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1.
Enteral immunonutrition versus enteral nutrition for patients undergoing oesophagectomy: a systematic review and meta-analysis.
Li, XK, Zhou, H, Xu, Y, Cong, ZZ, Wu, WJ, Luo, J, Jiang, ZS, Shen, Y
Interactive cardiovascular and thoracic surgery. 2020;(6):854-862
Abstract
OBJECTIVES According to retrospective studies, oesophageal carcinoma is the second deadliest gastrointestinal cancer after gastric cancer. Enteral immunonutrition (EIN) has been increasingly used to enhance host immunity and relieve the inflammatory response of patients undergoing oesophagectomy; however, conclusions across studies remain unclear. We aimed to evaluate the effect of EIN on the clinical and immunological outcomes of patients undergoing oesophagectomy. METHODS Four electronic databases (MEDLINE, Embase, Web of Science and Cochrane Library) were used to search articles in peer-reviewed, English-language journals. The mean difference, relative risk or standard mean difference with 95% confidence interval were calculated. Heterogeneity was assessed by the Cochran's Q test and I2 statistic combined with the corresponding P-value. The analysis was carried out with RevMan 5.3. RESULTS Six articles were finally included, with a total of 320 patients with oesophageal cancer. The meta-analysis results showed that EIN did not improve clinical outcomes (such as infectious complications, pneumonia, surgical site infection, anastomotic leak and postoperative hospital stay) or immune indices [referring to C-reactive protein, interleukin (IL)-6, IL-8, tumour necrosis factor-α]. Descriptive analysis suggested that EIN also increased the serum concentrations of IgG and the percentage of the B-cell fraction. Thus, its impact on IL-8 and IL-6 remains inconsistent. CONCLUSIONS The early-stage impact of EIN on immunological status in patients undergoing oesophagectomy is still unclear. According to the results of this meta-analysis, whether EIN could improve the clinical outcomes or biological status after oesophagectomy compared to standard enteral nutrition is uncertain. Since the impact of EIN is unclear, current guidelines that strongly advise the use of EIN should be changed, as the utility of EIN is very uncertain. More appropriately powered clinical studies are warranted to confirm its effectiveness.
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2.
Nutrition therapy in esophageal cancer-Consensus statement of the Gastroenterological Society of Taiwan.
Chen, MJ, Wu, IC, Chen, YJ, Wang, TE, Chang, YF, Yang, CL, Huang, WC, Chang, WK, Sheu, BS, Wu, MS, et al
Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus. 2018;(8)
Abstract
A number of clinical guidelines on nutrition therapy in cancer patients have been published by national and international societies; however, most of the reviewed data focused on gastrointestinal cancer or non-cancerous abdominal surgery. To collate the corresponding data for esophageal cancer (EC), a consensus panel was convened to aid specialists from different disciplines, who are involved in the clinical nutrition care of EC patients. The literature was searched using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the ISI Web of Knowledge. We searched for the best evidence pertaining to nutrition therapy in the case of EC. The panel summarized the findings in 3 sections of this consensus statement, based on which, after the diagnosis of EC, an initial distinction is made between the patients, as follows: (1) Assessment; (2) Therapy in patients with resectable disease; patients receiving chemotherapy or chemoradiotherapy prior to resection, and patients with unresectable disease, requiring chemoradiotherapy or palliative therapy; and (3) Formula. The resulting consensus statement reflects the opinions of a multidisciplinary group of experts, and a review of the current literature, and outlines the essential aspects of nutrition therapy in the case of EC. The statements are: Patients with EC are among one of the highest risk to have malnutrition. Patient generated suggestive global assessment is correlated with performance status and prognosis. Nutrition assessment for patients with EC at the diagnosis, prior to definitive therapy and change of treatment strategy are suggested and the timing interval can be two weeks during the treatment period, and one month while the patient is stable. Patients identified as high risk of malnutrition should be considered for preoperative nutritional support (tube feeding) for at least 7-10 days. Various routes for tube feedings are available after esophagectomy with similar nutrition support benefits. Limited intrathoracic anastomotic leakage postesophagectomy can be managed with intravenous antibiotics and self-expanding metal stent (SEMS) or jejunal tube. Enteral nutrition in patients receiving preoperative chemotherapy or chemoradiation provides benefits of maintaining weight, decreasing toxicity, and preventing treatment interruption. Tube feeding or SEMS can offer nutrition support in patients with unresectable esophageal cancer, but SEMS is not recommended for those with neoadjuvant chemoradiation before surgery. Enteral immunonutrition may preserve lean body mass and attenuates stress response after esophagectomy. Administration of glutamine may decrease the severity of chemotherapy induced mucositis. Enteral immunonutrition achieves greater nutrition status or maintains immune functions during concurrent chemoradiation.
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3.
