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Expansion of Microvascular Bed and Increased Solute Flux in Human Basal Cell Carcinoma in Vivo, Measured by Fluorescein Video Angiography¹

Division of Physiological Medicine (Dermatology), Department of Medicine [A. W. B. S., S. B. D., R. P., R. H. M., M. J. B. D., P. S. M.] and Department of Physiology [J. R. L.], St. George’s Hospital Medical School, London SW17 0RE, and Rare Cancers Division (Skin and Sarcoma), The Royal Marsden NHS Trust, Surrey SM2 5PT [P. S. M.], United Kingdom

Human basal cell carcinoma (BCC) offers a unique opportunity to assess directly the microvascular abnormalities in a human cancer in vivo. Our objectives were to assess angiogenesis, perfusion, and changes in small solute exchange kinetics. The microcirculation of BCC and a normal (control) skin site was studied in 15 patients by laser Doppler fluximetry and videoangiography after rapid i.v. fluorescein injection. Microvascular morphometry was analyzed off line. Sodium fluorescein accumulation/clearance was recorded for 30 min, and fluorescence intensity (FI) was quantified by computer analysis of videotape image gray levels. In BCCs, the microvascular area fraction was 2.6-fold greater, microvessel length density 2.0-fold greater, average vessel image width 2.1-fold greater, and red cell flux 3.9-fold greater than in control sites (P < 0.01, paired t tests). The initial rate of rise of FI over 10 s was 3-fold greater in BCC than control and correlated with vascular area fraction and red cell flux. Tissue then equilibrated faster in BCC, rate constant -(13.0 ± 5.6) x 10^-3 s^-1 (mean ± SD), than controls -(5.3 ± 1.7) x 10^-3 s^-1, and plasma clearance was 2.6-fold higher in BCC than controls (P < 0.01, paired t test). Similarly, the rate constant of the subsequent clearance phase was 2-fold greater in BCC, -(0.53 ± 0.19) x 10^-3 s^-1, than controls, -(0.27 ± 0.22) x 10^-3 s^-1 (P < 0.01). Removal rate constants were an order of magnitude slower than accumulation rate constants. The results demonstrate angiogenesis, increased perfusion, and a more rapid exchange of small solute in human BCC. FI itself is rejected as an index of permeability to small solutes (cf. 29) because it depends also on blood flow, endothelial area, microvascular volume, and interstitial fluid volume.

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