Longitudinal Assessment of Gut Hormone Secretion Following Upper Gastrointestinal Surgery for Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Esophagectomy Serial assessment: Fasting gut hormones, post-prandial gut hormone response to a standardized 400kcal meal |
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.
|
| Experimental: Gastrectomy Serial assessment: Fasting gut hormones, post-prandial gut hormone response to a standardized 400kcal meal |
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.
|
Outcome Measures
Primary Outcome Measures
- Post-prandial satiety gut hormone area under the curve [1 year]
Secondary Outcome Measures
- Body anthropometry [1 year]
Weight (kg)
- EORTC health related quality of life at one year [1 year]
Global health status score
- Subjective symptom scores [1 year]
Sigstad dumping score
- Fasting ghrelin concentration [1 year]
Eligibility Criteria
Criteria
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:
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Significant and persistent chemoradiotherapy complication
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Other previous upper gastrointestinal surgery
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Unwell or unable to eat
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Other disease or medications which may affect satiety gut hormone responses
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Active and significant psychiatric illness including substance misuse
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Cognitive or communication issues or any factors affecting capacity to consent to participation
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History of significant food allergy, certain dietary restrictions
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Confirmed or suspected residual or recurrent disease after surgery, synchronous or metachronous malignancy
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Significant surgical complication, aspiration risk or deterioration in performance
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Wellcome Trust-Health Research Board Clinical Research Facility, St. James's Hospital | Dublin | Ireland | D8 |
Sponsors and Collaborators
- St. James's Hospital, Ireland
- University College Dublin
- University of Dublin, Trinity College
Investigators
- Principal Investigator: John V Reynolds, MCh, FRCS, Department of Surgery, St. James's Hospital
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- Wellcome Trust-HRB Clinical Research Facility
- Conway Institute of Biomolecular and Biomedical Research
- Department of Surgery, Trinity College Dublin and St. James's Hospital
Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- CRFSJ 0058
- 2014-12 CA