The complications of isolated limb perfusion

The principle of regional perfusion using cytostatic drugs resulted from a study by Klopp et al. who found that pain was alleviated and tumor size reduced when small doses of nitrogen mustard were injected into the regional arterial blood flow. The best results were obtained when venous return from the area involved was blocked. In 1956, the meeting of a cardiothoracic surgeon, a plastic surgeon and an oncological surgeon in the Department of Surgery at Tulane University, New Orleans, Louisiana, resulted in the introduction of a new concept in the treatment of regionally recurrent malignant disease. It was postulated that if an area of the body could be isolated from the systemic circulation and sustained by an extracorporeal circuit utilizing a heart lung machine, it would be possible to produce a high concentration of a chemotherapeutic agent in the isolated perfusion circuit limited only by the toxicity to the sensitive structures within that area. At the end of the perfusion, the unbound drug could be removed, the circulation restored and any excisional surgery carried out as necessary. The patient would benefit by a maximal tumor chemotherapeutic exposure in the treated area while being protected from systemic toxicity. Ryan et al. developed techniques in the laboratory for isolation perfusion of the hind limb, mid gut, and liver of a dog. It was found that the dosage of nitrogen mustard tolerated in the hind limb was the equivalent of a single whole body systemic dose.