Sequential Portal Vein Ligation and Robotic-Assisted Hepatectomy Following Conversion Therapy for Initially Unresectable Hepatocellular Carcinoma

Summary

This protocol aims to demonstrate a multimodal treatment strategy for initially unresectable hepatocellular carcinoma by combining portal vein ligation with targeted and immune-based conversion therapy, followed by robotic-assisted right hepatectomy. The goal is to enable safe resection, optimize future liver remnant volume, and achieve favorable oncological outcomes.

Abstract

The goal of this protocol is to present a comprehensive multimodal approach for treating hepatocellular carcinoma (HCC) that is initially considered unresectable due to insufficient future liver remnant or advanced tumor burden. The strategy integrates oncological conversion therapy with functional liver regeneration techniques, followed by minimally invasive robotic resection. First, targeted therapy, immunotherapy, and interventional vascular treatment are applied to control tumor progression and enhance resectability. Subsequently, laparoscopic right portal vein ligation is performed to induce hypertrophy of the contralateral liver, ensuring adequate functional reserve. After reassessment, patients meeting surgical criteria undergo Da Vinci robot-assisted anatomical right hepatectomy using an anterior approach, which allows precise vascular dissection, reduced blood loss, and improved surgical safety. This protocol highlights the feasibility and advantages of combining systemic therapy, interventional procedures, and advanced robotic techniques to expand surgical eligibility, optimize perioperative outcomes, and achieve favorable oncological control in patients with complex or advanced HCC.

Introduction

Hepatocellular carcinoma (HCC) is one of the malignant tumors that severely impacts the health of Chinese citizens. According to the latest data from the National Cancer Center, the incidence of HCC ranks fourth among newly diagnosed cancers in China, while its annual mortality and mortality rate both rank second. Approximately 64% of Chinese HCC patients are already in the intermediate or advanced stages at initial diagnosis¹. Conversion therapy refers to interventions that enable initially unresectable HCC patients to become eligible for surgical resection. These interventions primarily include functional future liver remnant (FLR) conversion and oncological conversion². Functional FLR conversion aims to rapidly increase the functional FLR in patients with insufficient FLR, employing methods such as associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)³ and portal vein embolization (PVE)⁴. Oncological conversion involves systemic therapies combining targeted and immunotherapy⁵, transarterial interventional treatments², and radiotherapy⁶. Previous studies have confirmed that portal vein ligation can effectively induce hypertrophy of the required left liver lobe and is used to treat liver metastases and primary tumors⁷. Robot-assisted surgery is an indispensable part of modern liver surgery. Meta-analyses show that robotic liver resection (RLR) is associated with superior prognosis and perioperative outcomes compared with laparoscopic liver resection (LLR) in patients with HCC, and RLR exhibits better perioperative outcomes than open liver resection (OLR)⁸.

This protocol presents a case of massive HCC treated with combined targeted immunotherapy and vascular interventional oncological conversion, followed by laparoscopic right portal vein ligation for surgical conversion, and ultimately Da Vinci robot-assisted anterior approach anatomical right hepatectomy. The process of post-conversion hepatectomy for HCC is outlined.

The inclusion criteria is: Age <65 years old, normal liver function (Child-Pugh Class A, Indocyanine Green Retention Rate at 15 min (ICG-R15) <20%), insufficient FLR (normal liver, Standardized Residual Liver Volume Ratio (SRLVR) <30%; Accompanying chronic liver diseases and liver function impairment, SRLVR <40%), good general condition, good surgical torelance. The exclusion criteria include: Child-Pugh Class C; ICG-R15 >20%; Intrahepatic or distant metastasis.

Protocol

The research was performed in compliance with the institutional guidelines of the human research ethics committee at Shenzhen People's Hospital. The reagents and the equipment used are listed in the Table of Materials.

