2. SYNOPSIS
• Introduction
• ICG metabolism and properties
• Safety of ICG
• Clinical applications
1. HepatoBiliary surgery
2. Colorectal surgery
3. Gastric and Esophageal surgery
4. Oncosurgery
3. Introduction
• ICG - Non toxic, fluorescent iodide dye with rapid hepatic
clearance
• Uses of ICG
Localisation of anatomical structures
Delineation of diseased and normal tissue
Enhanced Localisation of tumours and lymph nodes
Intraoperative Assessment of margin status
Real-time visualisation of Organ Perfusion
5. ICG Metabolism
• Exclusively metabolised by the liver.
• The dye is cleared in the first 10 to 20 minutes after application, with a
half-life of generally 3 to 4 minutes.
• Its elimination is dependent on
1. Hepatocyte Function
2. Liver Blood Flow
3. Bile Secretion
6. Safety of ICG
• Of the injected ICG, 98% is bound to plasma proteins while the remaining 2% is free
in the serum
• The decomposition reaction of ICG releases singlet oxygen molecules that bind to the
breakdown products and thermally decompose into carbonyl compounds of low
toxicity.
• Because the singlet oxygen remains within the ICG system, the dye has an LD 50
(lethal dosage) of 50 to 80 mg/kg.
• With a standard dose of less than 2 mg/kg, ICG is virtually nontoxic, provided
the patient does not have an iodide allergy.
Desmettre T, Devoisselle JM, Mordon S. Fluorescence properties and metabolic features of
indocyanine green (ICG) as related to angiography. Surv Ophthalmol. 2000;45:15-27
7. ICG – Clinical applications in HepatoBiliary
Surgery
• HepatoBiliary Surgery
• Colorectal Surgery
• Upper GI Surgery
• Surgical Oncology
• Ophthalmology
• Neurosurgery
1. Liver function Measurement
2. Biliary Anatomy
3. In Hepatocellular Carcinoma
4. In Colorectal Liver metastasis
5. As a therapeutic agent
8. 1. Limitations of ICG in liver function
assessment
• Not reliable in patients with intrahepatic shunting or sinusoidal
capillarization.
• It is a measure of global liver function, so if there is heterogeneous
uptake in the liver, the results may be misleading.
• Finally, ICG testing does not incorporate the extent of resection, or
conversely, the volume of the remnant that will remain
9. 2. Biliary anatomy
• Surgeons performing hepatobiliary surgery are often faced with difficult and
aberrant anatomy, further contorted by pathology.
• One limitation to ICG biliary visualization may be the background
fluorescence from the liver; however this can be improved by precise
timing of ICG injection preoperatively
10. Identifying Extrahepatic Biliary anatomy in
HepatoBiliary surgery
• The exclusively hepatic metabolism of ICG, results in biliary excretion from 30
minutes after injection enables visualisation of the biliary anatomy, which is
useful during difficult cholecystectomies
• The majority of the studies included in the review used 2.5 mg administered
within 1 h before imaging - for lap cholecystectomy
Koong JK, Ng GH, Ramayah K, Koh PS and Yoong BK: Early identification of the critical view of
safety in laparoscopic cholecystectomy using indocyanine green fluorescence cholangiography:
A randomised controlled study. Asian J Surg. 44:537–543. 2021
11. :
Yusuke Tsuruda etal; Laparoscopic
cholecystectomy with aberrant bile duct detected by
intraoperative fluorescent cholangiography
concomitant with angiography: A case report –
international journal of surgery case reports ,
volume 51 2018, Pages 14-16
12. Role of ICG in minimally invasive
Hepatobiliary surgery
• ICG gains more and more recognition in minimally invasive liver surgery in
western countries
• Reason - haptic feedback for tumor identification is missing.
• Need other tools to reach sufficient oncological results.
• The intraoperative ultrasound and even the contrast-enhanced technique can
facilitate this demand but ICG adds more precision.
• ICG also helps in anatomical liver resections by identifying individual
segmental anatomy of the liver
13. 3. ICG in HCC
• In well-differentiated HCC cells higher expression of OATP and
natrium–taurocholate co-transporting polypeptides (NTCP) for admission of
lipoprotein-bound ICG
• In contrast to healthy hepatocytes the bile excretion is disturbed
• Retention of ICG after preoperative intravenous injection in tumorous
tissue
• Typical homogenous fluorescence pattern for well-differentiated HCCs
15. For identifying segmental anatomy in liver resection
• Ishizawa et al has demonstrated positive or negative staining techniques for
liver segment delineation in laparoscopic hepatic resections.
