Effects of early enteral nutrition containing ω-3 polyunsaturated fatty acids combined withintravenous infusion of alanyl-glutamine on inflammatory response and immune function of postoperative gastric cancer patients_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CUI Yaping , ZHAO Rui , WANG Yong , LI Zhigui , SU Xiangnan , WAN Qianyi , XIA Lin , ZHOU Yong ,  WU Xiaoting

Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding?author：

WU Xiaoting, Email: wxt1@medmail.com.cn

Keywords：

gastric cancer; ω-3 polyunsaturated fatty acids; alanyl-glutamine; inflammatory response; immune function

DOI：

10.7507/1007-9424.201904001

Video：

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Objective To investigate the effects of early enteral nutrition containing ω-3 polyunsaturated fatty acids combined with intravenous infusion of alanyl-glutamine on inflammatory response and immune function of postoperative gastric cancer patients.Methods A total of 110 patients, accepting radical operation for gastric cancer in West China Hospital of Sichuan University during October 2017 to December 2018, were prospectively incorporated in the study and were randomly divided into 2 groups equally. Patients in the control group were enterally fed with a formula containing ω-3 polyunsaturated fatty acids for 6 consecutive days after surgery. Patients in the experimental group accepted the same enteral feeding but combined with intravenous infusion of alanyl-glutamine (20 g/d). Both enteral feeding and intravenous infusion started within 24 hours after surgery. Peripheral venous blood was gathered within 3 days before surgery and on the morning of the first, third, and seventh postoperative days to detect inflammatory, immunological, and nutritional indexes. Complications, length of hospital stay, and hospital cost were also taken notes.Results Fifty-two patients in the control group and fifty-two patients in the experimental group respectively finished the study. In both groups, 3 patients withdrew from the study for inadequacy of radical operation. Neutrophilic granulocyte percentage, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) on the third postoperative day, C-reactive protein (CRP), procalcitonin (PCT), IL-6, and TNF-α on the seventh postoperative day, were significantly lower in the experimental group (P<0.05). Immunological indexes including immunoglobulin G (IGG), immunoglobulin A (IGA), percentage of CD3⁺ T cells, and percentage of CD4⁺ T cells, nutritional markers including total protein (TP), plasma albumin (ALB), and prealbumin (PAB) were significantly higher in the experimental group on the seventh postoperative day (P<0.05). When the study ended, none significant differences of the rates of both infectious complications (wound infection, intra-abdominal infection, pulmonary infection, urinary system infection, blood system infection, and anastomotic fistula) and noninfectious complications (diarrhea, abdominal distension, and abdominal pain) were observed between the two groups (P>0.05). Time of the first anal discharge, length of hospital stay, and hospitalization cost between the two groups were not significantly different neither (P>0.05).Conclusion Early enteral nutrition containing ω-3 polyunsaturated fatty acids combined with intravenous infusion of alanyl-glutamine contributes to reduce inflammatory response and improve immune function and nutrition status of patients with gastric cancer after surgery.

Citation： CUI Yaping, ZHAO Rui, WANG Yong, LI Zhigui, SU Xiangnan, WAN Qianyi, XIA Lin, ZHOU Yong, WU Xiaoting. Effects of early enteral nutrition containing ω-3 polyunsaturated fatty acids combined withintravenous infusion of alanyl-glutamine on inflammatory response and immune function of postoperative gastric cancer patients. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(7): 785-791. doi: 10.7507/1007-9424.201904001 Copy

