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      Effect of immunonutrition on colorectal cancer patients undergoing surgery: a meta-analysis

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          Immunonutrition has been used to prevent the complications after colorectal elective surgery. This systematic review aimed to analyze and assess the effect of immunonutrition on colorectal cancer patients who received elective surgery.


          Three electronic databases (Medline, Embase, Cochrane) were used to search the latent studies which investigated the effects of enteral immunonutrition (EIN) compared with standard enteral nutrition (EN) or parenteral immunonutrition (PIN) compared with standard parenteral nutrition (PN) on colorectal cancer patients who are undergoing surgery until 21st of April, 2017. Meta-analysis was conducted to calculate odd risk (OR), mean difference (MD), or standard mean difference (SMD) with 95% confidence interval (CI), and heterogeneity was tested by Q test.


          Nine publications were included. The meta-analysis results presented that EIN improved the length of hospital stay (pooled MD, 2.53; 95% CI, 1.29–3.41), infectious complications (pooled OR, 0.33; 95% CI, 0.21–0.53) which contains the Surgical Site Infections (pooled OR, 0.25; 95% CI, 0.22–0.58) and Superficial/Deep incisional infections (pooled OR, 0.27; 95% CI, 0.12–0.64); meanwhile, PIN improved the length of hospital stay (pooled MD, 2.66; 95% CI, 0.62–4.76), IL-6 (pooled MD, − 6.09; 95% CI, − 10.11 to − 2.07), CD3 (pooled MD, 7.50; 95% CI, 3.57–11.43), CD4 (pooled MD, 5.47; 95% CI, 2.54–8.40), and CD4/CD8 (pooled MD, 0.50; 95% CI, 0.22–0.78); the level of CD8 was lower (pooled MD, − 4.32; 95% CI, − 7.09 to − 1.55) in PIN.


          Immunonutrition could be an effective approach to enhance the immune function of colorectal cancer patients undergoing elective surgery and to improve the clinical and laboratory outcomes.

          Electronic supplementary material

          The online version of this article (10.1007/s00384-017-2958-6) contains supplementary material, which is available to authorized users.

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          Most cited references 39

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          Preoperative oral arginine and n-3 fatty acid supplementation improves the immunometabolic host response and outcome after colorectal resection for cancer.

          Previous trials showed that perioperative immunonutrition improved outcome in patients with gastrointestinal cancer. This study was designed to appraise the impact of the simple preoperative oral arginine and n-3 fatty acids supplementation on immune response, gut oxygenation, and postoperative infections. Two hundred patients with colorectal neoplasm were randomized to: (a) oral intake for 5 days before surgery of a formula enriched with arginine and n-3 fatty acids (pre-op group; n = 50); (b) same preoperative treatment prolonged after surgery by jejunal infusion (peri-op group; n = 50); (c) oral intake for 5 days before surgery of a standard isoenergetic, isonitrogenous formula (control group; n = 50); and (d) no supplementation before and after operation (conventional group; n = 50). The immune response was measured by phagocytosis ability of polymorphonuclear cells and delayed hypersensitivity response to skin tests. Gut oxygenation and microperfusion were assessed by polarographic probes and laser Doppler flowmetry, respectively. The 4 groups were comparable for demographics, comorbidity, and surgical variables. The 2 groups receiving immunoutrients (pre-op and peri-op) had a significantly better immune response, gut oxygenation, and microperfusion than the other 2 groups. Intent-to-treat analysis showed an overall infection rate of 12% in pre-op, 10% in peri-op, 32% in control, and 30% in conventional groups (P <.04 pre-op and peri-op vs control and conventional). Preoperative oral arginine and n-fatty acids improves the immunometabolic response and decreases the infection rate. Postoperative prolongation with such supplemented formula has no additional benefit.
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            Prevention of chemotherapy and radiation toxicity with glutamine.

