Most cancer experts believe that adequate lymph node (LN) dissection provides a survival benefit in the treatment of gastric cancer [1]. However, multiple vasculatures with complex lymphatic channels within the stomach anatomy increase the difficulty in performing a radical gastrectomy without postoperative morbidity [2]. Because a high level of proficiency is required in performing radical LN dissection, additional identification of potentially involved LNs may improve surgical outcomes [3].

We previously reported that injecting diluted indocyanine green (ICG) followed by near-infrared (NIR) imaging was clinically applicable for identifying LNs adjacent to the injection site in a preclinical animal model [4]. ICG injection aided not only in the detection of LNs but also in the detection of lymphatic channels; thus, it is a method with low toxicity and hypersensitivity that could help identify the complex anatomy of the perigastric lymphatic structures [4]. Although ICG showed rapid and extensive dispersion with adequate titration and quantification, a NIR-facilitated view can be transmitted to the operating monitor to allow the identification of anatomical structures only where the dye is present.

The aim of this study was to assess the feasibility of NIR imaging with ICG injection in investigating the completeness of laparoscopic LN dissection for gastric cancer.

This study aimed to investigate the clinical application of a NIR camera system for radical laparoscopic gastrectomy performed by experienced surgeons at a high-volume center. The current study reports the experience of one the earliest and largest adaptation of the NIR-ICG technique in laparoscopic LN dissection for gastric cancer.

Complete dissection of the infra-pyloric area is technically challenging owing to anatomical variations in the vasculature and conjoining of embryologic planes, whereas nodal metastasis to the right gastroepiploic vessels is frequent in lower- and middle-third gastric cancer [58]. Pylorus-preserving gastrectomy has a higher likelihood of leaving behind soft tissues after dissection than distal gastrectomy and removing tissues from the small branches of the artery and vein while preserving them requires a higher level of surgical skill [910]. Recently, intraoperative vascular imaging with the ICG fluorescence technique has been introduced to overcome this hurdle [11]. With this background, we reported the completeness of LN dissection of the infra-pyloric area during LPPG in addition to that during LDG. Although tissues with ICG uptake were more frequent in LPPG than in LDG, it failed to show a statistical difference.

One of the limitations of our study was a high false-positive rate. Among 15 additional tissue specimens with ICG uptake, only 2 actual LNs and 13 visceral adipose specimens were obtained. The high temperature of the energy device or forceful handling of the LNs might have compromised the nodal structure, causing its deformity. Owing to false positivity under this setting and because unnecessary soft tissue dissection in patients with early gastric cancer may lead to additional injury, cautious application is required.

Moreover, compared with previous modalities, the NIR camera can detect even a very small fraction of ICG from the operation field, which might be confusing in the early application of this technique. To overcome this issue, additional quantification of the ICG signal could provide complementary information to distinguish tissues with different levels of fluorescence uptake. A quantification method can offset the false-positive ICG tissues and deliver precise information about the targeted tissues.

It was difficult to consider the sample size of this study for 2 reasons. First, this was an investigational study evaluating the feasibility of the NIR-ICG technique in various partial gastrectomy settings [12]. Second, although various methods have been proven safe and useful in gastric cancer mapping, there are no reports about the completeness of LN dissection with the NIR-ICG technique, which made it difficult to calculate the number of samples required for the anticipated events to develop [131415]. Because the studied procedure was not performed or reported before the time of patient enrolment, it was difficult to follow the conventional sample size calculation. To compensate for this problem, we considered that this study should be categorized as an Innovation, Development, Exploration, Assessment, Long-term (IDEAL) phase 2a study, as introduced in previous publications about surgical [1617].

Randomization could have provided stronger evidence for this study; however, the current protocol of the NIR-ICG technique still requires further revision, and a randomized clinical trial should be conducted after more background data are collected about this technique and after establishment of a more sophisticated protocol [18].

In our experience, the key factor for successful lymphatic mapping was the delivery of the tracer. The concentration and amount of injection are associated with the timing and degree of dispersion. The correct concentration and dosage should be calibrated according to the design and purpose of the study. We adopted the concentration at the lowest limit of our preclinical study (0.05 mg/mL) to obtain an optimal outcome from multiple (4–6) injections along the stomach. Second, the submucosal injection skill is important. Deep injection causes intravascular injection, which results in total blurriness of adjacent organs. In cases of extraluminal spillage, even small amounts can contaminate the operation field. Meanwhile, when ICG was injected only within the surface of the mucosa, a lag time in the perfusion of ICG into the laminal flow of the lymphatic system was noted, making it difficult to determine whether the procedure was successful.

In this study, we had to exclude 1 case. Initially, we proceeded with the operation; however, during dissection along the pancreas, we found a serious vascular anomaly: the portal vein was running through the anterior surface of the pancreas head and across the second part of the duodenum, and the common hepatic artery was totally replaced by an aberrant hepatic artery from the left gastric artery. For the safety of the patient, we decided to drop the patient from the study, and the NIR camera was turned on during the rest of the operation. With ICG-enhanced fluorescence until the end of the operation, we were able to perform a rather comfortable and safe surgery owing to a virtual lymphangiogram, which allowed the surgeon to differentiate the lymphatic structures from other anatomical structures and avoid injury of the unfamiliar vascular anatomy. In this case, the additional visual information provided a higher level of confirmation for the operator to avoid potential injury and bleeding when performing the D2 dissection, which could be helpful even for highly experienced gastric surgeons. This NIR technique can provide guidance in dissecting lymphatic tissues with safe visual confirmation and can improve intraoperative decision making during complex lymphatic dissections.

In summary, this report showed the feasibility and efficacy of an NIR camera system in laparoscopic gastrectomy for gastric cancer, which was facilitated by our experience in LN mapping. The quality of the images depends on the preparation of the tracer and the quality of its injection. In our experience, the benefit of this technique seemed limited to standardized laparoscopic radical partial gastrectomy cases with a normal anatomy.

The clinical implication of this study is that even for surgeons with a high level of experience in laparoscopic D2 dissections, the NIR system can serve as a complimentary tool to confirm complete LN dissection in patients with atypical anatomy. Meanwhile, for inexperienced surgeons, to perform function-preserving surgeries, such as LPPG, additional confirmation of complete dissection should benefit the surgical procedure to overcome the limitation of insufficient LN dissection.