The Role of Indocyanine Green Fluorescence in Complex Laparoscopic Cholecystectomy Navigation

Summary

This protocol outlines the steps for fluorescence-guided laparoscopic cholecystectomy and elucidates the role of fluorescence navigation in diverse surgical scenarios.

Abstract

Laparoscopic cholecystectomy (LC) is the gold-standard treatment for cholelithiasis and cholecystitis. In difficult cases with severe inflammation and adhesions, the risk of bile duct injury (BDI) is significantly higher. Precise identification of anatomical biliary structures is essential to prevent such injuries. Conventional intraoperative visualization techniques (IVT) have limited clinical application due to their complexity, increased trauma, and high error rates. Near-infrared fluorescence (NIRF) imaging, utilizing indocyanine green (ICG) as a fluorescent dye, has emerged as an innovative IVT technique. It is increasingly recognized as a feasible, safe, and effective approach for LC. However, the efficacy of NIRF in difficult LC procedures remains unclear, and the optimal timing and dosage of ICG administration are yet to be established. This article outlines the main steps for performing fluorescence-guided difficult LC in a patient with acute gangrenous cholecystitis and evaluates the imaging effects of NIRF in various scenarios. The patient was positioned supine, with four trocars placed. Upon switching to fluorescence mode, the fluorescently labeled bile ducts were readily identified. Following fluorescence guidance, Calot's triangle was carefully dissected. The cystic duct (CD) and cystic artery (CA) were individually identified and clipped before the gallbladder was extracted. Finally, the surgical field was inspected in fluorescence mode to detect bile leakage. With satisfactory ICG imaging and a smooth procedure, the patient's postoperative recovery was uneventful. NIRF is a safe and effective technology that shows great promise for future clinical applications.

Introduction

Approximately 20% of adults worldwide are affected by biliary stones, which can lead to acute cholecystitis -- a painful, rapidly progressing, and potentially life-threatening condition¹. Timely surgical intervention is imperative for patients with cholecystitis. Laparoscopic cholecystectomy (LC) has become widely accepted as the standard treatment for this condition.

However, conventional surgical approaches may present significant challenges in complex cases. Severe inflammation or adhesions can render biliary tracts indistinct, increasing the risk of inadvertent injury to bile ducts or arteries². Bile duct injury (BDI) is one of the most severe and common complications in these complex LC procedures. It often results in irreversible, lifelong consequences and, in severe cases, fatal outcomes³. Precise identification of critical biliary structures, such as Calot's triangle, is essential for facilitating surgical procedures and minimizing potential damage⁴.

Traditional intraoperative visualization techniques (IVT) integrate cholangiography, ultrasound, and choledochoscopy, enabling real-time monitoring of biliary tracts. However, concerns such as radiation exposure, a notable margin of error⁵, and cumbersome procedures have hindered the widespread adoption of IVT.

Near-infrared fluorescence (NIRF) is a cutting-edge technique that allows easy switching between fluorescence and white-light modes through a single laparoscope, enabling real-time visualization of biliary tracts during surgery. This technique offers high sensitivity, specificity, and tissue penetration capabilities⁶. NIRF can effectively prevent bile duct injury (BDI) during laparoscopic cholecystectomy (LC), particularly in complex cases involving severe inflammation or adhesions⁷.

Compared to traditional IVT, NIRF is easier to implement, provides clearer visualization of biliary tracts, and does not cause additional trauma^8,9,10. Its fluorescent dye, indocyanine green (ICG), has been proven safe for human use by the Food and Drug Administration¹¹. ICG is typically injected intravenously before surgery; however, the timing and dosage of ICG injection remain uncertain^12,13. These factors are critical determinants of high-quality fluorescence imaging. Optimal ICG performance achieves a strong fluorescence signal in the bile ducts while minimizing background fluorescence from liver tissue¹⁴.

Through extensive exploration, we have identified the optimal timing and dosage of ICG injection as 0.25 mg administered 45 min preoperatively. This study aims to demonstrate the imaging effects of this timing and dosage in various complex surgical scenarios.

Protocol

This research was conducted in compliance with the guidelines of the human research ethics committee of the Fifth Affiliated Hospital of Sun Yat-sen University. Written informed consent was obtained from the patient for participation in this study. The criteria for complex laparoscopic cholecystectomy (LC) included: gallbladder wall edema with thickening ≥4 mm; gangrenous cholecystitis with or without perforation; a history of upper abdominal surgery; impacted stones in the gallbladder neck; Mirizzi syndrome or variations in the extrahepatic bile duct; and cases requiring transcystic common bile duct exploration. Details of the reagents and equipment used are provided in the Table of Materials.

