MSI in gastric cancer was associated with good overall survival, reflected in several favourable clinicopathological tumour characteristics.

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...

D2 procedure has been accepted in Far East as the standard treatment for both early (EGC) and advanced gastric cancer (AGC) for many decades. Recently EGC has been successfully treated with endoscopy by endoscopic mucosal resection or endoscopic submucosal dissection, when restricted or extended Gotoda's criteria can be applied and D1+ surgery is offered only to patients not fitted for less invasive treatment. Furthermore, two randomised controlled trials (RCTs) have been demonstrating the non inferiority of minimally invasive technique as compared to standard open surgery for the treatment of early cases and recently the feasibility of adequate D1+ dissection has been demonstrated also for the robot assisted technique. In case of AGC the debate on the extent of nodal dissection has been open for many decades. While D2 gastrectomy was performed as the standard procedure in eastern countries, mostly based on observational and retrospective studies, in the west the Medical Research Council (MRC), Dutch and Italian RCTs have been conducted to show a survival benefit of D2 over D1 with evidence based medicine. Unfortunately both the MRC and the Dutch trials failed to show a survival benefit after the D2 procedure, mostly due to the significant increase of postoperative morbidity and mortality, which was referred to splenopancreatectomy. Only 15 years after the conclusion of its accrual, the Dutch trial could report a significant decrease of recurrence after D2 procedure. Recently the long term survival analysis of the Italian RCT could demonstrate a benefit for patients with positive nodes treated with D2 gastrectomy without splenopancreatectomy. As nowadays also in western countries D2 procedure can be done safely with pancreas preserving technique and without preventive splenectomy, it has been suggested in several national guidelines as the recommended procedure for patients with AGC.

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MSI was confirmed as a significant predictor of long term outcome in a large series of GC with a long follow-up time, but the prognostic value is limited to selected histotypes of non-cardia tumors.

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CD44 isoforms are often upregulated in gastric cancer and have been associated with increased metastatic potential and poor survival. To evaluate the functional impact of O‐glycan truncation on CD44 we have analysed glyco‐engineered cancer cell models displaying shortened O‐glycans. Here, we demonstrate that induction of aberrant O‐glycan termination through various molecular mechanisms affects CD44 molecular features. We show that CD44 is a major carrier of truncated O‐glycans and that this truncation is accompanied by an increased hyaluronan binding capacity and affects extracellular shedding. In addition, short O‐glycans promoted the colocalization of CD44v6 with the receptor tyrosine kinase RON and concomitantly increased activation. Our in vitro findings were validated in gastric cancer clinical samples.