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increase when a more extended lymph node dissection is performed20. A more targeted and personalized treatment, including identi cation and dissection of truly or potentially involved lymph nodes, could result in improved gastric cancer treatment. Therefore, in both early gastric cancer and in resectable cases of advanced gastric cancer, accurate identi cation of true SLNs is of great importance.
Many di erent lymphatic tracers have been reported for SLN identi cation. The largest prospective multicenter trial until now used a combination of blue dye and radiolabeled tin colloids7. However, both tracers have disadvantages. Blue dye could alter the surgical  eld by dark staining, and only permits identi cation of super cially located lymph nodes. Moreover, in previous studies comparing radiolabeled colloids, blue dye, and NIR  uorescence for SLN detection in breast cancer patients, only 84 - 88 percent of the identi ed SLNs stained blue compared to 100 percent that were NIR  uorescent16;21. For the SLN procedure in skin melanoma blue dye staining was successful in only 73 percent22. Radiolabeled colloids only permit acoustic guidance during SLN identi cation, but no visual guidance. Besides, radioactive isotopes are scarce in many areas of the world. NIR  uorescence imaging could overcome these limitations as it only needs an imaging system and  uorescent tracer, and allows real-time optical identi cation of lymph nodes in up to ≈ 6 mm of tissue, for example in visceral dense fat tissue8.
Since Kusano et al.10 reported the  rst SLN procedure in gastric cancer using NIR  uorescence imaging, multiple studies con rmed the feasibility of this technique for both open and laparoscopic surgery11-15. All reported studies to date used ICG alone as lymphatic tracer, which resulted in detection of many  uorescent lymph nodes per patient. For example, Tajima et al.14 reported a mean number of 7.2 ± 7 SLN per patient and Fujita et al.11 a mean number of 9.3 ± 6.4 SLN per patient when using ICG as lymphatic tracer. This was possibly due to migration through the SLN to second tier nodes, and resection and pathological assessment of multiple nodes was still needed.
By combining ICG with nanocolloid, its hydrodynamic diameter increases from ≤ 1 nm (ICG) to 20 - 80 nm (ICG:Nanocoll). It has been shown that the hydrodynamic diameter of a lymphatic tracer has a major impact on the lymphatic migration and accumulation in lymph nodes. Molecules with a hydrodynamic diameter less than approximately 10 nm (for example ICG) have the potential to migrate through the SLN to second tier nodes, while
SLN detection in gastric cancer 31


































































































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