Change in Macro Molecular Composition of Interstitial Fluid from Swollen Arms after Breast Cancer Treatment, and Its Implications

Abstract

1. The pathophysiology of chronic arm oedema after treatment of breast cancer was investigated by collecting serum and subcutaneous interstitial fluid from the affected and contralateral arms by the wick method (both arms) and by aspiration (oedematous arm). The fluids were analysed for total protein, albumin, glycosaminoglycan and viscosity, and arm volume was measured. 2. Total protein concentration in the aspirated oedema fluid was 32.4 +/- 7.5 g/l (mean +/- SD throughout; n = 39). Protein concentration in wick fluid from the oedematous arm (35.8 +/- 7.3 g/l, n = 14) was not significantly different from that in aspirated fluid. The oedema protein concentrations were significantly lower than in wick fluid from the non-swollen arm (41.4 +/- 6.7 cmH2O, n = 13, P < 0.01, analysis of variance). This was surprising in view of the common assumption that, the condition being of lymphatic origin, the oedema protein concentration should be raised. 3. The ratio of aspirate protein concentration to serum protein concentration showed a weak but highly significant negative correlation with the percentage increase in arm volume (r = -0.47, n = 35, P < 0.005), again in contrast to conventional expectation. The demonstration of a reduced protein concentration in the swollen arm did not therefore depend solely on a comparison with the wick control results. The volume increased by on average 33% and the ratio of aspirate protein concentration to serum protein concentration averaged 0.52 +/- 0.11 on the swollen side and 0.64 +/- 0.13 on the unaffected side. 4. Serum protein concentration in the patients with arm swelling (61.2 +/- 4.9 g/l) was significantly lower than that in postmastectomy patients without this complication (65.0 +/- 6.2 g/l). Most of the decrease occurred in the albumin fraction (oedema patients, 38.3 +/- 5.1 g/l; control patients, 42.0 +/- 2.1 g/l). In oedema patients receiving the anti-oestrogen tamoxifen serum albumin concentration was on average 2.3 g/l lower than in oedema patients not under medication (P < 0.05, t-test). 5. Glycosaminoglycan concentration in oedema fluid was 0.8 +/- 0.14 g/l (n = 21) and 75% was sulphated. Along with the plasma protein this raised the relative viscosity of the fluid to 1.34 +/- 0.16 (n = 11). 6. The reduction in interstitial protein concentration in the swollen arm, contrary to expectation in lymphoedema, could be explained in several ways. One possible hypothesis in light of reported haemodynamic abnormalities in such arms is that capillary pressure rises, increasing capillary filtration rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Starling pressures in the human arm and their alteration in postmastectomy oedema.

“…For example, leg wick i (above) implies a protein concentration of 30-35 g I-', which is similar to that in human leg lymph collected over 24 h (mean 34-9 g l', Olszewski, 1991). (iii) Leg lymph protein concentration rises as high as 40 g I' after 3 days bed-rest with the leg at heart level (Olszewski, 1991) and this is close to the concentration in control arm wick-extracted fluid (41 g 1', Bates et al 1993). …”

“…Although oestrogen can influence the circulation, tamoxifen (an oestrogen-receptor blocker) seems difficult to implicate here because (a) only 13/51 patients received tamoxifen, (b) any putative effect on vascular tone would presumably be bilateral, whereas the oedema was unilateral, and (c) the severity of the swelling was not significantly different in those on tamoxifen (Bates et al 1993).…”

“…interstitial fluid is 17 % of normal arm volume, then 300 ml protein-free water (cf. 45 ml) would have to be added to the swollen arm overnight to produce the observed difference, if both arms had the same ni the previous day (Bates et al 1993). Overnight swelling would have a relatively greater effect if part of the excess volume were fibrous/fatty tissue, but these arms were not of the non-pitting 'brawny' (fibrosed) type seen in some lymphoedemas (Witte & Witte, 1991).…”

“…Could the reduced ri in the PMO arm merely be the result of the slight overnight swelling (45 ml) that follows in the wick-extracted fluid (Bates et al 1993). interstitial fluid is 17 % of normal arm volume, then 300 ml protein-free water (cf.…”

“…If net capillary filtration rate exceeds drainage rate, volume will increase; and if a stable arm volume is reached, filtration rate must then equal drainage rate (Fbldi, 1984 (Michel, 1984) where Lp is capillary wall hydraulic conductance, A is area, P is hydraulic pressure, or is colloid osmotic pressure (oncotic pressure), subscripts 'c', 'i' and 'p' refer to capillary blood, interstitial fluid and plasma respectively, and oC is the protein reflection coefficient (Michel, 1984 (Bates, Levick & Mortimer, 1993) and a preliminary communication given (Bates, Levick & Mortimer, 1991a).…”