According to the most recent global cancer burden data, gastric cancer ranks as the fifth most prevalent malignancy and the fourth leading cause of cancer-related mortality, with an overall mortality rate of 7.7 per 100,000 individuals (1). In China, the absence of extensive gastric endoscopy screening programs has led to the predominance of locally advanced gastric cancer cases (2–4). For upper-middle gastric cancer, total or proximal gastrectomy remains the primary curative treatment modalities. In laparoscopic total or proximal gastrectomy with digestive tract reconstruction, the Roux-en-Y method or gastric tube reconstruction are favored for its simplicity, small anastomosis size, and its efficacy in preventing reflux esophagitis (5, 6). At present, esophagojejunostomy or esophagogastrostomy are the primary methods used for digestive tract reconstruction in total or proximal gastrectomy for patients with proximal gastric cancer (7, 8).

Esophagojejunal or esophagogastric anastomotic leakage stands as significant and potentially life-threatening complication following total or proximal gastrectomy for gastric cancer, with reported incidence rates between 2.3% and 13.6%, and the possibility of mortality reaching as high as 50% (9, 10). Among the multifactorial causes implicated in anastomotic leakage, inadequate anastomotic vascular perfusion has emerged as a pivotal factor affecting the healing of anastomoses (3, 11). However, assessing anastomotic vascular perfusion during total gastrectomy particular challenges. Typically, it relies on the surgeon’s visual judgment of subtle changes in the color or pulsation of small blood vessels within the digestive tract wall, which may fall short in providing a comprehensive assessment of the risk of (12, 13).

Indocyanine green fluorescence imaging (IGFI) has demonstrated its potential as an innovative surgical navigation technology for the precise localization of sentinel lymph nodes across various cancer types, including breast cancer and lung cancer (14). This technique is grounded in the direct visualization of the fluorescence emitted by indocyanine green (ICG) upon intravenous administration and exposure to near-infrared (NIR) light (15). Additionally, there is a growing body of literature highlighting the expanding utility of ICG in organ reconstruction and the evaluation of vascular perfusion at gastrointestinal anastomoses (16).

Hence, the principal aim of this study is to present our findings regarding the efficacy of IGFI in assessing anastomotic blood supply during total or proximal gastrectomy for patients with gastric cancer. Our objective is to compare the results of this innovative approach with those of conventional total or proximal gastrectomy surgery, to explore the potential advantages of IGFI in enhancing patient outcome and care for gastric cancer treatment.

The findings from our study highlight the potential utility of IGFI in the context of assessing anastomotic blood supply during surgical procedures for gastric cancer, specifically esophagojejunostomy or esophagogastrostomy ( Figures 1 , 2 ). The results underscored several significant points that contribute to the ongoing discourse in the field.

The lower incidence of anastomotic leakage in the IGFI group underscores the potential clinical impact of this technology. During the course of the study, we observed that in six patients from the IGFI group, there was an intraoperative adjustment of the resection height prompted by insufficient perfusion, as indicated by IGFI. This dynamic response to real-time perfusion feedback highlights the adaptability afforded by IGFI in guiding surgical decisions. The rationale behind these adjustments was to optimize perfusion at the anastomotic site, potentially contributing to the subsequently observed lower anastomotic leakage rate in the IGFI group. Anastomotic leakage, a well-documented and severe postoperative complication, significantly impacts patient outcomes, elevating the risks of morbidity and mortality (6, 20). Adequate tissue perfusion stands as a pivotal factor for successful gastrointestinal tract anastomosis. Literature has confirmed the effectiveness of fluorescence-guided perfusion control, highlighting the significant value of this technology in reducing the risk of anastomotic leakage (21, 22). Through visual quantitative evaluation, it notably decreases the occurrence rate of postoperative anastomotic leakage attributed to impaired blood supply during surgery. The ability of IGFI to aid in the assessment of anastomotic blood supply, potentially reducing the likelihood of this complication, highlights its role in enhancing patient safety and improving surgical success rates (23, 24). Our findings suggest that real-time IGFI can effectively evaluate the blood supply at the resection margin during gastric cancer surgery. We recommend assessing blood flow pre-anastomosis, performing the corresponding anastomosis when satisfactory, and subsequently reassessing blood flow at the anastomotic site using IGFI. ICG rapidly diffuses from the blood vessels to the target anastomotic areas, and the fluorescence imaging remains stable for several minutes, with fluorescence gradually decreasing within 10 to 15 minutes. If necessary, a repeat ICG injection can be administered at this stage. In the IGFI group, anastomotic leakage occurred in two patients, compared to eight in the control group, with a statistically significant difference. However, the average hospital stay did not show a significant statistical difference. An in-depth review classified anastomotic leakage severity using the Clavien Dindo grading system. In the IGFI group, one patient had Grade A, and one had Grade B leakage, while in the control group, six had Grade A, one had Grade B, and one had Grade C leakage. Notably, Grade A cases in the IGFI group received timely discharge and oral antibiotic therapy, contributing to the overall comparable average hospital stay.

