PubMed · 13973705
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D REIBEL. 1962. Fat embolism.. https://pubmed.ncbi.nlm.nih.gov/13973705/
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BACKGROUND: We have previously described an alternative invasion-independent pathway of cancer metastasis in a murine mammary tumor model. This pathway is initiated by intravasation of tumor nests enveloped by endothelial cells of sinusoidal vasculature within the tumor. In this study, we examined whether evidence for the invasion-independent pathway of metastasis is present in human cancers. METHODS: Archival specimens of 10 common types of human cancers were examined for the presence of sinusoidal vasculature enveloping tumor nests and subsequently generated endothelial-covered tumor emboli in efferent veins. RESULTS: A percentage of tumor emboli in all cancers was found to be enveloped by endothelial cells, but these structures were particularly prevalent in renal cell carcinomas, hepatocellular carcinomas and follicular thyroid carcinomas. A common feature of the vasculature in these tumors was the presence of dilated sinusoid-like structures surrounding tumor nests. A high mean vascular area within tumors, an indication of sinusoidal vascular development, was significantly related to the presence of endothelial-covered tumor emboli. CONCLUSIONS: These results suggest that an invasion-independent metastatic pathway is possible in a wide variety of human cancers. Further investigation of this phenomenon may present new therapeutic strategies for the amelioration of cancer metastasis.
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Measurements of the relative Doppler power scattered by an embolus and the surrounding blood are widely used to infer the composition of the embolus. For a given embolus, measured embolus-to-blood ratio (MEBR) is affected by the Doppler sample volume shape, the geometrical relationship between the sample volume and the vessel, and the embolus trajectory through the blood vessel. The likely magnitudes of such effects were quantified using a model that allowed calculation of theoretical values of MEBR as a function of the geometrical relationship between a blood vessel and a defined sample volume. Overall, the effects of embolus trajectory, likely insonation angles, and plausible vessel misalignments introduced uncertainties in MEBR values of approximately 10 to 12 dB for a given vessel size. In practice, the only operator-controlled factors are the position and orientation of the transcranial Doppler probe on the patients' heads. Probe positioning can significantly affect MEBR and suboptimal positioning may result in the reduced detection of emboli.