Regeneration of Liver: Portal Vein Embolization Versus Radiofrequency Assisted Ligation for Liver Hypertrophy (REBIRTH)

Study Overview
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Brief Summary
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The aim of this study is to compare two different techniques (portal vein embolization and radiofrequency assisted liver partition with portal vein ligation) for increasing liver volume prior to major liver resection.

Detailed Description
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Liver resection remains the gold standard treatment for patients with liver tumours providing them the only chance for long-term survival. In up to 45% of cases that are amenable to surgical resection, an extended hepatectomy (removal of part of the liver) is usually necessary to achieve a clear resection margin. However, there must be enough liver left behind to meet the demands of the body. Indeed, liver failure due to insufficient remnant liver volume is still the principal cause of postoperative death following a major liver resection. The liver receives its main blood supply from two vessels (the portal vein and the hepatic artery). In order to decrease the complications and improve the safety of extensive liver surgery in patients with insufficient future liver remnant volume (FLRV), pre-operative embolization (i.e. blockage) of part of the portal vein can be undertaken. This has the effect of inducing growth of the liver on the unaffected side. Thus, when the resection is carried out, an increased FLRV (of around 12%) reduces post-operative liver failure. An alternative technique is to perform surgical ligation of the portal vein along with splitting of the liver. The diseased portion of liver is left in the body for 7-10 days while the healthy side is induced to grow. During this time, the diseased portion continues to support the body's requirement for liver function and reduces the risk of liver failure. FLRV has been shown to increase by around 74% with this technique. However, there are more postoperative complications with the alternative technique such as bile leaks. The aim of this study is to test a new way of splitting the liver so that the increased FLRV can be achieved without the increased complication rate.

Official Title
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Liver Regeneration: a Single-centre, Prospective, Randomised Controlled Trial Comparing Radiofrequency Assisted Liver Partition With Portal Vein Ligation (RALPP) With Portal Vein Embolization (PVE) for Preoperative Induction of Liver Hypertrophy in Patients With Insufficient Future Liver Remnant Volume for Major Liver Resection.

Conditions
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Liver Resection, Cancer

Intervention / Treatment
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* Procedure: Radiofrequency assisted liver partition with portal vein ligation (RALPP)
* Procedure: Portal vein embolization (PVE)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Any patient requiring right or extended right hepatectomy with FLRV less than 25% on preoperative volumetric study WHO performance status 0, 1 or 2 Patient able to comply with protocol requirements and deemed fit for surgical resection Written informed consent Exclusion Criteria: Inability to give informed consent Pregnancy WHO status 3 or 4 New York Heart Association Classification Grade III or IV

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Portal vein embolization (PVE)<br>Patients allocated to the PVE group will receive pre-intervention blood tests and a contrast enhanced CT scan of the abdomen. They will then have their portal vein embolized radiologically once their pre-intervention investigations have been completed and reviewed by the clinical team. Post-intervention investigations (blood tests and CT scan) will take place 4 weeks after the completion of the PVE. At this point, they will be listed to receive their definitive surgical hepatectomy. | Procedure: Portal vein embolization (PVE)<br> <br> |
| Experimental: Radiofrequency assisted liver partition and ligation (RALPP)<br>Patients allocated to the RALPP group will receive pre-intervention blood tests and a contrast enhanced CT scan of the abdomen. They will then have their right portal vein surgically ligated followed by radiofrequency ablation in situ splitting of the liver. Certain patients may additionally have a tumourectomy or wedge resection of the left liver lobe if clinically indicated. The RALPP procedure will occur once the patient's pre-intervention investigations have been completed and reviewed by the clinical team. Post-intervention investigations (blood tests and CT scan) will take place 2 weeks after the completion of the RALPP. At this point, they will be listed to receive their definitive surgical hepatectomy. | Procedure: Radiofrequency assisted liver partition with portal vein ligation (RALPP)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Liver Remnant Volume | Percentage change in remnant liver volume following intervention. This will be measured by volumetric analysis of CT scan. Positive number represents increases and negative number represents decreases. | 2 or 4 weeks post intervention (2 weeks post RALPP; 4 weeks post PVE) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative Liver Function Tests | Blood tests | Postoperatively (daily until discharge; then at clinic appointments up to 18 months from randomization) | 
| Number of Participants With Postoperative Complications (Dindo Clavien ≥Grade 3b) | As defined by Dindo Clavien classification of surgical complications (≥grade 3b). | Up to hospital discharge (estimated to be between 2 and 10 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver hypertrophy, Liver resection, Liver metastases, Portal vein ligation, Portal vein embolization, Radiofrequency splitting