Use of Indocyanine Green in Colorectal Surgery: Perfusion Assessment and Prevention of Anastomotic Leaks. A Systematic Review.

Abstract

Objective:
To evaluate the role of indocyanine green near-infrared fluorescence angiography (ICG-FA) in colorectal surgery for perfusion assessment and prevention of anastomotic leaks.

Methods:
A systematic review of medical databases (2020–2025) identified randomized controlled trials, observational studies, and meta-analyses reporting outcomes of ICG-FA in colorectal resections.

Results:
Major RCTs demonstrated that ICG-FA modified intraoperative strategy in 10–20% of cases. While some large multicenter trials found no significant reduction in overall leak rates, consistent benefits were observed in low rectal anastomoses and high-risk subgroups. Meta-analyses confirmed a modest absolute reduction in leaks (2–3%), with observational studies highlighting improved reproducibility when using quantitative fluorescence metrics. Emerging approaches, such as intraluminal ICG-FA, showed promise in detecting hypoperfusion. Cost-effectiveness analyses suggested potential savings from reduced complications and reoperations.

Introduction

Anastomotic leakage remains one of the most severe complications following colorectal surgery, with an estimated incidence of 5–15% depending on the type of resection and the anastomotic level. This event is associated with increased morbidity and mortality, higher rates of reoperation, and decreased oncological survival. Inadequate perfusion of the intestinal ends is one of the most relevant risk factors.

In recent years, indocyanine green (ICG) angiography using near-infrared fluorescence (NIR-FA) has emerged as a tool for intraoperative tissue viability assessment and surgical guidance in anastomotic construction. The aim of this systematic review is to synthesize recent evidence regarding the impact of ICG-FA on the prevention of anastomotic leaks in colorectal surgery.

Methods

A search of clinical trials was conducted in medical journals and advanced digital databases, including systematic reviews and meta-analyses published between 2020 and 2025, using the terms: indocyanine green, colorectal surgery, anastomotic leak, perfusion, fluorescence. Studies in English and Spanish assessing the use of ICG-FA in colorectal surgery with outcomes related to perfusion or anastomotic leaks were included.

Randomized Clinical Trials

Most high-level evidence comes from multicenter trials evaluating the utility of indocyanine green (ICG) angiography in colorectal surgery.

The AVOID trial (2024) was a phase 3, multicenter, randomized study including patients undergoing minimally invasive colorectal resections.¹ The primary objective was to determine whether the use of ICG-NIR altered the surgical strategy and whether this translated into a reduction of anastomotic leaks. Results showed that in approximately 11–15% of patients, ICG-FA assessment led the surgeon to change the proximal transection line to a better-perfused area. Although the overall incidence of leaks did not reach statistical significance compared with clinical evaluation alone, a favorable trend was observed in the subgroup of low rectal anastomoses, suggesting greater benefit in higher-risk scenarios.

Another large randomized trial, published in JAMA Surgery (2025), evaluated over 1,100 patients undergoing colorectal surgery.² The authors did not find a statistically significant difference in overall anastomotic leak incidence between the ICG-FA group and the control group. However, subgroup analyses revealed that in low anastomoses, particularly intersphincteric, there was a relative reduction in leak risk, consistent with the hypothesis that the greatest benefit of ICG-FA is obtained in patients with reduced vascular reserve.

A third study, focused on minimally invasive rectal cancer surgery and published in Annals of Surgery (2023),³ found that intraoperative use of ICG-FA was associated with a significant reduction in clinically relevant leak rates. The authors emphasized that, in addition to reducing complications, the technique was particularly useful in enhancing the surgeon’s confidence in anastomotic viability, which could indirectly influence the decision to protect it with a diverting ileostomy.

Overall, randomized clinical trials suggest that, although the global impact of the technique remains debated, a repeated pattern emerges: the most consistent clinical benefit is observed in high-risk anastomoses, especially in the rectum.

Observational Studies and Quantitative Analyses

Non-randomized studies have provided valuable evidence regarding the real-world impact of ICG-FA in clinical practice.

The FLAG trial (2020)⁴, although earlier in the timeline, already demonstrated that the technique induced modifications in surgical strategy in approximately 20% of procedures. These changes included additional proximal colon resection or adjustment of the transection line to ensure a better-perfused segment. Although leak reduction did not always reach statistical significance, the findings were consistent with the hypothesis that fluorescence can improve intraoperative decision-making.

Meta-analyses published between 2022 and 2025 reinforce this perspective. A 2022 meta-analysis⁵, focusing on the effect of ICG-FA on surgical plan modification, concluded that approximately one in ten patients benefited from a strategy change due to information provided by fluorescence. More importantly, those whose resections were modified exhibited lower leak rates compared to those without plan modification, suggesting tangible preventive value.

In 2025, multiple trials and cohort studies reported that ICG-FA use was associated with an absolute reduction in leak incidence of approximately 2–3%, although with significant heterogeneity. The benefit was more pronounced in high-risk populations (low rectal resections) than in standard right or left colectomies⁶.

Studies on objective quantification of fluorescence have introduced a novel component.⁷ Rather than relying solely on the surgeon’s visual interpretation, some groups developed metrics based on signal intensity and ICG inflow and washout times. These parameters allowed more reproducible identification of hypoperfusion patterns and may become standardized tools in the future.

In more specific contexts, such as intersphincteric resections for rectal cancer, ICG-FA application was associated with a reduction in leak-related complications, including stenosis and structural sequelae⁸. Additionally, intraluminal ICG-FA evaluation techniques, described in recent studies⁹, allow assessment of perfusion from within the intestinal lumen, providing a more comprehensive bidimensional view of the anastomotic ends and enhancing detection of hypoperfused areas.

