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Postoperative arginine-enriched immune modulating nutrition: Long-term survival results from a randomised clinical trial in patients with oesophagogastric and pancreaticobiliary cancer.
Adiamah, A, Rollins, KE, Kapeleris, A, Welch, NT, Iftikhar, SY, Allison, SP, Lobo, DN
Clinical nutrition (Edinburgh, Scotland). 2021;(11):5482-5485
Abstract
BACKGROUND & AIMS Immune modulating nutrition (IMN) has been shown to reduce postoperative infectious complications and length of stay in patients with gastrointestinal cancer. Two studies of IMN in patients undergoing surgery for head and neck cancer also suggested that this treatment might improve long-term survival and progression-free survival. In the present study, we analysed follow-up data from our previous randomised controlled trial of IMN, in patients undergoing surgery for oesophagogastric and pancreaticobiliary cancer, in order to evaluate the long-term impact on survival of postoperative IMN versus an isocaloric, isonitrogenous control feed. METHODS This study included patients undergoing surgery for cancers of the pancreas, oesophagus and stomach, who had been randomised in a double-blind manner to receive postoperative jejunostomy feeding with IMN (Stresson, Nutricia Ltd.) or an isonitrogenous, isocaloric feed (Nutrison High Protein, Nutricia) for 10-15 days. The primary outcome was long-term overall survival. RESULTS There was complete follow-up for all 108 patients, with 54 patients randomised to each group. There were no statistically significant differences between groups by demographics [(age, p = 0.63), sex (p = 0.49) or site of cancer (p = 0.25)]. 30-day mortality was 11.1% in both groups. Mortality in the intervention group was 13%, 31.5%, 70.4%, 85.2%, 88.9%, and 96.3% at 90 days, and 1, 5, 10, 15 and 20 years respectively. Corresponding mortality in the control group was 14.8%, 35.2%, 68.6%, 79.6%, 85.2% and 98.1% (p > 0.05 for all comparisons). CONCLUSION Early postoperative feeding with arginine-enriched IMN had no impact on long-term survival in patients undergoing surgery for oesophagogastric and pancreaticobiliary cancer.
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The Role of Immunonutrition in Patients Undergoing Pancreaticoduodenectomy.
Jabłońska, B, Mrowiec, S
Nutrients. 2020;(9)
Abstract
Pancreaticoduodenectomy (PD) is one of the most difficult and complex surgical procedures in abdominal surgery. Malnutrition and immune dysfunction in patients with pancreatic cancer (PC) may lead to a higher risk of postoperative infectious complications. Although immunonutrition (IN) is recommended for enhanced recovery after surgery (ERAS) in patients undergoing PD for 5-7 days perioperatively, its role in patients undergoing pancreatectomy is still unclear and controversial. It is known that the proper surgical technique is very important in order to reduce a risk of postoperative complications, such as a pancreatic fistula, and to improve disease-free survival in patients following PD. However, it has been proven that IN decreases the risk of infectious complications, and shortens hospital stays in patients undergoing PD. This is a result of the impact on altered inflammatory responses in patients with cancer. Both enteral and parenteral, as well as preoperative and postoperative IN, using various nutrients, such as glutamine, arginine, omega-3 fatty acids and nucleotides, is administered. The most frequently used preoperative oral supplementation is recommended. The aim of this paper is to present the indications and benefits of IN in patients undergoing PD.
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Combination of arginine, glutamine, and omega-3 fatty acid supplements for perioperative enteral nutrition in surgical patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST): A prospective, randomized, double-blind study.
Ma, C, Tsai, H, Su, W, Sun, L, Shih, Y, Wang, J
Journal of postgraduate medicine. 2018;(3):155-163
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Abstract
BACKGROUND Perioperative enteral nutrition (EN) enriched with immune-modulating substrates is preferable for patients undergoing major abdominal cancer surgery. In this study, perioperative EN enriched with immune-modulating nutrients such as arginine, glutamine, and omega-3 fatty acids was evaluated for its anti-inflammatory efficacy in patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST) receiving curative surgery. MATERIALS AND METHODS This prospective, randomized, double-blind study recruited 34 patients with gastric adenocarcinoma or gastric GIST undergoing elective curative surgery. These patients were randomly assigned to the study group, receiving immune-modulating nutrient-enriched EN, or the control group, receiving standard EN from 3 days before surgery (preoperative day 3) to up to postoperative day 14 or discharge. Laboratory and inflammatory parameters were assessed on preoperative day 3 and postoperative day 14 or at discharge. Adverse events (AEs) and clinical outcomes were documented daily and compared between groups. RESULTS No significant differences were observed between the two groups in selected laboratory and inflammatory parameters, or in their net change, before and after treatment. AEs and clinical outcomes, including infectious complications, overall complications, time to first bowel action, and length of hospital stay after surgery, were comparable between treatment groups (all P > 0.05). CONCLUSION Immune-modulating nutrient-enriched EN had no prominent immunomodulation effect compared with that of standard EN.
