EX vivo liver resection and auto transplantation for a giant hepatocellular carcinoma: A case report

Abstract

Introduction and importance

The curative options for locally advanced hepatocellular carcinomas involving the vessels are very limited. Ex vivo liver resection and auto transplantation (ERAT) is a novel surgical method, which has been used in the management of such complex liver space occupying lesions, which are rendered conventionally unresectable. This technique involves a complete hepatectomy, extracorporeal hepatic resection on the backbench, and then reimplantation of the remnant hepatic parenchyma. George et al. (2019) [1] In literature, Ex vivo liver resection and auto transplantation (ERAT) has been utilized in the management of both benign and malignant liver lesions, including hepatocellular carcinoma (HCC), cholangiocarcinoma, hepatic metastases, hepatic alveolar echinococcosis, focal nodular hyperplasia and hemangioma. Zawistowski et al. (2020) [2].

Case presentation

We report this case of a 28 years old male with a giant hepatocellular carcinoma, that deemed unresectable as it was closely abutting all three hepatic veins. After appropriate preoperative surgical planning, he underwent ex vivo liver resection and autotransplantation (ERAT). Patient had gradual uneventful recovery and he was discharged home on 12th postoperative day.

Clinical discussion

A radical (R0) resection is the main goal of the ex vivo liver resection and autotransplantation (ERAT) procedure, which can be used for curative intent in patients with liver lesions that are conventionally inoperable. It allows for precise extracorporeal resection, maximizes the residual liver volume and increases the likelihood of obtaining negative margins. Furthermore, the bench surgery in ice bath makes it easier to reconstruct the vasculature without the pressure of time constraints in situ, unlike conventional surgery, which can take a long time when done in a bleeding operative field. Zawistowski et al. (2020) [2].

Conclusion

For patients with complex liver lesions believed to be incurable with conventional surgical methods, ex vivo liver resection and autotransplantation (ERAT) provides an alternative.

Highlights

• •Ex vivo liver resection and auto transplantation (ERAT) is a novel surgical method.
• •ERAT has been utilized in the management of both benign and malignant liver lesions.
• •Case report of a giant hepatocellular carcinoma, that deemed unresectable.

1. Introduction

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and the sixth most prevalent cancer worldwide. Being devoid of symptoms in the initial phases of the disease, over 70 % of HCC patients acquire a diagnosis at an advanced stage, especially those with non-cirrhotic related HCC. [3]

Pakistan, like other developing nations, lacks established local guidelines for the diagnosis of Hepatocellular carcinoma (HCC), and there is usually late presentation with advanced liver cirrhosis. A significant percentage of these patients merely receive supportive care, and less than 15 % are subject to any curative treatment. [4] Surgical resection is the primary therapeutic strategy for HCC in non-cirrhotic liver. However, standard surgical techniques may not be possible when extensive vascular involvement is present in locally advanced tumors. With the emergence of innovative surgical strategies over the past few decades, the management of advanced Hepatocellular carcinoma has undergone significant evolution. The majority of such patients require a major hepatic resection, which can be accomplished with sophisticated surgical procedures because the liver function is preserved and the perioperative mortality is lower than in patients with cirrhotic liver. [5]

Ex vivo liver resection and auto transplantation (ERAT) is a novel surgical method, which has been used in the management of complex liver space occupying lesions, which are rendered conventionally unresectable. This advanced surgical technique involves liver explant, extracorporeal liver resection, vascular reconstruction, organ perfusion and then re-implantation. [1] First described by Pichlmayr et al. in 1988 [6], only a few cases of Ex vivo liver resection and auto transplantation (ERAT) have been reported in the literature so far. [7]

In preoperative surgical planning and decision-making, the location and extent of the tumor as well as status of the future liver remnant (FLR) is taken in to account. For meticulously selected cases, ex vivo liver resection and autotransplantation (ERAT) may be an appropriate approach with enhanced accessibility to the tumor, minimal blood loss, and a higher possibility of curative tumor resection. [8]

Here, we present a case of ex vivo liver resection and autotransplantation for a giant hepatocellular carcinoma with major vascular involvement, the work has been reported in line with the SCARE criteria. [9]

2. Case report

A 28 years old male presented in outpatient clinic with complaints of abdominal pain for the last 8 months. His medical, surgical and family history was not significant and examination findings were unremarkable. Hepatitis B virus surface antigen and hepatitis C virus antibodies were found to be negative in laboratory tests. Liver function tests revealed slightly elevated GGT and Alkaline Phosphatase. Serum levels of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) were normal.