            Malignancy produces a state of physiologic stress that is characterized by a relative deficiency of glutamine, a condition that is further exacerbated by the effects of cancer treatment. Glutamine deficiency may impact on normal tissue tolerance to antitumor treatment, and may lead to dose reductions and compromised treatment outcome. Providing supplemental glutamine during cancer treatment has the potential to abrogate treatment-related toxicity. We reviewed the available data on the use of glutamine to decrease the incidence and severity of adverse effects due to chemotherapy and/or radiation in cancer patients. We performed a search of the MEDLINE database during the time period 1980-2003, and reviewed the English language literature of both human and animal studies pertaining to the use of glutamine in subjects with cancer. We also manually searched the bibliographies of published articles for relevant references. The available evidence suggests that glutamine supplementation may decrease the incidence and/or severity of chemotherapy-associated mucositis, irinotecan-associated diarrhea, paclitaxel-induced neuropathy, hepatic veno-occlusive disease in the setting of high dose chemotherapy and stem cell transplantation, and the cardiotoxicity that accompanies anthracycline use. Oral glutamine supplementation may enhance the therapeutic index by protecting normal tissues from, and sensitizing tumor cells to chemotherapy and radiation-related injury. The role of glutamine in the prevention of chemotherapy and radiation-induced toxicity is evolving. Glutamine supplementation is inexpensive and it may reduce the incidence of gastrointestinal, neurologic, and possibly cardiac complications of cancer therapy. Further studies, particularly placebo-controlled phase III trials, are needed to define its role in chemotherapy-induced toxicity.
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              Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial.

              To determine if early enteral feeding, in an intensive care unit (ICU) patient population, using a formula supplemented with arginine, dietary nucleotides, and fish oil (Impact), results in a shorter hospital stay and a reduced frequency of infectious complications, when compared with feeding a common use enteral formula (Osmolite.HN). A prospective, randomized, double-blind, multicenter trial. ICUs in eight different hospitals. Of 326 patients enrolled in the study, 296 patients were eligible for analysis. They were admitted to the ICU after an event such as trauma, surgery, or sepsis, and met a risk assessment screen (Acute Physiology and Chronic Health Evaluation II [APACHE II] score of > or = 10, or a Therapeutic Intervention Scoring System score of > or = 20) and study eligibility requirements. Patients were stratified by age ( or = 60 yrs of age) and disease (septic or systemic inflammatory response syndrome). Patients were enrolled and full-strength tube feedings were initiated within 48 hrs of the study entry event. Enteral feedings were advanced to a target volume of 60 mL/hr by 96 hrs of the event. One hundred sixty-eight patients were randomized to receive the experimental formula, and 158 patients were randomized to receive the common use control formula. Both groups tolerated early enteral feeding well, and the frequency of tube feeding-related complications was low. There were no significant differences in nitrogen balance between groups on study days 4 and 7. Patients receiving the experimental formula had a significant (p = .0001) increase in plasma arginine and ornithine concentrations by study day 7. Plasma fatty acid profiles demonstrated higher concentrations of linoleic acid (p < .01) in the patients receiving the common use formula and higher concentrations of eicosapentaenoic and docosahexaenoic acid (p < .01) in the patients receiving the experimental formula. The mortality rate was not different between the groups and was significantly (p < .001) lower than predicted by the admission severity scores in both feeding groups. In patients who received at least 821 mL/day of the experimental formula, the hospital median length of stay was reduced by 8 days (p < .05). In patients stratified as septic, the median length of hospital stay was reduced by 10 days (p < .05), along with a major reduction in the frequency of acquired infections (p < .01) in the patients who received the experimental formula. In the septic subgroup fed at least 821 mL/day, the median length of stay was reduced by 11.5 days, along with a major reduction in acquired infections (both p < .05) in the patients who received the experimental formula. Early enteral feeding of the experimental formula was safe and well tolerated in ICU patients. In patients who received the experimental formula, particularly if they were septic on admission to the study, a substantial reduction in hospital length of stay was observed, along with a significant reduction in the frequency of acquired infections.

                Author and article information

                +86-25-85811925 , zhangjunfeng5_5@163.com
                +86-25-85811925 , wujuan1213@hotmail.com
                Int J Colorectal Dis
                Int J Colorectal Dis
                International Journal of Colorectal Disease
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                15 January 2018
                15 January 2018
                : 33
                : 3
                : 273-283
                ISNI 0000 0004 1765 1045, GRID grid.410745.3, School of Medicine and Life Sciences, , Nanjing University of Chinese Medicine, ; Box 21, 138 Xianlin Road, Nanjing, 210023 China
                © The Author(s) 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                Funded by: National Natural Science Foundation
                Award ID: 81473458
                Award ID: 81473593
                Award Recipient :
                Funded by: Jiangsu Qing Lan Project
                Award ID: JSQL-2014
                Award Recipient :
                Original Article
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                © Springer-Verlag GmbH Germany, part of Springer Nature 2018

                Gastroenterology & Hepatology

                immunonutrition, colorectal cancer, meta-analysis, surgery


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