Fluorescence microscopic demonstration and demarcation of doxorubicin extravasation. Experimental and clinical studies

Abstract

Extravasation of doxorubicin and its derivative epirubicin, cause severe progressive tissue necrosis that requires early excision of all affected tissues. Doxorubicin and epirubicin are autofluorescent and this characteristic can be used to demonstrate and delineate extravasation by the aid of fluorescence microscopic study. In a rat model doxorubicin was injected intradermally in declining concentrations and the minimal detectable concentration was found to be 0.02 mg/ml. Skin necrosis developed in rats injected with doxorubicin concentrations ranging from 0.02 mg/ml to 2 mg/ml. Clinically, fluorescence microscopic analysis of frozen sections was used in eight patients to assess whether doxorubicin or epirubicin extravasation had taken place. When all fluorescing tissue was removed, no necrosis ensued, but in one patient, where a slightly fluorescing area was ignored, necrosis developed later and excision of the tissue had to be performed.