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Perioperative glutamine supplementation restores disturbed renal arginine synthesis after open aortic surgery: a randomized controlled clinical trial.
Brinkmann, SJ, Buijs, N, Vermeulen, MA, Oosterink, E, Schierbeek, H, Beishuizen, A, de Vries, JP, Wisselink, W, van Leeuwen, PA
American journal of physiology. Renal physiology. 2016;(3):F567-75
Abstract
Postoperative renal failure is a common complication after open repair of an abdominal aortic aneurysm. The amino acid arginine is formed in the kidneys from its precursor citrulline, and citrulline is formed from glutamine in the intestines. Arginine enhances the function of the immune and cardiovascular systems, which is important for recovery after surgery. We hypothesized that renal arginine production is diminished after ischemia-reperfusion injury caused by clamping of the aorta during open abdominal aortic surgery and that parenteral glutamine supplementation might compensate for this impaired arginine synthesis. This open-label clinical trial randomized patients who underwent clamping of the aorta during open abdominal aortic surgery to receive a perioperative supplement of intravenous alanyl-glutamine (0.5 g·kg(-1)·day(-1); group A, n = 5) or no supplement (group B, n = 5). One day after surgery, stable isotopes and tracer methods were used to analyze the metabolism and conversion of glutamine, citrulline, and arginine. Whole body plasma flux of glutamine, citrulline, and arginine was significantly higher in group A than in group B (glutamine: 391 ± 34 vs. 258 ± 19 μmol·kg(-1)·h(-1), citrulline: 5.7 ± 0.4 vs. 2.8 ± 0.4 μmol·kg(-1)·h(-1), and arginine: 50 ± 4 vs. 26 ± 2 μmol·kg(-1)·h(-1), P < 0.01), as was the synthesis of citrulline from glutamine (4.8 ± 0.7 vs. 1.6 ± 0.3 μmol·kg(-1)·h(-1)), citrulline from arginine (2.3 ± 0.3 vs. 0.96 ± 0.1 μmol·kg(-1)·h(-1)), and arginine from glutamine (7.7 ± 0.4 vs. 2.8 ± 0.2 μmol·kg(-1)·h(-1)), respectively (P < 0.001 for all). In conclusion, the production of citrulline and arginine is severely reduced after clamping during aortic surgery. This study shows that an intravenous supplement of glutamine increases the production of citrulline and arginine and compensates for the inhibitory effect of ischemia-reperfusion injury.
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Arginine and citrulline and the immune response in sepsis.
Wijnands, KA, Castermans, TM, Hommen, MP, Meesters, DM, Poeze, M
Nutrients. 2015;(3):1426-63
Abstract
Arginine, a semi-essential amino acid is an important initiator of the immune response. Arginine serves as a precursor in several metabolic pathways in different organs. In the immune response, arginine metabolism and availability is determined by the nitric oxide synthases and the arginase enzymes, which convert arginine into nitric oxide (NO) and ornithine, respectively. Limitations in arginine availability during inflammatory conditions regulate macrophages and T-lymfocyte activation. Furthermore, over the past years more evidence has been gathered which showed that arginine and citrulline deficiencies may underlie the detrimental outcome of inflammatory conditions, such as sepsis and endotoxemia. Not only does the immune response contribute to the arginine deficiency, also the impaired arginine de novo synthesis in the kidney has a key role in the eventual observed arginine deficiency. The complex interplay between the immune response and the arginine-NO metabolism is further underscored by recent data of our group. In this review we give an overview of physiological arginine and citrulline metabolism and we address the experimental and clinical studies in which the arginine-citrulline NO pathway plays an essential role in the immune response, as initiator and therapeutic target.
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Molecular recognition of arginine by supramolecular complexation with calixarene crown ether based on surface plasmon resonance.
