Tissue distribution of epirubicin after severe extravasation in humans

Purpose As critical parameter after extravasation of cytotoxic vesicants, anthracyclines were determined in removed tissue from patients requiring surgical intervention due to tissue necrosis. We monitored their distribution within the affected lesion to establish a possible dose–toxicity relation. Methods From six patients scheduled for surgery, removed tissue flaps were systematically analysed by HPLC (epirubicin: 5 subjects; doxorubicin: 1 subject). Results After extravasation, tissue concentrations were highly variable with an individual anthracycline distribution pattern ranging from a few nanograms up to 17 µg per 100 mg tissue, which indicated a substantial difference in tissue sensitivity among patients. The resection borders coincided with the extension of the erythema and guided the surgical intervention after demarcation of the lesion, which occurred usually 2 or 3 weeks after extravasation. At that time, drug was hardly detected at the resection borders. Wound drains were negative for the extravasated drugs while showing a time profile of vascular growth factors and inflammatory cytokines, which was highly similar to routine surgery. In all six patients, surgical debridement with immediate wound closure led to healing within approximately 2 weeks, when therapy was resumed in all patients with reasonable time delay. Conclusion Surgical intervention after demarcation of the extravasation lesion allows for almost uninterrupted continuation of treatment independent of the amount of extravasated anthracycline. As even minor amounts of the vesicants may trigger tissue necrosis, preventive measures merit the highest priority.

Intraoperative MRI Features of Absorbable Oxidized Regenerated Cellulose During Cerebral Glioma Surgery

Objectives: Foreign body reaction to absorbable hemostatic agents may mimick recurrent brain tumor or abscess on postoperative MRI. Their appearance on intraoperative MRI and their use as resection borders marker have been not previously described. This study evaluates the intraoperative MRI appearance of absorbable oxidized regenerated cellulose in surgery of cerebralgliomas. Methods: 72 patients with cerebral gliomas were intraoperatively examined with high field MRI (1.5 T). 32 patients presented low-grade and 40 high-grade gliomas. After tumor resection the tumor bed was covered with absorbable oxidized regenerated cellulose. Results: The absorbable hemostat presented a hyperintense signal on MRI-T1 sequences in all patients. Tumor remnants under the hemostatic agent could be identified. Conclusions: Oxidized Regenerated Cellulose can be easily observed as a hyperintense signal lining covering the borders of the surgical cavity on intraoperative MRI-T1 sequences. It may be a useful marker of tumor resection borders of cerebral gliomas.