1.	Pan H, Cai S, Ji J, et al. The impact of nutritional status, nutritional risk, and nutritional treatment on clinical outcome of 2 248 hospitalized cancer patients: a multi-center, prospective cohort study in Chinese teaching hospitals. Nutr Cancer, 2013, 65(1): 62-70.
2.	石漢平, 李蘇宜, 王昆華, 等. 胃癌患者營養治療指南. 腫瘤代謝與營養電子雜志, 2015, 2(2): 37-40.
3.	Schattner M. Enteral nutritional support of the patient with cancer: route and role. J Clin Gastroenterol, 2003, 36(4): 297-302.
4.	Weimann A, Braga M, Carli F, et al. ESPEN guideline: clinical nutrition in surgery. Clin Nutr, 2017, 36(3): 623-650.
5.	McClave SA, DiBaise JK, Mullin GE, et al. ACG clinical guideline: nutrition therapy in the adult hospitalized patient. Am J Gastroenterol, 2016, 111(3): 315-334.
6.	Liu H, Ling W, Shen ZY, et al. Clinical application of immune-enhanced enteral nutrition in patients with advanced gastric cancer after total gastrectomy. J Dig Dis, 2012, 13(8): 401-406.
7.	Luo Z, Wang J, Zhang Z, et al. Efficacy of early enteral immunonutrition on immune function and clinical outcome for postoperative patients with gastrointestinal cancer. JPEN J Parenter Enteral Nutr, 2017, [Epub ahead of print].
8.	Dias Rodrigues V, Barroso de Pinho N, Abdelhay E, et al. Nutrition and immune-modulatory intervention in surgical patients with gastric cancer. Nutr Clin Pract, 2017, 32(1): 122-129.
9.	Cheng Y, Zhang J, Zhang L, et al. Enteral immunonutrition versus enteral nutrition for gastric cancer patients undergoing a total gastrectomy: a systematic review and meta-analysis. BMC Gastroenterol, 2018, 18(1): 11.
10.	郭志學, 王穎, 朱婭, 等. 胃癌胃大部分切除術后早期免疫增強型腸內營養支持治療效果分析. 河北醫藥, 2017, 39(3): 388-389, 393.
11.	趙得新, 朱甲明, 陳云波. 免疫增強型腸內營養對胃癌根治病人術后免疫功能和炎癥反應的影響. 中國實驗診斷學, 2011, 15(3): 428-430.
12.	Hall JC, Heel K, McCauley R. Glutamine. Br J Surg, 1996, 83(3): 305-312.
13.	Hammarqvist F, Wernerman J, Ali R, et al. Addition of glutamine to total parenteral nutrition after elective abdominal surgery spares free glutamine in muscle, counteracts the fall in muscle protein synthesis, and improves nitrogen balance. Ann Surg, 1989, 209(4): 455-461.
14.	Calder PC, Yaqoob P. Glutamine and the immune system. Amino Acids, 1999, 17(3): 227-241.
15.	Parry-Billings M, Baigrie RJ, Lamont PM, et al. Effects of major and minor surgery on plasma glutamine and cytokine levels. Arch Surg, 1992, 127(10): 1237-1240.
16.	Labow BI, Souba WW. Glutamine. World J Surg, 2000, 24(12): 1503-1513.
17.	Morlion BJ, Stehle P, Wachtler P, et al. Total parenteral nutrition with glutamine dipeptide after major abdominal surgery: a randomized, double-blind, controlled study. Ann Surg, 1998, 227(2): 302-308.
18.	Jacobi CA, Ordemann J, Zuckermann H, et al. The influence of alanyl-glutamine on immunologic functions and morbidity in postoperative total parenteral nutrition. Preliminary results of a prospective randomized trial. Zentralbl Chir, 1999, 124(3): 199-205.
19.	Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more " personalized” approach to cancer staging. CA Cancer J Clin, 2017, 67(2): 93-99.
20.	趙波, 昝建寶, 徐愛忠, 等. 谷氨酰胺聯合腸內營養對胃癌患者術后血清 C 反應蛋白及免疫功能的影響. 安徽醫藥, 2016, 20(5): 992-993, 994.
21.	Li NM, Liu F, Lv FY, et al. Influencing factors and interventional strategies for early enteral nutrition after gastric carcinoma surgery. J Cancer Res Ther, 2016, 12(2): 689-692.
22.	劉卓, 于杰. 免疫增強型腸內營養對胃癌根治患者術后免疫功能和炎癥反應的影響. 中華腫瘤防治雜志, 2011, 18(1): 66-67, 69.
23.	伍映鑫, 夏霖, 王勇, 等. 胃癌患者術前應用含 ω-3 不飽和脂肪酸的腸內營養制劑的臨床效果觀察. 中國普外基礎與臨床雜志, 2015, 22(3): 312-316.
24.	Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol, 2013, 75(3): 645-662.
25.	王新穎, 黎介壽. ω-3 多不飽和脂肪酸影響炎癥和免疫功能的基礎研究. 腸外與腸內營養, 2007, 14(1): 54-58.
26.	梁濤, 伍曉汀. ω-3 多不飽和脂肪酸對老年胃癌患者術后譫妄的預防作用. 中國普外基礎與臨床雜志, 2019, 26(2): 174-179.
27.	全竹富, 袁志超, 黎介壽. 丙氨酰-谷氨酰胺雙肽對術后腸道通透性和全身炎性反應的影響. 腸外與腸內營養, 2010, 17(1): 13-16.
28.	李幼生, 黎介壽. 谷氨酰胺二肽的研究進展. 中華胃腸外科雜志, 2002, 5(3): 232-233.
29.	Wilmore DW. The effect of glutamine supplementation in patients following elective surgery and accidental injury. J Nutr, 2001, 131(9 Suppl): 2543S-2549S.
30.	Lu CY, Shih YL, Sun LC, et al. The inflammatory modulation effect of glutamine-enriched total parenteral nutrition in postoperative gastrointestinal cancer patients. Am Surg, 2011, 77(1): 59-64.
31.	蔣冬. 谷氨酰胺聯合早期腸內營養支持對胃癌患者行 3D 腹腔鏡胃癌根治術后血清 T 細胞亞群水平及康復進程的影響. 臨床醫學工程, 2018, 25(2): 133-134.
32.	劉輝, 陳信義, 石玉春. 谷氨酰胺強化腸內營養對晚期胃癌患者免疫功能及營養指標的影響. 癌癥進展, 2018, 16(8): 1024-1027.

