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

Weight Loss Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02385630
• Other study ID #: CRFSJ 0058
• Secondary ID: 2014-12 CA
• Status: Completed
• Phase: N/A
• Start date: March 2015
• Est. completion date: July 2018

Study information

• Verified date: August 2021
• Source: St. James's Hospital, Ireland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

1. Significant and persistent chemoradiotherapy complication

2. Other previous upper gastrointestinal surgery

3. Unwell or unable to eat

4. Other disease or medications which may affect satiety gut hormone responses

5. Active and significant psychiatric illness including substance misuse

6. Cognitive or communication issues or any factors affecting capacity to consent to participation

7. History of significant food allergy, certain dietary restrictions

8. Confirmed or suspected residual or recurrent disease after surgery, synchronous or metachronous malignancy

9. Significant surgical complication, aspiration risk or deterioration in performance

Related Conditions & MeSH terms

• Esophageal Neoplasms
• Malnutrition
• Neoplasms
• Stomach Neoplasms
• Weight Loss

Intervention

Other:
• Standardized 400kcal semi-liquid meal
Used to assess post-prandial gut hormone response pre-operatively and at 10 days, 4 weeks, 6 months and 12 months post-operatively.

Locations

Country	Name	City	State
Ireland	Wellcome Trust-Health Research Board Clinical Research Facility, St. James's Hospital	Dublin

Sponsors (3)

Lead Sponsor	Collaborator
St. James's Hospital, Ireland	University College Dublin, University of Dublin, Trinity College

Country where clinical trial is conducted

Ireland, 

References & Publications (13)

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. — View Citation

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. — View Citation

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.000000000 — View Citation

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 — View Citation

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. — View Citation

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. — View Citation

le Roux CW, Welbourn R, Werling M, Osborne A, Kokkinos A, Laurenius A, Lönroth H, Fändriks 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Post-prandial satiety gut hormone area under the curve		1 year
Secondary	Body anthropometry	Weight (kg)	1 year
Secondary	EORTC health related quality of life at one year	Global health status score	1 year
Secondary	Subjective symptom scores	Sigstad dumping score	1 year
Secondary	Fasting ghrelin concentration		1 year

External Links

•   Conway Institute of Biomolecular and Biomedical Research
•   Department of Surgery, Trinity College Dublin and St. James's Hospital
•   Wellcome Trust-HRB Clinical Research Facility