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정맥 주입용 항암제에 의한 실험적 혈관외 연부조직손상에 관한 병리학적 연구 : Pathologic Study on Experimentally Induced Soft Tissue Injuries by Extravasated Anticancer Agents

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장자준; 함의근

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서울대학교 의과대학
Seoul J Med, Vol.24 No.2, pp. 191-205
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.
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