A Pilot Study of Gut-Brain Signaling after Octreotide Therapy for Unintentional Weight Loss after Esophagectomy

Conor F. Murphy, Nicholas Stratford, Neil G. Docherty, Brendan Moran, Jessie A. Elliott, Marie Louise Healy, Jason P. Mcmorrow, Narayanasamy Ravi, Anthony P. Goldstone, John V. Reynolds, Carel W. Le Roux

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Background: Recurrence-free patients after esophageal cancer surgery face long-term nutritional consequences, occurring in the context of an exaggerated postprandial gut hormone response. Acute gut hormone suppression influences brain reward signaling and eating behavior. This study aimed to suppress gut hormone secretion and characterize reward responses and eating behavior among postesophagectomy patients with unintentional weight loss. Methods: This pilot study prospectively studied postoperative patients with 10% or greater body weight loss (BWL) beyond 1 year who were candidates for clinical treatment with long-acting octreotide (LAR). Before and after 4 weeks of treatment, gut hormone secretion, food cue reactivity (functional magnetic resonance imaging), eating motivation (progressive ratio task), ad libitum food intake, body composition, and symptom burden were assessed. Results: Eight patients (7 male, age: mean ± SD 62.8 ± 9.4 years, postoperative BWL: 15.5 ± 5.8%) participated. Octreotide LAR did not significantly suppress total postprandial plasma glucagon-like peptide-1 response at 4 weeks (P = .08). Postprandial symptom burden improved after treatment (Sigstad score median [range]: 12 [2-28] vs 8 [3-18], P = .04) but weight remained stable (pre: 68.6 ± 12.8 kg vs post: 69.2 ± 13.4 kg, P = .13). There was no significant change in brain reward system responses, during evaluation of high-energy or low-energy food pictures, nor their appeal rating. Moreover, treatment did not alter motivation to eat (P = .41) nor ad libitum food intake(P = .46). Conclusion: The protocol used made it feasible to characterize the gut-brain axis and eating behavior in this cohort. Inadequate suppression of gut hormone responses 4 weeks after octreotide LAR administration may explain the lack of gut-brain pathway alterations. A higher dose or shorter interdose interval may be required to optimize the intervention.

Original languageEnglish
Pages (from-to)E204-E216
Number of pages13
JournalJournal of Clinical Endocrinology and Metabolism
Issue number1
Early online date30 Sept 2020
Publication statusPublished (in print/issue) - 31 Jan 2021

Bibliographical note

Funding Information:
This work was supported by the Irish Cancer Society, Ireland (scholarship award CRS17MUR to C.F.M.).

Publisher Copyright:
© 2020 The Author(s).

© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].


  • eating behavior
  • enteroendocrine signaling
  • esophagectomy
  • fMRI
  • food reward
  • gut-brain axis
  • weight loss


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