Ever since Kitai first performed fluorescent navigation of sentinel lymph nodes (SLNs) using indocyanine green (ICG) dye with a charge-couple device and light emitting diodes, the intraoperative use of near infrared fluorescence has served a critical role in increasing our understanding in various fields of surgical oncology. Here the authors review the emerging role of the ICG fluorophore in the development of our comprehension of the lymphatic system and its use in SLN mapping and biopsy in various cancers. In addition, they introduce the novel role of ICG-guided video angiography as a new intraoperative method of assessing microvascular circulation. The authors attempt to discuss the promising potential in addition to assessing several challenges and limitations in the context of specific surgical procedures and ICG as a whole. PubMed and Medline literature databases were searched for ICG use in clinical surgical settings. Despite ICG's significant impact in various fields of surgical oncology, ICG is still in its nascent stages, and more in-depth studies need to be carried out to fully evaluate its potential and limitations. Cancer 2011;117:4812-22. V C 2011 American Cancer Society.KEYWORDS: sentinel lymph node, indocyanine green, lymphedema, free flaps, axillary reverse mapping, sentinel lymph node biopsy.Near infrared (NIR; emission spectra of $700-850 nm) 1 fluorophores are probes that have gained immense interest in various fields of biomedicine because of their minimal interfering absorption and fluorescence from biological samples, inexpensive laser diode excitation, reduced scattering, and enhanced tissue penetration depth. 2 However, to date, only 1 NIR probe, indocyanine green (ICG) has been approved by the US Food and Drug Administration (FDA); methylene blue is another FDA-approved probe that displays NIR properties, however, it is not considered a pure NIR probe. The former, ICG, is a water-soluble, anionic, amphiphilic tricarbocyanine probe 3 with a hydrodynamic diameter of 1.2 nm, and excitation and emission wavelengths in serum at 778 and 830, respectively. 4,5 For several years, it has been used in ophthalmic angiography 6 and for determining cardiac output 7 and hepatic function. 8 However, it has only recently shown real practicability and feasibility in the field of surgical oncology. Three major domains where NIR-guided ICG fluorophores have appeared most promising are: 1) sentinel lymph node (SLN) detection, 2) evaluation of lymphedema, and 3) assessment of microvascular circulation of free flaps in reconstructive surgery. Although several reviews have discussed the importance of NIR fluorophores (including ICG), 9-13 in this review we limit our discussion specifically to ICG in an attempt to attain a better understanding of its impact and challenges it presents in the field of surgical oncology.Intraoperative SLN Mapping and Biopsy Using ICG The significance of cancer treatment management in relation to first lymphatic drainage from the tumor site, the SLN, was first proposed by Cabanas...

The purpose of this retrospective study was to compare the diagnostic value of four different imaging methods-computed tomography (CT), magnetic resonance (MR) imaging, ultrasonography (US), and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT-and their combined use for preoperative detection of cervical nodal metastases in head and neck squamous cell carcinoma (SCC). Sixty-seven patients (58 men and 9 women; mean age, 60.1 years) with head and neck SCCs underwent CT, MR, US, and PET/CT before surgery. First, each study was reviewed separately for the presence of nodal metastases. Then, the value of combined images was assessed based on a confidence rating score for each modality assigned by observers. These results were verified, on a level-by-level basis, with histopathologic findings. Histopathologic examination revealed nodal metastases in 74 of 402 nodal levels. The sensitivity, specificity, and accuracy were 77.0%, 99.4%, and 95.3% for CT and MR; 78.4%, 98.5%, and 94.8% for US; and 81.1%, 98.2%, and 95.0% for PET/CT, respectively. The comparison of these modalities showed no statistically significant difference among them (p > 0.05). The combination of CT, MR, US, and PET/CT improved sensitivity (86.5%), without loss of specificity (99.4%) and accuracy (97.0%), although the difference failed to reach statistical significance.

We found at least a 9.4% (15/160) prevalence of malignancy among ITN detected on CT. The further evaluation with US or biopsy should be performed, if an ITN shows CT features suggesting malignancy (calcification; AP/T ratio, >1.0; or mean attenuation value, >130 HU).

We found a significant association among ECS, lateral LN metastasis, tumor size (>5 mm), and central compartment LN metastasis in patients with PMC. A prophylactic neck dissection of the central compartment should be considered particularly in patients with ECS of the tumors, metastatic LN in the lateral neck, and a greater than 5 mm tumor size.