Triphasic contrast enhanced computed tomography scan demonstrated a large heterogeneously enhancing lesion involving segment 8 and 4 of the liver, close to the hepatic hilum. It measured approximately 12 × 10 × 8.4 cm (TR x AP x CC) and showed heterogeneous enhancement in all the phases with multiple areas of arterial enhancement and delayed washout. The lesion was closely abutting Left Hepatic Vein/Middle Hepatic Vein junction, Right Hepatic Vein and intrahepatic part of Inferior Vena Cava. (Fig. 1).

Fig. 1.

Lesion abutting Left Hepatic Vein/Middle Hepatic Vein junction and Right Hepatic Vein.

Anterolaterally the lesion was reaching up to the capsular margin of the liver. (Fig. 2) There was no evidence of any distant metastasis. These radiological findings were suggestive of hepatocellular carcinoma (HCC).

Fig. 2.

Lesion reaching up to the capsular margin of the liver.

Initially the patient was managed at another center and underwent 3 sessions of transarterial chemoembolization (TACE) with minimal response. Later on, he was referred to our liver transplant and hepatobiliary unit for further management.

The tumor was closely abutting the right hepatic vein and left hepatic vein/middle hepatic vein junction and it was very close to the porta hepatis, so conventional resection of the tumor was not possible. Considering the location of the tumor and abutment to the major hepatic vasculature, in vivo resection would have led to major perioperative hemorrhage.

After multidisciplinary team discussion, Ex vivo liver resection and auto transplantation (ERAT) was chosen as the safest oncological resection method, as tumor deemed unresectable with conventional resection techniques.

As a part of preoperative surgical planning patient underwent ultrasound guided liver parenchyma biopsy to assess the status of future liver remnant (FLR), which was unremarkable without any evidence of fibrosis.

Perioperative findings showed normal looking liver with a large tumor of around 12 × 8 × 9 cm in segment 4a and segment 8 of the liver. (Fig. 3) The tumor was encasing Middle Hepatic Vein and Left Hepatic Vein at intrahepatic portion near the hepatic hilum. In addition, Right Hepatic Vein was densely adherent to the tumor at its origin near Inferior Vena Cava.

Fig. 3.

Tumor involving segment 4a and segment 8 of the liver.

The left and right lobes of the liver were mobilized and filleted off the Inferior Vena Cava (IVC) by transfixing and dividing the caudate veins. The Right Hepatic Vein and Left Hepatic Vein/Middle Hepatic Vein common trunk were dissected. Using Cavitron Ultrasonic Surgical Aspirator (CUSA), in situ partial resection of the tumor was performed safely up to the level of hepatic veins. Hilar dissection was done and common bile duct was transected just above the cystic duct stump. As a part of surgical plan, gastroduodenal artery was ligated to obtain adequate length and caliber of common hepatic artery, which was then divided. Main portal vein was dissected, clamped and then divided. After IVC cross-clamping, auto graft was taken out for bench surgery in ice bath.

Tumor resection was resumed ex vivo and a portion of Left Hepatic Vein/Middle Hepatic Vein and Right Hepatic Vein was taken en bloc with the tumor at the point of dense adherence. (Fig. 4, Fig. 5) Reconstruction of all three veins was performed using Dacron vascular grafts (size 12 & 14 mm) and venoplasty was performed to obtain a single orifice.

Fig. 4.

HCC after complete excision.

Fig. 5.

Tumor abutment to Right Hepatic Vein (marked with black suture) and Middle Hepatic Vein/Left Hepatic Vein junction (marked with blue suture), enbloc excision performed ex vivo. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

After ex vivo tumor resection and venous reconstruction, auto graft was taken back for implantation. IVC cross clamping was done and reconstructed hepatic veins were sutured to the IVC, at the level of triangulation of all three hepatic veins. Then portal vein anastomosis was carried out. Hepatic veins' clamp was removed followed by the portal vein clamp and auto graft was re perfused. After that, hepatic artery was anatomosed. Intra-operative Doppler ultrasound showed homogenous liver parenchyma with good flow in hepatic artery and veins. In the end, biliary anastomosis was performed and auto transplantation was completed. The total duration of surgery was 11 h with cold ischemia time of 60 min and warm ischemia time of 52 min. During the procedure there was estimated blood loss of around 1500 ml and 3 pints PRBCs were transfused. Postoperative patient had gradual uneventful recovery and was discharged home on 12th postoperative day.

