Journal of the Korean Association of Oral and Maxillofacial Surgeons

The Korean Association of Oral and Maxillofacial Surgeons (대한구강악안면외과학회)
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EFFECT OF INDUCTION CHEMOTHERAPY ON FLAP SURVIVAL RATE IN MICROSURGERY

종양수술전 화학요법이 미세수술시 피판생존율에 미치는 영향

  • Kim, Uk-Kyu (Department of Oral and Maxillofacial Surgery, College of Dentistry, Pusan National University) ;
  • Kim, Yong-Deok (Department of Oral and Maxillofacial Surgery, College of Dentistry, Pusan National University) ;
  • Byun, June-Ho (Department of Oral and Maxillofacial Surgery, College of Dentistry, Pusan National University) ;
  • Shin, Sang-Hun (Department of Oral and Maxillofacial Surgery, College of Dentistry, Pusan National University) ;
  • Chung, In-Kyo (Department of Oral and Maxillofacial Surgery, College of Dentistry, Pusan National University)
  • 김욱규 (부산대학교 치과대학 구강악안면외과학교실) ;
  • 김용덕 (부산대학교 치과대학 구강악안면외과학교실) ;
  • 변준호 (부산대학교 치과대학 구강악안면외과학교실) ;
  • 신상훈 (부산대학교 치과대학 구강악안면외과학교실) ;
  • 정인교 (부산대학교 치과대학 구강악안면외과학교실)
  • Published : 2003.12.31
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Abstract

Purpose : Neoadjuvant chemotherapy is commonly used to treat cancer patients as adjunct treatment, but if the microvascular tissue transfer is performed simulataneously with cancer resection surgery, the induction chemotherapy might affect the survival rate of vascularized free flap. Our study will focus on the effect of induction chemotherapy on the free flaps which were made on white rat abdomen after injection of 5-FU. Materials and Methods: The experimental rat groups were divided into three groups (total 24 rats) as a normal control group, 24 hrs group after 5-FU injection, 3 days group after 5-FU injection. Inferior abdominal island flaps of 8 Sprague Dawley rats on each group were made and immediately were induced into an ischemic state by clamping the supplying inferior epigastric artery and vein with microvascular clamp for a hour to induce a similiar free flap circumstance, then the inferior abdominal skin flaps were reperfused by releasing the clamps. The flaps on abdomen were repositioned and sutured. The experimental data for flap survival rate was collected by digital photo taking, analysed by computer image program to compare with the flap luminosity. The rats were sacrificed at 3 days, 5 days, 7 days after flap preparation and specimens of the flap were taken and stained with H-E staining. The microscopic finding was made under magnification of 200 and 400. Results: 1. Gross findings on each groups showed the healing condition was good as following sequences; normal, 24 hrs group after chemotherapy, 3 days group after chemotherpy. 2. The values of flap luminosity for evaluation of flap survival rate also showed the same sequences as gross findings of healing state. 3. The microscopic findings of epidermis necrosis, inflammation state, dermis fibrosis, vessel change, fatty tissue layer thinning were compared with each group. The 3 days group after chemotherapy showed remarkably poor healing condition compared to other groups. Conclusion: Chemotherapy agents affected the healing process of free flap, but healing condition was recovered spontaneously as post-injection periods passed out. In opposite to our expectation, 3 days group showed the bad flap condition in comparing with 24 hours group which was considered as immatured body circulation state of chemotherapy agent. It showed that 3 weeks in human being after chemotherapy was not proper as timing of microvascular tissue transfer if 3 days group in rat was considered as same healing period of 3 weeks in human being. More delayed healing timing than 3 weeks might be required in clinical application of free tissue transfer.

총 24 마리의 백서를 선택하여 종양화학요법제의 하나인 5-FU를 복강내 투여한후 24 시간이 지난후 8마리에서는 하복부 동맥 및 정맥을 근간으로 한 하복부 피부 도상피판($2{\times}3cm^2$)울 좌, 우 2 개씩 형성하고 피판을 허혈상태를 유도하여 유리피판상태를 만들었다. 허혈상태를 1 시간정도유지한후 다시 혈류를 재개시켜 피판으로의 혈류를 재개시키고 상처부를 층별봉합 하였다. 그 후 3 일, 5 일, 7 일째 각각 2마리씩 희생하여 H-E staining하였다. 또한 술후 1 일, 3 일, 5 일, 7 일째 피판생존을 육안으로서 확인하고 피판의 survival rate를 비교하기 위하여 사진촬영하여 digital image를 얻은후 adobe software program을 이용하여 Image, Histogram기능을 써서 60,000 pixels(가로${\times}200$, 세로${\times}300$)상태에서 피판의 Luminosity(광도)정도를 수치화하였다. 마찬가지의 술식으로 5-FU를 투여후 3일이 경과된후 8마리를 동일한 부위에 동일한 피판을 써서 3 일, 5 일째 각각 2 마리에 대해 피판을 채취하여 H-E staining 하여 조직현미경상의 치유과정을 관찰하였다. 대조군으로서 복강내 5-FU를 투여받지않은 백서 8마리에서 동일한 도상 피부피판을 형성하고 3 일, 5 일, 7 일째되는 2마리씩 피판부위를 채취하여 H-E염색하여 조직치유반응을 광학현미경으로 관찰하였고 상기와 동일한 방식으로 피판의 생존율을 계산하여 다음의 결과를 얻었다. 1. 육안적 소견으로 치유의 순은 대조군, 항암 24 시간째군, 항암 3 일군순으로 빨리 치유되었다. 2. 피판생존율을 비교하기 위한 광도(Luminosity)의 차는 3군끼리 모두 유의한 차를 보였으며 평균치 비교에서는 대조군, 항암 24 시간째군, 항암 3 일군순으로 높았다. 3. 광학현미경상 조직치유의 정도는 5개 항목으로 나누어 관찰하였다. 전체적으로 대조군과 항암 24 시간군은 시일이 지날수록 치유가 되는 양상을 보였으나 항암 3 일군은 조직의 염증반응이 더 심해지는 양상을 보였다. epidermis necrosis관찰항목에서는 대조군에 비해 항암제투여군이 경도의 반응을 보였고 항암3 일군에서 가장 심하였다. Inflammation state는 3일째는 대조군에서 가장 높게 나타났으나 시일이 지남에 따라 감소한 반면 항암 3 일군은 시일이 지날수록 심해졌다. dermis fibrosis면에서는 항암 24 시간군에서 가장 크게 나타났다. vessel change는 대조군과 항암 24군에서는 거의 관찰되지 않았고 항암 3 일군에서는 중등도로 관찰되었다.fatty tissue layer thinning은 3 군모두에서 관찰되었고 항암 3 일군이 가장 심하게 나타났다. 이상의 실험결과를 보면 술전 항암제투여가 초기에 시행한 경우에는 조직의 치유에 초기 5 일정도까지는 영향을 미치나 7 일이 지나면 정상범주로 회복함을 알수 있었고 실험결과 항암제 투여후 3 일째 피판 형성한 군에서 피판치유가 늦어진 것으로 관찰되어 인체에서 항암 투여후 수술시기는 인체면역계가 회복하는 시기를 3주이상 경과후 적어도 4주째 수술시기를 정하는 것이 유리하리라 생각되었다.

Keywords

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