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Albumin Synthesis Rates Are Not Decreased in Hypoalbuminemic Cachectic Cancer Patients With an Ongoing Acute-Phase Protein Response

Fearon, Kenneth C. H. M.D.*; Falconer, J. Stuart M.B.Ch.B.*; Slater, Christine M.Ph.†; McMillan, Donald C. Ph.D.‡; Ross, James A. Ph.D.*; Preston, Tom Ph.D.†

Annals of Surgery:
Advances in Surgical Technique

Objective: To determine whether suppression of albumin synthesis contributes to the hypoalbuminemia observed in weight-losing cancer patients with evidence of an ongoing acute-phase protein response (APPR).

Background Data: Proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6) are known to downregulate albumin synthesis and increase acute-phase protein production in isolated hepatocytes. However, whether albumin synthesis is suppressed in hypoalbuminemic cancer patients with evidence of an ongoing acute-phase response is unknown.

Methods: Albumin synthesis rates were determined in six healthy controls and in six weight-losing pancreatic cancer patients with an ongoing APPR using a flooding dose technique with [2H5]-phenylalanine. The presence of an APPR was defined as a serum C-reactive protein concentration > 10 mg/L. Serum cytokines (TNF, IL-6) and soluble TNF receptors (sTNF-R 55 and 75), along with serum cortisol and insulin, were also measured in both groups.

Results: Cancer patients had reduced serum albumin (median 32 [range, 23-36] vs. 42 g/L [40-45]; p < 0.01) and increased serum C-reactive protein concentrations (72 [23-126] vs. <5 mg/L; p < 0.01) when compared with controls. TNF was not detected in either group. sTNF-R 55 levels were significantly elevated in the cancer patients (3.8 [1.9-8.1] vs. 1.2 pg/mL [0.9-2.2]; p < 0.01). Circulating IL-6, insulin, and cortisol concentrations were not significantly different between the groups. The intravascular albumin mass was lower (88 [56-93] vs. 133 g [105-177]; p < 0.01), but the intravascular albumin fractional synthetic rate was higher (13.9 [13.5-18.5] vs. 10.3%/d [71-11.3]; p < 0.01) in the cancer patients compared with the controls. The total intravascular albumin synthetic rate was, however, similar between the two groups (12.7 [7.7-15.7] vs. 11.7 g/d [8.5-18.7]; p NS).

Conclusions: In weight-losing pancreatic cancer patients with evidence of an ongoing APPR, hypoalbuminemia is not caused by a decreased rate of albumin synthesis.

Author Information

From the University Department of Surgery, Royal Infirmary, Edinburgh, United Kingdom;* the Isotope Biochemistry Laboratory, SURRC, East Kilbride, Glasgow, United Kingdom;† and the University Department of Surgery, Royal Infirmary, Glasgow, United Kingdom‡

Supported in part by The Scottish Office Home and Health Department Grant K/MRS/50/C1922 and by the Cancer Research Campaign.

Reprints are not available. Address for correspondence: Dr. K. C. H. Fearon, University Department of Surgery, Royal Infirmary, Edinburgh EH3 9JW, United Kingdom.

Accepted for publication October 16, 1996.

© Lippincott-Raven Publishers.