Authors
Panagiotis Kapsampelis1, Elisa C Calabrese2,3,4, Sunjay S Kumar5, Dena Shehata6, Varun Bansal7, Katie Carsky8, Austin Eason9, Himsikhar Khataniar10, Stefan Scholz11, María Rita Rodríguez-Luna12, Nisha Narula13, Jeffrey Chiu14, Subhashini Ayloo15, Farah Husain16, Ahmed Abou-Setta17, Ziad Awad18, Bethany J. Slater19, Deborah S. Keller20
Abstract
Background: Fluorescence image-guided surgery (FIGS) using indocyanine green (ICG) enhances intraoperative visualization. Its application spans various surgical fields, yet evidence on its influence on clinical outcomes remains inconsistent. This systematic review was conducted as part of a guideline development process to evaluate the effectiveness of FIGS with ICG across several different surgical applications.
Methods: A systematic review was carried out, including a literature search up to October 2022, addressing eight predefined key questions (KQs) on the role FIGS with ICG in thoracic duct identification, detection of distant cancer metastases and primary cancers, lymph node retrieval, and improved evaluation of anastomotic perfusion. The search was extended until September 2024 for colorectal anastomosis application. Eligible studies included randomized controlled trials (RCTs) and comparative observational studies. Meta-analyses were conducted where appropriate. The review is reported following PRISMA 2020 guidelines.
Results: Seven RCTs were pooled and found that FIGS with ICG reduced colorectal anastomotic leak rates (Odds Ration (OR) 0.58, 95%CI: 0.44–0.75). It also facilitated intraoperative changes in the transection point during colorectal anastomoses in RCTs (OR 35.15, 95%CI: 8.72–141.77). FIGS with ICG increased lymph node retrieval in gastrointestinal cancer surgeries by 6.32 nodes on average (95%CI: 4.43–8.22). Evidence regarding its role in thoracic duct identification, esophageal anastomoses, bariatric surgeries, and pediatric applications remained limited.
Conclusions: This systematic review demonstrates that FIGS with ICG improves outcomes in specific surgical applications, particularly in malignant lymph node retrieval and colorectal anastomotic leak reduction. However, its effectiveness varies depending on the surgical context and clinical question. Further high-quality studies are required to address remaining gaps and inform evidence-based guidelines for broader implementation.
Keywords: Systematic review · Meta-analysis · Fluorescence image-guided surgery (FIGS) · Indocyanine green (ICG) · Surgery
Abbreviations & acronyms
CI = Confidence Interval
FIGS = Fluorescence Image-guided Surgery
GI = Gastro-intestinal
GRADE = Grading of Recommendations, Assessment, Development, and Evaluations
ICG = Indocyanine Green
KQ = Key Questions
OR = Odds Ratio
PICO = Population, Intervention, Comparison, Outcome
RCT = Randomized Controlled Trial
RD = Risk Difference
RR = Risk Ratio
SAGES = Society of American Gastrointestinal and Endoscopic Surgeons
SD = Standard Deviation
Background
Advances in modern surgery have been significantly driven by technological innovations, which aim to reduce operative trauma, shorten recovery times, and improve the precision of surgical interventions. One such innovation is image-guided surgery that allows surgeons to navigate complex procedures with enhanced visualization of anatomical structures, especially during minimally invasive procedures [1]. In particular, Fluorescence Image-Guided Surgery (FIGS) has impacted the field by allowing real-time identification of several biological structures [2].
One of the most widely used fluorescent agents is Indocyanine Green (ICG). ICG has been used in clinical practice since the 1960s for liver function diagnostics and cardiac output monitoring [3, 4]. In recent decades, ICG has become the most widely used fluorescent agent in surgery due to its unique properties. It is a water-soluble dye that binds to albumin and rapidly distributes in the blood. It is almost exclusively excreted by the liver and is therefore present in the bile [5]. As a fluorophore, when ICG is excited by a light source at a specific wavelength, it emits a fluorescent signal at approximately 830 nm [6]. This signal is captured by a dedicated camera and can be superimposed on the white light image, providing real-time visualization that enhances the standard surgical image with critical additional information [5, 6]. These capabilities have led to its extensive application across many surgical subspecialties.
As surgical procedures become increasingly complex, the demand for precision and safety heightens, emphasizing the need for effective real-time imaging. Nevertheless, access to FIGS and ICG technologies remains limited in many healthcare settings. Addressing these disparities is crucial, and decisions on resource allocation and targeted implementation of ICG should be grounded on the best available evidence.
Due to the versatility and widespread use of FIGS with ICG, the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) set out to develop guidelines on its use across several different surgical applications. The aim of this systematic review and meta-analysis was to evaluate the existing evidence on the impact of FIGS with ICG on surgical outcomes, which will form the basis of the practice recommendations in the associated SAGES guidelines. Several key questions were addressed concerning the effectiveness of FIGS with ICG in identifying and assessing anatomical structures, lymphatic drainage, and perfusion in various gastrointestinal operations. A separate SAGES project is studying the use of ICG for intraoperative imaging of the common bile duct during laparoscopic cholecystectomy for prevention of bile duct injury.
Methods
Members of the SAGES Guideline Committee conducted the systematic review and meta-analysis. Contributors included experts in the field as well as trainees that received formal training in evidence synthesis and guideline development. The methodology was guided by the SAGES Guidelines Development Standard Operating Procedure [7], Cochrane Handbook for Systematic Reviews of Interventions [8] and the Methodological Expectations of Cochrane Intervention Reviews (MECIR) [9], and is reported according to the updated Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA 2020) [10]. Using the Population, Intervention, Comparator, Outcomes (PICO) framework, eight key questions (KQs) were created (Appendix A). Studies were not limited by the type or timing of ICG injection, and all injection methods were included in this analysis.
Key questions
- KQ1: Should the use of ICG versus no ICG be used for intraoperative identification of the thoracic duct?
- KQ2: Should ICG versus no ICG be used for intraoperative identification of distant (non-regional) cancer metastases?
- KQ3: Should ICG versus no ICG be used for intraoperative identification of primary cancers?
- KQ4: Should ICG versus no ICG be used in patients undergoing resection of gastrointestinal cancers for intraoperative identification of lymph nodes?
- KQ5: Should ICG versus no ICG be used prior to performing a colorectal anastomosis to improve the quality of the anastomosis?
- KQ6: Should ICG versus no ICG be used prior to performing an esophageal anastomosis in patients undergoing resection for esophageal cancer to improve the quality of the anastomosis?
- KQ7: Should ICG versus no ICG be used prior to performing a gastrointestinal anastomosis in patients undergoing bariatric or revisional bariatric operations to improve the quality of the anastomosis?
- KQ8: Should ICG versus no ICG be used in pediatric patients undergoing a to improve the quality of the anastomosis?
Literature Search and Eligibility Criteria
A comprehensive search strategy was conducted up to October 2022 with the assistance of the SAGES librarian for each KQ in PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and the World Health Organization’s International Clinical Trials Registry Platform (ICTRP). A repeat search was performed for KQ5 up to September 2024, prompted by experts in the field with knowledge of several RCTs that could better inform this question. The search strategies for all sources are listed in Appendix B.
We included randomized controlled trials (RCT) and non-randomized comparative studies published in the English language. We also included single-arm studies with more than 20 patients. We excluded case reports, single-arm studies with a total sample size of 20 patients or less, correspondence, lay press articles, narrative reviews, systematic reviews, records published in non-English languages and studies with published abstracts only.
Study Selection
Using the Covidence platform [11], abstract and title screening was performed by two different committee members with discrepancies resolved by a third reviewer. Following this, all eligible studies underwent full text review by the same process. Previously published systematic reviews’ reference lists were hand searched to ensure no relevant articles were missed. A PRISMA flow diagram representing this step for each KQ can be found in Appendix C.
Data Extraction and Risk of Bias
Using the Covidence platform [11], outcome extraction forms were completed on all eligible articles after full text review by two different committee members and followed by consensus. Again, discrepancies were resolved by a third reviewer. Risk of bias was also determined at the time of extraction using the revised Cochrane Risk of Bias 2 (RoB 2.0) tool for RCTs [8, 12] and the modified Newcastle-Ottawa scale for non-randomized, observational studies [13]. Table 1 represents a summary of all included articles. Details of timing, dosing, and route of administration for each study are given in Table 2.
Table 1 . Summary of all included articles


Table 2. Summary of ICG dosing, timing, and imaging system by study












Data Analysis
A quantitative synthesis using meta-analysis was performed on the identified studies that directly compared ICG with no ICG. Dichotomous data are presented as Mantel–Haenszel Odd Ratios (OR) with 95% confidence intervals (95%CI) or Risk Ratios (RR). Continuous data are presented as inverse variance weighted Mean Differences (MD) with 95%CI. We used forest plots to visualize meta-analysis results, with studies grouped by type (RCT or observational). Meta-analysis was performed in RevMan Version 5.4 [14] using the random-effects model. All analyses were supervised, reviewed, and revised by a statistician (A.A.) experienced in both evidence synthesis and systematic reviews. We followed Gagnier et al. recommendations for assessing clinical heterogeneity in systematic reviews and evaluated statistical heterogeneity using the I2 and χ2 statistics [15]. If an I2 greater than 40% was present, then source(s) of heterogeneity were explored. When no single source of heterogeneity was identified, we decided to present the
pooled results rather than a range of effect estimates. When ten or more studies were included in the meta-analysis, we created a funnel plot to detect risk of publication bias for that outcome [16].
Determining certainty of evidence
After synthesis, the Certainty of Evidence (CoE) was deter-mined using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach through the GRADEpro guideline development tool [17–19]. For each outcome, Certainty of Evidence (CoE), also called quality of evidence, was determined by evaluating the risk of bias, inconsistency, indirectness, and imprecision of the included studies [20–23]. Funnel plots were generated in RevMan for outcomes with more than 10 studies, and no evidence of publication bias was detected across any of the analyses. The level of certainty was downgraded if there were concerns in any of these domains. Methods outlined in the GRADE handbook were used to judge the certainty of evidence for each outcome of interest [24]. The evidence tables for each key question are provided in Appendix D. Table 3 presents the certainty of evidence levels and their interpretation.
Results
Key Question 1 (KQ1): Should the use of ICG versus no ICG be used for intraoperative identification of the thoracic duct?
We identified one prospective comparative observational study with high risk of bias (Fig. 1), Barnes et al. [25], and three single-arm studies [26–28] addressing this question. This provided limited investigational evidence as there was significant heterogeneity regarding methods, and no meaningful pooled analysis could be performed.
Figure 1: Risk of bias for the observational study included under KQ1 as assessed by the modified Newcastle Ottawa Scale.

Identification of structure
Barnes et al. showed no evidence of a statistical difference between ICG and no-ICG groups in identification of the tho-racic duct (OR 0.82, 95%CI 0.14 to 4.74; Very Low CoE) (Fig. 2) [25].
In adult patients undergoing esophagectomy, the single-arm studies by Yang and Vecchiato found that ICG had a thoracic duct identification rate of 93% [28] and 100% [27], respectively. A single-arm study looking at neonates undergoing surgery for tracheoesophageal fistula reported 100% identification rate of the thoracic duct with ICG [26].

Identification of injury
Barnes et al. found a higher injury identification rate of the thoracic duct with ICG (OR 18.04, 95%CI 0.92 to 354.91; Very Low CoE) (Fig. 3) [25].
The single-arm studies by Yang et al. [28] and Vecchiato et al. [27] reported injury identification rates of 7% and 11%, respectively, when using ICG. The study by Shirotsuki et al. on neonates reported an injury identification rate of 12.5% with ICG [26].

Chylothorax
Barnes et al. reported no instances of chylothorax in either group [25].
There were no events of chylothorax with ICG in the single-arm studies on adult populations [27, 28]. In the neonatal population, there was a leak rate of 12.5% with ICG [26].
Key Question 2 (KQ2): Should ICG versus no ICG be used for intraoperative identification of distant (non-regional) cancer metastases?
A total of three studies compared ICG with no ICG for intraoperative identification of distant cancer metastases. This included one RCT with low risk of bias (Fig. 4) [29] and two observational studies with low risk of bias (Fig. 5) 30, 31]. While the internal validity of these studies was respectable, they varied between each other with regard to tumor type with He et al. and Handgraaf et al. evaluating liver metastases from primary colorectal malignancy and Wang et al. evaluating liver metastases from neuroendocrine malignancy. Importantly, all studies included patients with and without neoadjuvant therapy, with no significant differ-ence between ICG and non-ICG groups. The variability in tumor type, neoadjuvant therapy exposure, ICG injection, and dose limit this analysis and must be considered in its interpretation.
Figure 2: Risk of bias for the RCT included under KQ2 as assessed by a Cochrane Risk of Bias tool.


Change in management
One observational cohort study reported on change in management [30]. In the observational study by Handgraaf et al., the ICG group had higher odds of having change in management compared to the non-ICG group (OR 2.35, 95%CI 1.02 to 5.43; Low CoE) (Fig. 6).

Correct identification of margin
One observational study reported on this outcome [31]. Wang et al. found that the odds of correct margin identifica-tion using ICG are higher compared to no ICG (OR 29.9, 95%CI 1.58 to 542.27; Low CoE) (Fig. 7).

R0 resection
Two observational studies reported on R0 resection [30, 31]. The pooled analysis showed there was no evidence of a statistically significant difference in R0 resection rates between the ICG and no-ICG groups (OR 2.05, 95%CI 0.98 to 4.31, I2 76%; Very Low CoE) (Fig. 8).

Operative time
Three studies reported on operative time, in minutes, with only two being included in the meta-analysis as the third reported median and interquartile range (IQR) instead of mean and standard deviation.
The RCT by He et al. showed there was no evidence of a difference between ICG and non-ICG groups with regard to operative time (MD − 32.16 min, 95%CI − 68.67 to 4.35; Low CoE) (Fig. 9) [29].
The observational study of Handgraaf et al. showed no evidence of a statistically significant difference in operative time between the two groups (MD 3 min, 95% CI 14.43 lower to 20.43 higher; Very Low CoE) (Fig. 9) [30].

Key Question 3 (KQ3): Should ICG versus no ICG be used for intraoperative identification of primary cancers?
A total of 11 studies met the inclusion criteria for this ques-tion, including one RCT with low risk of bias (Fig. 10) [32] and 10 observational studies with seven studies having high risk of bias and the remaining three with low risk of bias (Fig. 11) [33–42]. Four studies evaluated liver tumors, including the single RCT, Liu et al. [32, 35, 39, 42]. Six of the remaining observational studies evaluated gastric malig-nancy and a single observational study evaluated pancreatic head tumors. The variability in tumor type, neoadjuvant therapy exposure, ICG injection, and dose limit this analysis and must be considered in its interpretation.

F

Change in management
The outcome of change in management was reported by one RCT [32] and one observational study [36].
In the RCT by Liu et al., change in management was defined as the number of patients with newly harvested lymph nodes, with the odds of change in management being statistically higher in the ICG group (OR 21.00, 95%CI 4.92 to 89.56; Moderate CoE) (Fig. 12) [32].
In the observational study by Liu et al., change in management was defined as the number of harvested lymph nodes, which was significantly higher in the ICG group (MD 4.36, 95%CI 1.34 to 7.38; Very Low CoE) (Fig. 13) [36].


Correct identification of margin
The correct identification of margin was reported in one RCT [32] and one observational study [40]. The RCT found that odds of correct margin identification were higher in the ICG group (OR 9.33, 95%CI 1.05 to 82.78; Low CoE) (Fig. 14). The observational study found that there was no significant difference in correct identification of margin between the ICG and no-ICG groups (OR 11.69, 95%CI 0.64 to 214.88; Very Low CoE) (Fig. 14).

R0 resection
One RCT [32] and four observational studies [33–36] reported on negative resection margins (R0 resection). There was no evidence of a statistically significant difference between the ICG and no-ICG groups in both the RCT (RR 1.04, 95%CI 0.93 to 1.16; Low CoE) and the observational studies (RR 1.01, 95%CI 0.99 to 1.03, I2 0%; Very Low CoE) (Fig. 15). A subgroup analysis was done to separate out the study with hepatic tumors, Jiangxi et al. There was no appreciable change to the pooled analysis in conducting this subgroup analysis, and thus, the studies were left combined in a pooled analysis.

Operative time
There was one RCT [32] and eight observational studies [34, 36–42] reporting on operative time in minutes.
The RCT found no significant difference in operative time between the ICG and no ICG groups (MD 7.32, 95%CI -28.87 to 43.51; Low CoE) (Fig. 16). In the pooled analysis of observational studies, the ICG group had a statistically significant reduction in operative time compared to no ICG (MD − 25.24, 95%CI − 39.43 to − 11.06, I2 75%; Very Low CoE) (Fig. 16).
A subgroup analysis was done to separate out the studies with hepatic tumors, Mehdorn et al., and Zhang et al. There was no appreciable change to the pooled analysis in conducting this subgroup analysis and heterogeneity persisted with I2 greater than 50% in both groups, and thus, the studies were left combined in a pooled analysis.

Key Question 4 (KQ4): Should ICG versus no ICG be used in patients undergoing resection of gastrointestinal cancers for intraoperative identification of lymph nodes?
A total of 18 studies were identified for this key question including one RCT with low risk of bias (Fig. 17) [43] and 17 observational studies with eleven having high risk of bias and six with low risk of bias (Fig. 18) [34, 36, 37, 44–57]. Of these, 13 focused on gastric and gastroesophageal junction cancer [34, 36, 37, 44–47, 50–55], three on colorectal cancer [48, 49, 57], and one on intrahepatic cholangiocarcinoma [56]. Variability in primary tumor type and ICG injection methods must be taken into consideration when interpreting these data.


Total number of nodes retrieved
A total of 18 studies reported on this outcome, including one RCT [43] and 17 cohort studies [34, 36, 37, 44–57]. Out of these, one RCT [43] and 12 cohort studies [34, 36, 37, 44–47, 51, 53–55, 57] were included in the meta-analysis.
The RCT, Chen et al. [43], found that the use of ICG resulted in a higher number of lymph nodes being retrieved compared to no ICG (MD 8.50, 95%CI 5.23 to 11.77; High CoE) (Fig. 19).
The meta-analysis from the 12 cohort studies revealed that using ICG resulted in a higher number of retrieved lymph nodes compared to not using ICG (MD 5.66, 95%CI 4.44 to 6.88, I2 62%; Very Low CoE) (Fig. 19) [34, 36, 37, 44–47, 51, 53–55, 57].
The remaining five cohort studies reported the number of retrieved lymph nodes using median and IQR, and thus, their results were not included in the meta-analysis [48–50, 52, 56]. Across these studies, the median number of nodes retrieved was consistently higher in the ICG group compared to the non-ICG group. The median number of retrieved lymph nodes ranged from 7 to 43.5 for the ICG group and from 3.5 to 32 for the control group.

Number of positive nodes
A total of 18 studies examined the number of positive lymph nodes [34, 36, 37, 43–57].
Out of these, ten cohort studies reported the number of positive nodes as a dichotomous outcome indicating the presence or absence of positive lymph nodes in patients [37, 46–48, 50, 51, 53, 54, 56, 57]. The pooled analysis of 857 patients from these studies showed that the use of ICG did not significantly affect the likelihood of finding positive lymph nodes compared to not using ICG (OR 0.77, 95%CI 0.54 to 1.09, I2 12%; Very Low CoE) (Fig. 20).
The remaining studies, including one RCT [43] and seven cohort studies [34, 36, 44, 49, 52, 54, 55], reported the num-ber of positive nodes as a continuous outcome, indicating the number of positive lymph nodes retrieved for each patient. The RCT [43] found no evidence of a statistically significant difference in the number of positive nodes between the ICG group and the no-ICG groups (MD − 0.10, 95%CI − 2.57 to 2.37; High CoE) (Fig. 21). Across the 699 patients in the seven cohort studies, there was no difference in the number of positive nodes retrieved with or without ICG (MD 0.31, 95% CI 0.44 to 1.06, I2 44%; Very Low CoE) (Fig. 21).


Operative time
The outcome of operative time, in minutes, was reported by 18 studies [34, 36, 37, 43–57]. The RCT, Chen et al. found no evidence of a statistically significant difference in operative time between the ICG and no-ICG groups (MD 5.70, 95%CI − 5.94 to 17.34; Moderate CoE) (Fig. 22) [43]. A total of 13 of the observational studies were included in the pooled analysis with ICG resulting in a shorter operative time compared to no ICG (MD − 4.13, 95%CI − 6.90 to – 1.37, I2 66%; Very Low CoE) (Fig. 22) [34, 36, 37, 44–47, 50–53, 55, 57]. The remaining four cohort studies were not included in the meta-analysis because they reported operative time using median and IQR [48, 49, 54, 56].

Key Question 5 (KQ5): Should ICG versus no ICG be used prior to performing a colorectal anastomosis to improve the quality of the anastomosis?
In total, 40 studies were identified, including seven RCTs with five having low risk of bias and the remaining two with some concerns (Fig. 23) [53–59] and 33 observational stud-ies with varying risk of bias (Fig. 24) [43, 60–91]. These studies focused on various types of anastomoses for which our data are pooled and included both right, left, benign, and malignant colorectal disorders. All RCT data were limited to left-sided colorectal operations in our analysis. The variability in specific surgical techniques and patient populations must be taken into consideration when interpreting these results.


Anastomotic leak
A total of 40 studies reported on this outcome, including seven RCTs [58–64] and 33 observational studies [48, 65–96]. All of the identified studies were included in the meta-analysis.
In RCTs, the use of ICG significantly reduced left-sided colorectal anastomotic leak rates (OR 0.58, 95%CI 0.44 to 0.75, I2 0%; High CoE) (Fig. 25) compared to no ICG. Observational studies also reported a statistically significant reduction with ICG (OR 0.35, 95%CI 0.29 to 0.43, I2 0%; Very Low CoE) (Fig. 25).

Change in transection point
The change in transection point was included in 29 studies, specifically four RCTs [58, 59, 62, 64] and 25 observational studies [66–73, 75, 76, 78–85, 88, 90, 92–96].
RCTs demonstrated a statistically significant increase in change of the transection point when using ICG (OR 35.15, 95%CI 8.72 to 141.77, I2 0%; Low CoE) (Fig. 26). Observational studies similarly showed a statistically significant increase in transection point change (OR 19.49, 95%CI 12.73 to 29.83, I2 27%; Very Low CoE) (Fig. 26).

Local repair after anastomosis
Local repair after anastomosis is defined here as unplanned repair of the anastomosis after its creation during the index operation, such as oversewing. A single observational study reported no evidence of a statistically significant difference of local repair after anastomosis when ICG was used (7.89, 95%CI 0.94 to 66.54; Very Low CoE) (Fig. 27) [91].

Anastomotic stricture
Anastomotic stricture was reported in eight studies, including two RCTs [59, 60] and six observational studies [48, 71, 73, 77, 85, 87].
There was no evidence of a statistically statistical differ-ence in anastomotic stricture rates between the ICG and no-ICG groups in both RCTs (OR 0.33, 95%CI 0.05 to 2.15, I2 0%; Moderate CoE) (Fig. 28) and observational studies (OR 1.23, 95%CI 0.64 to 2.39, I2 19%; Very Low CoE) (Fig. 28).

Reoperation
In total, 28 studies were retrieved for this outcome. The seven RCTs included showed no evidence of a statistically significant difference in reoperation rates between the ICG and no-ICG groups (OR 0.90, 95%CI 0.62 to 1.30, I2 19%; High CoE) (Fig. 29) [58–64], and the 21 observational studies showed a statistically significant reduction in reoperation rates with ICG (OR 0.63, 95%CI 0.45 to 0.86, I2 0%; Very Low CoE) (Fig. 29) [48, 66–71, 76, 78–81, 84, 85, 88–90, 92–94, 96].

Reintervention
Reintervention rates were assessed in a total of 22 studies. Seven RCTs showed no significant difference in reintervention rates between the ICG and no-ICG groups (OR 1.23, 95%CI 0.79 to 1.91, I2 0%; Moderate CoE) (Fig. 30) [58–64]. Fifteen observational studies demonstrated a reduction in reintervention rates with ICG use (OR 0.57, 95%CI 0.38 to 0.84, I2 0%; Very Low CoE) (Fig. 30) [48, 67, 71, 74, 76, 82, 83, 85, 88, 90–94, 96].

Key Question 6 (KQ 6): Should ICG versus no ICG be used prior to performing an esophageal anastomosis in patients undergoing resection for esophageal cancer to improve the quality of the anastomosis?
We identified three retrospective cohort studies, one with low risk of bias and two with high risk of bias (Fig. 31), comparing the use of ICG compared with no ICG prior to performing an esophageal anastomosis in patients undergoing esophagectomy for esophageal cancer [97–99]. None of the included studies reported on the outcomes of stricture, re-resection after anastomosis, and local repair following anastomosis.

.
Anastomotic leak
All three retrospective cohort studies analyzed this outcome [97–99]. The pooled analysis of 670 patients showed that the ICG group had statistically significant lower odds of anastomotic leak (OR 0.51, 95%CI 0.29 to 0.88, I2 62%; Very Low CoE) (Fig. 32) compared with the no-ICG group.

Reoperation
Three studies reported this outcome [97–99]. There was no evidence of a statistically significant difference in reopera-tion rates between the two groups (OR 0.70, 95%CI 0.36 to 1.35, I2 0%; Very Low CoE) (Fig. 33).

Reintervention
The outcome of reintervention was examined in two stud-ies, which showed no evidence of a statistically significant difference between the two groups (OR 0.91, 95%CI 0.46 to 1.79, I2 46%; Very Low CoE) (Fig. 34) [92, 94].

Change in transection point before anastomosis
One study examined the effect of using ICG on changing the transection point before anastomosis [99]. The pooled analysis showed a non-statistically significant difference between the groups (OR 287.72, 95%CI 17.49 to 4732.20; Very Low CoE) (Fig. 35).

Key Question 7 (KQ7): Should ICG versus no ICG be used prior to performing a gastrointestinal anastomosis in patients undergoing bariatric or revisional bariatric operations to improve the quality of the anastomosis?
Two observational, comparative studies, one with high risk of bias and other with low risk of bias (Fig. 36), were included for this question [100, 101].
These studies focused on the outcomes of anastomotic leak and need for local repair after anastomosis. There were no comparative studies on the outcomes of anas-tomotic stricture, reoperation, reintervention, change of transection point before anastomosis and re-resection after anastomosis.

Anastomotic leak
Both studies provided comparative data [100, 101]. The study by Hagen et al. was not included in the quantitative analysis because it reported zero anastomotic leak events in both the ICG and non-ICG groups [100]. In the study by Kalmar et al., there was no evidence of a statistically significant difference between the ICG and non-ICG groups (OR 0.46, 95%CI 0.02 to 9.12; Very Low CoE) (Fig. 37) [101].

Local repair after anastomosis
Both studies provided comparative data and were pooled in a meta-analysis [100, 101]. The pooled analysis of 445 patients showed that the use of ICG resulted in statistically significant higher odds of local repair of the anastomosis compared to the non-ICG group (OR 9.61, 95%CI 1.02 to 90.18, I2 0%; Very Low CoE) (Fig. 38).

Key Question 8 (KQ8): Should ICG versus no ICG be used in pediatric patients undergoing a pull through to improve the quality of the anastomosis?
We identified a single-arm observational study providing data on the ICG group [102]. No comparative studies were identified for this key question.
The study reported that patients who received ICG had an anastomotic leak rate of 7.69% (1 out of 13 patients), no stricture events (0 out of 13), a reoperation rate of 7.69% (1 out of 13 patients), and a rate of change in the tran-section point before anastomosis of 30.77% (4 out of 13 patients). The study did not provide data on other relevant outcomes, including reintervention, re-resection after anastomosis, and local repair following anastomosis.
Discussion
In this systematic review we assessed the effectiveness of fluorescence image-guided surgery (FIGS) using indocyanine green (ICG) across various surgical applications in both adult and pediatric populations. Our objective was to determine whether the use of ICG enhances intraoperative identification of anatomical structures, detection of cancer metastases, lymph node retrieval, and the quality of anastomoses compared to standard surgical techniques without ICG.
Overview of findings
Our findings indicate that ICG fluorescence imaging is beneficial in improving lymph node retrieval during cancer resections (KQ4) and in reducing anastomotic leak rates in colorectal surgery (KQ5). However, the evidence is limited or inconclusive regarding its effectiveness in thoracic duct identification (KQ1), intraoperative identification of primary cancers (KQ3) and distant metastases (KQ2), esophageal anastomosis (KQ6), bariatric surgery anastomosis (KQ7), and pediatric pull-through procedures (KQ8).
Relationship to the literature
The strongest evidence emerged for the use of ICG in improving the quality of colorectal anastomoses (KQ5) where RCTs with low risk of bias and several observational studies demonstrated that the use of ICG significantly reduced left-sided colorectal anastomotic leak rates. Addi-tionally, surgeons were more likely to change the transection point before creating an anastomosis when using ICG, indi-cating enhanced intraoperative assessment of bowel perfu-sion. Our findings are in line with recent systematic reviews by Borg et al. [103], Emile et al.[104], Kazi et al. [105], and Lucarini et al. [106], all of which reported a reduc-tion in left-sided colorectal anastomotic leak rates with the use of ICG fluorescence imaging. Additionally, Emile and colleagues demonstrated that ICG use increases the likeli-hood of modifying the transection line [99]. Our systematic review expands upon previous work by being the first to report on the outcomes of reintervention, reoperation, and anastomotic stricture in the context of ICG use during colorectal surgery.
It is worth noting that the results of the recently com-pleted IntAct trial have not been included in our review as they have not yet been formally published. This large, multicentre RCT from Europe is evaluating the efficacy of ICG in reducing anastomotic leak rates after rectal cancer surgery [107]. Based on the preliminary data provided by the IntAct team, it appears that its findings further strengthen the evidence base for the use of ICG in colorectal anasto-mosis. In addition, the large Finish RCT, ICG-COLORAL was recently published in March 2025 examining the use of ICG in colorectal anastomosis but excluded low anterior resection. Their conclusions regarding left-sided colorectal anastomosis overall agree with our findings as well [108].
The role of FIGS with ICG in intraoperative identification of primary cancers (KQ3) and distant metastases (KQ2) has limited evidence. Although some studies suggest that ICG may lead to changes in surgical management or improve margin identification, significant differences in key outcomes like R0 resection rates or operative times between ICG and no-ICG groups were not observed. In comparison, the recent MiMic Trial [109] showed that FIGS with ICG during minimally invasive surgery for colorectal cancer liver metastases increased the rate of R0 resections and led to changes in surgical management in more than a quarter of the patients. However, these outcomes did not translate into significant improvements in long-term oncologic outcomes. These findings are partially consistent with our results and highlight the need for further high-quality research to determine the clinical value of ICG in the intraoperative identification of primary tumors and metastatic lesions and to determine the effect of ICG on long-term oncological outcomes.
The current evidence supports the use of ICG in gastrointestinal cancer surgery for lymph node identification, particularly in gastric and colorectal cancers. Similar to our findings, previous systematic reviews focused on colorectal cancer [110] and gastric cancer [111, 112] also showed that ICG increased lymph node yield without increasing positive node detection rates.
The retrieved observational studies comparing FIGS with ICG with none in esophageal anastomosis creation suggested that the intervention might be associated with lower rates of anastomotic leaks; however, the heterogeneity among studies was substantial. There were no significant differences in reoperation or reintervention rates between ICG and non-ICG groups. These results differ from the systematic review by Casas et al. which concluded that the use of ICG fluorescence imaging does not seem to reduce anastomotic leak rates in patients undergoing minimally invasive esophagectomy with intrathoracic anastomosis [113]. It is important to note though that all studies included in the Casas systematic review were single-arm studies without a comparison group [113]. This difference in design of included studies may account for the discrepancies in findings.
Similarly, evidence is limited for ICG use in bariatric surgery anastomosis, identification of the thoracic duct, and anastomotic integrity in pediatric pull-through surgery.
Limitations
The findings from this systematic review should be interpreted with certain limitations in mind. For many of the key questions, there was a lack of high-quality evidence, with a limited number of studies available, small sample sizes, and few or no RCTs, thus reducing the strength of the conclusions. In addition, heterogeneity was observed for several outcomes, likely due to differences in study design, patient populations, and surgical techniques. Also, many of the studies included in this review, both RCTs and observational studies, were deemed to have a high risk of bias. This significant heterogeneity and the high risk of bias reduce the quality of the evidence and make it difficult to draw definitive conclusions.
In addition to these study-specific limitations, there were specific challenges unique to the use of ICG. There was considerable variability in the application of FIGS using ICG between studies, including differences in route of administration, dosage, timing, and imaging systems. This variability may affect the consistency of results and hinder the establishment of an optimal intervention protocol for clinical practice. Additionally, several subgroup considerations, particularly in the oncologic-related key questions, could not be addressed due to the lack of outcome stratification by subgroup in the included studies. Some of these include neoadjuvant therapy exposure, radiation therapy exposure, and cancer type. Finally, certain applications of ICG, such as perfusion assessment, rely on subjective interpretation, which may introduce variability, affect reproducibility between studies, and challenge use in routine clinical practice.
Relevance to clinical practice and future research recommendations
This systematic review has shown several applications where there is a clear benefit from using ICG, whereas in other areas, there is a lack of robust, high-quality data, and its utility remains uncertain in these applications. Future research should focus on conducting larger RCTs to strengthen the evidence base and explore additional ICG applications in GI surgery. Additionally, standardized ICG administration protocols are needed to enhance consistency and comparability across studies. These directions, along with detailed guidance on clinical applications, will be discussed in greater depth in the accompanying SAGES guidelines for fluorescence image-guided surgery in gastrointestinal procedures in adults and children using indocyanine green.
Conclusion
Fluorescence image-guided surgery using ICG shows strong evidence in reducing anastomotic leak rates in colorectal surgery and improving lymph node retrieval in cancer resection. While promising results have been observed in other surgical applications, current evidence is limited or inconclusive, and further research is needed. The incorporation of ICG into surgical practice should be considered where robust evidence exists, with ongoing evaluation as more data become available.
Acknowledgements
The authors would like to thank Holly Ann Burt for her contribution to the literature search for all included studies, Mohammed Ansari for methodological guidance and Jun Xia for statistical expertise. We would also like to acknowledge Sarah Colón for her help in organizing the guidelines committee meetings and communications.
Funding statement: Funding support for the methodologist, research librarians, statistician, and guidelines fellows came from SAGES Education and Research Foundation (SERF) grant. The guidelines fellow (E.C.) is also funded by the Royal Australasian College of Surgeons (RACS) Foundation for Surgery. No industry support was used to create this guideline, nor was any industry input used for any stage of the development, dissemination, or implementation of this guideline. Standard disclosure forms were completed by all guideline contributors to evaluate for potential conflict of interest. Evaluation of these conflicts was made by the panel Chair, and no potential conflicts were deemed to have affected the decision.
Declarations/Disclosures: all conflicts of interest and financial ties were declared by the authors. All potential conflicts were reviewed and none influ-enced the design, analysis, or interpretation of the research presented in this manuscript. Panagiotis Kapsampelis is a clinical advisor to MyOpNotes, a digital platform for operation note creation. Elisa Cala-brese is a funded research fellow by the SERF grant and by the RACS Foundation for Surgery. Dena Shehata is a funded research fellow by the SERF grant. Farah Husain receives reteaching/speaking honorarium from Ethicon and W.L. Gore. Bethany Slater is a consultant for Hol-ogic. Deborah Keller’s institution affiliation has a grant from Arthrex; however, this is not to her and is to the institution only. Sunjay Kumar, Varun Bansal, Katie Carsky, Austin Eason, Himsikhar Khataniar, Ste-fan Scholz, María Rita Rodríguez-Luna, Nisha Narula, Jeffrey Chiu, Subhashini Ayloo, Ahmed Abou-Setta, and Ziad Awad have no con-flicts of interest or financial ties to disclose.
Ethics approval statement: Not applicable.
Patient consent statement: Not applicable.
Appendices
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Authors Affiliations
Panagiotis Kapsampelis1, Elisa C Calabrese2,3,4, Sunjay S Kumar5, Dena Shehata6, Varun Bansal7, Katie Carsky8, Austin Eason9, Himsikhar Khataniar10, Stefan Scholz11, María Rita Rodríguez-Luna12, Nisha Narula13, Jeffrey Chiu14, Subhashini Ayloo15, Farah Husain16, Ahmed Abou-Setta17, Ziad Awad18, Bethany J. Slater19, Deborah S. Keller20
- Leeds Institute of Emergency General Surgery, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
- Department of Surgery, University of California-East Bay, Oakland, CA, USA.
- Department of Surgery, University of Adelaide, The Queen Elizabeth Hospital, Adelaide, SA, Australia
- Research, Audit & Academic Surgery, Royal Australasian College of Surgeons, Adelaide, SA, Australia
- Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA
- Department of Surgery, Lahey Hospital and Medical Center, Burlington, MA, USA
- Department of Surgery, University of Colorado, Aurora, CO, USA
- Department of Surgery, Lenox Hill Hospital, Northwell Health, New York, NY, USA
- University of Florida College of Medicine, Gainesville, FL, USA
- Department of Internal Medicine, Allegheny General Hospital, Pittsburgh, PA, USA
- Division of General and Thoracic Pediatric Surgery, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
- Department of General Surgery, Hospital de Barcelona, Barcelona, Spain
- Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA
- Department of Surgery, Advent Health, Orlando, FL, USA
- Department of Surgery, Saginaw VA Health System, Saginaw, MI, USA
- Department of Surgery, University of Arizona College of Medicine Phoenix, Phoenix, AZ, USA
- Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada
- Department of Surgery, University of Florida College of Medicine – Jacksonville, Jacksonville, FL, USA
- Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada
- Division of Digestive Surgery, University of Strasbourg, Strasbourg, France
Corresponding author
Elisa Calabrese
Royal Australasian College of Surgeons
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