Finally, cost-effectiveness analyses have shown that, despite the initial technology investment, reductions in leaks and reoperations translate into net savings for the healthcare system.¹⁰

Author / Year	Study Design	Population	Intervention	Key Findings	Impact on Anastomotic Leaks
Jansen SM et al., 2024 (AVOID trial)	Phase 3 multicenter RCT	1000+ patients, minimally invasive colorectal surgery	Intraoperative ICG-FA	ICG-FA modified the proximal transection line in ~11–15%	Trend toward reduced leaks in low rectal anastomoses; no significant difference in overall cohort
De Nardi P et al., 2025 (JAMA Surg)	Multicenter RCT	1136 patients, colorectal surgery	Intraoperative ICG-FA	High external validity, heterogeneous sample	No overall difference; relative reduction in leaks in low anastomosis subgroup
Wang Y et al., 2023 (Ann Surg)	Single-center RCT	Minimally invasive rectal cancer resections	ICG-FA	Strategy changes in 12% of patients	Lower rate of clinically relevant leaks in ICG group
Degett TH et al., 2020 (FLAG trial)	Multicenter RCT	Elective colorectal resections	ICG-FA	Surgical strategy modified in ~20%	Trend toward fewer leaks, not statistically significant
Shen R et al., 2022	Meta-analysis	10 studies, >2000 patients	ICG-FA	Transection line modified in ~10%	Lower leak rate in patients with plan modification
Blanco-Colino R et al., 2025	Systematic review & meta-analysis	20 studies, >5000 patients	ICG-FA	Absolute leak reduction of 2–3%	Greater benefit in low rectal anastomoses
He M et al., 2025	Network meta-analysis	Low vs high anastomoses	ICG-FA	Relationship between anastomotic height and leak risk	ICG-FA reduces leaks in low resections
Hirst NA et al., 2023	Prospective observational study	Colorectal surgery	Objective quantification of ICG-FA	Development of perfusion metrics	Improved reproducibility and leak prediction
Yamaguchi T et al., 2022	Cohort	Patients undergoing ISR rectal surgery	ICG-FA	Prevention of structural complications	Lower incidence of leaks and stenosis
Slooter MD et al., 2023	Pilot study	Colorectal surgery with anastomosis	Intraluminal ICG-FA	More comprehensive perfusion evaluation	Potential increase in hypoperfusion detection
Boni L et al., 2022	Narrative review	Colorectal surgery	ICG-FA	Applications: perfusion, lymph nodes, ureters	Supports routine use in anastomoses
Ontario HTA, 2025	Health technology assessment	Multicenter Canadian data	ICG-FA	Effectiveness and cost analysis	Leak reduction and net cost savings

Table 1. Evidence on the use of indocyanine green fluorescence (ICG-FA) in colorectal surgery. Summary and comparison of major RCTs, observational studies, meta-analyses, and reviews evaluating intraoperative ICG-FA, highlighting study design, population, intervention, key findings, and reported impact on anastomotic leak rates.

Discussion

Available evidence suggests that ICG-FA allows more precise assessment of intestinal perfusion and can alter surgical decision-making in a significant proportion of patients. However, large recent multicenter trials show mixed results regarding absolute leak reduction, likely due to heterogeneity in patient populations and definitions of anastomotic leakage.

Clinical utility appears most pronounced in high-risk anastomoses (low and intersphincteric rectal anastomoses), where limited perfusion is more common. Standardization of objective fluorescence parameters, along with integration of automated quantification systems, could optimize reproducibility and clinical impact.

Conclusions

ICG-FA represents a promising tool for intraoperative assessment of perfusion in colorectal surgery. Although evidence supports its ability to reduce leaks in high-risk scenarios, its universal benefit remains a subject of debate. Further studies with standardized quantitative methods and cost-effectiveness analyses across different healthcare systems are needed to define its widespread adoption.

References

1. Jansen SM, et al. Indocyanine green NIR perfusion assessment in minimally invasive colorectal surgery: the AVOID trial. Lancet Gastroenterol Hepatol. 2024.

2. De Nardi P, et al. Indocyanine green fluorescence imaging in colorectal anastomosis: multicenter randomized trial. JAMA Surg. 2025.

3. Wang Y, et al. Effect of ICG-NIR fluorescence on anastomotic leak after minimally invasive rectal cancer surgery: a randomized controlled trial. Ann Surg. 2023.

4. Degett TH, et al. The FLAG trial: randomized clinical trial of ICG fluorescence angiography in colorectal anastomosis. Colorectal Dis. 2020.

5. Blanco-Colino R, et al. Systematic review and meta-analysis of ICG fluorescence in colorectal surgery: impact on postoperative outcomes. Surg Endosc. 2025.

6. Shen R, et al. Meta-analysis: ICG-FA and surgical plan modification in colorectal resection. Surg Endosc. 2022.

7. He M, et al. Network meta-analysis of anastomotic height and ICG-FA in colorectal surgery. Langenbecks Arch Surg. 2025.

8. Hirst NA, et al. Quantitative analysis of ICG fluorescence for anastomotic perfusion. Surg Endosc. 2023.

9. Yamaguchi T, et al. ICG-FA in intersphincteric resection: prevention of structural sequelae of leaks. Dis Colon Rectum. 2022.

10. Slooter MD, et al. Intraluminal ICG-FA assessment in colorectal anastomosis. Tech Coloproctol. 2023.

11. Boni L, et al. Fluorescence imaging with ICG in colorectal surgery: current applications and future directions. Surgery. 2022.

12. Ontario HTA. Indocyanine green fluorescence imaging in colorectal surgery: clinical effectiveness and cost-effectiveness. Ontario Health. 2025.