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...

Background: Sentinel lymph node (SLN) biopsy is a selective approach to axillary staging of breast cancer with reduced morbidity. Current detection methods including radioisotope and blue dye show good results but some drawbacks are remaining. Indocyanine green (ICG) fluorescence detection was evaluated as a new method for SLN biopsy in breast cancer allowing both transcutaneous visualization of lymphatic vessels and intraoperative identification of SLN. Methods: Forty-three women with clinically node negative breast cancer received subareolar injection of ICG for fluorescence detection of SLN. All patients underwent either planned axillary lymph node dissection (ALND) with SLN biopsy or selective SLN biopsy to determine need for ALND. Clinical feasibility, detection rate, sensitivity, and axillary recurrence after isolated SLN biopsy were analyzed. Results: Overall ICG fluorescence imaging identified 2.0 SLN in average in 42 of 43 patients (detection rate: 97.7%). Metastatic involvement of the SLN was found in 17 of 18 nodal positive patients by conventional histopathology (sensitivity: 94.4%). Immunohistochemistry revealed isolated tumor cells in five further cases. There was only one false-negative case in 43 patients (5.6%). In 17 of 23 overall nodal positive patients, the SLN was the only positive lymph node. After a median follow-up of 4.7 years none of the patients presented with axillary recurrence. Conclusion: ICG fluorescence imaging is a new method for SLN biopsy in breast cancer with acceptable sensitivity and specificity comparable to conventional methods. One advantage of this technique is that it allows transcutaneous visualization of lymphatic vessels and intraoperative lymph node detection without radioisotope.Keywords Sentinel lymph node biopsy Á Breast cancer Á Indocyanine green (ICG) Á Fluorescence imaging Á Surgery Abbreviations ALND Axillary lymph node dissection ICG Indocyanine green SLN Sentinel lymph node

The aim of this study was to compare CT, MRI and FDG-PET in the prediction of outcome of neoadjuvant radiochemotherapy in patients with locally advanced primary rectal cancer. A total of 23 patients with T3/4 rectal cancer underwent a preoperative radiochemotherapy combined with regional hyperthermia. Staging was performed using four-slice CT (n=23), 1.5-T MRI (n=10), and (18)F-FDG-PET (n=23) before and 2-4 weeks after completion of neoadjuvant treatment. Response criteria were a change in T category and tumour volume for CT and MRI and a change in glucose uptake (standard uptake value) within the tumour for FDG-PET. Imaging results were compared with those of pretherapy endorectal ultrasound and histopathological findings. Histopathology showed a response to neoadjuvant therapy in 13 patients whereas 10 patients were classified as nonresponders. The mean SUV reduction in responders (60+/-14%) was significantly higher than in nonresponders (37+/-31%; P=0.030). The sensitivity and specificity of FDG-PET in identifying response was 100% (CT 54%, MRI 71%) and 60% (CT 80%, MRT 67%). Positive and negative predictive values were 77% (CT 78%, MRI 83%) and 100% (CT 57%, MRI 50%) (PET P=0.002, CT P=0.197, MRI P=0.500). These results suggest that FDG-PET is superior to CT and MRI in predicting response to preoperative multimodal treatment of locally advanced primary rectal cancer.

ICG fluorescence allowed transcutaneous imaging of lymphatic vessels and SLN detection, thus combining the advantages of radioisotope and blue dye methods.

After radiochemotherapy, endosonography does not provide a satisfactory accuracy for preoperative staging of rectal cancer. New interpretation and diagnostic criteria are needed for the prediction of treatment response.

In combination with effective drainage, self-expanding plastic stents are an option for the treatment of oesophageal anastomotic leaks, and may reduce leak-related morbidity and mortality.

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ICG fluorescence imaging is a new, feasible method for SLNB of colon carcinoma and enables ultrastaging with improved accuracy but with limited validity due to the small number of cases. One advantage of this technique is real-time visualization of lymphatic vessels and SLNB without radiation exposure. Further, larger series are necessary to analyze the role of fluorescence-guided SLNB for colon cancer.