Immunonutrition stimulates immune functions and antioxidant defense capacities of leukocytes in radiochemotherapy-treated head & neck and esophageal cancer patients: A double-blind randomized clinical trial.
Talvas, J, Garrait, G, Goncalves-Mendes, N, Rouanet, J, Vergnaud-Gauduchon, J, Kwiatkowski, F, Bachmann, P, Bouteloup, C, Bienvenu, J, Vasson, MP
Clinical nutrition (Edinburgh, Scotland). 2015;(5):810-7
Abstract
BACKGROUND Immunonutrition has been reported to improve the immune status of perioperative cancer patients, thereby reducing complications and length of hospital stay. AIM: This study aimed to assess whether immunonutrition enriched in arginine, EPA & DHA and nucleotides could impact the immune cells responses in head & neck and esophageal cancer patients treated by radiochemotherapy (RCT). METHODS A double-blind clinical trial was carried out in 28 patients randomized into two groups, receiving either an immunomodulating enteral nutrition formula (IEN, n = 13, Impact(®), Nestlé) or an isoenergetic isonitrogenous standard enteral nutrition formula (SEN, n = 15) throughout RCT (5-7 weeks). After isolation from whole blood, immune cells metabolism and functions were assessed at the beginning (Db) and at the end (De) of RCT. RESULTS Immunonutrition maintained CD4(+)/CD8(+) T-lymphocyte counts ratio and CD3 membrane expression between Db and De. Polymorphonuclear cells CD62L and CD15 densities and ROS production were increased in IEN patients. Peripheral blood mononuclear cells (PBMC) production of pro-inflammatory prostaglandin-E2 was stable in IEN patients and lower than in SEN patients at De. Genes coding for immune receptors, antioxidant enzymes and NADPH oxidase subunits were overexpressed in the PBMC of IEN vs SEN patients at De. CONCLUSION Immunonutrition can enhance immune cell responses through the modulation of their phenotypes and functions. By modulating the gene expression of immune cells, immunonutrition could make it easier for the organism to adapt to the systemic inflammation and oxidative stress induced by RCT. CLINICAL TRIAL REGISTRATION This clinical trial has been registered on ClinicalTrial.gov website: NCT00333099.
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4.
Randomized study of antiinflammatory and immune-modulatory effects of enteral immunonutrition during concurrent chemoradiotherapy for esophageal cancer.
Sunpaweravong, S, Puttawibul, P, Ruangsin, S, Laohawiriyakamol, S, Sunpaweravong, P, Sangthawan, D, Pradutkanchana, J, Raungkhajorn, P, Geater, A
Nutrition and cancer. 2014;(1):1-5
Abstract
Concurrent chemoradiotherapy (CCRT) induces toxicities from inflammation and immunological suppression. Omega-3 fatty acids, glutamine, and arginine are therapeutic factors that can attenuate such inflammation and promote cellular immunity. The question is whether immunonutrition (IN) during CCRT reduces inflammation and improves the immune function in patients with esophageal squamous cell carcinoma (ESCC). Seventy-one locally advanced ESCC patients being treated with CCRT (5-FU and cisplatin) were randomized into 2 groups. The IN group received a combination of omega-3 fatty acids, glutamine, and arginine, whereas the control group received standard formula. The levels of C-reactive protein (CRP), tumor necrosis factor (TNF), interferon-gamma (IFN), interleukin (IL-6, IL-10), CD3, CD4, CD8, white blood cells, neutrophils, and total lymphocytes were measured before and during treatment. The levels of CRP (P = 0.001) and TNF (P = 0.014) increased more during treatment in the control group than the treatment group, whereas IFN, IL-6, and IL-10 were similar but not significantly. CD3, CD4, CD8, white blood cells, neutrophils, and total lymphocytes decreased more in the control group than in the treatment group, but not significantly. Enteral IN during CCRT reduced the increase of inflammatory cytokine levels.
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5.
Protein-protein interaction network analyses for elucidating the roles of LOXL2-delta72 in esophageal squamous cell carcinoma.
Wu, BL, Zou, HY, Lv, GQ, Du, ZP, Wu, JY, Zhang, PX, Xu, LY, Li, EM
Asian Pacific journal of cancer prevention : APJCP. 2014;(5):2345-51
Abstract
Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase (LOX) family, is a copper-dependent enzyme that catalyzes oxidative deamination of lysine residues on protein substrates. LOXL2 was found to be overexpressed in esophageal squamous cell carcinoma (ESCC) in our previous research. We later identified a LOXL2 splicing variant LOXL2-delta72 and we overexpressed LOXL2-delta72 and its wild type counterpart in ESCC cells following microarray analyses. First, the differentially expressed genes (DEGs) of LOXL2 and LOXL2-delta72 compared to empty plasmid were applied to generate protein-protein interaction (PPI) sub-networks. Comparison of these two sub-networks showed hundreds of different proteins. To reveal the potential specific roles of LOXL2- delta72 compared to its wild type, the DEGs of LOXL2-delta72 vs LOXL2 were also applied to construct a PPI sub-network which was annotated by Gene Ontology. The functional annotation map indicated the third PPI sub-network involved hundreds of GO terms, such as "cell cycle arrest", "G1/S transition of mitotic cell cycle", "interphase", "cell-matrix adhesion" and "cell-substrate adhesion", as well as significant "immunity" related terms, such as "innate immune response", "regulation of defense response" and "Toll signaling pathway". These results provide important clues for experimental identification of the specific biological roles and molecular mechanisms of LOXL2-delta72. This study also provided a work flow to test the different roles of a splicing variant with high-throughput data.
