Modern surgical strategies aim to reduce trauma by using functional imaging to improve surgical outcomes. This reviews considers and evaluates the importance of the fluorescent dye indocyanine green (ICG) to visualize lymph nodes, lymphatic pathways and vessels and tissue borders in an interdisciplinary setting. The work is based on a selective search of the literature in PubMed, Scopus, and Google Scholar and the authorsʼ own clinical experience. Because of its simple, radiation-free and uncomplicated application, ICG has become an important clinical indicator in recent years. In oncologic surgery ICG is used extensively to identify sentinel lymph nodes with promising results. In some studies, the detection rates with ICG have been better than the rates obtained with established procedures. When ICG is used for visualization and the quantification of tissue perfusion, it can lead to fewer cases of anastomotic insufficiency or transplant necrosis. The use of ICG for the imaging of organ borders, flap plasty borders and postoperative vascularization has also been scientifically evaluated. Combining the easily applied ICG dye with technical options for intraoperative and interventional visualization has the potential to create new functional imaging procedures which, in future, could expand or even replace existing established surgical techniques, particularly the techniques used for sentinel lymph node and anastomosis imaging.

/pdf/role-of-indocyanine-green-in-fluorescence-imaging-with-near-4kvl61cu55.pdf

Role of Indocyanine Green in Fluorescence Imaging with Near-Infrared Light to Identify Sentinel Lymph Nodes, Lymphatic Vessels and Pathways Prior to Surgery - A Critical Evaluation of Options.

Sentinel lymph node biopsy (SLNB) is still the standard of care for axillary nodal staging in patients with invasive breast cancer (BC) and clinically negative lymph nodes (LNs). It successfully replaced the more invasive and morbid axillary lymph node dissection (ALND). The actual standard for SLNB is the radioisotope (RI) with or without blue dye (BD) technique. Because of several drawbacks reported in worldwide experiences, new techniques have been developed in the last years: indocyanine green (ICG) fluorescence, superparamagnetic iron oxide (SPIO) nanoparticles and contrast-enhanced ultrasound (CEUS) using microbubbles. Whilst each technique has its own advantages/disadvantages they are increasing their efficacy and are candidate to represent a new standard for SLNB in next future. This is a comprehensive review of current limitations of conventional techniques besides the improvements and innovations of new methods which, anyway, need future randomized controlled trials to be fully validated.

/pdf/new-techniques-for-sentinel-node-biopsy-in-breast-cancer-49v77o110b.pdf

New techniques for sentinel node biopsy in breast cancer

Radioisotopes (RI) and blue dye (BD) are routinely used markers for staining during sentinel lymph node biopsy (SLNB) in breast cancer. Compared with traditional tracers, tracer performance of indocyanine green (ICG) has been controversial. A total of 21 studies were selected from the PubMed, EMBASE and Cochrane Library databases. Detection ability was judged based on four endpoints: i) The identification rate (IR) of the patients; ii) the IR of the sentinel lymph nodes (SLNs); iii) the IR of the positive SLNs; and iv) the false negative rate (FNR). Compared with BD, ICG was superior in terms of the IR of the patients [odds ratio (OR)=7.17; 95% CI, 3.98-12.94), the IR of the SLNs (OR=8.84; 95% CI, 6.71-11.66) and FNR (OR=0.20; 95% CI, 0.08-0.48) using a fixed-effects model. There was a significant difference in both the IR of the positive SLNs (OR=21.32; 95% CI, 2.84-160.14) and FNR (OR=0.46; 95% CI, 0.23-0.91) in the ICG vs. RI group. Furthermore, when using ICG at the recommended dose, a significant difference was found in the IR of the patients (OR=1.77; 95% CI, 1.09-2.85) and the IR of the SLNs (OR=21.62; 95% CI, 5.23-89.43) using a fixed-effects model. In the ICG vs. BD combined with RI group, there were no differences in either the IR of the patients (OR=5.10; 95% CI, 0.24-107.48) or the IR of SLNs (OR=5.10; 95% CI, 0.60-256.66). In conclusion, ICG was a better tracer compared with BD or RI alone and was not a worse tracer compared with BD combined with RI. The use of the recommended dose of ICG had an improved tracer effect. ICG is expected to be widely used in SLNB in view of its clinical advantages.

