How to detect inflammation?
Systemic inflammation syndrome in cancer patients can vary in degree1 but seems common2. One common feature of inflammation in cancer patients is altered metabolism, which differs from healthy people. This can vary in degree but impacts all relevant pathways, including metabolism of carbohydrates, lipids and proteins.2,3
Metabolism of carbohydrates3
- Glucose intolerance
- Increased hepatic gluconeogenesis
- Increased Cori cycle activity
- Decreased skeletal muscle glucose uptake
Metabolism of lipids3
- Hyperlipidemia
- Increased lipolysis
- Abnormal lipoprotein metabolism
- Decreased whole-body lipid stores
Metabolism of proteins3
- Increased whole-body protein turnover
- Increased hepatic protein synthesis, acute-phase proteins
- Increased skeletal muscle breakdown
The tumor itself produces mediators like cytokines (IL-1, IL-6, TNFa), which cause systemic inflammation that leads to a breakdown of muscle protein and fat tissue, and thus contributing to weight loss.4
Systemic inflammation syndrome frequently occurs in cancer patients and leads to an altered metabolism of macronutrients and a breakdown of fat and muscle stores in the body.
Inflammation markers
Albumin and postoperative complications
Low levels of serum hepatic transport proteins like albumin are considered as a negative acute-phase protein during inflammation.
The serum concentration of hepatic transport proteins is not only affected by inflammation but also by liver and renal function, hydration, pregnancy, iron deficiency and blood loss. The low levels of albumin can identify patients who are most morbid and, therefore, at risk of developing nutritional deficits and in need of careful monitoring.5
Preoperative serum albumin is a prognostic factor for complications after surgery.6
A systematic review of 15 studies on geriatric general surgery patients showed that weight loss and low serum albumin concentration were predictive parameters for postoperative complications.7
The ESPEN guideline for surgical patients6 recommends that serum albumin may also be considered for defining surgical patients at severe nutritional risk.
Serum albumin and the presence of at least one of the following criteria determine nutritional risk6:
Low levels of serum albumin show high postoperative risk in surgical cancer patients and can be part of systemic inflammation.
C-reactive protein (CRP)
CRP is the most frequently cited as an indicator of inflammation since the levels increase due to inflammation.5 CRP is seen as acute-phase protein. High levels of inflammatory markers like CRP were also associated with malnutrition and weight loss.8,9
High levels of CRP are associated with inflammation in cancer patients. Low albumin levels in combination with elevated CRP levels are associated with poor survival.6
Glasgow Prognostic Score (GPS)
The combination of elevated CRP and low albumin levels, called the Glasgow Prognostic Score (GPS), has independent prognostic value in patients with cancer.
There have been more than 60 studies (> 30,000 patients) that have examined and validated the use of the GPS or the modified GPS (mGPS) in a variety of cancer scenarios.10
Increased GPS/mGPS is associated with:
- increased loss of weight and muscle10
- poor prognosis10
- increased comorbidity10
- increased complications on treatment10
- less survival in various cancer types like colorectal cancer,11 inoperable pancreatic cancer,12 inoperable non–small-cell lung cancer,13 inoperable gastroesophageal cancer,14 hepatocellular carcinoma15 and many others
Measuring CRP and albumin provides information about the extent of systemic inflammation. The ESPEN recommends the modified GPS as a grading tool for inflammatory response as it is highly predictive of morbitiy and mortality in oncological patients.1
The GPS or mGPS are highly predictive of morbidity and mortality in cancer patients.
Nutritional assessments
References
1 Arends J, Bachmann P, Baracos V, Barthelemy N, Bertz H, Bozzetti F, et al. ESPEN guidelines on nutrition in cancer patients. Clin Nutr. 2017;36(1):11–48.
2 McMillan DC, Elahi MM, Sattar N, Angerson WJ, Johnstone J, McArdle CS. Measurement of the systemic inflammatory response predicts cancer-specific and non-cancer survival in patients with cancer. Nutr Cancer. 2001;41(1-2):64-9.
3 Argiles JM, Alvarez B, Lopez-Soriano FJ. The metabolic basis of cancer cachexia. Med Res Rev. 1997;17(5):477-98.
4 Arends J, Baracos V, Bertz H, Bozzetti F, Calder PC, Deutz NEP, et al. ESPEN expert group recommendations for action against cancer-related malnutrition. Clin Nutr. 2017;36(5):1187-96.
5 Pesce-Hammond K, Wessel J. Nutrition Assessment and Decision Making. In: Merritt R, editor. The ASPEN Nutrition Support Practice Manual. 2 nd ed: American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.); 2005:3-37.
6 Weimann A, Braga M, Carli F, Higashiguchi T, Hubner M, Klek S, et al. ESPEN guideline: Clinical nutrition in surgery. Clin Nutr. 2017;36(3):623-50.
7 van Stijn MF, Korkic-Halilovic I, Bakker MS, van der Ploeg T, van Leeuwen PA, Houdijk AP. Preoperative nutrition status and postoperative outcome in elderly general surgery patients: a systematic review. JPEN J Parenter Enteral Nutr. 2013;37(1):37-43.
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10 McMillan DC. The systemic inflammation-based Glasgow Prognostic Score: a decade of experience in patients with cancer. Cancer Treat Rev. 2013;39(5):534-40.
11 Nozoe T, Matono R, Ijichi H, Ohga T, Ezaki T. Glasgow Prognostic Score (GPS) can be a useful indicator to determine prognosis of patients with colorectal carcinoma. Int Surg. 2014;99(5):512-7.
12 Glen P, Jamieson NB, McMillan DC, Carter R, Imrie CW, McKay CJ. Evaluation of an inflammation-based prognostic score in patients with inoperable pancreatic cancer. Pancreatology. 2006;6(5):450-3.
13 Forrest LM, McMillan DC, McArdle CS, Angerson WJ, Dunlop DJ. Comparison of an inflammation-based prognostic score (GPS) with performance status (ECOG) in patients receiving platinum-based chemotherapy for inoperable non-small-cell lung cancer. Br J Cancer. 2004;90(9):1704-6.
14 Crumley AB, McMillan DC, McKernan M, McDonald AC, Stuart RC. Evaluation of an inflammation-based prognostic score in patients with inoperable gastro-oesophageal cancer. Br J Cancer. 2006;94(5):637-41.
15 Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Tanaka K, et al. The Glasgow Prognostic Score, an inflammation based prognostic score, predicts survival in patients with hepatocellular carcinoma. BMC cancer. 2013;13:52.