Improving the Current Management of Limb Malignant Melanoma

[摘要] Surgery remains the cornerstone in the treatment of malignant melanoma. The surgical treatment of primary and recurrent limb malignant melanoma ranges from wide local excision of the primary melanoma to elective and therapeutic lymph node dissection. The delivery of a chemotherapeutic agent via an isolated limb perfusion circuit has been available since 1957, yet its exact role remains to be defined. The theme of this thesis is "how can the current management of limb malignant melanoma be improved?" The work in this thesis was carried out in the Vascular Unit, at Gartnavel General Hospital, Glasgow and in the Animal and Scientific Laboratories of Glasgow University. In 1984 isolated limb perfusion (ILP) using melphalan was made available in Glasgow' for the treatment of primary and recurrent limb malignant melanoma and since then over 250 adjuvant and therapeutic ILPs have been performed. My analysis of the ILP results in the Glasgow unit showed that in the treatment of primary melanoma, ILP confers an improved disease free interval and possibly a small survival advantage. In the treatment of recurrent limb melanoma, therapeutic ILP is effective in the control of local and regional recurrence. I have analysed the results in specific subgroups of patients, i.e. when patients with subungual malignant melanoma undergoing ILP were matched (for age, site and tumour thickness) with patients treated with amputation only, no survival advantage was demonstrated in the perfused patients. Having analysed these results, I then addressed the issue of how the theoretically attractive concept of ILP could be improved and its role convincingly established. The components of my study are summarised below: 1) Improving the ILP circuit by: a) Introducing pulsatility to assess if it may be physiologically superior. b) Avoiding the compartment syndrome. c) Using a vasodilator to increase transcutaneous oxygen. 2) Assessing laser ablation as an alternative therapy for recurrent melanoma. 3) Accurate staging of malignant melanoma using lymphatic mapping. 4) Targeting radiotherapy in an animal model.The overall aim of this thesis was to find ways of improving the efficacy of ILP as a treatment for limb malignant melanoma. My studies have shown that: 1) Pulsatile flow is both logical, easy to produce and confers physiological advantages. The risk of a compartment syndrome in the perfused limb can be considerably reduced. 2) Local laser therapy is a safe and practical alternative for the palliation of local recurrence when ILP is not possible or has failed. 3) Accurate disease staging can be achieved using an intraoperative technique which may have important implications for future studies. 4) An animal model was successfully established showing that targeted radiotherapy is effective and that this mode of treatment may become a clinical possibility for patients with malignant melanoma.(Abstract shortened by ProQuest.).

[发布机构] University:University of Glasgow

[关键词] Medicine, Oncology