Background:
Gastric cancer is a worldwide challenge due to its spread, even epidemic in some areas, and the high mortality rates.
Lymphadenectomy is considered the fundamental step during radical gastrectomy for gastric cancer.
In recent years, some researchers have tried to find a way to improve the surgical identification of the lymphatic drainage routes and lymph node stations. This new surgical frontier is the so called "navigation surgery".
Among the different reported solutions, lately, the indocyanine green (ICG) has drawn attention. It is a fluorescence dye, that can be detected in the near infrared spectral band (NIR). The development of specific fluorescence imaging devices has allowed surgeons to visualize tumors, vascular and lymphatic structures.
Some advantages of the ICG are: reduced toxicity, absence of radioactivity, low cost, safe administration both intravenous and endoscopical through the submucosa or subserosa, protein binding without changing molecular structures, and macrophages interaction at the lymph node level.
This imaging technology has been used in colo-rectal and hepato-biliary surgery. However, up to date, the use of fluorescence imaging technology has not been extensively evaluated during lymphadenectomy for both early and advanced gastric cancer.
Methods:
General design: to evaluate the role of fluorescence imaging during lymphadenectomy for gastric cancer.
Type of study: interventional observational pilot study.
Duration: 12 months.
Inclusion criteria: positive biopsy, curative intent.
Experimental group: patients undergoing dissection assisted by ICG.
Control group: patients undergoing the same surgery without the injection of ICG.
Primary outcomes: Fluorescent lymph nodes (FLNs) identification rate, accuracy of the procedure, comparison with the control group on the total number of lymph nodes retrieved. Sample size: 20 patients in the experimental group, 20 patients in the control group.
Several new innovative fields will be addressed by this project.
First, the ICG spread along the lymphatic drainage pathways from the tumor area will be investigated during all steps of gastric dissection. From a technical point of view, a combined endoscopic and surgical procedure will be planned with the aim of standardize the use of this method in current clinical practice. Particularly, the project schema includes a gastroscopy with peritumoral submucosal injection of ICG, based on a specific protocol, the day before performing the gastrectomy with the fluorescence assistance.
Second, the feasibility of the procedure will be verified. The specimen will be divided by nodal stations and these further divided according to nodes fluorescence. By this way the pathological analysis will allow us to verify possible correlations among patient characteristics, stage of the disease, tumor site, lymphnodes fluorescence status, pathological lymphnodes status.
All these data can pave the way of a revolution in how lymphadenectomy is performed in gastric cancer and move to a patient-tailored surgery.
Third, a control group will allow a comparison with patients undergoing the same surgery but without fluorescence imaging with the purpose to evaluate the total number of lymphnodes retrieved both globally and according to the different nodes stations. This comparison is planned for a complete validation of the study.
In the last few years, the role of several techniques and contrast agents have been evaluated with the aim of improving the lymphnodes detection in gastric cancer. However, current published studies in the literature have only focused on the sentinel lymphnodes mapping
without being able to demonstrate any practical application to common surgical practice. As a result, the development of these procedures has gradually waned.
Therefore, our pilot study represents a milestone in the literature because no previous studies have evaluated the concept of the Navigation Surgery in gastric cancer.
The experimental group will be compared with a control group undergoing the same
surgery and the same method of specimen division but without the use of the indocyanine green injection, thus allowing us to quantify the differences with current standard procedures and estimate their statistical significance.
We assume that this procedure can help the surgeon during the visualization of the lymphatic tissue draining from the tumor site beyond the standardized lymphadenectomy. This innovative research will improve both the quality of surgery and the pathological staging assessment.
The application of this method can lead to a new frontier in surgery (the so called augmented reality), overcome the static concept of a standardized lymphadenectomy and moving to a patient-tailored approach. The superior accuracy in the analysis of the lymphnodes
and therefore in the tumor staging will give the patient possible relevant survival benefits.
Methods described in the past studies have several limitations that will be overcome by our study: lymphatic structures will be visualized even within the fat tissue, lymphatic channels can be better preserved avoiding their breakage, dissection can be safer performed along major vessels and the pancreatic edge.
The possible advantages from our study would offer greater benefit above all to surgeons in Western countries because of the higher prevalence of overweight / obese patients and the low incidences of gastric cancer. Moreover, the most interesting aspect is to observe
the role and effectiveness of the fluorescence-guided surgery in the advanced stages of the disease, common in the West, rather than in the early gastric cancer which is found in most Eastern patients.
These are exactly the points that makes the analysis and publication of data from a Western series of patients even more relevant than waiting for similar Eastern studies, that in any case cannot be totally adapted to our patients' characteristics.
However, this prospect clashes with the difficulty of planning and conducting such a study in Western countries because it requires: adequate volume of patients, technological availability, experience in gastric surgery, multidisciplinary management, organizational skills for patient management, expert endoscopists.
Therefore, this study represents a further opportunity because all the aforementioned needs have been carefully planned by involving in this project a referral center for gastric cancer surgery equipped with all the technological devices and a specific patient's pathway.