Longitudinal Assessment of Gut Hormone Secretion Following Upper Gastrointestinal Surgery for Cancer

NCT02385630 | Completed

• 2 other identifiers: CRFSJ 00582014-12 CA
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Surgery is the cornerstone of treatment for patients with oesophageal or gastric cancer, but while surgical removal of the tumour (oesophagectomy or gastrectomy) may offer the best chance of cure, these are major operations associated with specific long term complications. Weight loss and poor nutrition are relatively 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. The investigators research has demonstrated increased levels of chemical messengers (gut hormones) released from the gastrointestinal tract after meals in patients who have previously undergone upper gastrointestinal surgery. These chemical messengers play a role in signalling the feeling of fullness during and after a meal (satiety). Understanding the mechanisms involved in increased gut hormone secretion after these operations may allow us to use certain medications to block gut hormone release and hence reduce satiety allowing patients to eat more, regain weight and prevent nutritional complications after surgery. Exaggerated post-prandial satiety gut hormone responses following oesophagectomy have, however, only been established cross-sectionally and therefore the time course for development of increased gut hormone secretion is unknown. Data collected from this study will provide important information about optimal timing of therapeutic intervention in this patient group, while offering mechanistic insights with regard to the pathophysiologic process underlying post-operative early satiety.

Conditions

Esophageal Neoplasms; Stomach Neoplasms; Weight Loss; Malnutrition

Keywords

Longitudinal Studies; Esophagectomy; Gastrectomy; Hunger; Appetite; Glucagon-like Peptide 1; Peptide YY; Ghrelin; Satiety Response; Feeding Behavior; Meals; Postprandial Period

Outcome Measures

Primary Outcomes (1)

• Post-prandial satiety gut hormone area under the curve

  1 year

Secondary Outcomes (4)

• Body anthropometry

  1 year

• EORTC health related quality of life at one year

  1 year

• Subjective symptom scores

  1 year

• Fasting ghrelin concentration

  1 year

Study Arms (2)

Esophagectomy

EXPERIMENTAL

Serial assessment: Fasting gut hormones, post-prandial gut hormone response to a standardized 400kcal meal

Other: Standardized 400kcal semi-liquid meal

Gastrectomy

EXPERIMENTAL

Serial assessment: Fasting gut hormones, post-prandial gut hormone response to a standardized 400kcal meal

Other: Standardized 400kcal semi-liquid meal

Interventions

Standardized 400kcal semi-liquid meal OTHER

Used to assess post-prandial gut hormone response pre-operatively and at 10 days, 4 weeks, 6 months and 12 months post-operatively.

Esophagectomy; Gastrectomy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients scheduled to undergo two-stage, three-stage or transhiatal oesophagectomy with gastric conduit reconstruction OR total gastrectomy with Roux-en-Y reconstruction

You may not qualify if:

• Significant and persistent chemoradiotherapy complication
• Other previous upper gastrointestinal surgery
• Unwell or unable to eat
• Other disease or medications which may affect satiety gut hormone responses
• Active and significant psychiatric illness including substance misuse
• Cognitive or communication issues or any factors affecting capacity to consent to participation
• History of significant food allergy, certain dietary restrictions
• Confirmed or suspected residual or recurrent disease after surgery, synchronous or metachronous malignancy
• Significant surgical complication, aspiration risk or deterioration in performance

Sponsors & Collaborators

• St. James's Hospital, Ireland: lead
• University College Dublin: collaborator
• University of Dublin, Trinity College: collaborator

Study Sites (1)

Wellcome Trust-Health Research Board Clinical Research Facility, St. James's Hospital

Dublin, D8, Ireland

Location

Related Publications (13)

• Martin L, Lagergren J, Lindblad M, Rouvelas I, Lagergren P. Malnutrition after oesophageal cancer surgery in Sweden. Br J Surg. 2007 Dec;94(12):1496-500. doi: 10.1002/bjs.5881.

  PMID: 17668914 BACKGROUND

• Martin L, Lagergren P. Long-term weight change after oesophageal cancer surgery. Br J Surg. 2009 Nov;96(11):1308-14. doi: 10.1002/bjs.6723.

  PMID: 19847871 BACKGROUND

• Donohoe CL, McGillycuddy E, Reynolds JV. Long-term health-related quality of life for disease-free esophageal cancer patients. World J Surg. 2011 Aug;35(8):1853-60. doi: 10.1007/s00268-011-1123-6.

