Fractal heterogeneity of peripheral blood flow: Implications for hematogenous metastases

Background and Objectives: To determine how inhomogeneities in blood perfus ion might affect the number of metastases that develop within an individual with cancer. Methods: Experiments with lung metastases in mice, involving 320 treatment groups and 3165 mice, were reviewed. Inhomogeneities in the distribution of metastases amongst identically treated mice were analyzed by calculating t he relative dispersion and clumping index. Results: The relative dispersion exhibited fractal self-similarity on chang e of scale, and paralleled the effects observed with pulmonary blood flow. Clustering of metastases was also apparent: a minority of mice developed re latively large numbers of metastases; a majority of mice developed few meta stases. Conclusions: Clustering of lung metastases occurred within groups of identi cally treated mice, and could be attributed to inhomogeneous blood perfusio n. Consequently, the number of metastases in any individual was highly vari able and correlated only partly with malignant potential. Inhomogeneities i n blood flow favored the development of relatively few metastases, such tha t solitary or nil metastasis should occur more frequently than expected fro m chance alone. J. Surg. Oncol. 2000;74:116-121. (C) 2000 Wiley-Liss, Inc.