Summary
In East Asia, the role of lymph node (LN) mapping in assisting surgical lymphadenectomy, which is integral to the management of gastric cancer, has been explored. We sought to evaluate its safety and utility in Western patients. Thirteen patients with nonmetastatic gastric adenocarcinoma received endoscopic, peritumoural, submucosal indocyanine green fluorescence (ICG) injections before surgery, and ICG was assessed intraoperatively using a laparoscopic detection system. All patients underwent a laparoscopic subtotal gastrectomy, and 10 of them received D2 lymphadenectomies. ICG-mapped LNs fell outside the D1 distribution in all cases, outside the D1+ distribution in 54%, and within the D2 distribution in all cases. There were no ICG-related allergies, procedural complications, or perioperative deaths. We conclude that ICG LN mapping is safe and feasible in assisting LN dissections and localizing the primary tumour in Western patients. D2 dissections should be performed in patients with advanced gastric cancer, as LNs drained outside the D1/D1+ distributions in most cases.
Adequate lymphadenectomies for tumour staging and negative margins are critical to minimize disease recurrence1 in patients with gastric cancer, as they frequently present with locally advanced disease. In East Asian countries, the standard treatment for locally advanced disease includes a D2 lymphadenectomy, as it is associated with longer overall survival (OS);1 however, D2 dissections are not commonly performed in Western countries owing to concerns with associated morbidity and mortality.2 Lymph node (LN) mapping with indocyanine green fluorescence (ICG) has been explored in East Asian countries as a useful technique to support D2 dissections and outline resection margins.3 It has also been shown to identify skip metastases where positive LNs fall outside a typical dissection range,4 emphasizing the need to perform extended lymphadenectomies. We aimed to assess the safety and utility of ICG-specific LN mapping in defining draining nodal stations and resection margins to help guide the extent of lymphadenectomy in laparoscopic gastric cancer resections among Western patients.
Technique
All patients received endoscopic submucosal peritumoural ICG injections immediately before laparoscopic surgical resection to facilitate LN mapping. Approximately 1 mL of 0.25 mg/mL ICG was injected into each of the 4 quadrants of the peritumoural submucosal layer. About 1 mg of total ICG was used for each case.
The ICG-fluorescent LNs, primary tumour, LN basins, and tracts were visualized using a PINPOINT endoscopic fluorescence imaging camera (Stryker) with 3 modes (Pinpoint mode, SPY mode, colourized mode) (Figure 1). The LN dissection and subtotal gastrectomy were performed according to recommended gastric cancer treatment guidelines.1 A D1 dissection involves removal of LN basins 1, 3, 4, 5, 6 and 7. A D1+ dissection refers to a D1 dissection and removal of LN basins 8a and 9. The D2 dissection involves a D1+ dissection and removal of LN basins 11p and 12a.1
Detecting indocyanine green fluorescence with laparoscopic fluorescence imaging camera.
Safety and feasibility
Thirteen patients with histologically proven nonmetastatic gastric adenocarcinoma underwent LN mapping and laparoscopic subtotal gastrectomy (Table 1). We observed no ICG-related allergic reactions or procedural complications. Only 1 patient had a grade III Clavien–Dindo complication in the form of an upper gastrointestinal (GI) bleed owing to home use of a blood thinner. There was no 60-day perioperative mortality.
Baseline patient characteristics
Lymph node distribution
All patients had more than 16 LNs harvested, with a median of 26 LNs (interquartile range [IQR] 24–34). Four patients had disease-positive LNs (Table 2). ICG-mapped LNs fell outside the D1 distribution in all cases and outside the D1+ distribution in 54% of cases but were all within the D2 distribution (Figure 2). In total, 66%, 62%, 50% and 14% of resected 8, 9, 11p and 12-a LN basins in the D2 distribution were ICG-lit, respectively. One patient had pathologic 12a LN that was not ICG-lit (Table 3).
Detection of a basin 9 lymph node.
Perioperative clinical management and outcomes
Patient-specific nodal mapping
Primary tumour mapping
We used ICG mapping to determine the distance of resection from the primary tumour (Figure 3). Only 1 patient had a focal microscopic positive distal margin with discontiguous isolated tumour cells.
Mapping of the proximal margin of the primary tumour.
Discussion
We evaluated the application of LN mapping using ICG fluorescence in laparoscopic gastrectomies in a Western gastric cancer population. We found no associated adverse events and few postoperative complications (31%), which highlights the potential of ICG LN mapping to be adopted safely and effectively for this purpose. The absence of allergic reactions to ICG in our patient cohort is comparable to the results of other studies;3 thus, we deem ICG mapping safe to incorporate.
We assessed the utility of ICG LN mapping in assisting extended LN dissections in Western patients with locally advanced gastric cancers. All patients had LNs outside the D1 distribution, and more than half had LNs outside the D1+ distribution (54%). East Asian5 and Western4 studies have reported the detection of ICG-lit LNs in the D2 distribution, complementing our findings. More specifically, Tummers and colleagues4 found that 95% of LNs were outside D1 and 33% were outside the D1+ distribution; rates were slightly lower but similar in our study. Among our 4 patients with node-positive disease, only 1 had disease in the D2 distribution (basin 12a). Although this node was not ICG-lit, we emphasize how D2 lymphadenectomies can be useful in accounting for skip metastases, which frequently occur in areas outside the D1 dissection range.4 Although we did not find ICG-lit LNs outside the D2 dissection plane, the identification of such LNs (i.e., basin 14v) has also been documented in the past.4 Additionally, harvesting more than 16 LNs is crucial to accurate staging, treatment, and OS.1 We were able to harvest an adequate number of LNs (> 16) using LN mapping, which compliments the findings of an East Asian trial that showed the ability to harvest more LNs using ICG.5 Overall, ICG LN mapping is a feasible and effective method to encourage laparoscopic D2 lymphadenectomies, in adherence to the Japanese guidelines,1 as the majority also have locally advanced disease (69%).
ICG mapping is also effective in isolating the primary tumour to achieve negative margins. One patient had a focal positive distal margin in our study, but these were isolated tumour cells discontiguous from the primary tumour. ICG mapping has been reported to have 100% accuracy for achieving negative tumour margins3 and can be similarly used to reliably obtain negative margins in Western patients with locally advanced disease.
Our assessment was limited by our small sample; we evaluated only patients undergoing a laparoscopic resection. The declining incidence of gastric cancers in the Western population also limits the ability to draw statistically significant conclusions on safety and efficacy of the ICG LN mapping procedure. Future prospective studies are required to assess the impact of ICG LN mapping on long-term patient outcomes to better establish its role in laparoscopic gastrectomies.
Conclusion
ICG mapping was safe and effective in identifying LNs outside the D1 distribution, assisting D2 lymphadenectomy and localizing the primary tumour in the laparoscopic setting for locally advanced gastric cancers. It can be a useful tool in laparoscopic gastrectomies in Western patients with gastric cancer.
Acknowledgement
The authors thank the surgical oncologists at Vancouver General Hospital for their expertise and advice on the project.
Footnotes
Poster Presentation at American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, January 15–17, 2021
Competing interests: None declared.
Contributors: Both authors contributed substantially to the conception, writing and revision of this article and approved the final version for publication.
- Accepted November 17, 2021.
This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/
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