• During positive segmental staining, the portal vein is punctured under
sonographic guidance through the liver surface with slow injection of ICG.
• In the negative staining technique, the Glissonean pedicle that corresponds
to the segments to be resected is dissected and clamped, followed by the use
of intravenous ICG, which stains the remaining liver.
16. Adrian K H Chiow, Seoung Yoon Rho, Ian J.Y. Wee, Lip Seng Lee, Gi Hong Choi, Robotic ICG
guided anatomical liver resection in a multi-centre cohort: an evolution from “positive staining”
into “negative staining” method, HPB, Volume 23, Issue 3, 2021, Pages 475-482
17. 4. Role of ICG as therapeutic agent in liver
tumors – animal study
• The characteristic of ICG to accumulate in HCC cells is a topic that
Inagaki et al. focused on in an experimental study.
• They examined ICG-conjugated chemotherapeutics, Gemcitabine,
Doxorubicin, in vitro and in vivo in nude mice and found that ICG-
conjugated Gemcitabine seems to be less toxic against normal cells and
show better effects against tumor cells in contrast to unconjugated
Gemcitabine
18. 5. ICG in colorectal liver metastasis
• CRLM is accessible for ICG visualization as well.
• A surrounding fringe of immature hepatocytes with reduced bile
excretion capacity shows a rim-type fluorescence pattern
• But it is only useful for subcapsular lesions, as the depth of penetrance is
limited to 8 mm for NIR imaging
20. To summarize
Fluorescence guided HPB surgery, has assisted surgeons in enhancing visualisation
and minimizing complications.
ICG is easily available, noninvasive and with wide margin of safety
When faced with difficult calots dissection, ICG gives a road map for dissection.
In minimally invasive approach in complex HPB surgeries, ICG overcomes the
limitations of loss of haptic feedback to some extent
21. References
1. ICG fluorescence imaging in colorectal surgery: a snapshot from the ICRAL study group -
Baiocchi et al. BMC Surg (2021) 21:190
2. A Review of Indocyanine Green Fluorescent Imaging in Surgery - Jarmo T. Alander
International Journal of Biomedical Imaging Volume 2012, Article ID 940585, 26 pages
3. Indocyanine Green: Historical Context, Current Applications, and Future Considerations
Michaela B. Reinhart Surgical Innovation 1–10 , Sagepub 2015, DOI:
10.1177/1553350615604053
4. indocyanine green-based fluorescence imaging in visceral and hepatobiliary and pancreatic
surgery: State of the art and future directions - Gian Luca Baiocchi World J Gastroenterol
2018 July 21; 24(27): 2921-2930
Editor's Notes
elated to its historic basis in analogue photography. The company is headquartered in Rochester, New York, and is incorporated in New Jersey.
For the assessment of preoperative liver function, static and dynamic tests are available. The Child-Turcotte-Pugh (CTP) [10,11] and model for end-stage liver disease (MELD) [12,13] scoring systems are well-known methods for the static assessment of liver function and are useful for predicting postoperative morbidity and mortality [14,15,16,17]. However, static laboratory tests are sometimes insensitive at predicting postoperative liver functional reserve. Thus, dynamic liver function tests have been used in deciding about the operability of patients with underlying liver disease.
Preoperative MRI image. The cystic duct is shown (arrow). MRI reveals no anomalous bile duct.
Findings from Calot’s triangle during laparoscopic cholecystectomy. (a) A linear structure (arrowhead) is seen posterior to the cystic artery (arrow) under normal light. (b) The structure thought to represent an aberrant bile duct (arrowhead) shows fluorescence under near-infrared light. (c)The cystic artery (arrow) shows fluorescence under near-infrared light after intravenous injection of 2 ml of ICG during the operation. Posterior to the cystic artery, an aberrant bile duct is evident (arrowhead).
Findings of the aberrant bile duct after laparoscopic cholecystectomy. (a) The aberrant bile duct (arrowhead) branching from the right side of the common hepatic duct appears well preserved under normal light. (b) The aberrant bile duct (arrowhead) shows fluorescence under near-infrared light
Reason - haptic feedback for tumor identification is missing during these procedures, other tools become mandatory to reach sufficient oncological results.
Figure 1. a) Ischaemic demarcation line after inflow occlusion of right pedicle in planned right hemi hepatectomy.
b) ICG demarcation line much clearer at the superior and inferior surface after injection of intravenous ICG to demonstrate demarcation line.
c) Ischaemic demarcation line unclear at the superior surface.
d) ICG demarcation line much clearer at the superior surfac