/pdf/comparisons-of-icg-fluorescence-with-conventional-tracers-in-45kqwp5xz2.pdf

Comparisons of ICG‑fluorescence with conventional tracers in sentinel lymph node biopsy for patients with early‑stage breast cancer: A meta‑analysis

Purpose The combination of indocyanine green and methylene blue (ICG + MB) was reported to be an efficient tracer method in sentinel lymph node biopsy (SLNB). However, whether this method is superior to MB only or carbon nanoparticles (CN) is controversial. This study was to evaluate the efficacy of the three methods in SLNB for breast cancer, and to analyze its influencing factors. Methods One hundred eighty patients with early breast cancer were recruited and randomly divided into 3 groups. Each group comprising of 60 patients with SLNB using ICG + MB, MB, and CN, respectively. Then the 3 groups were compared in detection rate, mean number of SLNs, and the detection rates and number of metastatic sentinel lymph nodes (SLNs). Results The detection rate of SLNs was 100% (60 of 60) in ICG + MB group, 96.7% (58 of 60), and 98.3% (59 of 60) in MB and CN group, respectively, with no significant difference (P = 0.362). Totally, 204 SLNs (mean ± standard deviation [SD] [range], 3.4 ± 1.4 [2-8]) were detected in ICG + MB group, 102 (1.7 ± 0.7 [0-3]) and 145 (2.4 ± 0.7 [0-6]) in MB and CN group, indicating significant difference (P < 0.001). The detection rate of metastatic SLN was 23.3% (14 of 60) in ICG + MB group, which was higher than 18.3% (11 of 60) and 20% (11 of 60) in MB and CN group, respectively, but showed no statistical significance (P = 0.788). Conclusion ICG + MB method was superior to MB only and CN only methods in the mean number of SLNs, thus predicting axillary lymph node metastasis more accurately. Therefore, in areas where the standard method is not available, ICG + MB may be more suitable as an alternative tracer for SLNB.

/pdf/comparative-study-of-indocyanine-green-combined-with-blue-505vhgf2z7.pdf

Comparative study of indocyanine green combined with blue dye with methylene blue only and carbon nanoparticles only for sentinel lymph node biopsy in breast cancer

Sentinel lymph nodes (SLNs) are the first lymph nodes that receive lymphatic drainage from the breast. However, all stained lymph nodes are dissected as SLNs during surgery. The present study aimed to identify and preserve the stained non-SLNs and evaluate the safety during sentinel lymph node biopsy (SLNB) in breast cancer. SLNB was performed with a methylene blue and indocyanine green double-tracer technique. The first lymph node, which was connected with lymphatic vessels from the breast, was designated as the true SLN. The lymph node that was directly connected with the output lymphatic duct of the SLN was defined as post-SLN (poSLN), whereas the stained poSLN was designated as non-SLN. Both the stained SLN and non-SLN were sent to the pathological department for definitive diagnosis. The present study demonstrated that intraoperative dissection of the lymphatic network could distinguish true SLNs and stained non-SLNs. The number of stained lymph nodes was time-dependent. Not all stained lymph nodes were real SLNs, whereas the poSLNs would be stained if the staining time interval was inappropriate. The data indicated that the poSLNs were negative for metastasis when the SLNs were negative for metastasis. Stained lymph nodes may contain non-SLNs in addition to SLNs. Resection of all stained lymph nodes is not recommended. To reduce the morbidity due to SLNB complications, the identification and preservation of stained non-SLNs during SLNB is feasible and warrants further study in the era of precision medicine.

/pdf/identification-and-preservation-of-stained-non-sentinel-2dnbpmcgjb.pdf

Identification and preservation of stained non-sentinel lymph nodes in breast cancer.

Clinical utility of the additional use of blue dye for indocyanine green for sentinel node biopsy in breast cancer.

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Clinical utility of the additional use of blue dye for indocyanine green for sentinel node biopsy in breast cancer.