Currently, rectal cancer ranks third among all common malignant tumors worldwide and is primarily treated with laparoscopic surgery. Anastomotic fistulas are a serious postoperative complication of rectal cancer surgery, which adversely affects patient recovery and prognosis (1). A key contributing factor to anastomotic fistulas is insufficient blood supply to the anastomotic site (2,3). However, reducing the incidence of postoperative anastomotic fistulas in laparoscopic surgery for rectal cancer remains challenging. At present, surgeons mainly rely on subjective judgement when assessing intestinal blood supply during laparoscopic surgery, such as whether the tissue around the anastomosis appears reddish, if the small arteries are pulsating or if there is bleeding at the incisal edge. This approach carries a risk of error, which can lead to the occurrence of anastomotic fistulas (4). This is particularly critical in radical surgery for rectal cancer, wherein blood supply to the proximal colon, following high ligation of the inferior mesenteric artery, depends on the marginal artery arc. If blood supply to the proximal colon is inaccurately assessed and anastomosis is performed, postoperative anastomotic fistulas may develop.

Indocyanine green (ICG) fluorescence imaging is a simple and effective method for evaluating tissue perfusion during laparoscopic surgery. It is safe and feasible, demonstrating promising potential for clinical application (5,6). ICG is a near-infrared contrast agent known for its biocompatibility (7,8). When exposed to external light with wavelengths ranging from 750 to 800 nm, ICG emits near-infrared light at longer wavelengths. Due to the inherent property of ICG to emit light within the near-infrared spectrum, it is typically unaffected by potential spontaneous fluorescence arising from blood components, such as hemoglobin and water. Leveraging on this characteristic, the ICG molecular fluorescence imaging system integrates fluorescence reception and imaging with fluorescence excitation. It applies a computer image processing system that is coupled to a highly sensitive near-infrared fluorescence camera and a near-infrared excitation light source to produce ICG fluorescence images. Upon administration into the human body, ICG undergoes metabolism in the liver and is excreted in its intact molecular form through the bile duct, ultimately being eliminated through the feces. Notably, it does not participate in the enterohepatic circulation and exhibits relatively rapid metabolic clearance. The present study aimed to investigate the efficacy of ICG fluorescence imaging by retrospectively analyzing its application in laparoscopic radical resection for rectal cancer and examining the clinical and pathological characteristics, surgical outcomes, postoperative recovery and complications. The feasibility and safety of ICG fluorescence imaging for assessing the blood supply at the anastomotic site are discussed, providing evidence-based support for its future application in colorectal surgeries.

Anastomotic fistulas are a severe complication following rectal cancer surgery, which leads to prolonged hospital stays, increased costs and higher mortality rates, adversely affecting short- and long-term outcomes of patients (11-13). Despite advances in neoadjuvant therapy and the implementation of total mesorectal excision, as well as the development of laparoscopic surgical instruments and improvements in surgical techniques, the incidence of anastomotic fistula in colorectal cancer surgery has not significantly decreased (14). Anastomotic fistulas can be caused by various factors and are highly dependent on anastomotic blood supply. Following inferior mesenteric artery ligation at its root during radical resection of rectal carcinoma, the blood supply to the residual distal intestine depends on the middle and inferior rectal arteries (15). Blood supply to the proximal colon is provided by the middle colic artery, marginal arterial arcades or Riolan's arch (16,17). If the marginal arterial arcades remain intact, the blood supply to the descending colon is typically sufficient. It has been reported that anastomotic fistulas may occur when blood flow is <70% of normal levels, although the exact percentage required for reliable intestinal healing remains elusive (18). Compared with postoperative prevention and management, intraoperative real-time evaluation of anastomotic perfusion is considered to be a more reliable approach for preventing anastomotic fistulas (19). At present, intraoperative assessment of blood supply to the anastomosis greatly relies on the experience of the surgeon, which involves observing the degree of intestinal peristalsis, colour, mesenteric fat appendage and mesenteric arterial pulsation. In addition, surgeons may check for active bleeding by cutting the marginal vessels or fat appendages. However, this method is prone to errors. Previous reports revealed that the sensitivity of subjective assessment is only 61.3%, with a specificity of 88.5% (4). In obese patients, wherein blood vessels are buried deep in the fat tissue or in cases where the colon does not exhibit clear ischaemic boundaries within a short time, it is challenging to accurately evaluate blood supply (20). Therefore, in rectal cancer surgery, accurately assessing blood supply to the intestinal segments and anastomosis intraoperatively whilst promptly modifying the surgical approach in cases of poor blood supply may help reduce or prevent the occurrence of anastomotic fistulas.