1. Pan H, Cai S, Ji J, et al. The impact of nutritional status, nutritional risk, and nutritional treatment on clinical outcome of 2 248 hospitalized cancer patients: a multi-center, prospective cohort study in Chinese teaching hospitals. Nutr Cancer, 2013, 65(1): 62-70.
2. 石漢平, 李蘇宜, 王昆華, 等. 胃癌患者營養治療指南. 腫瘤代謝與營養電子雜志, 2015, 2(2): 37-40.
3. Schattner M. Enteral nutritional support of the patient with cancer: route and role. J Clin Gastroenterol, 2003, 36(4): 297-302.
4. Weimann A, Braga M, Carli F, et al. ESPEN guideline: clinical nutrition in surgery. Clin Nutr, 2017, 36(3): 623-650.
5. McClave SA, DiBaise JK, Mullin GE, et al. ACG clinical guideline: nutrition therapy in the adult hospitalized patient. Am J Gastroenterol, 2016, 111(3): 315-334.
6. Liu H, Ling W, Shen ZY, et al. Clinical application of immune-enhanced enteral nutrition in patients with advanced gastric cancer after total gastrectomy. J Dig Dis, 2012, 13(8): 401-406.
7. Luo Z, Wang J, Zhang Z, et al. Efficacy of early enteral immunonutrition on immune function and clinical outcome for postoperative patients with gastrointestinal cancer. JPEN J Parenter Enteral Nutr, 2017, [Epub ahead of print].
8. Dias Rodrigues V, Barroso de Pinho N, Abdelhay E, et al. Nutrition and immune-modulatory intervention in surgical patients with gastric cancer. Nutr Clin Pract, 2017, 32(1): 122-129.
9. Cheng Y, Zhang J, Zhang L, et al. Enteral immunonutrition versus enteral nutrition for gastric cancer patients undergoing a total gastrectomy: a systematic review and meta-analysis. BMC Gastroenterol, 2018, 18(1): 11.
10. 郭志學, 王穎, 朱婭, 等. 胃癌胃大部分切除術后早期免疫增強型腸內營養支持治療效果分析. 河北醫藥, 2017, 39(3): 388-389, 393.
11. 趙得新, 朱甲明, 陳云波. 免疫增強型腸內營養對胃癌根治病人術后免疫功能和炎癥反應的影響. 中國實驗診斷學, 2011, 15(3): 428-430.
12. Hall JC, Heel K, McCauley R. Glutamine. Br J Surg, 1996, 83(3): 305-312.
13. Hammarqvist F, Wernerman J, Ali R, et al. Addition of glutamine to total parenteral nutrition after elective abdominal surgery spares free glutamine in muscle, counteracts the fall in muscle protein synthesis, and improves nitrogen balance. Ann Surg, 1989, 209(4): 455-461.
14. Calder PC, Yaqoob P. Glutamine and the immune system. Amino Acids, 1999, 17(3): 227-241.
15. Parry-Billings M, Baigrie RJ, Lamont PM, et al. Effects of major and minor surgery on plasma glutamine and cytokine levels. Arch Surg, 1992, 127(10): 1237-1240.
