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Is immunonutrition superior to standard enteral nutrition in reducing postoperative complications in patients undergoing esophagectomy? A meta-analysis of randomized controlled trials.
Zhuo, ZG, Luo, J, Song, HYDTN, Alai, GH, Shen, X, Lin, YD
Journal of B.U.ON. : official journal of the Balkan Union of Oncology. 2021;(1):204-210
Abstract
PURPOSE Perioperative enteral nutrition supports are recommended in esophagus cancer patients. Immunonutrition contains immuno-enhancing nutrients in addition to standard formula. These new nutrients are thought to be efficacious in reducing inflammatory response and improving postoperative immune response and they have been proved to be better than standard enteral nutrition in reducing postoperative complications in gastric cancer. However, if it would lead to a better clinical outcome in patients undergoing esophagectomy remains controversial. METHODS A systematic literature search was performed in the online database of PubMed, Medline, EMBASE and Cochrane Library. The relevant studies were screened out of the results by reading titles and abstracts. Then, we read the full-texts to finally confirm the studies included in this meta-analysis. RESULTS Six randomized controlled trials having enrolled 638 patients were included in the final analysis. The pooled analysis didn't show statistically significant difference between immunonutrition group and standard nutrition group in reducing postoperative complications. CONCLUSIONS The postoperative complications are comparable between immunonutrition and the standard enteral nutrition in patients undergoing esophagectomy, but its value in severe malnutrition patients is undetermined, whereas the high tolerance and other advantages brought by the immunonutrition should not be overlooked and need to be further proved.
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Immunonutrition in Patients with Pancreatic Cancer Undergoing Surgical Intervention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Yang, FA, Chen, YC, Tiong, C
Nutrients. 2020;(9)
Abstract
Immunonutrition is administered to improve the outcome of patients with pancreatic cancer undergoing surgery. However, its effect and mechanism of action remain unclear. Therefore, we conducted this systematic review and meta-analysis to assess its effects on postoperative outcome and the immune system. Randomized controlled trials (RCTs) were identified and data extracted by two reviewers independently from electronic databases from their inception to 31 October 2019. The result was expressed as the risk ratio (RR) for categorical variables and mean difference (MD) for continuous variables with 95% confidence intervals (CIs). Six RCTs published from 1999 and 2016, with a total of 368 patients, were included. The results revealed that immunonutrition significantly decreased the rate of infectious complications (RR = 0.47, 95% CI (0.23, 0.94), p = 0.03) and the length of hospital stay (MD = -1.90, 95% CI (-3.78, -0.02), p = 0.05) by modulating the immune system, especially in preoperative group in subgroup analysis. We therefore recommend that patients with pancreatic cancer undergoing surgery could take the advantage of immunonutrition, especially in the preoperative period.
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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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The Impact of Preoperative Immune Modulating Nutrition on Outcomes in Patients Undergoing Surgery for Gastrointestinal Cancer: A Systematic Review and Meta-analysis.
Adiamah, A, Skořepa, P, Weimann, A, Lobo, DN
Annals of surgery. 2019;(2):247-256
Abstract
OBJECTIVE To define the influence of preoperative immune modulating nutrition (IMN) on postoperative outcomes in patients undergoing surgery for gastrointestinal cancer. BACKGROUND Although studies have shown that perioperative IMN may reduce postoperative infectious complications, many of these have included patients with benign and malignant disease, and the optimal timing of such an intervention is not clear. METHODS The Embase, Medline, and Cochrane databases were searched from 2000 to 2018, for prospective randomized controlled trials evaluating preoperative oral or enteral IMN in patients undergoing surgery for gastrointestinal cancer. The primary endpoint was the development of postoperative infectious complications. Secondary endpoints included postoperative noninfectious complications, length of stay, and up to 30-day mortality. The analysis was performed using RevMan v5.3 software. RESULTS Sixteen studies reporting on 1387 patients (715 IMN group, 672 control group) were included. Six of the included studies reported on a mixed population of patients undergoing all gastrointestinal cancer surgery. Of the remaining, 4 investigated IMN in colorectal cancer surgery, 2 in pancreatic surgery, and another 2 in patients undergoing surgery for gastric cancer. There was 1 study each on liver and esophageal cancer. The formulation of nutrition used in all studies in the treated patients was Impact (Novartis/Nestlé), which contains ω-3 fatty acids, arginine, and nucleotides. Preoperative IMN in patients undergoing surgery for gastrointestinal cancer reduced infectious complications [odds ratio (OR) 0.52, 95% confidence interval (CI) 0.38-0.71, P < 0.0001, I = 16%, n = 1387] and length of hospital stay (weighted mean difference -1.57 days, 95% CI -2.48 to -0.66, P = 0.0007, I = 34%, n = 995) when compared with control (isocaloric isonitrogeneous feed or normal diet). It, however, did not affect noninfectious complications (OR 0.98, 95% CI 0.73-1.33, P = 0.91, I = 0%, n = 1303) or mortality (OR 0.55, 95% CI 0.18-1.68, P = 0.29, I = 0%, n = 955). CONCLUSION Given the significant impact on infectious complications and a tendency to shorten length of stay, preoperative IMN should be encouraged in routine practice in patients undergoing surgery for gastrointestinal cancer.
