Cancer, Liver Resection
Conditions
Keywords
Liver hypertrophy, Liver resection, Liver metastases, Portal vein ligation, Portal vein embolization, Radiofrequency splitting
Brief summary
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
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.
Interventions
PROCEDURERadiofrequency assisted liver partition with portal vein ligation (RALPP)
PROCEDUREPortal vein embolization (PVE)
Sponsors
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Liver Remnant Volume | 2 or 4 weeks post intervention (2 weeks post RALPP; 4 weeks post PVE) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Liver Function Tests | Postoperatively (daily until discharge; then at clinic appointments up to 18 months from randomization) | Blood tests |
| Number of Participants With Postoperative Complications (Dindo Clavien ≥Grade 3b) | Up to hospital discharge (estimated to be between 2 and 10 days) | As defined by Dindo Clavien classification of surgical complications (≥grade 3b). |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Portal Vein Embolization (PVE) Patients allocated to the PVE group received pre-intervention blood tests and a contrast enhanced CT scan of the abdomen. They then had their portal vein embolized radiologically once their pre-intervention investigations were completed and reviewed by the clinical team.
Post-intervention investigations (blood tests and CT scan) occurred 4 weeks after the completion of the PVE. At this point, they were listed to receive their definitive surgical hepatectomy.
Portal vein embolization (PVE) | 24 |
| Radiofrequency Assisted Liver Partition and Ligation (RALPPS) Patients allocated to the RALPP received pre-intervention blood tests and a contrast enhanced CT scan of the abdomen. They then had their right portal vein surgically ligated followed by radiofrequency ablation in situ splitting of the liver. Certain patients may also have had a tumourectomy or wedge resection of the left liver lobe if clinically indicated. The RALPPS procedure occurred once the patient's pre-intervention investigations were completed and reviewed by the clinical team.
Post-intervention investigations (blood tests and CT scan) occurred 2 weeks after the completion of the RALPPS. At that point, they were listed to receive their definitive surgical hepatectomy.
Radiofrequency assisted liver partition with portal vein ligation (RALPPS) | 26 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abandoned | 4 | 3 |
| Overall Study | Disease progression | 4 | 2 |
| Overall Study | Insufficient FLRV | 4 | 0 |
Baseline characteristics
| Characteristic | Portal Vein Embolization (PVE) | Radiofrequency Assisted Liver Partition and Ligation (RALPPS) | Total |
|---|---|---|---|
| Age, Continuous | 64.3 years STANDARD_DEVIATION 8.9 | 62.4 years STANDARD_DEVIATION 10.2 | 63.3 years STANDARD_DEVIATION 9.5 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Male | 12 Participants | 15 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 1 / 26 |
| other Total, other adverse events | 13 / 24 | 10 / 26 |
| serious Total, serious adverse events | 1 / 24 | 4 / 26 |
Outcome results
Primary
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.
Time frame: 2 or 4 weeks post intervention (2 weeks post RALPP; 4 weeks post PVE)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Portal Vein Embolization (PVE) | Changes in Liver Remnant Volume | 18.4 percentage change | Standard Deviation 9.8 |
| Radiofrequency Assisted Liver Partition and Ligation (RALPPS) | Changes in Liver Remnant Volume | 80.7 percentage change | Standard Deviation 13.7 |
Secondary
Number of Participants With Postoperative Complications (Dindo Clavien ≥Grade 3b)
As defined by Dindo Clavien classification of surgical complications (≥grade 3b).
Time frame: Up to hospital discharge (estimated to be between 2 and 10 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Portal Vein Embolization (PVE) | Number of Participants With Postoperative Complications (Dindo Clavien ≥Grade 3b) | 1 Participants |
| Radiofrequency Assisted Liver Partition and Ligation (RALPPS) | Number of Participants With Postoperative Complications (Dindo Clavien ≥Grade 3b) | 4 Participants |
Secondary
Postoperative Liver Function Tests
Blood tests
Time frame: Postoperatively (daily until discharge; then at clinic appointments up to 18 months from randomization)
Population: Data not collected