1. Confirming the treatment indication

1. Identify the solid space-occupying lesion in the right lobe of the liver.
   NOTE: In this case, the basic clinical characteristics include: 61-year-old male; Chief complaint: Incidental finding of a liver mass on abdominal imaging 1 week ago; Past Medical history: HBV infection for 10 years, maintained on entecavir antiviral therapy; BMI: 28.07kg/m²; PE: No positive sign.
   1. Perform CT to confirm the diagnosis and assess resectability.
      NOTE: For the present study, SLV is 1267.2mL, and the actual liver volume is 2450.58 mL. In the case of right hepatectomy, the FLR is 445.25 mL, and SRLVR is 35.1%. The ICG-R15 is 4.8% (Table 1). The resectable operation meets the criteria of ICG-R15 value <10% and SRLVR ≥40%, according to the Expert Consensus on Precise Hepatectomy by the Chinese Society of Research Hospitals for Hepatobiliary and Pancreatic Surgery.
2. Make clinical decisions and initiate Oncological Conversion Therapy based on the Multidisciplinary team (MDT).
   NOTE: In this case, since the SRLVR didn’t reach 40%, a conversion therapy was applied before radical surgery. It combined targeted immunotherapy and vascular interventional oncological conversion, followed by laparoscopic right portal vein ligation for surgical conversion, and ultimately, the robot-assisted anterior approach anatomical right hepatectomy was performed.

2. Oncologically conversion therapy

1. Apply Drug-eluting Transarterial Chemoembolisation (D-TACE) therapy after diagnosis.
2. Three days later, apply targeted therapy (Lenvatinib, 8 mg qd) and immunotherapy (Tislelizumab, 300 mg, q3w).
3. One month later, reassess the conversion efficacy.
   NOTE: In this case, the new result showed that ICG-R15 is 5.5% and SRLVR is 0.376.

3. First-stage operation: Laparoscopic Right Portal Vein Ligation (L-PVL)

1. Reassess the resectability of the tumor and FLR measurement before surgery (Table 1).
2. Suspend targeted therapy for 1 week and immunotherapy 2 weeks before the surgical operation.
3. Place the patient in the supine position. Administer general anesthesia according to standard protocols.
4. Insert trocars at the inferior umbilical margin, subxiphoid region, and 2 cm below the right midclavicular line costal margin, and explore the abdominal cavity.
5. Perform cholecystectomy.
   1. Dissect the cystic triangle, then divide the cystic duct and artery.
   2. Mobilize the gallbladder via antegrade dissection.
6. Perform Laparoscopic Right Portal Vein Ligation (L-PVL).
   1. Dissect the right hepatic pedicle (RHP) intrafascially.
   2. Isolate the right hepatic artery (RHA).
   3. Dissect the right portal vein (RPV). Apply vascular clips to obstruct the RPV. Confirm the ischemic line between the left and right liver.
   4. Inject ICG solution (1:1000, 3 mL) intravenously, and confirm left liver fluorescence after 5 min.
   5. Remove the clips, ligate the RPV with absorbable clips.
7. Extract the gallbladder, remove the trocars, and close the abdominal incision.

4. Second-stage operation: Robotic-Assisted Right Hepatectomy (RARH)

1. Ten to fourteen days later, reassess SLRVR and ICG-R15 (Figure 1A, Figure 2, and Table 1).
2. Position the patient in a supine and split-leg position, with the right flank elevated 45° and the right arm suspended.
3. Administer general anesthesia.
4. Place four robotic ports at the right umbilical margin (2 cm), right anterior axillary line (5 cm below the costal margin), left rectus border (3 cm above the umbilicus level), and left anterior axillary line (4 cm below the costal margin), respectively. Place an assistant port at the right midclavicular line (3 cm above the umbilicus level) (Figure 3B).
5. Perform a thorough exploration of the abdominal cavity.
6. Perform Da Vinci Robot-Assisted Laparoscopic Anterior Approach Anatomical Hepatectomy.
   1. Re-dissect the right hepatic artery and portal vein and ligate them to confirm the ischemic line (Figure 4A).
   2. Mobilize the liver. Divide the round ligament, the falciform ligament, and the partial coronary ligament. Separate the adhesion caused by the first operation at the hepatic hilum. Dissect the short hepatic veins draining the right liver (Figure 4B).
   3. Perform Intraoperative Ultrasound Assessment: Identify tumor boundaries, hepatic veins, and port vein branches.
   4. Intravenously inject ICG solution (1:1000, 3 mL) to reconfirm left liver fluorescence (Figure 1C).
   5. Transect the Liver parenchyma.
      1. Begin parenchymal division along the ischemic line, then proceed along the plane of the middle hepatic vein (MHV). Expose and divide the V5 and V8 hepatic vein tributaries.
         NOTE: The parenchyma was further dissected along the MHV to the cranial aspect of the right pedicle.
      2. Divide the caudate lobe anterior to the retrohepatic inferior vena cava (IVC). Divide the RHP with a stapler, ensuring no injury to the left pedicle.
      3. Divide the parenchyma between the MHV and IVC toward the second hepatic hilum. Isolate the root of RHV and circumferentially divide it with a stapler after transecting the right triangular ligament.
   6. Extract the right liver. Remove robotic arms and perform a midline laparotomy.
      NOTE: The specimen was extracted intact via the laparotomy.
   7. Confirm hemostasis via laparoscopy and close the incisions.
   8. One month postoperatively, perform transvascular interventional therapy once more, and resume the combined Immune-Targeted therapy for six months (Figure 2).