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Enteral immunonutrition versus enteral nutrition for gastric cancer patients undergoing a total gastrectomy: a systematic review and meta-analysis.
Cheng, Y, Zhang, J, Zhang, L, Wu, J, Zhan, Z
BMC gastroenterology. 2018;(1):11
Abstract
BACKGROUND Nutrition support is a common means for patients with gastric cancer, especially for those undergoing elective surgery. Recently, enteral immunonutrition (EIN) was increasingly found to be more effective than enteral nutrition (EN) in enhancing the host immunity and eventually improving the prognosis of gastric cancer patients undergoing gastrectomy. However, the results reported were not consistent. This meta-analysis aimed to assess the impact of EIN for patients with GC on biochemical, immune indices and clinical outcomes. METHODS Four electronical databases (Medline, EMBASE, Scopus and Cochrane library) were used to search articles in peer-reviewed, English-language journals. Mean difference (MD), Relative risk (RR), or standard mean difference (SMD) with 95% confidence interval (CI) were calculated. Heterogeneity was assessed by Cochrane Q and I2 statistic combined with corresponding P-value. The analysis was carried out with RevMan 5.3. RESULTS Seven studies involving 583 patients were eligible for the pooled analysis. EIN, when beyond a 7-day time-frame post-operatively (D ≥ 7), increased level of CD4+ (SMD = 0.99; 95% CI, 0.65-1.33; P < 0.00001), CD4+/ CD8+ (SMD = 0.34; 95% CI, 0.02-0.67; P = 0.04), the IgM (SMD = 1.15; 95% CI, 0.11-2.20; P = 0.03), the IgG (SMD = 0.98; 95% CI, 0.55-1.42; P < 0.0001), the lymphocyte (SMD = 0.69; 95% CI, 0.32-1.06; P = 0.0003), and the proalbumin (SMD = 0.73; 95% CI, 0.33-1.14; P = 0.0004). However, those increased effects were not obvious within a 7-day time-frame post-operatively (D < 7). The levels of CD8+ and other serum proteins except proalbumin were not improved both on D ≥ 7 and D < 7. Clinical outcomes such as systemic inflammatory response syndrone (SIRS) (MD, - 0.89 days; 95% CI, - 1.40 to - 0.39; P = 0.005), and postoperative complications (RR, 0.29; 95% CI, 0.14-0.60; P = 0.001) were significantly reduced in EIN group. Pulmonary infection and length of hospitalization (LHS) were not improved no matter what time after surgery. CONCLUSIONS EIN was found to improve the cellular immunity, modulate inflammatory reaction and reduce postoperative complication for GC patients undergoing radical gastrointestinal surgery. Exclusion of grey literature and non-English language studies was the key limitation in this study.
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Impact of Early Enteral Nutrition on Nutritional and Immunological Outcomes of Gastric Cancer Patients Undergoing Gastrostomy: A Systematic Review and Meta-Analysis.
Nikniaz, Z, Somi, MH, Nagashi, S, Nikniaz, L
Nutrition and cancer. 2017;(5):693-701
Abstract
OBJECTIVES The present systematic review and meta-analysis study evaluated the impact of early enteral nutrition (EN) on postoperative nutritional and immunological outcomes of gastric cancer (GC) patients. METHOD The databases of PubMed, Embase, Springer, and Cochrane library were searched till September 2016 to identify studies which evaluated the effects of EN compared with parenteral nutrition (PN) on postoperative immunological and nutritional status and hospitalization time in GC patients. Mean difference (MD) or standard mean difference (SMD) was calculated and I-square statistic test was used for heterogeneity analysis. RESULTS The present systematic review and meta-analysis have consisted of seven trials, containing 835 GC patients. According to the result of meta-analysis, compared with PN, EN significantly resulted in more increase in the level of albumin [MD = 2.07 (0.49, 3.64)], prealbumin [MD = 9.41 (049, 33.55)], weight [MD = 1.52 (0.32, 2.72)], CD3+ [SMD = 1.96 (1.50, 2.43)], CD4+ [SMD = 2.45 (1.97, 2.93)], natural killers [MD = 5.80 (3.75, 7.85)], and also a decrease in the hospitalization time [MD=-2.39 (-2.74, -2.03)]. CONCLUSION The results demonstrated that early administration of EN is more effective in improving postsurgical nutrition status and immune index in GC patients. So, based on these results, postoperative early administration of EN is recommended for GC patients where possible.
