Trans-Arterial Indocyanine Green Staining for Precise Anatomical Hepatectomy of Liver Segments VII and VIII

Summary

Laparoscopic anatomical hepatectomy has gained global recognition in liver surgery. However, delineating tumor boundaries in liver segments VII and VIII presents distinct technical challenges. This protocol utilizes trans-arterial indocyanine green (ICG) staining to accurately identify liver subsegments, facilitating complete tumor resection while preserving functional liver volume.

Abstract

Anatomical hepatectomy for resectable hepatocellular carcinoma (HCC) is performed with precision using the Glissonean system, ultrasound imaging, and indocyanine green (ICG) fluorescence staining to define liver segments, enhancing surgical radicality and preserving liver volume. However, laparoscopic clamping and ultrasound-guided ICG staining for deep-seated tumors in liver segments VII and VIII pose challenges due to the depth of the Glissonean ducts and other technical limitations. This study aimed to overcome these obstacles by exploring a protocol using trans-arterial ICG staining, a technique specifically tailored for complex anatomical hepatectomy of liver segments VII and VIII. In this method, an interventionalist accessed the right femoral artery and advanced to the celiac trunk for arteriography, followed by strategic placement of a microcatheter into the tumor's blood supply vessel to facilitate surgical resection. During the operation, ICG was injected through the microcatheter to fluorescently label the tumor's liver segment, enabling precise anatomical resection under fluorescence guidance. This trans-arterial ICG staining approach allows for the accurate identification of tumor subsegments, facilitates complete resection, and optimizes liver function preservation, ultimately improving oncological outcomes without increasing surgical complication rates.

Introduction

Hepatocellular carcinoma (HCC) is the most prevalent malignant tumor of the digestive system, ranking fourth in incidence in China and first globally. HCC accounts for an estimated 50% of annual new cases and deaths worldwide¹. Laparoscopic anatomical hepatectomy is one of the primary radical treatments for patients with early-stage HCC^2,3. According to the Glissonean system, the liver's intricate architecture allows for precise division into eight distinct segments, each with its own blood supply, bile duct, and vascular drainage. This anatomical segmentation is based on Glisson's capsule, which envelops each segment and provides a structural basis for the functional and surgical divisions of the liver⁴. Although the extent of resection can be determined based on the ischemic areas of the liver surface, the intersegmental anatomical planes rely more on hepatic vein orientation or the operator's subjective visual assessment⁵.

Technological advancements have enabled hepatobiliary surgeons to perform anatomical hepatectomy using ultrasound guidance and indocyanine green (ICG) fluorescence staining to identify specific liver segments, leading to improved radical outcomes and increased residual hepatic volume^6,7. ICG staining provides clear demarcation of the plane for deep hepatic resection and is categorized into positive and negative staining⁸. However, for tumors located in segments VII and VIII, the Glissonean ducts penetrate deep into the liver parenchyma, making laparoscopic clamping and subsequent negative staining challenging⁹.

Beyond the conventional negative staining method, positive staining can be performed by injecting ICG directly into the portal vein of the target segment under ultrasound guidance, precisely delineating liver segment boundaries. However, this technique presents challenges due to the technical limitations of ultrasound guidance and variations in portal vein branching patterns^10,11. Additionally, accurately accessing specific portal vein branches for targeted positive staining is often complex. The variability in portal vein anatomy introduces uncertainty that may affect procedural accuracy, even for experienced surgeons. Given these challenges, developing novel techniques to enhance the precision of liver segment identification has become critical in hepatobiliary surgery. Advancements that facilitate efficient navigation of the liver's intricate vascular landscape are urgently needed to ensure accurate positive staining results.

Hepatic arteriography is a cutting-edge diagnostic technique that involves minimally invasive catheterization of the hepatic artery combined with the strategic injection of a contrast agent. This imaging method provides a clear view of the liver's intricate vascular network, a crucial step in visualizing and mapping the blood supply of hepatocellular carcinoma (HCC)¹². Furthermore, the hepatic artery supplies up to 90% of the blood to HCCs. Consequently, hepatic arteriography is a vital tool for precise tumor identification and the formulation of targeted treatment plans, including precision trans-arterial chemoembolization and hepatic artery infusion chemotherapy^13,14.

This study investigated a protocol using trans-arterial indocyanine green (ICG) staining, a technique specifically tailored for complex anatomical hepatectomy of liver segments VII and VIII. This method enables the precise injection of ICG into the targeted hepatic vasculature, allowing vivid visualization of the liver's anatomical segments, accurate identification of the target hepatic pedicle, and clear demarcation of the hepatic resection plane. The selective ICG fluorescence staining of specific blood vessels supplying the affected segments labels the liver's intricate structure, providing surgeons with a real-time, high-definition map of the liver segments. This level of precision not only ensures complete tumor excision but also optimizes the preservation of residual liver function, ultimately improving postoperative quality of life. This advancement significantly enhances oncological outcomes by achieving a balance between effective tumor removal and liver function maintenance. Moreover, this technique does not introduce additional surgical risks or complications. Finally, integrating this protocol into hepatic arteriography represents an evolution in surgical standards for HCC, ensuring that affected patients receive the safest, most effective, and most innovative care.

