospective, randomized clinical trial on perioperative feeding with an arginine-, omega-3 fatty acid-, and RNA-enriched enteral diet: effect on host response and nutritional status.

BACKGROUND: The use of immune-enhancing enteral diets in the postoperative period has given contrasting results. The purpose of this prospective, randomized, double-blinded clinical study was to evaluate the effect of immunonutrition given perioperatively on cytokine release and nutritional parameters. METHODS: Patients with cancer of the stomach or colo-rectum were eligible. Subjects consumed 1 L/d of either a control enteral formula (n = 25; control group) or a formula supplemented with arginine, omega-3 fatty acids, and RNA (n = 25; verum group) for 1 week before surgery. Both formulas were given by mouth. Six hours after the operation, jejunal infusion with the same diets was started and maintained for 7 days. Blood was drawn at different time points to assess albumin, prealbumin (PA), transferrin, cholinesterase activity, retinol binding protein (RBP), interleukin-2 receptors alpha (IL-2Ralpha), IL-6, and IL-1 soluble receptors (IL-1RII). The composite score of delayed hypersensitivity response (DHR) to skin test also was determined (the higher the score, the lower the immune response). RESULTS: During the 7 days of presurgical feeding, none of the above parameters changed in either group. Eight days after operation, in the control group, the concentration of PA and RBP was lower than in the verum group (0.18 vs 0.26 g/L for PA and 30.5 vs 38.7 mg/L for RBP; p < .05). IL-2Ralpha concentration was 507 pg/mL in the verum group vs 238 pg/mL in the control group (p < .001), whereas IL-6 and IL-1RII were higher in the control group than in the verum group (104 vs 49 and 328 vs 183 pg/mL, respectively; p < .01). The DHR score was 0.68 in the control group vs 0.42 in the verum group (p < .05). CONCLUSIONS: Perioperative feeding with a supplemented enteral diet modulates cytokine production and enhances cell-mediated immunity and the synthesis of short half-life proteins.