Discussion
cancer, tumor, avascular
TUMOR, POSTOPERATIVE COMPLICATIONS, CANCER, EVENT, COMPLICATION, INTRAOPERATIVE BLOOD LOSS
The Greeneye study was designed to assess whether NIR visualization after peritumoral ICG injection improves the effectiveness of laparoscopic lympadenectomy by increasing the number of retrieved lymph nodes. Preoperative endoscopy performed with the only goal of ICG peritumoral injection poses several organization, economic and patients’ related concerns. For this reason, we designed the study with a Simon optimal two-stage design, so that the trial could be stopped after the first eight cases in case of futility. Because retrieval of nonnodal tissue (nodal noncompliance) has been repeatedly reported in NIR-guided lymphadenectomy, we considered nodal noncompliance as a potentially harmful event, and in each patient NIR was considered useful only if the number of additional retrieved nodes was higher than the number of nonnodal tissues (response > 0). Overall, response was > 0 in 7 cases (38.9%): the null hypothesis of having < 20% patients with response > 0 was rejected, and the study confirmed that NIR visualization after ICG injection might positively influence the quality of lymphadenectomy in laparoscopic subtotal gastrectomy for cancer.Several studies, and a recent meta-analysis, suggest that fluorescence guided LND allows for a higher number of LNs harvested with respect to standard LND, possibly reducing intraoperative blood loss and without impact on operative time and postoperative complications.From a clinical standpoint, in this series NIR visualization and the resulting nodal retrieval did not have a significant impact overall: neither appropriateness of lymphadenectomy (in terms of LNs retrieved) nor staging (in terms of metastatic nodes) was affected by the additional removal of fluorescent stations. However, in one patient the fluorescent station that was harvested resulted in the fourth metastatic node (more than 47 LNs retrieved), potentially changing the curative impact of the surgical procedure; in four patients fluorescent staining with nodal tissue was found outside the D2 area (4sa, 11d, and 13), potentially representing an unexpected area of tumor drainage. Because no stage migration nor increased adequacy of lymphadenectomy were achieved, whether the statistical benefit of the procedure resulted in a clinically meaningful benefit remains uncertain.We further analyzed our data to check whether any patient or tumor related characteristic was associated with the possibility of retrieving additional nodal tissue thanks to ICG staining. Interestingly, as shown in Table We found that, after standard lymphadenectomy was performed, the LN station that was most frequently fluorescent, thus most commonly harvested with NIR visualization, was station 6. Lymphadenectomy in the infrapyloric area is considered a challenging procedure because of the conformation of this area and needs high anatomical knowledge and surgical expertise to be performed systematically. When LN dissection is not performed correctly along the avascular planes, LN retrieval may be inadequate. Previous studies showed that ICG fluorescence during laparoscopic gastrectomy facilitates lymphadenectomy in the subpyloric region and might allow for a higher number of harvested LNs in this area.This study has some limitations. First, the number of patients is small; even if the primary endpoint was met, the generalizability of results might be limited by the relative heterogeneity of tumor stages. Second, in this study, we did not observe any complication directly correlated with the EGDS and the preoperative submucosal injection of ICG, nor resulting from the retrieval of fluorescent tissue at the end of LND. Analyses on long-term oncological outcomes could not be performed due to small sample size and insufficient follow-up. The time spent for the NIR-guided retrieval of additional nodal stations was 12 (range 8–16) minutes, which appeared to minimally impact on the total operative time as observed in most studies.