1. Fluorescence imaging preparation and patient positioning

1. Administer 0.25 mg of ICG via a peripheral vein injection 45 min before the surgery.
   NOTE: Dissolve 1 vial of ICG (25 mg) in 10 mL of normal saline. Inject 1 mL of the solution into 100 mL of normal saline for dilution. Administer 10 mL of the diluted solution via intravenous injection 45 min before the surgery.
2. Set up the DPM-I fluorescence system, a dual-channel image-guided device, to operate in white-light (380-665 nm) and near-infrared (810-1200 nm) spectrums.
3. Position the patient in a supine position. After inducing general anesthesia (following institutionally approved protocols) and completing all safety procedures (hood, sterile gloves, and sterile scrub), create a sterile field. Perform trocar insertion using a four-port method¹⁵.

2. Fluorescence-guided visualization and identification of biliary structures

1. Switch to fluorescence mode to locate the bile ducts.
   NOTE: In fluorescence mode, the stained bile duct structure may be directly visible or revealed after simple separation of encysted fat tissue (Figure 1A).
2. Follow the fluorescence navigation to carefully dissect and isolate the cystic duct (CD) and cystic artery (CA) using a cautery hook to achieve the critical view of safety, also known as Calot's Triangle.
   NOTE: In fluorescence mode, the CD exhibits a fluorescent signal, while the CA does not show any fluorescent signal.
3. Apply Hem-O-lock clips to both the CD and CA after identifying and distinguishing the bile ducts. Place two clips proximally and one distally on the CD. Place one clip proximally and one clip distally on the CA.
   NOTE: Identify the CD-common bile duct (CBD) junction carefully to prevent inadvertent injury to the CBD.

3. Removal of gallbladder

1. Dissect the gallbladder from its fossa, divide the cystic duct (CD) and cystic artery (CA) between the clips using scissors, and place the gallbladder in an extraction bag.
2. Employ white-light mode to detect any bleeding and switch to fluorescence mode to confirm the absence of bile leakage upon completion of the cholecystectomy.
3. Remove the gallbladder from the abdominal cavity, place a drainage tube at the gallbladder fossa, and close the abdomen using 4-0 polyglactin. Suture the skin with a 3-0 non-absorbable suture.
   NOTE: Cut the CD only after confirming there is a single duct entering the gallbladder, especially in cases of biliary anatomy variations such as a right accessory hepatic duct.

4. Postoperative monitoring and management

1. Review inflammatory markers postoperatively.
2. Remove the abdominal drainage tube when the drainage is clear and less than 50 mL per day.
3. Administer prophylactic antibiotics as needed based on the patient's clinical status and surgeon's recommendation.
4. Monitor the patient for signs of infection, including fever, redness, or swelling at the surgical site.
5. Schedule a follow-up consultation within 7-10 days to assess recovery.

Results

Following the surgical procedure outlined in the protocol (Figure 2), fluorescence-guided laparoscopic cholecystectomy (LC) was successfully performed in three patients with difficult gallbladders. There were no conversions to open surgery and no occurrences of bile duct injury (BDI) during the procedure. No bile leakage was observed in fluorescence mode, as demonstrated in the accompanying video. The intraoperative and postoperative outcomes are summarized in Table 1.

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Discussion

Laparoscopic cholecystectomy (LC) has long been regarded as the gold standard treatment for cholelithiasis and cholecystitis. However, conventional surgical approaches often pose significant challenges in cases involving acute inflammation, gangrene, perforation, and anatomical variations-collectively referred to as difficult gallbladders¹⁶. These challenging conditions significantly increase the risks of bile duct injury (BDI) and cystic artery (CA) injury.

BDI is one ...

Materials

Name	Company	Catalog Number	Comments
3-0 MERSILK	JOHNSON MEDICAL (CHINA) LTD.	SA84G	The Suture Material
4-0 Coated VICRYL	ETHICON	VCP310	The Suture Material
Endoscopic Fluorescence Imaging System	ZHUHAI DI PU MEDICAL TECHNOLOGY CO., LTD.	H380022041YF	Fluorescence Laparoscope Equipment
Hem-O-lock Clips	SINOLINKS MEDICAL INNOVOATION, INC.	B240714	Hem-O-lock Clips
Indocyanine Green for Injection	DANDONG YICHUANG PHARMACEUTICAL CO., LTD.	H20055881	Fluorescence Dye