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6.
[Effect of early enteral nutrition on immune response and clinical outcomes after esophageal cancer surgery].
Zhao, G, Cao, S, Zhang, K, Xin, Y, Han, J, Dong, Q, Cui, J
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery. 2014;(4):356-60
Abstract
OBJECTIVE To evaluate the effect of early enteral nutrition(EEN) on immune response and clinical outcomes after esophageal cancer operation. METHODS Sixty patients with esophageal cancer undergoing radical operation between March 2010 and July 2011 were randomly divided into two groups using envelope method: EEN group(n=30, administration of water and enteral nutrition early after operation) and TPN group(n=30, administration of total parenteral nutrition). Two groups both received 7-day nutrition support. Immune indexes(CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+)) and serum nutritional indexes(albumin, pre-albumin, transferrin) were measured before operation and 1-, 3-, and 7-day after operation. The time to first flatus, length of postoperative hospital stay, total hospitalization cost, and postoperative complication were recorded. RESULTS As compared to TPN group, the time to first flatus was significantly shorter in EEN group[(66.5±7.3) h vs. (75.1±6.8) h, P<0.01], as was hospital stay[(7.8±1.1) d vs. (9.3±1.3) d, P<0.01]. Total hospitalization cost[(36 210±3810) yuan vs. (39 731±4013) yuan, P<0.01] was lower in EEN group as compared to TPN group. There was no significant difference in postoperative complication rate between the two groups[13.3%(3/30) vs. 20.0%(6/30), P>0.05]. The levels of CD3(+), CD4(+), CD4(+)/CD8(+), albumin, prealbumin and transferrin were significantly higher in EEN group as compared to TPN group on postoperative day 3 and 7(all P<0.05), while CD8(+) was significantly lower in EEN group(P<0.05). CONCLUSION EEN can promote early recovery of gastrointestinal function, improve nutritional and immune function, and therefore lead to fast postoperative recovery in esophageal cancer patients.
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Immunonutrition in patients undergoing esophageal cancer resection.
Mudge, L, Isenring, E, Jamieson, GG
Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus. 2011;(3):160-5
Abstract
Specialized nutritional support containing immunonutrients such as arginine, omega-3 fatty acids, and ribonucleic acid significantly reduces the incidence of postoperative infective complications and hospital length of stay in elective surgery patients. However, immunonutrition use is not standard practice in esophago-gastric units internationally. This review provides a clinical update regarding the use of immunonutrition in patients undergoing major gastrointestinal surgery and, in particular, esophageal cancer resection, and provides direction for future collaborative research. A review of MEDLINE and Cochrane Library databases was conducted for randomized controlled trials or meta-analyses. A recent meta-analysis demonstrated that preoperative immunonutrition use significantly reduces hospital length of stay and the incidence of postoperative complications in patients undergoing major elective surgery, particularly for gastrointestinal malignancies. Only three small randomized controlled trials have evaluated immunonutrition use in patients exclusively undergoing esophageal cancer surgery. These were unable to determine whether immune-enhancing formulae positively influence key clinical outcomes such as mortality, hospital and intensive care unit length of stay, and postoperative morbidity in this patient group. Currently, there is insufficient evidence to recommend routine use of immunonutrition in patients undergoing esophageal cancer surgery. Future collaborative research should evaluate whether: (i) immunonutrition use positively influences key clinical outcomes in this population; (ii) these patients benefit from preoperative supplementation with an immune-enhancing formula or whether they require postoperative continuation (perioperative approach) to combat their risk of complications after surgery; and (iii) these formulae can be used safely in those patients who develop sepsis.
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8.
Enteral nutrition enriched with eicosapentaenoic acid (EPA) preserves lean body mass following esophageal cancer surgery: results of a double-blinded randomized controlled trial.
