Alternative Methods for Axillary Sentinel Lymph Node Dissection
Stephanie A. Valente
Stephen R. Grobmyer
Axillary lymphatic mapping for sentinel node (SN) biopsy is the standard procedure for the surgical staging of patients with early-stage breast cancer. Sentinel lymph node (SLN) biopsy has been shown to be safe, accurate, and limits the need for traditional axillary dissection in most patients (1). Conventionally, SLN lymphatic mapping for breast cancer has involved the use of colloid radiotracer labelled with technetium 99 (2), visible blue dye (methylene blue or isosulfan blue) (3), or a combination of both (4). Best mapping results are achieved with periareolar, subdermal injection of the tracer (5,6). SLNs are defined as axillary lymph nodes in which there is the accumulation of one or more of these tracers or dyes above defined thresholds (7). Studies have demonstrated that there is surgeon-associated variation in both the number of SLNs removed and in the likelihood of finding a positive SLN (8). In large studies involving experienced surgeons, the SN detection rate using dual mapping with Tc and a visible dye is approximately 99%, therefore, use of both methods combined is recommended by some to achieve the highest accuracy of SLN biopsy and to reduce the false-negative rate (1,9).
Both traditional mapping techniques also have drawbacks that may limit their routine use (10). 99mTc-labeled radiotracer injection requires nuclear medicine licensing, radioactive material handling regulations, and patient inconvenience with painful periareolar injections typically occurring before surgery. Although there are reports of surgeons performing Tc injections in the operating suite, this still requires regulatory resources and is not common (11). Blue dye injections can be performed during surgery, but risk skin necrosis with methylene blue injection, inhibiting its use for nipple-sparing mastectomies, and there is a risk of anaphylaxis with isosulfan blue dye injection (12,13).
Alternative techniques including indocyanine green (ICG) dye, and superparamagnetic iron oxide (SPIO) have been utilized for SLN mapping in an effort to overcome some of the limitations of traditional methods.
Indocyanine Green (ICG)
ICG is a fluorescent dye with moderate optical properties that can be detected using near-infrared (NIR) cameras. ICG has been used in humans for over 50 years and has an excellent safety profile (14). There are many uses for ICG during image-guided surgery. After intravenous injection, it can be used for NIR angiography of blood vessels, skin flap perfusion for mastectomies, identification of the extrahepatic bile ducts, and identification of oncologic tumor metastases (15). ICG also has been reported by numerous authors to be safely used for subcutaneous injection and sentinel node (SN) mapping in gastrointestinal cancer (16), melanoma (17), and breast cancer (18,19,20,21). The use of ICG for lymphatic mapping and SLN identification offers many potential advantages over the use of other lymphatic mapping techniques including the ability to inject the material while the patient is in the operating room under anesthesia, the ability to use NIR to directly, instantly visualize lymphatic anatomy and flow, with no special material handling required, and low cost (20,22).
Recent studies have demonstrated high concordance in the number of breast cancer SLN identified between ICG and traditional Tc or blue dye mapping techniques, signifying the benefit of NIR-guided SN biopsy for standard use (21,23,24,25,26,27). In the modern treatment of breast cancer, the importance of SLN biopsy has focused on appropriately staging patients in order to customize adjuvant treatment recommendations.
Superparamagnetic Iron Oxide (SPIO)
SPIO is the newest described lymphatic mapping tracer which consists of a dextran-coated magnetic nanoparticle that is injected subareolar into the breast and travels to the SLNs within minutes and can last for up to 30 days (28). The injected material is identified in the SLNs with the use of a hand-held magnetometer as well as visualized on a preoperative MRI (29).
Indocyanine Green (ICG)
NIR guided, ICG SLN mapping can be performed in breast cancer patients undergoing SLN either primarily or after neoadjuvant chemotherapy (27,30,31). ICG SN mapping has been compared to either Tc, blue dye, or both and consistently been found to be just as effective with rates over 95% (18,19,21,23,24,26,27,32,33,34,35,36,37,38). Specifically, ICG safely performs similarly to traditional SLN mapping in regard to the number of SNs identified, rate of failed mapping, and identification of pathologically positive SNs (27).