16. Labow BI, Souba WW. Glutamine. World J Surg, 2000, 24(12): 1503-1513.
17. Morlion BJ, Stehle P, Wachtler P, et al. Total parenteral nutrition with glutamine dipeptide after major abdominal surgery: a randomized, double-blind, controlled study. Ann Surg, 1998, 227(2): 302-308.
18. Jacobi CA, Ordemann J, Zuckermann H, et al. The influence of alanyl-glutamine on immunologic functions and morbidity in postoperative total parenteral nutrition. Preliminary results of a prospective randomized trial. Zentralbl Chir, 1999, 124(3): 199-205.
19. Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more " personalized” approach to cancer staging. CA Cancer J Clin, 2017, 67(2): 93-99.
20. 趙波, 昝建寶, 徐愛忠, 等. 谷氨酰胺聯合腸內營養對胃癌患者術后血清 C 反應蛋白及免疫功能的影響. 安徽醫藥, 2016, 20(5): 992-993, 994.
21. Li NM, Liu F, Lv FY, et al. Influencing factors and interventional strategies for early enteral nutrition after gastric carcinoma surgery. J Cancer Res Ther, 2016, 12(2): 689-692.
22. 劉卓, 于杰. 免疫增強型腸內營養對胃癌根治患者術后免疫功能和炎癥反應的影響. 中華腫瘤防治雜志, 2011, 18(1): 66-67, 69.
23. 伍映鑫, 夏霖, 王勇, 等. 胃癌患者術前應用含 ω-3 不飽和脂肪酸的腸內營養制劑的臨床效果觀察. 中國普外基礎與臨床雜志, 2015, 22(3): 312-316.
24. Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol, 2013, 75(3): 645-662.
25. 王新穎, 黎介壽. ω-3 多不飽和脂肪酸影響炎癥和免疫功能的基礎研究. 腸外與腸內營養, 2007, 14(1): 54-58.
26. 梁濤, 伍曉汀. ω-3 多不飽和脂肪酸對老年胃癌患者術后譫妄的預防作用. 中國普外基礎與臨床雜志, 2019, 26(2): 174-179.
27. 全竹富, 袁志超, 黎介壽. 丙氨酰-谷氨酰胺雙肽對術后腸道通透性和全身炎性反應的影響. 腸外與腸內營養, 2010, 17(1): 13-16.
28. 李幼生, 黎介壽. 谷氨酰胺二肽的研究進展. 中華胃腸外科雜志, 2002, 5(3): 232-233.
29. Wilmore DW. The effect of glutamine supplementation in patients following elective surgery and accidental injury. J Nutr, 2001, 131(9 Suppl): 2543S-2549S.
30. Lu CY, Shih YL, Sun LC, et al. The inflammatory modulation effect of glutamine-enriched total parenteral nutrition in postoperative gastrointestinal cancer patients. Am Surg, 2011, 77(1): 59-64.
31. 蔣冬. 谷氨酰胺聯合早期腸內營養支持對胃癌患者行 3D 腹腔鏡胃癌根治術后血清 T 細胞亞群水平及康復進程的影響. 臨床醫學工程, 2018, 25(2): 133-134.
32. 劉輝, 陳信義, 石玉春. 谷氨酰胺強化腸內營養對晚期胃癌患者免疫功能及營養指標的影響. 癌癥進展, 2018, 16(8): 1024-1027.

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effects of early enteral nutrition containing ω-3 polyunsaturated fatty acids combined withintravenous infusion of alanyl-glutamine on inflammatory response and immune function of postoperative gastric cancer patients

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