In our study, we found that older age and low preoperative albumin levels were independent risk factors for anastomotic leakage after esophagectomy. These findings are consistent with those of previous studies (25–27). However, some studies (28) have reported that age is not a risk factor for anastomotic leakage or that older age may actually reduce the risk. These conflicting findings may be due to a number of factors, such as differences in study populations, surgical techniques, and definitions of anastomotic leakage. Further research is needed to clarify the role of age in anastomotic leakage after gastric cancer surgery.

The observed lack of a statistically significant difference in operative time between the two groups (p=0.098) necessitates further investigation with a larger sample size to enhance the power of the analysis. Employing propensity score matching, along with a multivariable regression analysis that integrates recognized confounders, may offer a promising result to illuminate the genuine relationship between group assignment and operative time.

The results of our study have the potential to have a significant impact on current surgical practice for gastric cancer. First, our findings suggest that IGFI is a feasible and safe tool for intraoperative assessment of anastomotic blood supply. IGFI could be used to identify patients with suboptimal anastomotic blood supply. This information could then be used to make intraoperative adjustments to the anastomosis, such as selecting a different resection point. Also, our findings also suggest that IGFI may be associated with a lower incidence of postoperative anastomotic leakage. This is a promising finding, as it suggests that IGFI could be used to reduce the risk of this serious complication.

Despite the notable findings, our study has several limitations that should be considered. The retrospective nature of the study design inherently limits the ability to establish causal relationships, and the lack of propensity score matching in our study could potentially introduce bias and affect the robustness of our findings. The relatively limited sample size might have affected the statistical power and precision of the study, warranting caution in interpreting the findings. Additionally, the absence of long-term follow-up data restricts the ability to assess the enduring impact of IGFI on patient outcomes beyond the immediate postoperative period. Future studies, especially prospective, randomized trials with larger sample sizes and longer follow-up durations are necessary to address these limitations and further elucidate the clinical implications of IGFI in the context of gastric cancer surgeries.

In conclusion, our study supports the integration of IGFI as a valuable intraoperative tool for assessing anastomotic blood supply during esophagojejunostomy or esophagogastrostomy for gastric cancer (29). The findings emphasize the potential of IGFI to contribute to more efficient surgical procedures, reduced postoperative complications, and improved patient outcomes. Further research and clinical validation are necessary to fully elucidate the benefits of IGFI and its role in enhancing the standard of care for patients undergoing gastric cancer surgeries.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

The studies involving humans were approved by National Cancer Center, Chinese Academy of Medical Sciences. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements.

PW: Conceptualization, Data curation, Formal analysis, Writing – original draft. YT: Data curation, Formal analysis, Investigation, Project administration, Validation, Writing – original draft. YD: Data curation, Investigation, Software, Validation, Writing – review & editing. YZ: Conceptualization, Funding acquisition, Methodology, Writing – review & editing.