ICG fluorescence imaging is a simple and effective method for real-time intraoperative visualisation. It is primarily used clinically for tumor localisation, lymph node tracing and tissue perfusion monitoring, for which it has been proven to be safe and feasible (21). ICG is a non-radioactive near-infrared imaging agent, meaning that no protective measures are required during surgery (22). Considering that stained tissues are not observable under visible light, ICG does not affect the surgical field, prolong operative time or increase complexity (23). In addition, ICG is a cost-effective imaging agent. Despite all these advantages, the use of ICG fluorescence imaging requires specialized laparoscopic equipment, which may limit its widespread application. After entering the bloodstream and reaching the target tissue, ICG can be excited using lasers or light in the near-infrared wavelength, emitting fluorescence within 1 min in regions with good perfusion (24). This fluorescence is then observed using a laparoscopic fluorescence imaging system. During surgery, the Sherwinter scoring system can be used to semi-quantitatively assess intestinal perfusion. In 2010, Kudszus et al (25) were the first to apply ICG fluorescence imaging in evaluating anastomotic perfusion during colorectal cancer surgery, where the results were positive. In another study by Ris et al (26), ICG fluorescence imaging was used in 30 patients during colorectal resection and reconstruction, with successful imaging in 29 patients. Specifically, ~35 sec after ICG injection, fluorescence appeared, but no anastomotic fistula was observed postoperatively. A meta-analysis by Blanco-Colino and Espin-Basany (27), which included 1,302 patients, concluded that the use of ICG significantly reduced postoperative anastomotic fistula incidence (ICG group vs. non-ICG group, 1.1 vs. 6.1%; P=0.02). In another 2020 Japanese multi-center retrospective study involving 422 patients with rectal cancer, where ICG fluorescence imaging was used intraoperatively, surgical decisions were altered in 5.7% patients owing to ICG imaging findings. This resulted in a ~6% reduction in the rate of postoperative anastomotic fistulas, a decrease in the reoperation rate and shortened hospital stays (6).

Therefore, ICG fluorescence imaging is efficient and precise in evaluating intestinal blood supply. This technique eliminates the need for repeated intraoperative assessments, significantly reducing operative time and accurately delineating the resection margins, thereby minimising anastomotic complications caused by poor perfusion. The core cost-effectiveness of ICG fluorescence imaging is primarily attributed to its ability to reduce complication risks. The single-use cost associated with ICG is significantly lower compared with the expenses incurred from treating postoperative complications (28). Traditional staining agents, such as methylene blue and nano-carbon, exhibit various disadvantages, including local adhesion issues, suboptimal visualization and even the potential for abdominal cavity infections (29). Consequently, in comparison to conventional staining techniques, ICG offers enhanced advantages in terms of real-time performance, safety and accuracy in assessing microcirculation. As a result, it has emerged as one of the most cost-effective dynamic assessment tools for evaluating blood perfusion. In the present study, two cases were observed in whom, despite the proximal intestinal blood supply appearing normal under white light, clear ischemia was determined under fluorescence imaging. The accurate assessment provided by ICG fluorescence imaging enabled the intraoperative resection of ischemic bowel segments, preventing postoperative anastomotic ischemia and fistulas. The ischemia in these two cases may have been due to poor rotation of the descending colon, resulting in mesocolon thickening and sigmoid colon adhesions. During surgery, mesocolon trimming may have damaged the marginal artery, where ligating the inferior mesenteric artery without preserving the left colic artery possibly worsened the blood supply to the proximal colon. No obvious signs of ischemia were detected during surgery. Without intraoperative ICG fluorescence imaging, postoperative anastomotic fistulas due to ischaemia may have occurred. If fluorescence intensity diminishes during surgery, additional ICG can be administered intravenously to enhance imaging quality. Although the present study did not include a control group, the conclusions drawn are consistent with findings from other studies, all of which suggest that ICG fluorescence imaging can effectively assess the blood supply of anastomoses, thereby reducing the incidence of postoperative anastomotic leakage (30-32).

