Isolated Limb Perfusion for Melanoma

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Isolated limb perfusion with high-dose chemotherapy is an accepted treatment modality to achieve locoregional control in advanced melanoma of the extremities. The drug of choice is melphalan. Tumor necrosis factor-α is frequently added to melphalan in bulky disease, and this combination may be an option for repeat perfusion for recurrent melanoma after a first perfusion. Results of perfusions performed with tissue temperatures between 37°C and 38°C seem to be equivalent to those of the perfusions performed under mild hyperthermic conditions. Perfusion cannot be recommended as an adjunct to wide local excision in patients who have primary melanoma. Adjuvant perfusion in repeatedly recurrent limb melanoma, however, may be of value because it lengthens the limb recurrence-free interval and decreases the number of lesions per recurrence significantly. Regional toxicity of perfusion should be mild when risk factors are taken into account.

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Technique

During ILP, the major artery and vein supplying the limb are clamped at the desired level, collateral vessels are ligated, and a tourniquet is applied around the limb proximal to the region of ILP. After insertion of catheters into the major vessels, the isolated limb is perfused by extracorporeal circulation that is oxygenated and propelled by a heart-lung machine. A melphalan dose of 13 mg/L of perfused tissue in the upper limb and 10 mg/L in the lower limb is added to the perfusate [2]. The

Adjuvant isolated limb perfusion for primary melanoma

The best available evidence on the value of adjuvant ILP after excision of primary melanoma is the report on a large, multicenter, randomized clinical trial from 11 centers in seven countries that was performed between 1984 and 1994 and was conducted by the European Organization for Research and Treatment of Cancer (EORTC) in collaboration with the World Health Organization (WHO) and North American Perfusion Group (NAPG) [14]. This report comprises 852 patients who had a so-called “high-risk

Regional toxicity and long-term morbidity

Because a relation between toxicity and treatment outcome has not been demonstrated for ILP with melphalan [34], it is important to keep the side effects of the procedure restricted to a minimum. Risk factors for more severe acute regional toxicity, such as considerable erythema, edema with blistering, damage to deep tissues with compartmental syndromes, and, rarely, even amputation, have recently been identified [13], [35]. The two most important risk factors in this respect are tissue

Future perspectives

ILP has a long-standing track record for local disease control of recurrent melanoma. Now, many patients can be managed with less invasive procedures, such as laser ablation, ILP can be reserved for truly unresectable recurrences. Conversely, because it has been demonstrated that ILP has a significant effect on micrometastases, its application in resectable lesions may be useful in patients who frequently have recurrences. In this respect, the recently developed microarray technique could be a

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