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[Early versus traditional postoperative oral feeding in patients undergoing elective colorectal surgery: a meta-analysis of safety and efficacy].
Zhang, K, Cheng, S, Zhu, Q, Han, Z
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery. 2017;(9):1060-1066
Abstract
OBJECTIVE To compare the outcomes of early oral feeding (EOF) and the traditional oral feeding (TOF) in postoperative patients with colorectal cancer using Meta-analysis. METHODS The databases of PubMed, SCI, Ovid, The Cochrane Library, CNKI, CBM, VIP and Wanfang Data were searched to collect randomized controlled trial (RCT) about EOF versus TOF in patients undergoing elective colorectal surgery. The retrieval time span was from inception to June 1, 2016. The studies were screened according to the inclusion and exclusion criteria. The data were extracted and the quality was evaluated by 2 reviewers independently. The Meta-analysis was conducted using RevMan 5.2 software. RESULTS A total of 14 studies with 1 807 patients (906 cases in EOF group and 901 cases in TOF group) were included. The time to first passage of flatus (MD=-16.11 h, 95%CI:-18.27 to -13.94 h, P=0.00), postoperative hospital stay (MD=-1.92 d, 95%CI:-2.83 to -1.01 d, P=0.00), hospitalization cost (ten thousand yuan) (MD=-0.58, 95%CI:-0.71 to -0.46, P=0.00) were less in EOF group compared to TOF group. EOF patients had lower total complication rate (OR=0.68, 95%CI:0.48 to 0.95, P=0.03), in which the pulmonary infection (OR=0.27, 95%CI:0.13 to 0.53, P=0.00), pharyngolaryngitis (OR=0.06, 95%CI:0.04 to 0.11, P=0.00) were lower than those in TOF group, while the tube reinsertion (OR=2.34, 95%CI:1.08 to 5.07, P=0.03) was higher. The incidence of anastomotic leakage, nausea, vomiting, abdominal distension, diarrhea, and wound infection between two groups was not significantly different(all P>0.05). There was no significant difference between two groups in IgM (P>0.05), while the IgA (MD=0.3, 95%CI:0.12 to 0.48, P=0.00), IgG (MD=2.13 ,95%CI:0.82 to 3.44, P=0.001), CD4+ (MD=3.80, 95%CI:2.55 to 5.04, P=0.00), CD4+/CD8+ (MD=0.22, 95%CI:0.04 to 0.41, P=0.02) in EOF group were higher than those in TOF group. Postoperative CRP decreased rapidly in EOF group (MD=-30.10, 95%CI:-48.07 to -12.13, P=0.00), and IL-6 was not significantly different (P>0.05). EOF patients had higher serum albumin level 5 days after operation (MD=3.27, 95%CI: 2.48 to 4.07, P=0.00). CONCLUSIONS EOF can promote gas passage and defecation, reduce postoperative hospital stay and treatment costs. Also, it can decrease the incidence of complications and postoperative inflammation, and maintain immune function.
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The effects of enteral immunonutrition in upper gastrointestinal surgery: A systematic review and meta-analysis.
Wong, CS, Aly, EH
International journal of surgery (London, England). 2016;:137-50
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Abstract
AIM: The beneficial of immunonutrition on overall morbidity and mortality remains uncertain. We undertook a systematic review to evaluate the effects of immune-enhancing enteral nutrition (IEN) in upper gastrointestinal (GI) surgery. METHODS Main electronic databases [MEDLINE via Pubmed, EMBASE, Scopus, Web of Knowledge, Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Library, and clinical trial registry (ClinicalTrial.gov)] were searched for studies reported clinical outcomes comparing standard enteral nutrition (SEN) and immunonutrition (IEN). The systematic review was conducted in accordance with the PRISMA guidelines and meta-analysis was analysed using fixed and random-effects models. RESULTS Nineteen RCTs with a total of 2016 patients (1017 IEN and 999 SEN) were included in the final pooled analysis. The ratio of patients underwent oesophagectomy:gastrectomy:pancreatectomy was 2.2:1.2:1.0. IEN, when administered post-operatively, was associated with a significantly lower risk of wound infection (risk ratio (RR) 0.59, 95% confidence interval (CI) 0.40 to 0.88; p = 0.009) and shorter length of hospital stay (MD -2.92 days, 95% CI -3.89 to -1.95; p < 0.00001). No significant differences in other post-operative morbidities of interest (e.g. anastomotic leak and pulmonary infection) and mortality between the two groups were identified. CONCLUSIONS Overall, our analysis found that IEN decreases wound infection rates and reduces length of stay. It should be recommended as routine nutritional support as part of the Enhanced Recovery after Surgery (ERAS) programmes for upper GI Surgery.
