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LETTER TO THE EDITOR |
Department of Surgery, City of Hope National Cancer Center, Duarte, California.
Blue Dye for Sentinel Lymph Node Mapping: Not Too Sensitive, but Too Hypersensitive?
In the June issue of the Annals of Surgical Oncology, Leong and colleagues report three patients with malignant melanoma in whom administration of isosulfan blue (Lymphazurin) for the intraoperative sentinel lymph node (SLN) mapping resulted in anaphylactic complications.1 We also have recently encountered a severe, albeit not anaphylactic, hypersensitivity reaction after isosulfan blue injection in a 63 year-old-woman with a 2.55 mm, Clark’s Level IV nonulcerated malignant melanoma of the posterior leg who underwent wide re-excision and a SLN biopsy. The patient, devoid of known allergies, had received 1 mCi of unfiltered 99mTc sulfur colloid, injected preoperatively around the previous excision site, and the resulting lymphoscintigram identified an inguinal sentinel lymph node. Four milliliters of 1% isosulfan blue were injected intradermally prior to the skin preparation at the scar site, which was then widely excised with 2 centimeter margins. During primary closure, it was noted that the posterior leg and thigh rapidly developed multiple raised erythematous areas (Fig. 1). Diphenhydramine (Benadryl, 25 mg) was given intravenously, but the urticaria progressed onto the torso. Subsequently, 100 mg of hydrocortisone were administered intravenously, and the urticaria slowly faded. There was no sign of anaphylaxis or hemodynamic manifestations. Under guidance of a gamma probe, a small incision was made in the inguinal area, and three blue channels were seen leading to a single "hot" SLN. The node was not harboring tumor cells on histopathologic evaluation. The patient was admitted overnight for observation. She had no further signs of allergic response and was discharged the following morning.
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Professor of Surgery, University of California, San Francisco.
Reply to Letter to the Editor From Robert S. Krouse and Roderich E. Schwarz
Thank you for referring to me the letter by Drs Krouse and Schwarz entitled "Blue Dye for Sentinel Lymph Node Mapping: Not Too Sensitive, but Too Hypersensitive?" The utility of the routine use of blue dye for intraoperative mapping is probably not needed when a radiotracer sentinel lymph node technique is to be performed. In the literature, it has been well established that a combination of two techniques using radiotracer and blue dye are superior to blue dye alone.1–3 The issue is whether both techniques recognize the same sentinel lymph node which needs to be determined. For melanoma with respect to multiple anatomical sites, it is imperative to have a preoperative lymphoscintigraphy. Because preoperative lymphoscintigraphy has been established as a standard for detection of sentinel lymph nodes in the appropriate basins, and that almost 100% of the time the sentinel lymph node can be harvested when it is identified by preoperative lymphoscintigraphy, it is somewhat redundant to use a second tracer to further enhance the visualization of the sentinel lymph node. In fact, without the radiotracer, it takes a much longer time and a wider dissection area in order to track down the sentinel lymphatics to a blue lymph node. Occasionally, even with the visualization of blue lymphatic channels, it may not lead to a blue lymph node. Likewise, blue lymphatics may not be seen despite the fact that there is a blue lymph node. On the other hand, when a preoperative lymphoscintigraphy identifies the sentinel lymph node, it can be harvested almost 100% of the time without the blue dye. Therefore, in general for melanoma cases, the addition of blue dye is certainly not necessary. On the other hand, in cases of breast cancer when preoperative lymphoscintigraphy is not able to localize the sentinel lymph node, injection of blue dye will definitely help because the sentinel lymph node is usually found in the axillary region. If the sentinel lymph node is identified by preoperative lymphoscintigraphy, the harvesting rate of the sentinel lymph node in breast cancer is also significantly enhanced.4
Furthermore, we have recently analyzed our database in which both the blue dye and radiotracer were used for a group of 326 melanoma patients. Blue dye alone would miss 27.5% of the sentinel lymph node being positive for melanoma. Furthermore, if only the most radioactive sentinel lymph node were resected within each nodal basin, a failure rate of 18.2% would be encountered. We conclude that radiotracer mapping is a superior method over blue dye staining for identifying sentinel lymph nodes with micrometastasis.
Krouse and Schwarz have eloquently stated all the reasons for the use of blue dye to be limited and not of necessity if indeed a radiotracer is being used. In view of the potential allergic and/or anaphylactic reactions to blue dye and other side effects such as blue coloration of the skin and blue urine lasting for over several days, use of blue dye should be limited.5 Furthermore, the extra cost of the blue dye and the injection time in the operating room can also be eliminated.
In summary, based on the scientific evidence available in the literature and the potential severe anaphylactic reactions, I agree with the authors that blue dye should only be used in a restrictive fashion when there is doubt about the identification of the sentinel lymph node by preoperative lymphoscintigraphy. Certainly, surgeons who continue to use the blue dye should be aware of potential anaphylactic reactions and appropriate treatment for such reactions.
REFERENCES
This article has been cited by other articles:
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  L. L. Montgomery, A. C. Thorne, K. J. Van Zee, J. Fey, A. S. Heerdt, M. Gemignani, E. Port, J. Petrek, H. S. Cody III, and P. I. Borgen Isosulfan Blue Dye Reactions During Sentinel Lymph Node Mapping for Breast Cancer Anesth. Analg., August 1, 2002; 95(2): 385 - 388. [Abstract] [Full Text] [PDF]
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