정맥 주입용 항암제에 의한 실험적 혈관외 연부조직손상에 관한 병리학적 연구

Abstract

Necrosis of skin and subcutaneous tissue following inadvertent extravasation of cytotoxic drugs has been a serious complication of cancer chemotherapy. Since the pathogenesis of this lesion has not been explored in depth, the above disorder has proved to be notoriously difficult to treat. The main objective of this study was (0 investigate basic histopathologic changes of tissue damage and to allow thereby the development of rational approaches to prevention and management. A total of 90 male Sprague-Dawley rats weighing around 150 gms were divided into three groups for experiment. Each groups was used of 30 animals, whieh were injected respectively 2mgjkg of Adriamycin, 33. 3mgjkg of 5- FU and 3. 5mgjkg of Cisplatin through intradermal and subcutaneous routes. Challenging injections of normal saline, anti-cancer agent with and without Dexamethasone were set consistently at three sites of the shaved dorsum of trunk. Observations of skin and soft tissue injuries in the injection site were carried out by gross examination and light microscopy at 2, 6. 24 hours and 3,7 days following the injection. The specimen from each injection site were taken and prepared for histopathologic investigation and then hematoxylineosin, acid orcein-Giernsa, Masson's trichrome and van Gieson stainings were applied. The results and summary of the experiment were as follows: 1. The gross findings at the injection sites of normal saline and !j-FU were unremarkable changes, otherwise that of Adriamycin and Cisplatin were remarkable and developed distinet hyperemia at 24 hours, with good demarcation and central discoloration at 3 days through 7 days. In the injection site of anti-cancer agents, the morphologic difference between combining use with and without dexamethasone was not conspicuous. 2. In the microscopic findings, the injection sites of normal saline and 5- FU showed edema and mild inflammatory reaction of subcutis, otherwise that of Adriarnycin and Cisplatin revealed extensive coagulative necrosis. In the soft tissue injuries. the In" tradermal injection group was more severe than the subcutaneous injection group. 3. The chronological histopathologic findings in the group of Adriamycin and Cisplatin injection exhibited mild edema and focal inflammatory reaction in the dermis and subcutis at 2~6 hours, focal necrosis in the epidermis and the muscle coat at 24 hours, extensive wide coagulative necrosis in the epidermis through the muscle coat at 3~7 days. But neither vasculit ies, fibroblastic proliferation nor granulation formation were observed until 7 days. 4. The injection of Dexamthasone could not prevent the progression of the necrotic inflammatory lesion, but only lessencd the degree of necrosis and inflammatory response. In summary, the main pathologic findings of soft tissue injuries induced by extravasation of anticancer agents were extensive coagulation necrosis and associated inflammatory response. The mechanism of necrosis was considered that of direct cytotoxicity. The main difference with general traumatic injury rested on lacking of fibroblastic proliferation and granulation formation until 7 days, which was compatible findings to prolonged healing. The effect of steroid was only approved reduction of the degree of necrosis and inflammatory reaction.