Leonard Angka1,2, Andre B Martel1,2,3,4, Juliana Ng1, Amanda Pecarskie5, Manahil Sadiq1, Ahwon Jeong1, Marlena Scaffidi1, Christiano Tanese de Souza1, Michael A Kennedy1, Shaheer Tadros3,4, Rebecca C Auer6,7,8,9,10. 1. Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. 2. Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada. 3. Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada. 4. Division of General Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada. 5. Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada. 6. Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. rauer@toh.ca. 7. Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada. rauer@toh.ca. 8. Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada. rauer@toh.ca. 9. Division of General Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada. rauer@toh.ca. 10. Centre for Infection, Immunity, and Inflammation, University of Ottawa, Ottawa, ON, Canada. rauer@toh.ca.
Abstract
BACKGROUND: Surgery results in severe impairment of natural killer (NK) cell cytotoxicity (NKC) and activity (NKA, cytokine secretion), and a dramatic drop in arginine levels. Postoperative immunosuppression is associated with increased complications and recurrence. Perioperative arginine is reported to reduce postoperative complications. Because arginine modulates NK cell function, this study aimed to determine whether perioperative consumption of arginine-enriched supplements (AES) can improve NK cell function in colorectal cancer (CRC) surgery patients. METHODS: This study randomized 24 CRC patients to receive the AES or isocaloric/isonitrogenous control supplement three times a day for five days before and after surgery. The AES contained 4.2 g of arginine per dose (12.6 g/day). The primary objective was to determine whether AES improved NKC by 50 % compared with the control group after surgery. RESULTS: On surgery day (SD) 1, NKC was significantly reduced postoperatively in the control group by 50 % (interquartile range [IQR], 36-55 %; p = 0.02) but not in the AES group (25 % reduction; IQR, 28-75 %; p = 0.3). Furthermore, AES had no benefit in terms of NKA or NK cell number. Compliance was much greater preoperatively (>91 %) than postoperatively (<46 %). However, despite excellent preoperative compliance, arginine was rapidly cleared from the blood within 4 h after consumption and therefore, did not prevent the postoperative drop in arginine. CONCLUSIONS: Oral consumption of arginine immunonutrition resulted in a modest improvement in NKC after surgery but was unable to prevent postoperative arginine depletion or the suppression of NKA (ClinicalTrials.gov NCT02987296).
BACKGROUND: Surgery results in severe impairment of natural killer (NK) cell cytotoxicity (NKC) and activity (NKA, cytokine secretion), and a dramatic drop in arginine levels. Postoperative immunosuppression is associated with increased complications and recurrence. Perioperative arginine is reported to reduce postoperative complications. Because arginine modulates NK cell function, this study aimed to determine whether perioperative consumption of arginine-enriched supplements (AES) can improve NK cell function in colorectal cancer (CRC) surgery patients. METHODS: This study randomized 24 CRC patients to receive the AES or isocaloric/isonitrogenous control supplement three times a day for five days before and after surgery. The AES contained 4.2 g of arginine per dose (12.6 g/day). The primary objective was to determine whether AES improved NKC by 50 % compared with the control group after surgery. RESULTS: On surgery day (SD) 1, NKC was significantly reduced postoperatively in the control group by 50 % (interquartile range [IQR], 36-55 %; p = 0.02) but not in the AES group (25 % reduction; IQR, 28-75 %; p = 0.3). Furthermore, AES had no benefit in terms of NKA or NK cell number. Compliance was much greater preoperatively (>91 %) than postoperatively (<46 %). However, despite excellent preoperative compliance, arginine was rapidly cleared from the blood within 4 h after consumption and therefore, did not prevent the postoperative drop in arginine. CONCLUSIONS: Oral consumption of arginine immunonutrition resulted in a modest improvement in NKC after surgery but was unable to prevent postoperative arginine depletion or the suppression of NKA (ClinicalTrials.gov NCT02987296).
Authors: Brice Gaudillière; Gabriela K Fragiadakis; Robert V Bruggner; Monica Nicolau; Rachel Finck; Martha Tingle; Julian Silva; Edward A Ganio; Christine G Yeh; William J Maloney; James I Huddleston; Stuart B Goodman; Mark M Davis; Sean C Bendall; Wendy J Fantl; Martin S Angst; Garry P Nolan Journal: Sci Transl Med Date: 2014-09-24 Impact factor: 17.956
Authors: Rashmi Seth; Lee-Hwa Tai; Theresa Falls; Christiano T de Souza; John C Bell; Marc Carrier; Harold Atkins; Robin Boushey; Rebecca A Auer Journal: Ann Surg Date: 2013-07 Impact factor: 12.969
Authors: Elke K M Tjeertes; K H J Ultee; R J Stolker; H J M Verhagen; F M Bastos Gonçalves; A G M Hoofwijk; S E Hoeks Journal: World J Surg Date: 2016-11 Impact factor: 3.352