Protocol

This study protocol adhered to the ethical guidelines established by the relevant committee on human experimentation and conformed to institutional and national standards, as well as the principles outlined in the 1964 Declaration of Helsinki and its subsequent amendments. Ethical approval for this study was granted by the Institutional Review Board of the Ethics Committee of Guangdong Provincial People's Hospital. Informed consent was obtained from the patient included in this study, who provided written consent for the publication of anonymized information. The indications and contraindications for synchronous interventions align broadly with those for laparoscopic radical hepatocellular carcinoma surgery but include specific considerations. The inclusion criteria consisted of watershed resection of liver subsegments, such as S4A, S8V, and S8D, particularly when the segmental portal vein was difficult to puncture; a clearly defined vascular supply; and multiple tumor nodules confined to the same liver segment or lobe. The exclusion criteria included complex vascular conditions, such as arteriovenous fistula, vascular variants, or vascular occlusion, as well as a known allergy to contrast media. The details of the reagents and equipment used are listed in the Table of Materials.

1. Preoperative preparation

1. Sterilize the surgical instruments and verify the functionality of the equipment before the operation.
2. Clean the abdominal skin and ensure no drinking for 6 h before surgery.

2. Transcatheter hepatic artery embolization procedure

1. Sterilize the right thigh and arrange the surgical sheets.
2. Anesthetize the patient with 2% lidocaine and perform arterial puncture at a site approximately 1.5 cm inferior to the right inguinal ligament.
3. Visualize the tumor blood supply. Identify the tumor's blood supply originating from the branches of the right hepatic artery within segments VII and VIII (A7 and A8, respectively)¹⁵.
4. Inject ICG (1:500 dilution, 3 mL) into A7 (where the tumor is primarily located in segment VII), deliver the embolization coil to A7 via a microcatheter, and release the embolization coil to block blood flow to A7¹⁶.
5. Place a microcatheter into A8 for intraoperative ICG injection.
6. Pressurize the puncture site created in step 2.2 and proceed promptly to the laparoscopic anatomical hepatectomy stage.

3. Laparoscopic anatomical hepatectomy of liver segments VII/VIII

1. Separate adhesions between the abdominal cavity and the right liver using an ultrasound scalpel.
2. Visualize fluorescent staining at the edge of the tumor in segment S7 after switching from normal laparoscopy to ICG fluorescence mode.
3. Free the perihepatic ligament and separate tumor adhesion from the diaphragm.
4. Perform intraoperative ICG staining (1:500 dilution, 3 mL) of A8 through a pre-positioned microcatheter in A8.
5. Reconfirm tumor boundaries (located in segments S7 and S8, approximately 8 cm × 7 cm) using ultrasound.
6. Make a pre-cut line along the fluorescence boundary.
   NOTE: Since the tumor is approximately 8 cm × 7 cm, the pre-cut line should be slightly larger than the tumor margins to ensure complete resection while maintaining oncological safety.
7. Incise the liver parenchyma using an ultrasonic scalpel.
   NOTE: Since the tumor is approximately 8 cm × 7 cm, the liver parenchyma incision should extend at least 1 cm beyond the fluorescence boundary to ensure a safe margin.
8. Clamp the intersegmental vessels between segments S6 and S7, followed by transection.
9. Expose the terminal end of the right hepatic vein, clamp, and transect.
10. Expose Glisson's pedicle using the extrafascial approach¹⁷.
11. Clamp and transect the hepatic short veins.
12. Adequately expose the Glisson's pedicles of segments 7 and 8 (G7, G8).
13. Transect the Glisson's pedicle of segment 7 using a cutting occluder.
14. Adequately expose the Glisson's pedicle of segment 8 (G8).
15. Pass a size 4-0 suture and use a cutting occluder to transect the Glisson's pedicle of segment 8 (G8).
16. Expose the origin of the right hepatic vein.
17. Transect the origin of the right hepatic vein using a cutting occluder.
18. Extract the tumor through a minimally invasive subxiphoid incision.

4. Postoperative care and monitoring

1. Transfer the patient to the intensive care unit (ICU) or a high-dependency unit for close monitoring of vital signs, including blood pressure, heart rate, oxygen saturation, and urine output.
2. Administer postoperative pain management using patient-controlled analgesia (PCA) or intravenous analgesics as per institutional protocols.
3. Monitor for signs of bleeding or hemorrhage by assessing drainage output from the surgical site and checking hemoglobin levels at regular intervals.
4. Gradually reintroduce oral intake, starting with clear fluids and advancing to a regular diet as tolerated, while monitoring for signs of nausea, vomiting, or gastrointestinal discomfort.
5. Schedule regular follow-up visits to monitor liver regeneration, tumor recurrence (if applicable), and overall recovery through imaging and blood tests.
   NOTE: For this study, follow-up was conducted the first month after surgery, followed by every 3 months for 2 years post-surgery.

Results

Preoperative three-dimensional (3D) liver reconstruction and hepatic arteriography of the patient revealed that the tumor was primarily vascularized by branches A7 and A8 of the hepatic artery (Figure 1). An embolization coil was used to occlude branch A7, and a microcatheter was placed in branch A8 for the intraoperative injection of indocyanine green (ICG) (Figure 2).

Following transcatheter hepatic artery embolization, ICG was inje...

Discussion

The upper posterior regions of the liver, specifically segments VII and VIII, present significant challenges in anatomical demarcation. As a result, precisely identifying and resecting these segments are complex yet critical aspects of hepatic surgery^18,19. The trans-arterial indocyanine green (ICG) staining approach during anatomical hepatectomy provides distinct advantages in managing tumors in these segments.

Tumors in segments VII ...

Materials

Name	Company	Catalog Number	Comments
B-scan ultrasonography	BK Medical	Pro Focus 2202
Curved Cutter Stapler	ETHICON	ECH45C
FloNavi Endoscopic Fluorescence Imaging System	OptoMedic Group	FloNavi 2100
Microcatheter	Hengrui Pharmaceuticals Co., Ltd.	C2215045