혈관외로 유출된 Mitomycin-C에 의한 조직괴사 예방을 위한 Dimethyl Sulfoxide와 Sodium Thiosulfate의 효과

The Effects of Dimethyl Sulfoxide and Sodium Thiosulfate for the Prevention of Tissue Necrosis due to Extravasaion of Mitomycin-C

실험용 쥐를 이용하여 항암 약제인 mitomycin-c를 피하 주사하여 인위적으로 혈관외 유출을 시켜 조직 괴사를 유발하였다. 조직 괴사를 예방하기 위하여 치료 시작시간에 따른 dimethyl sulfoxide의 국소 도포와 sodium thiosulfate의 진피내 주사의 치료 효과를 비교하고 조직학적 검사를 실시하여 다음과 같은 결과를 얻었다. 1. Mitomycin-C가 혈관외로 유출될 경우 dimethyl sulfoxide를 6시간 이내에 국소 도포하면 괴사를 예방할 수 있었고, 24시간 이내에 치료를 시작해도 괴사 면적에 유의한 감소를 가져올 수 있었다(p<0.01). 2. Sodium thiosulfate 진피내 주사를 할 경우에는 12시간 이내에는 괴사를 예방할 수 있었으나 24시간이 경과한 후에는 치료 효과가 없었다(p<0.01). 3. MMC에 의한 괴사는 비균성 응고성 괴사였으며, 염증 반응이나 육아 조직은 나타나지 않았으며, 국소 도포와 진피내 주사 방법에 따른 조직학적 변화를 제외한 차이는 없었다. 4. MMC의 혈관외 유출로 피부병변을 최소화 시킬 수 있는 방법은 DMSO와 STS의 즉시 병합치료가 좋은 효과를 얻을 수 있을 것으로 추측된다.

Extravasation of toxic chemotherapeutic agents cause severe skin ulceration and necrosis which often need secondary surgical intervention. Still, there were not established antidote agent in case of extravasation with mitomycin-c. Dimethyl sulfoxide is known as an effective chemical scavenger of toxic hydroxyl free radical and sodium thiosulfate also was demonstrated significant protector from mitomycin-c induced ulceration by a few experimental studies. Author investigated necrotic area of mitomycin-c injected site and compare to the effectiveness of topical treatment with dimethyl sulfoxide and intradermal injection of sodium thiosulfate according to starting times, forty five mice were divided into 3 groups. Control group(n=5) had no treatment after subcutaneous injection of mitomycin-c. Experimental group I and II were 20 mice treated dimethyl sulfoxide and sodium thiosulfate, respectively. Depending on the starting time of treatment, group I and II were subdivided into 1, 2, 3 and 4 as immediate, 6 hours, 12 hours and 24 hours after mitomycin-c injection. Histologic studies of the necrotic area and survival area after treatment were performed using hematoxylin-eosin staining. The mean necrotic area of group I was significantly decreased depending on the starting time of treatment compared with control group(p<0.01). The results means there was no necrosis area which was treated with topical sodium thiosulfate within 6 hours, and it showed also significant decrease of necrosis area within 24 hours. There was also no necrosis area in group II-1 and significant decrease of necrosis area II-2 and III-3. But, effctiveness of intradermal injection of sodium thiosulfate was not found in group II-4 which was started after 24 hours. Hisotolgic findings showed a bland coagulative necrosis without inflammatory changes and no granulation tissue. The significant difference that cytoplasmic loss of subcutaneous fat and decrease number of hair follicles between two groups resulted from the methods of treatment by topical application and intradermal injection. In conclusion, immediate treatments with topical dimethyl sulfoxide or intradermal injection of sodium thiosulfate signifcantly prevents necrosis by extravasation of mitomycin-c.