Inflammatory and nutritional biomarkers serve as critical indicators for assessing the prognosis of patients with colorectal cancer. Preoperative malnutrition and systemic inflammatory status significantly impair the tissue repair capacity and immune defence mechanisms of these patients, thereby elevating the risk of poor anastomotic tissue healing post-surgery, which in turn increases the incidence of anastomotic fistula (33). Once an anastomotic fistula occurs, it triggers a severe local and systemic inflammatory response that exacerbates catabolism and nutritional depletion within the body, creating a vicious cycle that severely compromises both short-term recovery and long-term oncological outcomes for patients (34). Consequently, close monitoring of these inflammatory and nutritional biomarkers during the perioperative period is invaluable for predicting the risk of anastomotic fistula formation in addition to evaluating overall prognosis. Shu et al (35) previously indicated that low serum Ca²⁺ levels on the first postoperative day are an independent risk factor affecting overall survival and progression-free survival in patients with colorectal cancer. Additionally, Li et al (36) previously identified that the comprehensive immune-inflammation index can serve as a reliable biomarker for prognostication in non-metastatic colorectal cancer cases. The predictive scoring model developed from this index can effectively forecast survival duration following surgery in patients with non-metastatic colorectal cancer whilst aiding clinical decision-making. Similar studies have further corroborated the utility of both the comprehensive immune-inflammation index and albumin-globulin ratio as dependable indicators for predicting overall survival among patients with colorectal cancer. Notably, elevated comprehensive immunoinflammatory indices coupled with a reduced albumin-globulin ratio was found to be associated with poorer prognostic outcomes (37). A previous report has proposed a novel prognostic model, which integrates the (neutrophils x platelets)/(lymphocytes x hemoglobin) ratio along with the absolute monocyte count. This model demonstrated superior predictive accuracy compared with that of individual markers and exhibited high predictive performance for 1-, 3- and 5-year survival rates (38). Zhang et al (39) discovered that by assessing preoperative serum nutritional biomarkers, such as the Onodera Prognostic Nutritional Index and inflammatory indicators (such as the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio), it was possible to effectively predict the risk of anastomotic fistula in patients undergoing rectal cancer surgery. Furthermore, the intraoperative application of ICG fluorescence imaging technology allowed for the real-time assessment of intestinal blood perfusion. This technique has been shown to reduce the incidence of anastomotic fistulas, thereby minimizing this serious complication and preventing subsequent inflammatory storms and nutritional status deterioration triggered by such events. Consequently, this approach significantly enhanced postoperative recovery processes and improved long-term survival outcomes for patients.

The present study has several limitations. The inclusion of only 12 patients resulted in a limited sample size and the potential biases were not sufficiently controlled for, which somewhat reduced the statistical power. In addition, the present study presented a single-group case series and did not include comparisons with traditional intraoperative blood supply assessments, making it challenging to fully demonstrate the advantages of ICG technology. The postoperative follow-up period was relatively short, preventing an evaluation of long-term complications, where it remains unclear whether the short-term benefits observed in the present study can be translated into long-term outcomes. Therefore, supplementary follow-up is necessary in subsequent stages. Future research will need to focus on increasing the sample size, extending the follow-up duration, establishing a randomized control group and initiating prospective multi-center studies to clearly define endpoints and control for various confounding factors or potential biases, thereby further validating the findings of the present study.

In conclusion, the present study demonstrated that ICG fluorescence imaging is safe, reliable and convenient for evaluating intraoperative blood flow during laparoscopic surgery for rectal cancer. This technique allowed the real-time assessment of blood supply, reducing the risk of postoperative anastomotic fistulas.