Histopathology showed moderately differentiated hepatocellular carcinoma measuring 12 × 7.5 × 5.5 cm involving segment 4a and segment 8. The tumor was 0.5 cm away from the posterior surface of liver, 0.9 cm from the resection margin, 0.2 cm from the Middle Hepatic Vein/Left Hepatic Vein junction, 0.8 cm away from the Right Hepatic Vein and 0.1 cm from the liver capsule. Total four lymph nodes were found and all were tumor free. Perineural and vascular invasion was present.

Patient has been on regular outpatient follow ups with serum Alpha Fetoprotein (AFP) levels and surveillance imaging, with no evidence of recurrence at 45 months post procedure.

3. Discussion

Ex vivo liver resection and auto transplantation (ERAT) is a novel surgical technique which has been used in the management of complex liver lesions involving major hepatic vasculature. It involves performing a complete hepatectomy, ex vivo liver resection with ice bath, and then re implanting the auto graft. [1]

Pichlmayr et al. first demonstrated this complex surgical method in 1988 [6], since then this technique has been utilized in the management of conventionally irresectable liver lesions. In literature, Ex vivo liver resection and auto transplantation (ERAT) has been a useful curative option for both benign and malignant liver lesions, including hepatocellular carcinoma, cholangiocarcinoma, hepatic metastases, hepatic alveolar echinococcosis, focal nodular hyperplasia and hemangioma. [1] A radical (R0) resection is the main goal of the ERAT procedure, which can be used for curative intent in patients with liver lesions that are conventionally inoperable. It allows for precise extracorporeal resection, maximizes the residual liver volume and increases the likelihood of obtaining negative margins. Furthermore, the bench surgery in ice bath makes it easier to reconstruct the vasculature without the pressure of time constraints in situ, unlike conventional surgery, which can take a long time when done in a bleeding operative field, unnecessarily prolonging the warm ischemia time. [2] In our case, intraoperative blood loss was estimated to be around 1500 ml, without any major transfusion protocols requirements.

However, Ex vivo liver resection and auto transplantation (ERAT) is a technically demanding surgery requiring a multidisciplinary approach along with meticulous intraoperative and postoperative care. Appropriate patient selection is required for satisfactory postoperative outcomes, thus it is important to take into account the patient's functional status, the type of disease, the quality of future liver remnant (FLR), and the reason of being conventionally irresectable. A liver biopsy can yield extra details that will help evaluate the auto graft's quality thus avoiding any major complication related to graft failure. To be considered suitable for Ex vivo liver resection and auto transplantation (ERAT), our patient had undergone ultrasound guided liver parenchyma biopsy to rule out any underlying liver fibrosis. H. Wen et al. also suggested that additional insights about graft's adequacy could be obtained by preoperative liver biopsy, thus avoiding postoperative graft complications. [10]

Careful patient selection enhances postoperative outcomes, as Ex vivo liver resection and auto transplantation (ERAT) carries a significant morbidity and mortality. [11] Bile leak, sepsis, pleural effusion, respiratory failure, major vasculature thrombosis and hepatic insufficiency have been reported as postoperative complications after ERAT, with hepatic insufficiency being the most severe complication. [10] None of these mentioned complications was observed in our reported case.

Considering artificial vascular reconstructions, prophylactic anticoagulation is recommended and even after discharge, postoperative surveillance for vascular complication is required. [12] In our case, oral anticoagulation in the form of warfarin sodium was continued for 2 years. Patients undergoing Ex vivo liver resection and auto transplantation (ERAT) must have meticulous follow-up imaging studies following the procedure to guarantee that vasculature patency is preserved.

4. Conclusion

Ex vivo liver resection and auto transplantation (ERAT) is technically challenging procedure with a significant mortality and morbidity, however with careful patient selection, preoperative preparation and meticulous follow up after the surgery it may offer reasonable outcomes for complex liver lesions believed to be incurable with conventional surgical methods.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Ethical approval

Ethical approval is not required for case reports as advised by Institutional Review Board.

Sources of funding

There are no funding sources.

Author contribution

Noureen Kanwal: Study design, data collection, data analysis and writing the paper.

Jahanzaib Haider: Study design, data collection, data analysis and writing the paper.

Siraj Haider: Study design, data collection, data analysis and writing the paper.

Mohammad Iqbal: Study design, data collection, data analysis and writing the paper.

Kiran Amir: Study design, data collection, data analysis and writing the paper.

Faisal Saud Dar: Study design, data collection, data analysis and writing the paper.

Guarantor

Noureen Kanwal.

Registration of research studies

Not applicable.

Conflict of interest statement

The authors declare that they have no competing interests.