Chen, H, Gu, L, Yin, Y, Koh, K, Lee, J
International journal of molecular sciences. 2011;(4):2315-24
Abstract
Arginine plays an important role in cell division and the functioning of the immune system. We describe a novel method by which arginine can be identified using an artificial monolayer based on surface plasmon resonance (SPR). The affinity of arginine binding its recognition molecular was compared to that of lysine. In fabrication of an arginine sensing interface, a calix[4]crown ether monolayer was anchored onto a gold surface and then characterized by Fourier Transform infrared reflection absorption spectroscopy, atomic force microscopy, and cyclic voltammetry. The interaction between arginine and its host compound was investigated by SPR. The calix[4]crown ether was found to assemble as a monolayer on the gold surface. Recognition of calix[4]crown monolayer was assessed by the selective binding of arginine. Modification of the SPR chip with the calix[4]crown monolayer provides a reliable and simple experimental platform for investigation of arginine under aqueous conditions.
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The pharmacodynamics of L-arginine.
Böger, RH
The Journal of nutrition. 2007;(6 Suppl 2):1650S-1655S
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Abstract
L-arginine is a precursor for nitric oxide (NO) synthesis. NO is a ubiquitous mediator that is formed by a family of enzymes named NO synthases. In the brain, NO acts as a neurotransmitter; in the immune system, NO acts as a mediator of host defense; and in the cardiovascular system, NO mediates the protective effects of the intact endothelium, acting as a vasodilator and endogenous antiatherogenic molecule. About 5 g of L-arginine is ingested each day in a normal Western diet. L-arginine plasma levels are not significantly reduced in most disease conditions, except end-stage renal failure during hemodialysis treatment. Nonetheless, intravenous or dietary (oral) administration of relatively large doses of L-arginine has been shown to result in enhanced NO formation in subjects with impaired endothelial function at baseline. In several controlled clinical trials, long-term administration of L-arginine has been shown to improve the symptoms of cardiovascular disease. However, in other trials L-arginine was not beneficial, and in a recent study, the authors reported higher mortality of subjects receiving L-arginine than those receiving placebo. Recently it became clear that endogenous levels of asymmetric dimethylarginine (ADMA), a competitive inhibitor of L-arginine metabolism by NO synthase, may determine a subject's response to L-arginine supplementation. L-arginine appears to exert no effect in subjects with low ADMA levels, whereas in subjects with high ADMA levels, L-arginine restores the L-arginine/ADMA ratio to normal levels and thereby normalizes endothelial function. In conclusion, the effects of L-arginine supplementation on human physiology appear to be multicausal and dose-related. Doses of 3-8 g/d appear to be safe and not to cause acute pharmacologic effects in humans.
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Role of enteral immunonutrition in patients with gastric carcinoma undergoing major surgery.
Chen, DW, Wei Fei, Z, Zhang, YC, Ou, JM, Xu, J
Asian journal of surgery. 2005;(2):121-4
Abstract
OBJECTIVE To evaluate the influence of postoperative immunonutrition on immune and nutritional parameters in patients with gastric carcinoma. METHODS From September 2002 to August 2003, 40 patients with gastric carcinoma who had undergone major surgery were randomly divided into an immunonutrition group and standard nutrition group, each of 20 patients. On postoperative Day 2, patients in the standard nutrition group received a standard enteral formula, while those in the immunonutrition group received an enteral formula enriched with glutamine, arginine and omega-3 fatty acids. Nutritional support was continued for 7 days. Blood samples were obtained to determine plasma albumin, prealbumin and transferrin on Days 0, 5 and 9. On Days 0, 1 and 9, blood samples were collected to detect immunoglobulin (Ig) A, IgG, IgM, CD4 and CD8 cell counts, the ratio of CD4/CD8, interleukin (IL)-2, IL-6 and tumour necrosis factor (TNF)-alpha, respectively. RESULTS There were no significant differences between the two groups in protein and immune parameters preoperatively and no significant differences in management perioperatively. No serious adverse effects were recorded with the two formulas. Postoperative procedures were smooth in both groups. On Day 9, serum levels of prealbumin and transferrin were higher in the immunonutrition group than in the standard nutrition group (p<0.01). After 7 days' nutritional support, patients in the immunonutrition group had higher levels of immunoglobulin, CD4 cell counts, CD4/CD8 ratio and IL-2 than those in the control group, whereas IL-6 and TNF-alpha levels were significantly lower in the immunonutrition group. CONCLUSION Compared with standard enteral nutrition, enteral immunonutrition can improve defence mechanisms and modulate inflammatory action after major elective surgery for gastric carcinoma.