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Efficacy of glutamine-enriched enteral feeding formulae in critically ill patients: a systematic review and meta-analysis of randomized controlled trials.
Mottaghi, A, Yeganeh, MZ, Golzarand, M, Jambarsang, S, Mirmiran, P
Asia Pacific journal of clinical nutrition. 2016;(3):504-12
Abstract
Critically ill patients usually suffer from catabolic stress that could lead to malnutrition and nutritional support therefore is essential to maintain lean body mass, improve metabolic and immune response and decrease rate of mortality and comorbidity in these patients. This meta-analysis was aimed to evaluate effect of glutamineenriched enteral nutrition in critically ill patients. In order to obtain randomized clinical trial studies (RCTs), international databases including MEDLINE and Google scholar and also electronic resources in Iran, including IRAN MEDEX, IRAN DOC, SID, Magiran were systematically searched without language and publication restriction before December 2014. The final included number of studies for meta-analysis was 10. The methodological quality of eligible studies was assessed by four investigators using the Jadad 5-point scale, a scale containing three items describing randomization, blinding and fate of participants. We analyzed data from the included studies using STATA version 12.0, and calculated a pooled odds ratio for dichotomous data and mean differences for continuous data with 95% confidence intervals (CIs). There was no significant difference in mortality in elevated pooled odds ratios (p-value=0.070). A funnel plot was drawn for evaluation of publication bias, but none was found. The fixed effect model shows significant reduction in gut permeability in who received enteral feeding enriched with glutamine (-0.84, 95% CI=-1.25 to -0.44), moreover the funnel plot did not show publication bias. Based on the available data, our meta-analysis showed that enteral glutamine (Gln) supplementation increased mortality rate, though non-significantly, but decreased gut permeability significantly.
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Immunonutrition Support for Patients Undergoing Surgery for Gastrointestinal Malignancy: Preoperative, Postoperative, or Perioperative? A Bayesian Network Meta-Analysis of Randomized Controlled Trials.
Song, GM, Tian, X, Zhang, L, Ou, YX, Yi, LJ, Shuai, T, Zhou, JG, Zeng, Z, Yang, HL
Medicine. 2015;(29):e1225
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Abstract
Enteral immunonutrition (EIN) has been established to be as a significantly important modality to prevent the postoperative infectious and noninfectious complications, enhance the immunity of host, and eventually improve the prognosis of gastrointestinal (GI) cancer patients undergoing surgery. However, different support routes, which are the optimum option, remain unclear. To evaluate the effects of different EIN support regimes for patients who underwent selective surgery for resectable GI malignancy, a Bayesian network meta-analysis (NMA) of randomized controlled trials (RCTs) was conducted. A search of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) was electronically searched until the end of December 2014. Moreover, we manually checked reference lists of eligible trials and review and retrieval unpublished literature. RCTs which investigated the comparative effects of EIN versus standard enteral nutrition (EN) or different EIN regimes were included if the clinical outcomes information can be extracted from it. A total of 27 RCTs were incorporated into this study. Pair-wise meta-analyses suggested that preoperative (relative risk [RR], 0.58; 95% confidence interval [CI], 0.43-0.78), postoperative (RR, 0.63; 95% CI, 0.52-0.76), and perioperative EIN methods (RR, 0.46; 95% CI, 0.34-0.62) reduced incidence of postoperative infectious complications compared with standard EN. Moreover, perioperative EIN (RR, 0.65; 95% CI, 0.44-0.95) reduced the incidence of postoperative noninfectious complications, and the postoperative (mean difference [MD], -2.38; 95% CI, -3.4 to -1.31) and perioperative EIN (MD, -2.64; 95% CI, -3.28 to -1.99) also shortened the length of postoperative hospitalization compared with standard EN. NMA found that EIN support effectively improved the clinical outcomes of patients who underwent selective surgery for GI cancer compared with standard EN. Our results suggest EIN support is promising alternative for operation management in comparison with standard EN, and perioperative EIN regime is the optimum option for managing clinical status of patients who underwent selective surgery for GI cancer.