Ryan, AM, Reynolds, JV, Healy, L, Byrne, M, Moore, J, Brannelly, N, McHugh, A, McCormack, D, Flood, P
Annals of surgery. 2009;(3):355-63
Abstract
BACKGROUND Esophagectomy represents an exemplar of controlled major trauma, with marked metabolic, immunologic, and physiologic changes as well as an associated high incidence of complications. Eicosapentaenoic acid (EPA) enriched enteral nutrition (EN) modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the peri-operative period is unclear. OBJECTIVES To examine the effects of perioperative EPA enriched EN on the metabolic, nutritional, and immuno-inflammatory response to esophagectomy, and on postoperative complications. METHODS In a double-blind design, patients were randomized to a standard EN formula or a formula enriched with 2.2 g EPA/d for 5 days preoperatively (orally) and 21 days postoperatively (jejunostomy). Segmental bioelectrical impedance analysis was performed preoperatively and on POD 21. Postoperative complications were monitored, as well as the acute phase response, coagulation markers, and serum cytokines. RESULTS Fifty-three patients (28 EPA, 25 standard) completed the study, and both groups were well matched. Serum and peripheral blood mononuclear cell (PBMC) membrane EPA levels were significantly increased in the EPA group. There was no difference in the incidence of major complications. The EPA group maintained all aspects of body composition postoperatively, whereas patients in the standard EN group lost significant amounts of fat-free mass (1.9 kg, P = 0.030) compared with the EPA group [leg (0.3 kg, P = 0.05), arm (0.17 kg, P = 0.01), and trunk (1.44 kg, P = 0.03)]. The EPA group had a significantly (P < 0.05) attenuated stress response for TNFalpha, IL-10, and IL-8 compared with the standard group. CONCLUSIONS EPA supplemented early EN is associated with preservation of lean body mass post esophagectomy compared with a standard EN. These properties may merit longer-term study to address its impact on recovery of function and quality of life in models of complex surgery or multimodal cancer treatment regimens.
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9.
[Postoperative nutritional management for esophageal cancer patients].
Ikeda, K, Kimura, Y
Kyobu geka. The Japanese journal of thoracic surgery. 2008;(8 Suppl):726-30
Abstract
High incidence of malnutrition is found in esophageal cancer patients. It is well known that to maintain good nutritional preoperative condition is very important to prevent postoperative morbidity and mortality. Hence, preoperative oral or nasogastric feeding is recommended when the patient is malnourished, at a total dose of 30 kcal/kg/day. During postoperative period, enteral nutrition should be primarily performed because of its favorable effects on immune-status and intestinal integrity to avoid septic complications. It is also important to keep circulatory volume sufficient to provide oxygen demand during catabolic phase, which leads earlier recovery from critical illness. Enteral nutrition should be immediately started afterward. An initial dose of 5-10 kcal/kg/day of the enteral nutrition is performed from the 1st or 2nd postoperative day and gradually increased to the full dose at 30 kcal/kg/ day. In cases of not administering scheduled dose of the enteral nutrition, either total or peripheral parenteral nutrition is required complementing total caloric intake. When total parenteral nutrition is used, blood glucose level should be controlled less than 150 mg/dl by pertinently administering insulin or limiting glycemic intake. Immunonutrition is promising nutritional management for critical surgical patients such as those performed esophageal cancer surgery. Continuing immune-enhancing diet at a dose of 750 to 1,000 ml/day for 5 to 7 days before surgery is necessary to bring good postoperative outcome.
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10.
Chemoprevention in gastrointestinal cancers: current status.
Grau, MV, Rees, JR, Baron, JA
Basic & clinical pharmacology & toxicology. 2006;(3):281-7
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Abstract
Chemoprevention, pharmacological intervention for disease prevention, aims to intervene in pathways that lead to clinical disease before the disease occurs. Cancer chemoprevention is a relatively new field, but for gastrointestinal cancers, clinical trials have highlighted the chemopreventive potential of several agents. For colorectal neoplasia, trials with aspirin and other non-steroidal anti-inflammatory drugs (NSAIDS) and calcium have demonstrated the most significant reductions of risk. In observational studies, NSAIDs also consistently appear to protect against oesophageal and gastric cancer. Calcium, and perhaps vitamin D, are also promising and have the advantage of being inexpensive, safe interventions. For the prevention of oesophageal cancer, antitumour-B and retinamide have provided hopeful results, although it is not clear that these findings can be extrapolated from the study populations in Asia to western countries. Evidence from China suggests that a combination of beta-carotene, alpha-tocopherol and selenium may protect against oesophageal cancer, but the relative importance of each agent is unclear, and, again, their effects in other populations has not yet been assessed. Mass immunization against hepatitis B seems to be the most effective means of reducing the incidence of hepatocellular cancer worldwide. In addition, treatment with interferon alpha in patients chronically infected with hepatitis C virus shows considerable promise, given the increasing prevalence of hepatitis C virus carriage in recent years. TJ-9, polyprenoic acid and anti-aflatoxin compounds are also possible avenues that deserve future research.