Treatment of cutaneous and subcutaneous tumors with electrochemotherapy using intralesional bleomycin.

BACKGROUND: Electrochemotherapy (ECT) is performed by locally administering a chemotherapeutic agent in combination with electric pulses. Previous clinical studies have demonstrated the effectiveness of ECT. In these initial trials, the drug was administered intravenously, followed by administration of electric pulses directly to the tumor. This study was initiated to determine whether an intralesional injection of the drug in combination with electric pulses could provide an improved result. A group of 34 patients was studied. METHODS: The dose of intralesional bleomycin was based on tumor volume. This was followed 10 minutes later by 6 or 8 99-microsec pulses of electricity at an amplitude of 1.3 kV/cm. Both the bleomycin and the electric pulses were administered after 1% lidocaine with epinephrine solution was injected around the treatment site. RESULTS: All patients responded to the treatment. Responses were observed in 142 (99%) of 143 metastatic nodules or primary tumors within 12 weeks, with complete responses observed in 130 (91%) of the nodules. No complete responses were observed in nodules treated with bleomycin only or electric pulses only. Random biopsies confirmed the clinical findings. All patients tolerated the procedure well, and no significant side effects were noted. Muscle contraction was evident during administration of each electric pulse but promptly subsided after the pulse. CONCLUSIONS: ECT was shown to be an effective local treatment for cutaneous malignancies. The results suggest that ECT may have a tissue-sparing effect and result in minimal scarring. ECT may be a suitable alternative therapy for the treatment of basal cell carcinoma, local or regional recurrent melanoma, and other skin cancers.

The clinical relevance of sentinel lymph nodes identified with radiolymphoscintigraphy.

BACKGROUND: The purpose of this case report is to illustrate the utility of radio-guided mapping of sentinel lymph nodes (SLN's) as demonstrated by the technique's successful identification of nodes containing metastatic disease that would have been left behind if only the visual-oriented vital blue dye mapping technique had been used. METHOD: The patient underwent preoperative lymphoscintigraphy and intra-operative lymphatic mapping using vital blue dye and radiolymphoscintigraphy using the Neoprobe (handheld gamma probe). Nodes which were blue and/or "hot" (i.e., radioactive counts were three times the background count) were considered SLN's. RESULTS: Four SLN's were harvested, all of which were "hot" but only one of which was both "hot" and blue. Pathology revealed that the two SLN's positive for metastatic disease were not blue. CONCLUSION: While the blue dye lymphatic mapping technique provides the surgeon with a visual road map in the identification of SLN's, the Neoprobe increases the success rate of localization when compared to vital blue dye mapping due to the reliable migration of radiocolloid to the SLN's in the regional basin. Radiolymphoscintigraphy also increases the accuracy and efficiency of the SLN harvest by providing a directed dissection to the level of the nodes in the basin. The Neoprobe increases the yield of SLN's, some of which are clinically relevant since they contain metastatic disease.

The role of selective lymphadenectomy in the management of patients with malignant melanoma.

BACKGROUND: A novel surgical technique based on selective lymphadenectomy was used to stage 132 patients with intermediate and thick cutaneous malignant melanoma. Preoperative and intraoperative lymph node mapping techniques were used to ascertain regional lymph node basins at risk for metastasis, and to identify the first node(s) the afferent lymphatics encounter in the basin, defined as the "sentinel" node(s). It has been shown that the histology of the sentinel node reflects the histology of the rest of the nodal bain, and according to preliminary studies using this technique, the likelihood of bypassing the sentinel node(s) to "higher" level nodes is less than 2%. Epidemiologic studies indicate that the long-term survival of patients with melanomas of intermediate thickness or greater is significantly compromised if regional lymph nodes are involved. Yet, the utility of performing lymph node dissections for the purposes of staging only is controversial, not only because of the morbidity and expense of the procedure, but the lack of proven survival benefit. OBJECTIVE: In the present study, we performed preoperative and intraoperative lymphatic mapping, harvested clinically normal sentinel nodes, and examined them for micrometastasis by light microscopy. Both conventional stains and immunocytochemistry for S-100 protein and HMB-45 antibodies were performed, and only those patients with documented micrometastasis received complete lymph node dissections. RESULTS: The sentinel node(s) was identified in each of the patients. Micrometastatic disease was detected in 31 (23%) of the patients by selective lymphadenectomy, and the sentinel node(s) was the only node involved in 83% of the cases upon subsequent complete nodal dissection. CONCLUSION: Our preliminary results suggest that selective lymphadenectomy following lymphatic mapping is an effective procedure for staging melanoma patients with lesions of intermediate thickness or greater. Our results indicate that sentinel lymph nodes may be successfully identified and harvested in the majority of patients, and that they may be examined for the first evidence of micrometastasis without the need of a complete nodal dissection. Information as to whether micrometastases are present in the sentinel node would be valuable in staging patients, and identifying candidates for complete nodal dissections. We are participating in a National Cancer Institute-sponsored multicenter trial to ascertain whether this surgical approach can impact on the recurrence rate and survival of patients with stage 1 and 2 melanoma.

Interleukin 15 induction of lymphokine-activated killer cell function against autologous tumor cells in melanoma patient lymphocytes by a CD18-dependent, perforin-related mechanism.

Interleukin 15 (IL-15) is a novel cytokine that shares no homology with IL-2, but it requires the use of beta and gamma chains of the IL-2 receptor complex for binding and signaling. In vitro studies have shown induction of CTL and lymphokine-activated killer (LAK) cell activity in peripheral blood mononuclear cells (PBMCs) from normal donors by IL-15 against known tumor targets. The present study attempts to define the role of IL-15 in generating LAK activity from melanoma patient lymphocytes. PBMCs of patients newly diagnosed with metastatic melanoma were incubated with different doses of recombinant human IL-15 and tested against autologous tumor cells, LAK sensitive cell lines (i.e., FMEX and Daudi), as well as the natural killer-sensitive cell line K562, in a 15-h 51Cr release assay. The effect of IL-15 was found to be both time and dose dependent, with peak activity detected after 2 or 3 days of culture with 100 ng/ml of this cytokine. LAK and not CTL activity in patient PBMCs was detected by the inability of mAbs against CD4, CD8, and MHC class I to effectively block lysis of autologous tumor and FMEX melanoma cells. In addition, interaction via the CD18 adhesion molecule was shown to be critical in IL-15-induced LAK-mediated lysis of autologous tumor cells. Finally, incubation of patient PBMCs with IL-15 for 6 h resulted in the up-regulation of perforin mRNA transcription. These findings suggest that LAK activity can be generated from melanoma patient PBMCs in the presence of IL-15 to lyse autologous tumor cells in a non-MHC-restricted manner. This new cytokine may play an important role in antitumor immunity with a possible use for cancer immunotherapy.