Meta-analysis of Glutamine on Immune Function and Post-Operative Complications of Patients With Colorectal Cancer

Abstract

The aim of this meta-analysis was to evaluate the clinical significance of glutamine in the management of patients with colorectal cancer (CRC) after radical operation. Electronic databases, including PubMed, EMBASE, MEDLINE, Cochrane Library, Chinese Biomedical Database (CBM), China National Knowledge Infrastructure (CNKI), VIP medicine information system (VIP), and Wanfang electronic databases were comprehensively searched from inception to 30, July 2021. Prospective randomized trials with glutamine vs. routine nutrition or blank therapy were selected. The immune function related indicators (including IgA, IgG, IgM, CD4+, CD8+, and the ratio of CD4+/CD8+), post-operative complications [including surgical site infection (SSI), anastomotic leakage, and length of hospital stay (LOS)], and corresponding 95% confidence intervals (CIs) were assessed in the pooled analysis. Subsequently, the heterogeneity between studies, sensitivity, publication bias, and meta-regression analysis were performed. Consequently, 31 studies which contained 2,201 patients (1,108 in the glutamine group and 1,093 in the control group) were included. Results of pooled analysis indicated that glutamine significantly improved the humoral immune function indicators [including IgA (SMD = 1.15, 95% CI: 0.72–1.58), IgM (SMD = 0.68, 95% CI: 0.48–0.89), and IgG (SMD = 1.10, 95% CI: 0.70–1.50)], and the T cell immune function indicators [including CD4+ (SMD = 0.76, 95% CI: 0.53–0.99) and the ratio of CD4+/CD8+ (SMD = 0.92, 95% CI: 0.57–1.28)]. Meanwhile, the content of CD8+ was decreased significantly (SMD = −0.50, 95% CI: −0.91 to −0.10) followed by glutamine intervention. Pooled analysis of SSI (RR = 0.48, 95% CI: 0.30–0.75), anastomotic leakage (RR = 0.23, 95% CI: 0.09–0.61), and LOS (SMD = −1.13, 95% CI: −1.68 to −0.58) were decreased significantly in glutamine group compared with control group. Metaregression analysis revealed that the covariate of small-sample effects influenced the robustness and reliability of IgG outcome potentially. Findings of the present work demonstrated that glutamine ought to be applied as an effective immunenutrition therapy in the treatment of patients with CRC after radical surgery. The present meta-analysis has been registered in PROSPERO (no. CRD42021243327).Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO, Identifier: CRD42021243327.

Inmunonutrición en el paciente oncológico quirúrgico: actualización y estado del arte

“…En una revisión sistemática y metaanálisis publicada en el 2019, donde se incluyeron 19 ensayos clínicos con 1387 pacientes, se demostró que en aquellos pacientes que van a cirugía electiva por cáncer gastrointestinal, el uso de la IMN con glutamina enteral perioperatoria disminuyó el riesgo de las complicaciones posoperatorias (formación de fístulas e infecciones) un 48% (RR 0,52; IC 95% 0,38-0,71), también hubo una disminución en los días de la estancia hospitalaria (1,57 días, IC 95% -2,48, -0,66) (9) . Otro metaanálisis, publicado en el 2021 por Yang y colaboradores (16) , con 31 ensayos controlados aleatorizados (ECA) y 2201 pacientes, demostró que el uso de la glutamina perioperatoria en pacientes con cáncer colorrectal mejoraba la respuesta humoral CD4 (DE = 0,76, IC 95% 0,53-0,99), inmunoglobulina (Ig) G (DE = 1,10; IC 95% 0,70-1,50); por otro lado, se demostró una menor estancia hospitalaria (DE = -1,13; IC 95% -1,68 a -0,58 días), así como menor riesgo de fuga de la anastomosis (RR = 0,23; IC 95% 0,09-0,61).…”

Reprogramming of glutamine metabolism and its impact on immune response in the tumor microenvironment

“…Meanwhile, glutamine transporter mutants have been shown to promote metabolic reprogramming of tumors [ 5 – 7 ]. Recent studies have shown that glutamine is also an important raw material for the immune system, and plays a major role in regulating lymphocyte functions such as, the release of secretory factors; proliferation; and their general maintenance [ 8 ].…”

Paving the Path for Immune Enhancing Nutrition in Colon Cancer: Modulation of Tumor Microenvironment and Optimization of Outcomes and Costs

“…Although clinical outcomes in CRC have improved dramatically over the past 50 years, several factors may influence the result [8]. First, the high cellular turnover during tumorigenesis leads to a dysregulation of the host immune response.…”

“…Prevalence of malnutrition in CRC patients ranges from 45% to 60% and is significantly higher following radical surgery [10]. Together with the surgery-related impaired immune response, which induces a systemic inflammatory response syndrome, malnutrition accounts for most postoperative complications [8,11]. Complications, in turn, significantly worsen the short-term clinical results, length of stay (LOS) and hospital costs, impairing long-term oncological outcome and patient's quality of life [12][13][14][15][16][17].…”

“…Several reviews and meta-analysis have demonstrated the beneficial effects of IN by pooling results of randomized control trials [22][23][24]. IN has been shown to have the potential to reduce postoperative complications and LOS, as well as improve humoral and T-cell immune function [8,25]. To date, IN support is recommended by the European Society for Clinical Nutrition and Metabolism (ESPEN) for malnourished patients and is also included in ERAS (Enhanced Recovery After Surgery) protocols [26,27].…”