Muscle Wasting in Cancer (MWIC)

One way cancer affects people is through weight loss. During this weight loss (called cachexia), all types of body tissue are lost, but there is a greater rate of muscle loss than fat. Cancer patients with cachexia show decreased quality of life, decreased response to treatment (e.g. chemotherapy), increased complications from surgery, and shorter overall survival. The Investigators aim to identify molecular (and patient) factors within the tissues and bodily fluids of patients with cancer and cachexia in order to identify patients at risk of weight loss, and identify potential therapies. For this, the Investigators aim to take patient samples (muscle, fat, tumour, urine and blood) whilst patients are asleep (general anaesthesia) during their operation to remove the cancer. These samples, and similar samples taken in previous studies, will be analysed in the laboratory. Along with the sample taking, the Investigators aim to perform nutritional assessments of patients before and after surgery to get an accurate picture of their weight loss. This will include simple measurements (e.g. height/weight), and computer reanalysis of their initial diagnostic computed tomography (CT) scans (this study will not require any additional scans for patients). The Investigators also aim to assess how their muscles function, by asking them to perform walk tests and wear a physical activity meter, and assess their quality of life through questionnaires. The Investigators aim to perform nutritional and functional assessments pre-surgery and at 2-3 appointments post-surgery, up to a period of 12 months. At these timepoints, the Investigators also aim to take repeat blood and urine samples, and where possible, one additional thigh muscle biopsy. Repeated assessments allow comparison between "cancer" and "cured" states. The study will take 2 years for patient recruitment. For comparison, the Investigators also aim to examine similar tissue and fluid samples (except tumour) from non-cancer patients who are having surgery for benign conditions (e.g. hernia).

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Patients identified at multidisciplinary team meetings (MDT) as having oesophagogastric, hepatobiliary, and colorectal cancer suitable for resection
* Patients over 18 years of age
* Patients identified at surgical clinic as being planned for an abdominal operation for a non-cancer, non-inflammatory condition

Exclusion Criteria:

* Patients with inflammatory conditions or other condition other than cancer that might cause muscle wasting
* Patients without the capacity to consent
* Members of vulnerable groups
* Patients not undergoing abdominal surgery
* Patients undergoing totally minimally invasive (laparoscopic) surgery, with no open or hand-assisted component affording easy access to rectus muscle biopsy

• BACKGROUNDFearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos VE. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011 May;12(5):489-95. doi: 10.1016/S1470-2045(10)70218-7. Epub 2011 Feb 4. PMID 21296615
• BACKGROUNDBaumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, Garry PJ, Lindeman RD. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol. 1998 Apr 15;147(8):755-63. doi: 10.1093/oxfordjournals.aje.a009520. PMID 9554417
• BACKGROUNDMourtzakis M, Prado CM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab. 2008 Oct;33(5):997-1006. doi: 10.1139/H08-075. PMID 18923576
• BACKGROUNDMacDonald AJ, Greig CA, Baracos V. The advantages and limitations of cross-sectional body composition analysis. Curr Opin Support Palliat Care. 2011 Dec;5(4):342-9. doi: 10.1097/SPC.0b013e32834c49eb. PMID 21986910
• BACKGROUNDAwad S, Tan BH, Cui H, Bhalla A, Fearon KC, Parsons SL, Catton JA, Lobo DN. Marked changes in body composition following neoadjuvant chemotherapy for oesophagogastric cancer. Clin Nutr. 2012 Feb;31(1):74-7. doi: 10.1016/j.clnu.2011.08.008. Epub 2011 Aug 27. PMID 21875767
• BACKGROUNDKhal J, Hine AV, Fearon KC, Dejong CH, Tisdale MJ. Increased expression of proteasome subunits in skeletal muscle of cancer patients with weight loss. Int J Biochem Cell Biol. 2005 Oct;37(10):2196-206. doi: 10.1016/j.biocel.2004.10.017. Epub 2004 Dec 7. PMID 16125116
• BACKGROUNDEley HL, Skipworth RJ, Deans DA, Fearon KC, Tisdale MJ. Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2alpha may signal skeletal muscle atrophy in weight-losing cancer patients. Br J Cancer. 2008 Jan 29;98(2):443-9. doi: 10.1038/sj.bjc.6604150. Epub 2007 Dec 18.