  PMID: 21553202 BACKGROUND

• Yamamoto K, Takiguchi S, Miyata H, Adachi S, Hiura Y, Yamasaki M, Nakajima K, Fujiwara Y, Mori M, Kangawa K, Doki Y. Randomized phase II study of clinical effects of ghrelin after esophagectomy with gastric tube reconstruction. Surgery. 2010 Jul;148(1):31-8. doi: 10.1016/j.surg.2009.11.026. Epub 2010 Jan 21.

  PMID: 20096432 BACKGROUND

• Miyazaki T, Tanaka N, Hirai H, Yokobori T, Sano A, Sakai M, Inose T, Sohda M, Nakajima M, Fukuchi M, Kato H, Kuwano H. Ghrelin level and body weight loss after esophagectomy for esophageal cancer. J Surg Res. 2012 Jul;176(1):74-8. doi: 10.1016/j.jss.2011.09.016. Epub 2011 Oct 3.

  PMID: 22137988 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.

  PMID: 21440118 BACKGROUND

• Doki Y, Takachi K, Ishikawa O, Miyashiro I, Sasaki Y, Ohigashi H, Nakajima H, Hosoda H, Kangawa K, Sasakuma F, Motoori M, Imaoka S. Ghrelin reduction after esophageal substitution and its correlation to postoperative body weight loss in esophageal cancer patients. Surgery. 2006 Jun;139(6):797-805. doi: 10.1016/j.surg.2005.11.015.

  PMID: 16782437 BACKGROUND

• le Roux CW, Welbourn R, Werling M, Osborne A, Kokkinos A, Laurenius A, Lonroth H, Fandriks L, Ghatei MA, Bloom SR, Olbers T. Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Ann Surg. 2007 Nov;246(5):780-5. doi: 10.1097/SLA.0b013e3180caa3e3.

  PMID: 17968169 BACKGROUND

• Papamargaritis D, le Roux CW, Sioka E, Koukoulis G, Tzovaras G, Zacharoulis D. Changes in gut hormone profile and glucose homeostasis after laparoscopic sleeve gastrectomy. Surg Obes Relat Dis. 2013 Mar-Apr;9(2):192-201. doi: 10.1016/j.soard.2012.08.007. Epub 2012 Aug 24.

  PMID: 23183113 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.

  PMID: 8319842 BACKGROUND

• le Roux CW, Borg C, Wallis K, Vincent RP, Bueter M, Goodlad R, Ghatei MA, Patel A, Bloom SR, Aylwin SJ. Gut hypertrophy after gastric bypass is associated with increased glucagon-like peptide 2 and intestinal crypt cell proliferation. Ann Surg. 2010 Jul;252(1):50-6. doi: 10.1097/SLA.0b013e3181d3d21f.

  PMID: 20562614 BACKGROUND

• Elliott JA, Docherty NG, Eckhardt HG, Doyle SL, Guinan EM, Ravi N, Reynolds JV, Roux CWL. Weight Loss, Satiety, and the Postprandial Gut Hormone Response After Esophagectomy: A Prospective Study. Ann Surg. 2017 Jul;266(1):82-90. doi: 10.1097/SLA.0000000000001918.

  PMID: 27455150 RESULT

• Elliott JA, Docherty NG, Murphy CF, Eckhardt HG, Doyle SL, Guinan EM, Ravi N, Reynolds JV, le Roux CW. Changes in gut hormones, glycaemic response and symptoms after oesophagectomy. Br J Surg. 2019 May;106(6):735-746. doi: 10.1002/bjs.11118. Epub 2019 Mar 18.

  PMID: 30883706 RESULT

Related Links

• Wellcome Trust-HRB Clinical Research Facility
• Conway Institute of Biomolecular and Biomedical Research

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms; Weight Loss; Malnutrition; Feeding Behavior

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Nutrition Disorders; Nutritional and Metabolic Diseases; Behavior, Animal; Behavior

Study Officials

• John V Reynolds, MCh, FRCS

  Department of Surgery, St. James's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Surgical Research Fellow

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: March 11, 2015
• Study Start: March 1, 2015
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: August 18, 2021

Record last verified: 2021-08

Locations

IE (1)