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

J Clin Endocrinol Metab. 2021 Jan 1;106(1):e204-e216. doi: 10.1210/clinem/dgaa697.

Abstract

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.

Keywords: eating behavior; enteroendocrine signaling; esophagectomy; fMRI; food reward; gut-brain axis; weight loss.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / surgery
  • Aged
  • Brain / drug effects
  • Brain / physiology
  • Delayed-Action Preparations / therapeutic use
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / surgery
  • Esophagectomy* / adverse effects
  • Feasibility Studies
  • Female
  • Gastrointestinal Hormones / metabolism
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / innervation
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Octreotide / therapeutic use*
  • Pilot Projects
  • Postoperative Complications / drug therapy
  • Postoperative Complications / etiology
  • Postprandial Period
  • Reward
  • Satiety Response / drug effects
  • Satiety Response / physiology
  • Signal Transduction / drug effects
  • Wasting Syndrome / drug therapy*
  • Wasting Syndrome / etiology
  • Weight Loss / drug effects
  • Weight Loss / physiology

Substances

  • Delayed-Action Preparations
  • Gastrointestinal Hormones
  • Octreotide