![]() However, the period of cooling has varied, with sometimes the cold compress being applied for 15-30 min every 1-2 days, or sometimes continuously for 1-3 hrs, and in fact the mechanism of the effect of such compresses remains unclear. For drugs that bind to DNA, local cooling has been reported to reduce absorption of the drug by skin tissue after leakage. Ĭooling causes local vasoconstriction, thus limiting diffusion of the drug into tissue, whereas warming causes local vasodilatation, and promotes absorption of the drug. Animal experiments have demonstrated that cooling decreases ulceration, but other reports have indicated that neither cooling nor warming reduces the ulcer size or healing period. Furthermore, local cooling reduces the area that needs to be surgically resected, and decreases a recall phenomenon. Local injection of steroid and application of dexrazoxane have been also recommended for extravasation of DOX. Other reported therapies have included infusion of saline and hyaluronidase or wash-out at the leakage site. Application of a hot compress is also recommended for treatment of extravasation. DOX extravasation causes pain and necessitates cessation of treatment for wound healing, sometimes for a long period, and skin grafting and flap surgery may be necessary. DOX is classified in a vesicant drug that can cause serious injury to skin tissue when it leaks out of blood vessels. ![]() The reported frequency of extravasation of infused anticancer drugs is 0.01-6.5% in Europe and America. Since its introduction in 1975, DOX has been used in rituximab plus cyclophosphamide, DOX, vincristine, and prednisolone therapy, adriamycin, bleomycin, vinblastine and dacarbazine therapy, and modified cyclophosphamide, vincristine, doxorubicin and methotrexate therapy for lymphomas. Consequently, these results suggested that the cold pack for the extravasation of DOX might reduce inflammation.ĭoxorubicin (DOX) is a commonly used anthracycline anticancer drug. mRNA for CD88, IL-8RA and TRPV1 was detectable by reverse transcription-polymerase chain reaction in both the cold and hot pack groups. The number of nerve fascicles expressing TRPV1 was higher in the hot group than in the cold group on days 1, 3 and 14. The numbers of inflammatory cells expressing CD88 and IL-8RA were significantly lower in the cold group than that in the other groups at almost time points and in the hot groups at later time points, respectively. The neutrophil count in the lesion was significantly higher in the hot group than in the cold (3 hrs) and control groups. Macroscopic observation showed that the area of the skin lesion was significantly smaller in the cold group than in the control group, but was significantly larger in the hot group. Immunofluorescence and RT-PCR for C5a receptor (CD88), interleukin-8 receptor (IL-8RA), and transient receptor potential cation channel subfamily V member 1 (TRPV1) were also performed. We injected 20 μl of doxorubicin (DOX) (1 μg/μl) subcutaneously into the dorsal area in mice and observed the resulting skin lesions macroscopically and histologically from day 1 to day 14 thereafter in groups treated with a cold pack (18-20☌) and a hot pack (38-40☌) or left untreated (control). ![]() In the present study, we investigated a part of the mechanism responsible for the effects of hot and cold compresses for extravasation of doxorubicin. ![]()
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