Results

In the context of the described technique, the representative results demonstrate that robotic hepatectomy, when combined with conversion therapy and L-PVL, achieves both functional liver regeneration and oncologic downstaging. As shown in Table 1, baseline liver volumetric parameters prior to any intervention included an SRLVR of 35.1% and a total liver volume (TLV) of 2450.58 mL. After conversion therapy (D-TACE, targeted therapy, immunotherapy), ICG-R15 rose slightly to 5.5% while SRLVR reached 37.6%,...

Discussion

A critical step in this protocol is the integration of oncological and functional conversion strategies prior to surgical resection. The timing and sequence of targeted therapy, immunotherapy, and interventional treatment are essential to downstage the tumor while maintaining liver function⁹. Similarly, laparoscopic portal vein ligation plays a decisive role in stimulating hypertrophy of the FLR, and accurate reassessment of liver volume is required before proceeding to hepatectomy

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Absorbable hemostatic dressing	Ethicon	2082	Surgical  hemostasis
Bipolar coagulating.	YOUSHI	101.017A.3	Electrosurgical hemostasis
Cadiere forceps	INTUITIVE	470049	Disposable Non Destructive Grasping Forceps in Da Vinci Xi
Continuous Firing Clip Applier and Stapling Clips	Johnson &Johnson	LT200	Vessel Ligation
Disposable Urethral Catheter Tray	STAR	20162141618	Pringle's maneuvor
Drainage tube	BAINUS MEDICAL	SY-Fr22-C	Abdominal fluid drainage
ENDOPATH XCEL Trocars	Johnson &Johnson	2CB12LT/2CB5LT	Laparoscopic port access
Endoscopic linear cutting stapler cartridges	Ethicon	GST60W	Vascular stapler cartridge
Endoscopic linear cutting stapler cartridges	Ethicon	GCFLGB	Hepatic pedicle stapler cartridge
Endoscopic retrieval bag	HUANKANG	20162220561	Specimen retrieval
Fenstrated Bipolar Forceps	INTUITIVE	471205	Disposable Bipolar coagulating in Da Vinci Xi
Harmonic ACE curved shears	INTUITIVE	480275	Disposable Ultrasonic shears in Da Vinci Xi
Indocyanine Green for Injection	Yi Chuang	H20055881	intraoperative fluorescence imaging
Intraoperative ultrasound	HITACHI	ALOKA-UST5418	Vessel/tumor localization
Laparoscopic suction irrigation	KANGJI	101.149	Fluid evacuation/blunt dissection
Ligating Clip	Wedu MedicaL	WD-JZ 3S	Vessel ligation
PDS synthetic absorbable surgical sutures	Johnson &Johnson	W9109H	Bile duct closure
Peng's multiple operative dissector, PMOD	SHUYOU SURGICAL	SY-IIIA (N)-1	Tissue dissection/hemostasis
Powered Plus Articulating Endocscopic Linear Cutter	Ethicon	PSEE60A	Laparoscopic stapler
Prolene Polypropylene non-absorbable sutures	Johnson &Johnson	W8761/W8710/W8706	Vessel closure
Retrieval basket	Cook Medical	NTSE-045065-UDH	Bile duct stone extraction
Surgical Endoscopic Instrument Control System	INTUITIVE	Da Vinci Xi (SK3164)	Surgical control system