The Effect of Satiety Gut Hormone Modulation on Appetitive Drive After Upper Gastrointestinal Surgery

Summary

Improvements to treatment strategies for patients with cancers of the upper gastrointestinal tract have produced a large population of people who remain free from cancer recurrence in the long term following treatment. Surgery is the cornerstone of treatment for patients with these cancers, but while surgical removal of the tumour may offer the best chance of cure, these are major operations associated with specific long term complications. Weight loss and poor nutrition are common problems among patients who attain long-term cancer remission and cure after surgery. The mechanisms underlying these problems are not well understood and therefore treatment options are limited. Our research has demonstrated increased levels of chemical messengers (gut hormones) released from the gastrointestinal tract after meals in patients who have previously undergone this type of surgery. These chemical messengers play a role in controlling appetite and interest in food, and increased levels after surgery may reduce interest in eating. Understanding the role of gut hormones in the control of appetite may allow us to use certain medications to block gut hormones and hence increase appetite, allowing patients to eat more and regain weight, preventing nutritional problems after surgery. In this study, the investigators aim to determine whether exaggerated gut hormone secretion causes reduced appetite and interest in food after surgery. The information gained from this study may help us to develop treatments for patients with weight loss and nutritional problems after surgery.

Timeline

Start

2015-03

Primary completion

2018-03

Completion

2018-03

Publications

• Background Miras AD, Jackson RN, Jackson SN, Goldstone AP, Olbers T, Hackenberg T, Spector AC, le Roux CW. Gastric bypass surgery for obesity decreases the reward value of a sweet-fat stimulus as assessed in a progressive ratio task. Am J Clin Nutr. 2012 Sep;96(3):467-73. doi: 10.3945/ajcn.112.036921. Epub 2012 Jul 25.
• Background HODOS W. Progressive ratio as a measure of reward strength. Science. 1961 Sep 29;134(3483):943-4. doi: 10.1126/science.134.3483.943.
• Background Miholic J, Orskov C, Holst JJ, Kotzerke J, Pichlmayr R. Postprandial release of glucagon-like peptide-1, pancreatic glucagon, and insulin after esophageal resection. Digestion. 1993;54(2):73-8. doi: 10.1159/000201016.
• Background Haverkort EB, Binnekade JM, Busch OR, van Berge Henegouwen MI, de Haan RJ, Gouma DJ. Presence and persistence of nutrition-related symptoms during the first year following esophagectomy with gastric tube reconstruction in clinically disease-free patients. World J Surg. 2010 Dec;34(12):2844-52. doi: 10.1007/s00268-010-0786-8.
• Background Koizumi M, Hosoya Y, Dezaki K, Yada T, Hosoda H, Kangawa K, Nagai H, Lefor AT, Sata N, Yasuda Y. Postoperative weight loss does not resolve after esophagectomy despite normal serum ghrelin levels. Ann Thorac Surg. 2011 Apr;91(4):1032-7. doi: 10.1016/j.athoracsur.2010.11.072.
• Background le Roux CW, Aylwin SJ, Batterham RL, Borg CM, Coyle F, Prasad V, Shurey S, Ghatei MA, Patel AG, Bloom SR. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg. 2006 Jan;243(1):108-14. doi: 10.1097/01.sla.0000183349.16877.84.
• Elliott JA, Docherty NG, Haag J, Eckhardt HG, Ravi N, Reynolds JV, le Roux CW. Attenuation of satiety gut hormones increases appetitive behavior after curative esophagectomy for esophageal cancer. Am J Clin Nutr. 2019 Feb 1;109(2):335-344. doi: 10.1093/ajcn/nqy324.

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