Fluorescence Image-Guided Lymphadenectomy Using Indocyanine Green and Near Infrared Technology in Robotic Gastrectomy

Background Gastric cancer is the fourth most widespread cancer in the world and is characterized by high mortality rates [1, 2]. A multidisciplinary context, in which surgery plays the main role, is essential to offer the best therapeutic strategy. Lymph node involvement in gastric cancer is present in 2-18% when the depth of the tumor invasion is limited to the mucosal or submucosal layer, but rises to 50% when the tumor involves the subserosa [3]. Lymphadenectomy is a fundamental surgical phase that must guarantee the oncological radicality and allow an appropriate tumor staging. Although it is among the most relevant factors influencing long-term survival, its extension and standardization is still the subject of much debate. The two latest editions of the Japanese Gastric Cancer Association (JGCA) guidelines [4] recommend a dissection on different levels (D1, D1 +, D2) depending on the type of gastrectomy and the clinical stage of the tumor. In recent years, some researchers have tried to apply the concept of "sentinel lymph node" to gastric cancer [5-7]. Although some do not consider that terminology the appropriate one in the context of gastric cancer, because of the multidirectional gastric lymphatic flows, several studies have highlighted interesting aspects, such as: limiting an extensive lymphatic dissection when not necessary, identifying the drainage routes outside the standard anatomical planes, possible assistance in minimally invasive procedures [8]. Most of the experiences in lymph nodes mapping were performed with a radio-isotope (Tc99m) associated or not with the intraoperative use of vital dyes (Blue dye). More recently, the properties of the ICG have been studied. This is a fluorescence dye, that can be detected in the NIR [9, 10]. The development of imaging tools using "NIR / ICG" technology is therefore an innovative approach for visualizing tumors, vascular structures, lymphatic channels, and lymph nodes [11]. Some advantages of the ICG are: reduced toxicity, absence of radioactivity, low cost, safe administration both intravenously and endoscopically through the submucosa or subserosa, protein binding without changing molecular structures, macrophages interaction at the lymph node level. Devices for fluorescence imaging are currently available in both open and minimally invasive surgery.

In this field, robotic surgery has been becoming of great interest thanks to the manufacturing of new instruments which, compared to laparoscopy, allow to improve manual skills and gentleness in challenging movements [12]. The Da Vinci Xi robotic system has also produced an innovative imaging technology for ICG visualization made up with a laser source integrated in the robotic camera (Firefly). The surgeon at the console has therefore a 3-D vision that can switch to the fluorescence mode without the need to change the camera. Few clinical experiences have been reported to date [12]. Published articles refer to assistance in colo-rectal and hepato-biliary surgery for vessels or biliary structures visualization, while its use during lymph node dissection for gastric cancer has not yet been the subject of study protocols.

Hypothesis: fluorescence imaging during lymphadenectomy in gastric cancer can significantly improve the quality of the dissection through a better visualization of anatomical planes and allow tailored dissections. Moreover, the tumor status in the fluorescent nodes could predict the nodes status in the overall specimen with high accuracy rate.

Methods General study design: the overall objective is verifying the feasibility and the role of a lymphadenectomy assisted by fluorescence imaging during robotic gastrectomy.

Two levels of investigation are planned: