Indocyanine Green and Hepatobiliary Surgery: An Overview of the Current Literature

Abstract

Indocyanine green (ICG) is an inert polypeptide that almost totally binds to high molecular weight plasma proteins; it is cleared by the hepatocytes and directly excreted into the bile with a half-life of about 3–5 minutes. Specific systems are required to see fluorescent images. The use of this dye has been reported in different surgical specialties, and the applications in hepatobiliary surgery are widening. Being firstly used to evaluate the preoperative liver function, intra- and postoperative dynamic checking of hepatic activity has been reported and integrated within perioperative protocols allowing a tailored treatment allocation. Intravenous injection (IV) or injection into the gallbladder can ease difficult cholecystectomy. Biliary leakage detection could be enhanced by IV ICG injection. Although with some contrasting results, the use of ICG for both delineating the limits of the resection and tumor-enhanced visualization was demonstrated to improve short- and long-term outcomes. Although the lack of strong evidence still precludes the introduction of this tool in clinical practice, it harbors great potential in liver surgery.

Introduction

Indocyanine green (ICG) is an inert, tricarbocyanine organic anion‐transporting polypeptide. It almost totally binds to high molecular weight plasma proteins, including albumin, alpha 1-, and beta-lipoproteins. The protein structure is not altered, and, consequently, intravenous (IV) toxicity is avoided. Because it contains iodine, ICG administration should be avoided in the presence of thyrotoxicosis or iodine allergy; otherwise, adverse reactions are rare (1 every 40000 people).¹

In the serum, the ICG has excitation and emission wavelengths of 778 and 830 nm, respectively. This wavelength excited by near-infrared (NIR) light is not visible to the human eye; therefore, fluorescence images are obtainable through ICG fluorescence systems equipped with interferential filters.

ICG was approved for medical use by the Food and Drug Administration in 1957, and ICG fluorescence imaging gained great attention in various procedures of different surgical specialties, that is, to detect the lymphatic flow in the extremities, the sentinel lymph nodes in breast or gastrointestinal cancers, to evaluate blood flow during coronary artery bypass grafting, or clipping cerebral artery aneurysms.² Since the 1980s, ICG has been used in hepatobiliary operations for several purposes, including perioperative hepatic function assessment or to identify segmental boundaries, bile ducts, and liver cancers, especially in cirrhotic livers.³ In open surgery, standard lights should be switched off to see the fluorescence, and a NIR camera is needed forcing the surgeon to look away from the operative field and to put down the surgical instruments. In laparoscopic surgery, the NIR camera is integrated in the great majority of the systems providing fluorescence imaging or, in the most recent systems, a superimposed imaging of the fluorescence over the operative field. The Firefly^TM camera (Intuitive, Sunnyvale, CA, USA) is integrated into the da Vinci Surgical Systems (Intuitive, Sunnyvale, CA, USA) and can easily be used to intraoperatively visualize ICG accumulation. The simplicity of use of the last two systems caused the great expansion of the use of ICG and the studies behind it.

This review aims to describe the actual state of the art of the use of ICG in hepatobiliary surgery providing practical information for educational purposes or routine daily use in different perioperative steps, laying the foundation for future applications and further developments of this useful tool.

Hepatic Function Assessment

Since posthepatectomy liver failure (PHLF) represents a dreadful event, the preoperative assessment of liver function or the early recognition of this complication is crucial, especially after extended resection or in cirrhotic patients.

The assessment of liver function was the first use of ICG in liver surgery. After IV injection of 0.5 mg/kg of the dye, ICG bound to plasma proteins is cleared by the hepatocytes and directly excreted into the bile having a half-life of about 3–5 minutes. The ICG is not subjected to metabolism or enterohepatic circulation.¹ Consequently, the ICG retention rate after 15 from administration (ICG-R15) and the ICG plasma disappearance rate (ICG-PDR) can reflect liver function.

The introduction of the LiMON^TM (Pulsion Medical Systems, Munich, Germany) and the DDG 2001 (Nihon Kohden, Japan) systems, which allow the measure of ICG clearance through pulse spectrophotometry in less than 10 minutes, made this assessment even simpler.¹ Therefore, using the ICG clearance test is still reported in several guidelines recommending patient management, especially in Asian communities.^4,5 The Makuuchi algorithm suggests the tolerable extension of the liver resection considering the ICG retention test (Fig. 1).⁶

FIG. 1.

Makuuchi algorithm⁶ for the cirrhotic patient decision-making process.

Several authors confirmed the predictive value of this test^5,6 and its better performance in prognosticating postoperative liver failure when compared with the Child or MELD score.⁷

However, this algorithm was empirically developed almost three decades ago by evaluating only a few patients.⁸ Other models have been suggested.⁹ For example, the Albumin Indocyanine Green Evaluation (ALICE), further integrated with the measurement of portal hypertension in the subgroup of intermediate-risk patients (ALICE grade 2), has been proposed for patients undergoing surgery for hepatocarcinoma (HCC).¹⁰

The ICG test results corrected for the future liver remnant volume were also proposed.^11–14 Kobayashi et al. reported that the ICG clearance of the remnant liver could predict the development of subclinical postoperative liver failure in patients undergoing liver resection for both HCC and metastases with high sensitivity. The authors proposed a cutoff value of 0.05, above which no life-threatening postoperative liver failure was ever seen.^13,14 Between 0.05 and 0.10, subclinical postoperative liver failure could be observed, and therefore, corrective measures should be applied.¹⁴ However, this evaluation presumes a similar function within all the liver parenchyma, but cholestasis or portal thrombosis may impair the function of different liver areas.¹⁵

In the field of transplantation surgery, the results of the ICG clearance test of brain dead donors well correlate with graft availability and survival.¹⁶ Asencio et al. recently proposed a cutoff value of 10% for ICG-PDR measured in brain dead donors immediately before organ procurement. This value proved to identify livers that were further discarded.¹⁷ ICG tests also exhibited the capacity to predict the quality of the graft during ex situ normothermic perfusion.¹⁸ Although further studies are needed, this finding may help in reducing unnecessary efforts and costs.

Dynamic intraoperative ICG clearance evaluation is another possibility in predicting PHLF. Although actual data are scarce and probably not sufficient to suggest a modification of the preoperative surgical plans, this assessment may be promising.¹⁹ Thomas et al. performed an intraoperative evaluation of ICG test values before and after selectively clamping the arterial and portal pedicles of the segments to be resected comparing them with those before abdominal closure. The authors found this intraoperative assessment as a feasible and valuable tool in the case of anatomical resections, though with some limits, mostly hyperbilirubinemia and intraoperative fluctuation of liver perfusion.²⁰ Sato et al. performed a similar study evaluating the concordance between intraoperative ICG-PDR in predicting PHLF, which was .834 and even higher (.923) in the subgroup of patients with preoperative biliary drainage.²¹

Finally, some authors reported the usefulness of early postoperative reassessment of ICG clearance in both cirrhotic and noncirrhotic patients and in recipients after transplantation.¹ The ICG test performed on postoperative day (PoD) 1 after resective surgery seems a valuable tool for early detection of PHLF in both Eastern and Western series.^22–24 Similarly, from the 90s, several studies suggested the strong early predictive role of the ICG test executed on PoD 1, in prognosticating graft dysfunction/failure and graft/recipient survival, although the optimal cutoff level has not been established yet.^1,25–29 Early detection of impaired liver function would allow the introduction of aggressive corrective measures.

The ICG clearance test is feasible, repeatable, quite inexpensive, and scarcely invasive, especially if compared with other functional imaging tools including scintigraphy or functional magnetic resonance.³⁰ However, the results are strictly related to liver perfusion and may be unreliable with a bilirubin level higher than 3 mg/mL due to the competition for the same hepatocytic carrier between bilirubin and ICG.¹ Furthermore, repetitive assessments should be performed with an interval of at least 30 minutes to avoid misleading results due to the residual of the previous injection.³¹

Practical tips: the ICG clearance test is feasible, repeatable, quite inexpensive, and scarcely invasive. To test liver function, the dose of IV ICG injection may be different according to the chosen methodology to perform the test; usually, 0.5 mg/Kg body weight is used. Hyperbilirubinemia, impaired liver perfusion, and repeated tests without an adequate interval are the main confounding factors.

Intraoperative Applications

Cholecystectomy

A lot of anatomical biliary anomalies could be found, and the failure to identify them could cause an iatrogenic injury. With an incidence ranging from 0.15% to 0.6%, iatrogenic biliary lesions remain among the most feared complications during laparoscopic cholecystectomy.^32,33

A standard intraoperative cholangiography could be performed to clarify the anatomy of the biliary ducts, but it has some limitations, including prolongation of the operative time, the 2D imaging, and minimal radiation exposure. Since the first intraoperative ICG cholangiography reported in 2009,³⁴ several studies, including randomized control trials (RCT), have reported ICG as a valid tool to highlight biliary anatomy in both open and laparoscopic procedures.^35–37 ICG use could improve the visualization of the critical view of safety (CVS)³⁸ and provide additional visual information, especially in mini-invasive surgery, because laparoscopy is a two-dimensional surgery and lacks depth perception and haptic feedback. In 2020, the noninferiority of ICG cholangiography compared with the X-ray technique for the visualization of the extrahepatic biliary tree was reported.³⁹

The FALCON study, an international multicenter RCT, demonstrated a significantly faster recognition of hilar structures using IV ICG injection.⁴⁰ On the contrary, the SCOTCH study, a prospective nonrandomized trial on cholecystectomy performed by trainees, did not show a significantly shorter time to achieve the CVS with ICG use but the surgeon’s satisfaction was higher.⁴¹ A huge meta-analysis including 22 studies and 3457 patients showed significantly better results with ICG in terms of better recognition of the cystic duct, reduction of the operative time, and conversion rates.⁴²

Many studies aimed to identify the correct dose and time of ICG IV injection.⁴³ In a prospective analysis of 146 patients, Aranda et al. demonstrated the best results with the standard dose of 2.5 mg when compared with the dose of 0.05 mg/Kg. Injection between 2 and 6 hours before the surgery was related to the best visualization of biliary structures, but even the administration of the dye 30 minutes before the intervention significantly improved the CSV visualization.⁴⁴ Ladd et al. performed a multicentric RCT to compare ICG IV injection on the day of the operation of low (0.05 mg) or standard dose (2.5 mg) through surgeon-blinded qualitative and quantitative scores. Probably due to the reduction of background fluorescence, significantly better results were found in the low-dose group.⁴⁵ Similarly, in a small RCT with 40 patients, Huang et al. achieved the best results with the administration of .1 mg 30 minutes before surgery.⁴⁶

On the other hand, Graves et al. in a small single-arm study showed that direct injection into the gallbladder can clearly define the extrahepatic biliary anatomy minimizing bile duct injuries and allowing a better visualization of the dissection plane. With this technique, the cystic artery is not highlighted, but it can be followed through the contrast with the fluorescent gallbladder.⁴⁷ Direct injection could be especially useful in cases of severe gallbladder inflammation or obese patients when it is more difficult to identify the correct planes.^48,49

In a small prospective study by Castagneto-Gissey et al., IV and intracholecystic (IC) injections were compared. Depending on gallbladder size, an average of 5 mL of the dye, 25 mg/5 mL diluted in 10 mL of distilled water, was used for the IC injection at the beginning of the procedure. The limits of the IC use were hydrops of the gallbladder, significantly higher postoperative pain in case of cholecystic content spillage, the injection into the gallbladder wall causing liver fluorescence, and the presence of stone at the infundibulum requiring their mobilization to allow ICG flow. The IV administration of ICG was performed at the concentration of 0.01 mg/kg 45 minutes before surgery. The images were evaluated independently by two surgeons. The limit of the IV injection was the background liver fluorescence. In conclusion, both methods proved useful in reducing operative time and improving structure visualization.⁵⁰

Practical tips: Because there is still no strong evidence about a significant reduction of biliary complications, the routine use of ICG should not be mandatory. However, ICG could have an important role in difficult cholecystectomies or in the presence of aberrant structures. Both have pros and cons, IV administration of .01–0.05 mg/kg or a standard dose of 2.5 mg is given up to 30 minutes before surgery. IC injections can be administered with 5 mL of 25 mg/5 mL of ICG diluted in 10 mL of distilled water at the beginning of the procedure.

Biliary leak detection

Biliary leak (BL) is still one of the most common complications after hepatectomy with an incidence of about 10%. This condition may be caused by biliary injury, bile oozing from the liver cut surface, or insufficiency of the bilioenteric anastomosis and may be associated with liver failure, sepsis, and consequently, prolonged hospital stays.⁵¹

There are no standard methods for detecting small or occult BLs at the end of the resection. The most used tests are performed with intrabiliary injection (usually through the cystic duct stump) of the nontoxic and low-cost saline solution, air, methylene blue, or the White test using fat emulsion solutions or propofol. The sensitivity to detect microleakage was quite low, and on the other hand, the increased pressure in the biliary system could highlight leakages that may be not clinically significant.⁵² Sakaguchi et al. conducted a prospective study comparing intrabiliary injection of 4–8 mL of 0.05 mg/mL ICG or saline solution at the end of hepatic surgery. After analyzing 59 patients, they reported higher but not significant detection rates of bile leaks (30% versus 19%) with the intrabiliary injection of low doses of ICG.⁵³

There is an ongoing prospective trial evaluating the routine use of systemic administration of ICG after hepatectomy for better BL detection.⁵⁴

However, although easily repeatable during the same procedure, this intraoperative test cannot exclude the possibility of postoperative bile leakage because BL could have several causes and, for example, can occur from ducts that are not in communication with the main biliary tree (i.e., orphan duct), or may be the consequence in a few days of ischemic damage.^52,53

Finally, as reported for colorectal surgery,⁵⁵ ICG could also improve the outcomes of bilio-enteric anastomosis allowing the visualization of both blood perfusion and integrity of the suture. In particular, Ma et al. reported the best results in injecting the dose of 0.25 mg/kg 24 hours before the intervention, thus avoiding a hard-to-see image or excessive fluorescence.⁵⁶

Practical tips: An intrabiliary injection of 4–8 mL of 0.05 mg/mL ICG usually from the cystic duct stump during the procedure or the IV injection of 0.25 mg/kg 24 hours before surgery could enhance BL detection. Excessive pressure in injecting the dye through the biliary system should be avoided to reduce false-positive rates.

Vascular anatomy for anatomical resections

Anatomical liver resections performed after segments and subsegments subdivision are a cornerstone in oncologic liver surgery, mostly in the case of HCC, improving survival and reducing postoperative complications.⁵⁷

With the great majority of the evidence coming from case reports or case series from Asian countries, ICG fluorescence can be used as a guide—combined with the usual techniques such as intraoperative ultrasonography (US) and preoperative Computed Tomography (CT) and Magnetic Resonance (MR) images—in parenchymal transection facilitating the identification of hepatic segments, in both open and laparoscopic surgery, improving postoperative outcomes.^58,59 Although up to five different staining techniques have been described,⁶⁰ simplifying, the injection of the dye can determine a “positive staining” when ICG is injected into the portal pedicles feeding the tumor. Compared with the use of the Vital blue dye, the clamping of the hepatic artery is not necessary, and the color is much more persistent with a clearer demarcation. The “negative staining” is obtained when the fluorescent dye is injected intravenously after clamping the Glissonean pedicle of the hepatic segment involved in the resection through a Glissonean or transfissural approach.⁵⁸ Positive staining seems feasible and safe with a reported success rate of about 80% and 26 minutes needed to be performed.⁶¹ According to the experience of Xu et al., it seems to be more useful in performing segmentectomy or subsegmentectomy.⁶² However, it requires a high degree of proficiency with IOUS.⁶³ Negative staining seems easier to perform, avoids portal puncture, and could be used when there is an infiltration of the tumor-bearing portal branch. It is preferable when major resections or resections of left/anterior segments are required.^62,64 Time and administration dose should be tailored for each patient.⁶⁵

An interesting use was reported by Kogure et al. They injected the ICG into the portal pedicle of the paracaval segment to be preserved during a right hepatectomy. This could be particularly useful when the future liver remnant volume is quite small.⁶⁶

Another appealing application was presented by Xie et al. After the “cone units” concept,⁶⁷ they performed subsegmental resections of the right posterior segments after transarterial super selective embolization of the feeding artery with lipiodol and ICG before surgery in 13 patients with early-stage HCC. The staining success rate was 85%, an R0 resection was performed in all the patients, and no severe complications occurred. They also analyzed the causes of unsuccess.⁶⁸

Liu et al. were the first to analyze both the intraoperative outcomes and the prognostic impact of ICG in anatomical resections for HCC. They performed a 1:1 propensity score-matched analysis including 100 patients comparing conventional laparoscopy and ICG-enhanced procedures (27 patients with tumor fluorescence imaging, 8 with positive staining, and 15 with negative staining). For positive staining, 5–10 mL of 0.025 mg/mL of ICG (25 mg of ICG diluted with 10 mL of sterile water then 1 mL [2.5 mg] of this solution diluted with 100 mL of saline) were used according to the segment volume. For negative staining, 10–20 mL of the same solution was used. With a median follow-up of 34 months, the ICG group showed significantly better results in terms of R0 resections, resection margin distance, blood loss, and DFS (independently associated with R0).⁶⁹ Although analyzing together different uses of ICG, they demonstrated that ICG could improve postoperative results in experience centers with no/low adjunctive risks.

However, since no strong evidence is available, Alomari et al. recently proposed a monocentric RTC to compare the results of positive and negative staining in laparoscopic resections. Positive staining will be performed with a slow injection of 1 mL of a 0.025 mg/mL ICG solution in the portal branch feeding the tumor punctured under ultrasound guidance, a dedicated probe is available. Negative staining with IV injection of 0.5 mg/kg after clamping the portal pedicle feeding the tumor. The extrahepatic Glissonean approach will be used.⁷⁰ ICG staining will be subjectively scored and compared with three-dimensional preoperative planning, short-term results, and disease-free survival will be also evaluated. The results are expected in the early 2027.⁷¹

However, this modality of the evaluation of the segmental vascularization of the liver presents some difficulties. First, there could be technical difficulties in administering the ICG in the portal branch after exposing and clamping it. Second, negative staining may not work in the presence of vascular anomalies, i.e., the Hyrtl artery or other collateral circulations.^62,72

Practical tips: Both positive and negative staining have pros and cons. The choice should be tailored according to the procedure to be performed and to the expertise of the surgeon. For positive staining, 1–10 mL of 0.025 mg/mL of ICG (ranges 0.025–12.5 mg/kg) can be used. For negative staining, 2.5 mg is usually injected (ranges 0.025–25 mg/kg).

Cancer localizations

After IV injection, the ICG remains fixed to pathological areas of the liver, particularly around nonhepatocellular tumors, where hepatocytes are underactive.⁷³ Therefore, ICG has emerged as a potentially useful tool for the intraoperative detection of hepatic neoplasms.

Gotoh et al. first introduced the use of intraoperative fluorescence imaging after the observation of a fluorescence pattern of HCC in patients whose hepatic function has been previously tested with ICG.⁷⁴ In parallel, Ishizawa described a fluorescence pattern for colorectal liver metastasis (CRLM).³⁴ Different hepatic lesions may result in a different fluorescence pattern. HCC presents 3 different types of fluorescence signal: a total fluorescence type (well‐differentiated HCC), a partial fluorescence type (moderately differentiated HCC), and a rim fluorescence type (poorly differentiated HCC).² ICG sensitivity in detecting HCC has been reported to reach 99% with a 6% false positive.⁷⁵ The incidence of false positives is higher (up to 40%) in patients with atypical nonmalignant lesions, with decreased liver function due to cirrhosis, or preoperative chemotherapy, but this could be reduced by increasing the time between ICG injection and the procedure or adjusting the dose.^69,75 Residual cancer or vein tumor thrombus can be detected on the cut surface with ICG.⁷⁶ Even unexpected distant HCC metastasis could be detected through the use of ICG.⁷⁷ (Fig. 2-3)

FIG. 2.

Clear visualization of a single Sg6 HCC. HCC, hepatocarcinoma.

FIG. 3.

Clear visualization of a single Sg3 HCC. HCC, hepatocarcinoma.

CRLM presented with a rim‐type fluorescence signal. This pattern is caused by immature hepatocytes with a decreased bile excretion ability surrounding the tumor.⁷⁸ The use of fluorescence may be particularly useful after chemotherapy which can cause a partial/complete regression or necrosis of the lesions which become more difficult to see with the naked eye, especially in laparoscopic surgery.⁷⁹ In general, the sensitivity of CRLM identification with ICG ranges from 73% to 100%, and several studies reported a significantly higher detection rate of unexpected lesions compared with conventional resections.^64,80–82 In particular, Boogerd et al. compared the sensitivity of different imaging techniques in detecting liver malignancies. Of the 20 patients finally included in the study, 10 of them were affected by CRLM. Sensitivities and positive predictive values of the different techniques were 80% and 71% for CT scan, 84% and 80% for MRI, 88% and 77% for IOUS, and 92% and 75% with ICG. Interestingly, although not statistically significant, the sensitivity of all the traditional imaging techniques markedly decreased with lesions smaller than 10 mm compared with ICG, and the use of fluorescence allowed for the detection of three lesions not identified by other techniques. Furthermore, the combined use of ICG and IOUS allowed the reaching of 100% sensitivity and 70% positive predictive value.⁸³ Small superficial lesions missed at the intraoperative ultrasound evaluation could be highlighted with ICG and the maintenance of a correct transection plane (and, eventually, an R0 resection) could be improved with ICG while resecting deeper located lesions.^64,72,84 However, the fluorescent rim could be smaller than 5 mm, and consequently, an R0 resection could not be assured in every report (due to different R0 definitions)⁸⁰ (Fig. 4-5).

FIG. 4.

(a). ICG visualization of Sg 6–7; (b). ICG visualization of Sg3 metastatic lesions. ICG, indocyanine green.

FIG. 5.

(a). Preoperative MRI scan; (b). intraoperative visualization under near-infrared light. A single synchronous metastasis from colorectal cancer. The patient received neoadjuvant chemotherapy and a liver-first approach.

Intrahepatic cholangiocarcinoma (ICC) displayed an intermediate fluorescence pattern with the majority showing a rim-staining while a minority presenting with a complete or partial fluorescence.⁷⁷

A recently published meta-analysis including 959 laparoscopic resections for liver malignancies (446 patients operated with the aid of ICG and 513 treated without the use of ICG) showed a significantly higher R0 rate, less necessity of intraoperative blood transfusion, and shorter hospital stay with similar postoperative morbidity in the ICG group of patients compared with those treated with conventional surgery.⁸⁵ Another meta-analysis reported also a shorter operative time, lower postoperative complications, and a better 1-year disease-free survival rate.⁸⁶ Similar results were also reported for the robotic technique.^87,88

A limitation of this technique is the depth of tissue penetration of fluorescence signal of less than 8 mm from the hepatic surface. Another limitation is represented by the excessive background fluorescence in case of ICG overdose which cannot be reduced. Indeed, the timing of injection and optimal dosage of ICG are important issues for the success and the standardization of the technique. The optimal dose of ICG is still unknown and may vary according to hepatic function. Several studies reported an IV ICG administration of 0.25–0.5 mg/kg from 12 hours to 14 days before surgery, while others proposed an intraoperative injection.^2,65,89

Chen et al. proposed a score based on preoperative blood tests to predict a good or poor hepatic clearance ability to adjust their standard preoperative ICG dose of 5 mg 24 hours before surgery.⁹⁰

Practical tips: To enhance tumor visualization, 0.25 mg/kg (up to 0.5 mg/kg) represents the most commonly used dose administered 12 hours before surgery. Dose and timing should be adjusted according to liver function.

Other applications

Lymphadenectomy

Survival is highly influenced by node status and that lymphatic outflow may differ in each person; in particular, some main pathways have been identified, namely, the hepato-cholecystic-retropancreatic pathway, the hepato-celiac pathway, the hepato-mesenteric pathway, and the diaphragmatic pathway.⁹¹

Visualization of extrahepatic biliary structures may be helpful during the lymphadenectomy of the porta hepatis, whenever required.

Although within isolated reports, Ruzzenente et al. published the results of a prospective pilot study with 18 patients with ICC evaluating the role of the ICG in highlighting the lymphatic out-flow from the liver and the sentinel lymph node retrieving in hepatobiliary cancers. Emphasizing the importance of a correct but tailored lymphadenectomy, they proposed the peritumoral injection of 1 mL of 25 mg of ICG in 20 mL of water. The lymphatic pathway was visible in 77.8% of the patients within 3 minutes of the injection. The sentinel lymph node was detected in 77.2% of the patients, confirmed by pathological examination in 92.3% of the patients, and resulted positive in a quarter of the patients.⁹¹ Similar results have been previously reported.⁹²

Transplantation: Living donor

Biliary complications are the most common ones during donor hepatectomy, and they are avoided by the recognition of biliary structures and by optimal bile duct dissection-line of the liver graft.⁹³ Recently, real-time ICG NIR fluorescence techniques have been used to divide the bile duct during laparoscopic living donor hepatectomy. The amount of IV injected ICG was 2.5 mg/kg 15–30 minutes before hilar plate dissection.⁶⁴

The cholangiography using ICG seems superior to conventional cholangiography because it does not involve radiation and it shows a 3D spatial direction and relationships between structures.⁹³ This is an easy and safe technique that allows intraoperative visualization of biliary anatomy (including aberrant bile ducts), leading to an efficient and rapid dissection of the hilar plate. The amount of intrabiliary injected ICG was 0.05 mg/kg. The limit of this technique is represented by the patients with high body mass index because it cannot easily delineate bile ducts covered with adipose or connective tissue.⁹³

As reported above, cholangiography can be performed with IV or intrabiliary injection of the ICG. Furthermore, IV ICG injection could be useful in checking vascularization and the integrity of the bile duct anastomosis.⁹⁴

Future Prospectives

In recent years, the second NIR window, NIR-II, with a different wavelength of 1000–1700 nm. has been studied.⁹⁵ It is not disturbed by the operative room lights, it can reduce photon absorption and scattering effects of deep tissue, allows a deeper view (up to 1 cm), a better spatial resolution, reduces tissue autofluorescence providing a better contrast and, definitively, an upgrade of the tool.⁹⁶ A quantitative analysis of the signal-to-background ratio, tumor-to-background ratio, and tumor-to-normal tissue ratio has been performed showing the great superiority of the NIR-II over NIR-I with significantly higher sensitivity and specificity in tumor detection.⁹⁵

ICG remains the most used fluorophore, although other dyes are under evaluation.^96,97 In particular, fluorophores combined with polyethylene glycol or with cancer antibodies are expected to be further developed for human use allowing better and more precise visualization of tumor margins.^98,99

Multimodal imaging systems combining NIR and other imaging techniques are another promising field of study.

Preliminary results of NIR-II and photodynamic therapy integration for HCC on animal models seem promising.¹⁰⁰

Finally, in the era of artificial intelligence and machine learning techniques, Hardy et al. reported their use combined with the ICG fluorescence to improve the R0 resection rate and the intraoperative detection of unexpected CRLM.¹⁰¹

Conclusion

In conclusion, the simplicity of the use of ICG makes it one of the most used dyes in general surgery. A growing body of literature is demonstrating that this technique is easily reproducible and reliable with relatively low costs and without side effects. Moreover, this method gives the possibility to carry out more clean resections, ensuring a higher rate of disease-free margins. Further improvements in the imaging system and standardization of the ICG usage (dose and timing) are expected, allowing this technique to be a part of the standard clinical practice.

Footnotes

Authors’ Contributions

L.F.: writing—original draft preparation and reviewing. M.R., M.N.R., and A.T.: reviewing and editing. S.B.: reviewing and editing. F.M. and C.A.: writing—original draft preparation. I.B.: conceptualization, writing—original draft preparation, review, and editing. G.L.G.: writing—original draft preparation, reviewing, and editing.

Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

References

De Gasperi

, Mazza

, Prosperi

. Indocyanine green kinetics to assess liver function: Ready for a clinical dynamic assessment in major liver surgery? World J Hepatol, 2016; 8(7):355–367; doi: 10.4254/wjh.v8.i7.355

Rossi

, Tarasconi

, Baiocchi

, et al. Fluorescence guided surgery in liver tumors: Applications and advantages. Acta Biomed, 2018; 89(9–S):135–140; doi: 10.23750/ABM.V89I9-S.7974

Terasawa

, Ishizawa

, Mise

, et al. Applications of fusion-fluorescence imaging using indocyanine green in laparoscopic hepatectomy. Surg Endosc, 2017; 31(12):5111–5118; doi: 10.1007/S00464-017-5576-Z

Omata

, Cheng

A-L

, Kokudo

, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: A 2017 update. Hepatol Int, 2017; 11(4):317–370; doi: 10.1007/s12072-017-9799-9

Kokudo

, Hasegawa

, Shirata

, et al. Assessment of preoperative liver function for surgical decision making in patients with hepatocellular carcinoma. Liver Cancer, 2019; 8(6):447–456; doi: 10.1159/000501368

Makuuchi

, Kosuge

, Takayama

, et al. Surgery for small liver cancers. Semin Surg Oncol, 1993; 9(4):298–304; doi: 10.1002/ssu.2980090404

Wang

, Zhao

, Ma

, et al. Comparison of the ability of Child-Pugh score, MELD score, and ICG-R15 to assess preoperative hepatic functional reserve in patients with hepatocellular carcinoma. J Surg Oncol, 2018; 118(3):440–445; doi: 10.1002/JSO.25184

Mise

, Hasegawa

, Satou

, et al. How has virtual hepatectomy changed the practice of liver surgery?: Experience of 1194 virtual hepatectomy before liver resection and living donor liver transplantation. Ann Surg, 2018; 268(1):127–133; doi: 10.1097/SLA.0000000000002213

Santol

, Kim

, Gregory

, et al. An APRI+ALBI based multivariable model as preoperative predictor for posthepatectomy liver failure. Ann Surg, 2023; doi: 10.1097/SLA.0000000000006127

10.

Shirata

, Kokudo

, Arita

, et al. Albumin-Indocyanine green evaluation (ALICE) grade combined with portal hypertension to predict post-hepatectomy liver failure. Hepatol Res, 2019; 49(8):942–949; doi: 10.1111/hepr.13327

11.

Yokoyama

, Nishio

, Ebata

, et al. Value of indocyanine green clearance of the future liver remnant in predicting outcome after resection for biliary cancer. Br J Surg, 2010; 97(8):1260–1268; doi: 10.1002/bjs.7084

12.

Kim

, Kim

, Park

, et al. Volumetric analysis and indocyanine green retention rate at 15 min as predictors of post-hepatectomy liver failure. HPB (Oxford), 2015; 17(2):159–167; doi: 10.1111/hpb.12295

13.

Kobayashi

, Kiya

, Sugawara

, et al. Expanded makuuchi’s criteria using estimated indocyanine green clearance rate of future liver remnant as a safety limit for maximum extent of liver resection. HPB (Oxford), 2019; 21(8):990–997; doi: 10.1016/j.hpb.2018.12.001

14.

Kobayashi

, Kiya

, Nishioka

, et al. Indocyanine green clearance of remnant liver (ICG-Krem) predicts postoperative subclinical hepatic insufficiency after resection of colorectal liver metastasis: Theoretical validation for safe expansion of Makuuchi’s criteria. HPB (Oxford), 2020; 22(2):258–264; doi: 10.1016/j.hpb.2019.06.013

15.

Narasaki

, Noji

, Wada

, et al. Intraoperative real-time assessment of liver function with near-infrared fluorescence imaging. Eur Surg Res, 2017; 58(5–6):235–245; doi: 10.1159/000477347

16.

Tang

, Han

, Chen

, et al. Donor indocyanine green clearance test predicts graft quality and early graft prognosis after liver transplantation. Dig Dis Sci, 2017; 62(11):3212–3220; doi: 10.1007/s10620-017-4765-x

17.

Asencio

, Cortese

, López Baena

, et al. Evaluation of plasma disappearance rate indocyanine green clearance as a predictor of liver graft rejection in donor brain death. Transplant Proc, 2020; 52(5):1472–1476; doi: 10.1016/j.transproceed.2020.01.084

18.

Lau

, Ly

, Ewenson

, et al. Indocyanine green: A novel marker for assessment of graft quality during ex situ normothermic machine perfusion of human livers. Artif Organs, 2023; 48(5):472–483; doi: 10.1111/AOR.14696

19.

Akita

, Sasaki

, Yamada

, et al. Real-time intraoperative assessment of residual liver functional reserve using pulse dye densitometry. World J Surg, 2008; 32(12):2668–2674; doi: 10.1007/s00268-008-9752-0

20.

Thomas

, Weninger

, Angele

, et al. Intraoperative simulation of remnant liver function during anatomic liver resection with indocyanine green clearance (LiMON) measurements. HPB (Oxford), 2015; 17(6):471–476; doi: 10.1111/hpb.12380

21.

Sato

, Kenjo

, Suzushino

, et al. Predicting post-hepatectomy liver failure using intra-operative measurement of indocyanine green clearance in anatomical hepatectomy. World J Surg, 2021; 45(12):3660–3667; doi: 10.1007/S00268-021-06289-9

22.

Sugimoto

, Okochi

, Hirota

, et al. Early detection of liver failure after hepatectomy by indocyanine green elimination rate measured by pulse dye-densitometry. J Hepatobiliary Pancreat Surg, 2006; 13(6):543–548; doi: 10.1007/s00534-006-1114-4

23.

de Liguori Carino

, O’Reilly

, Dajani

, et al. Perioperative use of the LiMON method of indocyanine green elimination measurement for the prediction and early detection of post-hepatectomy liver failure. Eur J Surg Oncol, 2009; 35(9):957–962; doi: 10.1016/j.ejso.2009.02.003

24.

Haegele

, Reiter

, Wanek

, et al. Perioperative non-invasive indocyanine green-clearance testing to predict postoperative outcome after liver resection. PLoS One, 2016; 11(11):e0165481; doi: 10.1371/journal.pone.0165481

25.

Tsubono

, Todo

, Jabbour

, et al. Indocyanine green elimination test in orthotopic liver recipients. Hepatology, 1996; 24(5):1165–1171; doi: 10.1002/hep.510240531

26.

Hori

, Iida

, Yagi

, et al. K(ICG) value, a reliable real-time estimator of graft function, accurately predicts outcomes in adult living-donor liver transplantation. Liver Transpl, 2006; 12(4):605–613; doi: 10.1002/lt.20713

27.

Levesque

, Saliba

, Benhamida

, et al. Plasma disappearance rate of indocyanine green: A tool to evaluate early graft outcome after liver transplantation. Liver Transpl, 2009; 15(10):1358–1364; doi: 10.1002/lt.21805

28.

Olmedilla

, Lisbona

, Pérez-Peña

, et al. Early measurement of indocyanine green clearance accurately predicts short-term outcomes after liver transplantation. Transplantation, 2016; 100(3):613–620; doi: 10.1097/TP.0000000000000980

29.

Cherchi

, Vetrugno

, Zanini

, et al. Indocyanine green dye clearance test: Early graft (dys)-function and long-term mortality after liver transplant. Should we continue to use it? An observational study. J Clin Monit Comput, 2020; 35(3):505–513; doi: 10.1007/s10877-020-00493-z

30.

, Xu

, Wu

, et al. Evaluation of liver function using Gd-EOB-DTPA-enhanced MRI with T1 mapping. BMC Med Imaging, 2023; 23(1):73; doi: 10.1186/S12880-023-01028-Z

31.

Vos

, Wietasch

JKG

, Absalom

, et al. Green light for liver function monitoring using indocyanine green? An overview of current clinical applications. Anaesthesia, 2014; 69(12):1364–1376; doi: 10.1111/anae.12755

32.

Vlek

, van Dam

, Rubinstein

, et al. Biliary tract visualization using near-infrared imaging with indocyanine green during laparoscopic cholecystectomy: Results of a systematic review. Surg Endosc, 2017; 31(7):2731–2742; doi: 10.1007/S00464-016-5318-7

33.

Liu

, Kong

, Diana

, et al. Near-infrared cholecysto-cholangiography with indocyanine green may secure cholecystectomy in difficult clinical situations: Proof of the concept in a porcine model. Surg Endosc, 2016; 30(9):4115–4123; doi: 10.1007/S00464-015-4608-9

34.

Ishizawa

, Fukushima

, Shibahara

, et al. Real-time identification of liver cancers by using indocyanine green fluorescent imaging. Cancer, 2009; 115(11):2491–2504; doi: 10.1002/CNCR.24291

35.

Gupta

, Singh

, Mishra

, et al. Efficacy and outcome of indocyanine green-based intraoperative cholangiography using near-infrared fluorescence imaging: A prospective study. J Minim Access Surg, 2024; 20(1):89–95; doi: 10.4103/JMAS.JMAS_228_22

36.

Fassari

, Bianucci

, Lucchese

, et al. Fluorescence cholangiography for laparoscopic cholecystectomy: How, when, and why? A single-center preliminary study. Minim Invasive Ther Allied Technol, 2023; 32(5):264–272; doi: 10.1080/13645706.2023.2265998

37.

Losurdo

, Giunta

, Modica

, et al. Near-infrared indocyanine green fluorescent cholangiography in urgent and emergency laparoscopic cholecystectomy: A preliminary study after propensity score-matched study. Eur J Trauma Emerg Surg, 2023; 50(1):275–281; doi: 10.1007/S00068-023-02340-7

38.

Stolz

, Foxhall

, Gibson

, et al. Improving the safety of laparoscopic cholecystectomy with indocyanine green dye using critical view of safety plus. Am Surg, 2023; 89(7):3136–3139; doi: 10.1177/00031348231161659

39.

Lehrskov

, Westen

, Larsen

, et al. Fluorescence or X-ray cholangiography in elective laparoscopic cholecystectomy: A randomized clinical trial. Br J Surg, 2020; 107(6):655–661; doi: 10.1002/BJS.11510

40.

van den Bos

, Schols

, Boni

, et al. Near-infrared fluorescence cholangiography assisted laparoscopic cholecystectomy (FALCON): An international multicentre randomized controlled trial. Surg Endosc, 2023; 37(6):4574–4584; doi: 10.1007/S00464-023-09935-6

41.

Ortenzi

, Corallino

, Botteri

, et al. Safety of laparoscopic cholecystectomy performed by trainee surgeons with different cholangiographic techniques (SCOTCH): A prospective non-randomized trial on the impact of fluorescent cholangiography during laparoscopic cholecystectomy performed by trainees. Surg Endosc, 2024; 38(2):1045–1058; doi: 10.1007/S00464-023-10613-W

42.

Lie

, Irawan

, Sudirman

, et al. Efficacy and safety of near-infrared florescence cholangiography using indocyanine green in laparoscopic cholecystectomy: A systematic review and meta-analysis. J Laparoendosc Adv Surg Tech A, 2023; 33(5):434–446; doi: 10.1089/LAP.2022.0495

43.

López-Sánchez

, Garrosa-Muñoz

, Pardo Aranda

, et al. Dose and administration time of indocyanine green in near-infrared fluorescence cholangiography during laparoscopic cholecystectomy (DOTIG): Study protocol for a randomised clinical trial. BMJ Open, 2023; 13(3):e067794; doi: 10.1136/BMJOPEN-2022-067794

44.

Pardo Aranda

, Gené Škrabec

, López-Sánchez

, et al. Indocyanine green (ICG) fluorescent cholangiography in laparoscopic cholecystectomy: Simplifying time and dose. Dig Liver Dis, 2023; 55(2):249–253; doi: 10.1016/J.DLD.2022.10.023

45.

Ladd

, Zarate Rodriguez

, Lewis

, et al. Low vs standard-dose indocyanine green in the identification of biliary anatomy using near-infrared fluorescence imaging: A multicenter randomized controlled trial. J Am Coll Surg, 2023; 236(4):711–717; doi: 10.1097/XCS.0000000000000553

46.

Huang

, Chen

, Kuang

, et al. Real-time fluorescent cholangiography with indocyanine green in laparoscopic cholecystectomy: A randomized controlled trial to establish the optimal indocyanine green dose within 30 min preoperatively. Surg Today, 2023; 53(2):223–231; doi: 10.1007/S00595-022-02563-Y

47.

Graves

, Ely

, Idowu

, et al. Direct gallbladder indocyanine green injection fluorescence cholangiography during laparoscopic cholecystectomy. J Laparoendosc Adv Surg Tech A, 2017; 27(10):1069–1073; doi: 10.1089/LAP.2017.0070

48.

Huang

, Du

, Wang

, et al. Application of intraoperative fluorescence imaging with indocyanine green in the difficult gallbladder: A comparative study between indocyanine green-guided fluorescence cholangiography and conventional surgery. J Laparoendosc Adv Surg Tech A, 2023; 33(4):404–410; doi: 10.1089/LAP.2022.0467

49.

Hiwatashi

, Okumura

, Setoyama

, et al. Evaluation of laparoscopic cholecystectomy using indocyanine green cholangiography including cholecystitis: A retrospective study. Medicine (Baltimore), 2018; 97(30):e11654; doi: 10.1097/MD.0000000000011654

50.

Castagneto‐gissey

, Russo

, Iodice

, et al. Intracholecystic versus Intravenous Indocyanine Green (ICG) injection for biliary anatomy evaluation by fluorescent cholangiography during laparoscopic cholecystectomy: A case-control study. J Clin Med, 2022; 11(12); doi: 10.3390/JCM11123508

51.

Ijichi

, Takayama

, Toyoda

, et al. Randomized trial of the usefulness of a bile leakage test during hepatic resection. Arch Surg, 2000; 135(12):1395–1400; doi: 10.1001/ARCHSURG.135.12.1395

52.

Kaibori

, Ishizaki

, Matsui

, et al. Intraoperative indocyanine green fluorescent imaging for prevention of bile leakage after hepatic resection. Surgery, 2011; 150(1):91–98; doi: 10.1016/J.SURG.2011.02.011

53.

Sakaguchi

, Suzuki

, Unno

, et al. Bile leak test by indocyanine green fluorescence images after hepatectomy. Am J Surg, 2010; 200(1):e19–e23; doi: 10.1016/J.AMJSURG.2009.10.015

54.

Hanaki

, Goto

, Tokuyasu

, et al. Efficacy of indocyanine green systemic administration for bile leak detection after hepatectomy: A protocol for a prospective single-arm clinical trial with a historical control group. BMJ Open, 2023; 13(3):e068223; doi: 10.1136/BMJOPEN-2022-068223

55.

Tang

, Du

, Tao

, et al. Effect of indocyanine green fluorescence angiography on anastomotic leakage in patients undergoing colorectal surgery: A meta-analysis of randomized controlled trials and propensity-score-matched studies. Front Surg, 2022; 9:815753; doi: 10.3389/FSURG.2022.815753

56.

, Deng

, Ma

, et al. Real-time indocyanine green fluorescence technique reduces anastomotic leakage in bilioenteric anastomosis: A case report and literature review. Photodiagnosis Photodyn Ther, 2023; 42:103609; doi: 10.1016/J.PDPDT.2023.103609

57.

Hasegawa

, Kokudo

, Imamura

, et al. Prognostic impact of anatomic resection for hepatocellular carcinoma. Ann Surg, 2005; 242(2):252–259; doi: 10.1097/01.SLA.0000171307.37401.DB

58.

Ishizawa

, Zuker

, Kokudo

, et al. Positive and negative staining of hepatic segments by use of fluorescent imaging techniques during laparoscopic hepatectomy. Arch Surg, 2012; 147(4):393–394; doi: 10.1001/ARCHSURG.2012.59

59.

Berardi

, Colasanti

, Meniconi

, et al. The applications of 3D imaging and indocyanine green dye fluorescence in laparoscopic liver surgery. Diagnostics (Basel), 2021; 11(12); doi: 10.3390/DIAGNOSTICS11122169

60.

Kobayashi

, Kawaguchi

, Kobayashi

, et al. Portal vein territory identification using indocyanine green fluorescence imaging: Technical details and short-term outcomes. J Surg Oncol, 2017; 116(7):921–931; doi: 10.1002/JSO.24752

61.

Lan

, Tang

, Wei

, et al. Indocyanine green fluorescence staining based on the “hepatic pedicle first” approach during laparoscopic anatomic liver resection. Surg Endosc, 2022; 36(11):8121–8131; doi: 10.1007/S00464-022-09237-3

62.

, Chen

, Meng

, et al. Laparoscopic anatomical liver resection guided by real-time indocyanine green fluorescence imaging: Experience and lessons learned from the initial series in a single center. Surg Endosc, 2020; 34(10):4683–4691; doi: 10.1007/S00464-020-07691-5

63.

Rethy

, Langø

, Mårvik

. Laparoscopic ultrasound for hepatocellular carcinoma and colorectal liver metastasis: An overview. Surg Laparosc Endosc Percutan Tech, 2013; 23(2):135–144; doi: 10.1097/SLE.0B013E31828A0B9A

64.

Wang

, Teh

CSC

, Ishizawa

, et al. Consensus guidelines for the use of fluorescence imaging in hepatobiliary surgery. Ann Surg, 2021; 274(1):97–106; doi: 10.1097/SLA.0000000000004718

65.

Wakabayashi

, Cacciaguerra

, Abe

, et al. Indocyanine green fluorescence navigation in liver surgery: A systematic review on dose and timing of administration. Ann Surg, 2022; 275(6):1025–1034; doi: 10.1097/SLA.0000000000005406

66.

Kogure

, Kumon

, Matsuki

, et al. Right hemihepatectomy preserving the fluorescently visible paracaval portion of the caudate lobe. Glob Health Med, 2023; 5(6):377–380; doi: 10.35772/GHM.2023.01063

67.

Takasaki

. Glissonean pedicle transection method for hepatic resection: A new concept of liver segmentation. J Hepatobiliary Pancreat Surg, 1998; 5(3):286–291; doi: 10.1007/S005340050047

68.

Xie

, Qiu

, Liao

, et al. Transhepatic arterial approaches for ICG injection to guide laparoscopic anatomical hepatectomy: A case series study. Asian J Surg, 2024; 47(2):916–922; doi: 10.1016/J.ASJSUR.2023.10.105

69.

Liu

, Wang

, Ma

, et al. Short- and long-term outcomes of indocyanine green fluorescence navigation—versus conventional-laparoscopic hepatectomy for hepatocellular carcinoma: A propensity score-matched, retrospective, cohort study. Ann Surg Oncol, 2023; 30(4):1991–2002; doi: 10.1245/S10434-022-13027-5

70.

Saiura

, Yamamoto

, Sakamoto

, et al. Safety and efficacy of hepatic vein reconstruction for colorectal liver metastases. Am J Surg, 2011; 202(4):449–454; doi: 10.1016/J.AMJSURG.2010.08.040

71.

Alomari

MAM

, Wakabayashi

, Colella

, et al. Comparing the accuracy of positive and negative indocyanine green staining in guiding laparoscopic anatomical liver resection: Protocol for a randomised controlled trial. BMJ Open, 2023; 13(9):e072926; doi: 10.1136/BMJOPEN-2023-072926

72.

Patel

, Rehman

, McKay

, et al. Use of near-infrared fluorescence techniques in minimally invasive surgery for colorectal liver metastases. J Clin Med, 2023; 12(17); doi: 10.3390/JCM12175536

73.

Nakaseko

, Ishizawa

, Saiura

. Fluorescence-guided surgery for liver tumors. J Surg Oncol, 2018; 118(2):324–331; doi: 10.1002/JSO.25128

74.

Gotoh

, Yamada

, Ishikawa

, et al. A novel image-guided surgery of hepatocellular carcinoma by indocyanine green fluorescence imaging navigation. J Surg Oncol, 2009; 100(1):75–79; doi: 10.1002/JSO.21272

75.

Ishizawa

, Masuda

, Urano

, et al. Mechanistic background and clinical applications of indocyanine green fluorescence imaging of hepatocellular carcinoma. Ann Surg Oncol, 2014; 21(2):440–448; doi: 10.1245/S10434-013-3360-4

76.

, Su

, Fang

, et al. Residual cancerous lesion and vein tumour thrombus identified intraoperatively using a fluorescence navigation system in liver surgery. ANZ J Surg, 2019; 89(7–8):E308–E314; doi: 10.1111/ANS.15282

77.

Abo

, Nanashima

, Tobinaga

, et al. Usefulness of intraoperative diagnosis of hepatic tumors located at the liver surface and hepatic segmental visualization using indocyanine green-photodynamic eye imaging. Eur J Surg Oncol, 2015; 41(2):257–264; doi: 10.1016/J.EJSO.2014.09.008

78.

Van Der Vorst

, Schaafsma

, Hutteman

, et al. Near-infrared fluorescence-guided resection of colorectal liver metastases. Cancer, 2013; 119(18):3411–3418; doi: 10.1002/CNCR.28203

79.

Baiocchi

, Diana

, Boni

. Indocyanine green-based fluorescence imaging in visceral and hepatobiliary and pancreatic surgery: State of the art and future directions. World J Gastroenterol, 2018; 24(27):2921–2930; doi: 10.3748/WJG.V24.I27.2921

80.

Handgraaf

HJM

, Boogerd

LSF

, Höppener

, et al. Long-term follow-up after near-infrared fluorescence-guided resection of colorectal liver metastases: A retrospective multicenter analysis. Eur J Surg Oncol, 2017; 43(8):1463–1471; doi: 10.1016/J.EJSO.2017.04.016

81.

Piccolo

, Barabino

, Pesce

, et al. Role of indocyanine green fluorescence imaging in minimally invasive resection of colorectal liver metastases. Surg Laparosc Endosc Percutan Tech, 2022; 32(2):259–265; doi: 10.1097/SLE.0000000000001037

82.

Cai

, Hong

, Pan

, et al. Does using indocyanine green fluorescence imaging for tumors help in determining the safe surgical margin in real-time navigation of laparoscopic hepatectomy? A retrospective study. Ann Surg Oncol, 2023; 30(4):1981–1987; doi: 10.1245/S10434-022-12893-3

83.

Boogerd

LSF

, Handgraaf

HJM

, Lam

, et al. Laparoscopic detection and resection of occult liver tumors of multiple cancer types using real-time near-infrared fluorescence guidance. Surg Endosc, 2017; 31(2):952–961; doi: 10.1007/S00464-016-5007-6

84.

Achterberg

, Sibinga Mulder

, Meijer

RPJ

, et al. Real-time surgical margin assessment using ICG-fluorescence during laparoscopic and robot-assisted resections of colorectal liver metastases. Ann Transl Med, 2020; 8(21):1448–1448; doi: 10.21037/ATM-20-1999

85.

Zhou

, Zhou

, Du

, et al. Safety and effectiveness of indocyanine green fluorescence imaging-guided laparoscopic hepatectomy for hepatic tumor: A systematic review and meta-analysis. Front Oncol, 2023; 13:1309593; doi: 10.3389/FONC.2023.1309593

86.

, Cui

, Jia

, et al. A meta-analysis of short-term and long-term effects of indocyanine green fluorescence imaging in hepatectomy for liver cancer. Photodiagnosis Photodyn Ther, 2023; 42:103497; doi: 10.1016/J.PDPDT.2023.103497

87.

Mehdorn

, Richter

, Hess

, et al. The role of ICG in robot-assisted liver resections. J Clin Med, 2022; 11(12); doi: 10.3390/JCM11123527

88.

Rompianesi

, Pegoraro

, Ramaci

, et al. Preoperative planning and intraoperative real-time navigation with indocyanine green fluorescence in robotic liver surgery. Langenbecks Arch Surg, 2023; 408(1):292; doi: 10.1007/S00423-023-03024-X

89.

Liberale

, Bourgeois

, Larsimont

, et al. Indocyanine green fluorescence-guided surgery after IV injection in metastatic colorectal cancer: A systematic review. Eur J Surg Oncol, 2017; 43(9):1656–1667; doi: 10.1016/J.EJSO.2017.04.015

90.

Chen

Z-R

, Zeng

Q-T

, Shi

, et al. Laboratory scoring system to predict hepatic indocyanine green clearance ability during fluorescence imaging-guided laparoscopic hepatectomy. World J Gastrointest Surg, 2023; 15(7):1442–1453; doi: 10.4240/WJGS.V15.I7.1442

91.

Ruzzenente

, Conci

, Isa

, et al. The LIver SEntinel LYmph-node (LISELY) study: A prospective intraoperative real time evaluation of liver lymphatic drainage and sentinel lymph-node using near-infrared (NIR) imaging with Indocyanine Green (ICG). Eur J Surg Oncol, 2022; 48(12):2455–2459; doi: 10.1016/J.EJSO.2022.06.035

92.

Zhang

, Zhang

, Zhu

, et al. Clinical application of indocyanine green fluorescence imaging in laparoscopic lymph node dissection for intrahepatic cholangiocarcinoma: A pilot study (with video). Surgery, 2022; 171(6):1589–1595; doi: 10.1016/J.SURG.2021.09.032

93.

Hong

, Lee

, Kim

, et al. Optimal bile duct division using real-time indocyanine green near-infrared fluorescence cholangiography during laparoscopic donor hepatectomy. Liver Transpl, 2017; 23(6):847–852; doi: 10.1002/LT.24686

94.

Panaro

, Benedetti

, Pineton de Chambrun

, et al. Indocyanine green fluorescence angiography during liver and pancreas transplantation: A tool to integrate perfusion statement’s evaluation. Hepatobiliary Surg Nutr, 2018; 7(3):161–166; doi: 10.21037/HBSN.2017.07.02

95.

, Fang

, Li

, et al. First-in-human liver-tumour surgery guided by multispectral fluorescence imaging in the visible and near-infrared-I/II windows. Nat Biomed Eng, 2020; 4(3):259–271; doi: 10.1038/S41551-019-0494-0

96.

Zhang

, Hu

, Tian

, et al. A narrative review of near-infrared fluorescence imaging in hepatectomy for hepatocellular carcinoma. Ann Transl Med, 2021; 9(2):171–171; doi: 10.21037/ATM-20-5341

97.

Ding

, Li

, Xu

, et al. PEGylation regulates self-assembled small-molecule dye-based probes from single molecule to nanoparticle size for multifunctional NIR-II bioimaging. Adv Healthc Mater, 2018; 7(23):e1800973; doi: 10.1002/ADHM.201800973

98.

Shi

, Huttad

, Tan

, et al. NIR-II imaging of hepatocellular carcinoma based on a humanized anti-GPC3 antibody. RSC Med Chem, 2021; 13(1):90–97; doi: 10.1039/D1MD00313E

99.

Zhao

, Li

, Wu

, et al. A tumor-microenvironment-responsive lanthanide-cyanine FRET sensor for NIR-II luminescence-lifetime in situ imaging of hepatocellular carcinoma. Adv Mater, 2020; 32(28):e2001172; doi: 10.1002/ADMA.202001172

100.

Jia

, Xu

, Wang

, et al. NIR-II emissive AIEgen photosensitizers enable ultrasensitive imaging-guided surgery and phototherapy to fully inhibit orthotopic hepatic tumors. J Nanobiotechnology, 2021; 19(1):419; doi: 10.1186/S12951-021-01168-W

101.

Hardy

, Epperlein

, Dalli

, et al. Real-time administration of indocyanine green in combination with computer vision and artificial intelligence for the identification and delineation of colorectal liver metastases. Surg Open Sci, 2023; 12:48–54; doi: 10.1016/J.SOPEN.2023.03.004