Blood salvage and cancer surgery: a meta‐analysis of available studies

BACKGROUND: Intraoperative blood salvage (IBS) is a technique that is frequently used in major blood loss surgery. Classically, it is avoided during cancer surgery where a fear exists of entraining cancer cells into the shed blood. In this study, all reports of this practice were collected to determine if this fear is warranted. STUDY DESIGN AND METHODS: A literature search was performed including the search phrases “blood salvage,”“intraoperative blood salvage,”“cell salvage,”“cell saver,”“cell saving,”“autotransfusion,” and “autologous transfusion.” Data extracted from suitable papers included the authors' names, publication year, cancer type, exclusion criteria, sample size, length of follow‐up, and the mean patient age. The primary endpoint of this meta‐analysis was a comparison of the odds ratio (OR) for cancer recurrence or the development of metastases. RESULTS: Eleven studies were included in the analysis. The pooled summary of the OR was 0.65 (95% confidence interval, 0.43‐0.98; p = 0.0391) using a random‐effects model. Measures of heterogeneity, Q‐statistics (p = 0.1615) and I² (30.90%), did not indicate a high degree of between‐study variability. CONCLUSIONS: While significant variability existed between studies, this meta‐analysis suggests that outcomes after the use of IBS are not inferior to traditional intraoperative allogeneic transfusion. An adequately powered prospective, randomized trial of IBS use is required to determine its true risk during cancer surgery.     

The distribution of erythrocyte phospholipids in hereditary spherocytosis demonstrates a minimal role for erythrocyte spectrin on phospholipid diffusion and asymmetry

In the human erythrocyte membrane phosphatidylcholine and sphingomyelin reside mainly in the outer leaflet, whereas the aminophospholipids, phosphatidylethanolamine and phosphatidylserine, are mainly found in the inner leaflet. Maintenance of phospholipid asymmetry has been assumed to involve interactions between the aminophospholipids and the membrane skeleton, in particular spectrin. To investigate whether spectrin contributes to maintaining the phospholipid transbilayer distribution and kinetics of redistribution, we studied erythrocytes from hereditary spherocytosis patients whose spectrin levels ranged from 34% to 82% of normal. The phospholipid composition and the accessibility of membrane phospholipids to hydrolysis by phospholipases were in the normal range. Spin-labeled phosphatidylserine and phosphatidylethanolamine analogues that had been introduced into the outer leaflet were rapidly transported at 37 degrees C to the inner leaflet, whereas the redistribution of spin-labeled phosphatidylcholine was slower. The kinetics of transbilayer movement of these spin-labeled phospholipid in all samples was in the normal range and was not affected by the level of spectrin. Although these erythrocyte membranes contained as little as 34% of the normal level of spectrin and were characterized by several physical abnormalities, the composition, distribution, and transbilayer kinetics of the phospholipids were found to be normal. We therefore conclude that spectrin plays, at best, only a minor role in maintaining the distribution of erythrocyte membrane phospholipid.     

Epidermal growth factor (EGF) inhibits the secretomotor response of the thyroid: effects of EGF on radioiodine turnover and fluid transport in cultured porcine thyroid cells

Thyrotrophin (4-256 microU/ml) promoted an increase in the rate of release of radioiodine from the organic iodine pool of cultured porcine thyroid cells in follicular formations. This action of TSH was antagonized by low concentrations of epidermal growth factor (EGF; 0.1-5 nmol/l). The maximal effect of EGF was reached by 0.5 nmol/l. EGF (0.5-5 nmol/l) also inhibited the stimulatory effect of 8-chloro cyclic AMP (0.06-1.0 nmol/l) on radioiodine turnover. Exposure of thyroid cultures to media with a calcium concentration of 17.7 mumol/l (1% of normal) resulted in a very marked increase in the rate of release of radioiodine. The effect of TSH in low-calcium media was to inhibit the increased release of radioiodine, and EGF (0.5 nmol/l) antagonized this inhibitory effect of TSH. The calcium ionophore, A23187, stimulated radioiodine release in a dose-dependent fashion, and EGF (1.7 nmol/l) inhibited this response. Fluid transport in thyroid monolayers was stimulated by prostaglandin E2 (PGE2; 1 mumol/l). EGF (5 nmol/l) also stimulated fluid transport, but antagonized the effect of PGE2 added subsequently. It was concluded that EGF exerted acute antagonistic effects on thyroid cell responses in vitro to cyclic AMP and agents promoting accumulation of cyclic AMP in time-frames too short for these inhibitory effects to be attributable to the dedifferentiative effect of the growth factor.     

Regulation of growth hormone (GH) bioactivity by a recombinant human GH-binding protein

The in vitro biological effects of serum GH-binding protein (GHBP) were measured in the mouse 3T3-F442A preadipocyte adipogenesis assay during GH stimulation. Coincubation of increasing concentrations of human (h) GH (0.14-4.5 nM) with 4.2 nM recombinant hGHBP-(1-247) in serum-free medium shifted the hGH dose-response curve to the right over the range 0.14-0.9 nM. When the hGH concentration was fixed at 0.45 nM, a dose-dependent inhibition of GH bioactivity was seen over the range of 0.1-11.3 nM GHBP, with an ED50 of 3 nM. The presence of serum had no effect on the inhibitory properties of GHBP. When 2% pooled human serum was added to incubation medium containing 0.45 nM hGH and GHBP (0.6 nM-5.7 nM), the effect of GHBP was again inhibitory, with an ED50 of 1.2 nM. Two percent serum alone was adipogenic, but at this low serum concentration it is likely that some factor other than GH is responsible. In a homologous receptor assay, the binding of [125I]hGH to IM-9 lymphocytes was inhibited in a dose-dependent manner by increasing concentrations of hGHBP in the physiological range, providing further support for the idea that GHBP can regulate the bioactivity of GH by blocking the binding of free GH to target tissues in vivo. Our results suggest that one function of GHBP is to dampen the biological effects of pulsatile GH secretion by reducing free GH during secretory pulses. This effect combined with an increased half-life of circulating GH would have the effect of flattening the hormone secretory profile at the target tissue level.