Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Hypertrophy

Neoplasm Metastasis

Liver Neoplasms

Neoplasms, Second Primary

Neoplastic Processes

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Central Nervous System Depressants

All Drugs and Chemicals

Analgesics

Antipyretics

Hematinics

Antineoplastic Agents

Anesthetics

Liver Extracts

Ethiodized Oil

Portal Vein Embolisation Patients in this group will undergo embolisation of branch of portal vein (interventional radiological procedure)

Liver Venous Deprivation Patients in this group will undergo simultaneous embolization of branch of the portal vein and one or two hepatic veins (interventional radiological procedure)

Associating Liver Partition and Portal vein Ligation for Staged hepatectomy: Patients in this group will undergo surgical ligation of portal vein branch with partial liver transection (surgical procedure)

The procedure is performed under general anesthesia. Ultrasound-guided percutaneous, transhepatic puncture of the branch of the portal vein is performed and a vascular sheath is inserted on the guidewire. A system of catheters and guidewires is inserted through the sheath. Embolization is performed using a homogeneous mixture of Glubran 2 glue and Lipiodol (volume ratio 1:8-1:9). After filling the entire volume of the branch of the portal vein, all catheters, guidewires and the vascular sheaths are removed. A dressing is left over the access site and removed the next day. After treatment the patient is given analgesics and antipyretics if necessary.

The procedure is performed under general anesthesia. Ultrasound-guided percutaneous, transhepatic puncture of the branch of the portal vein is performed and a vascular sheath is inserted on the guidewire. A system of catheters and guidewires is inserted through the sheath. A similar puncture of the hepatic vein or veins is then performed; sometimes with access via the internal jugular vein. Embolization of the portal branch is performed using a homogeneous mixture of Glubran 2 glue and Lipiodol (volume ratio 1:8-1:9). Embolization of the right hepatic vein or veins begins with the insertion of a vascular plug (Amplatzer) approx. 2 cm from the confluence of the vein(s). The remaining part of the hepatic vein(s) is then filled with a homogeneous mixture of histacryl glue and Lipiodol (volume ratio 1:1).

A dressing is left over the access site and removed the next day; patient is given analgesics and antipyretics if necessary.

The ALPPS procedure will be performed in the operating theatre, under general anesthesia, preferably using a minimally invasive (laparoscopic) technique.

The procedure consists of surgical ligation or clipping of the branch of the portal vein with a vascular clip and in partial transection of the parenchyma at the plane of the future resection planned in the second stage (partial transection, approx. 75% of the transection plane).

ALPPS

Karolina Grąt, PhD

Krzysztof Korzeniowski, MD

Krzysztof Lamparski, MD

Konrad Pełka, MD

Jolanta Kunikowska, Prof.

Łukasz Masior, PhD

Michał Grąt, Prof.

Liver resection is the treatment of choice in patients with malignant liver lesions. Unfortunately, the surgery is not always an option, as in same patients the future remnant liver (FRL) is too small to supply all the functions. Therefore, some additional methods have been proposed to increase the size of the FRL.

The aim of this study is to compare the efficacy and safety of three methods of increasing the future remnant liver - Portal Vein Embolization (PVE) - embolization of one of the portal branches; Liver Vein Deprivation (LVD) - embolization both of the portal branch as well as the hepatic vein; and partial ALPPS (Associating Liver Partition and Portal vein Ligation for Staged hepatectomy) - ligation of portal vein branch with partial liver transection.

The efficacy of those three methods will be assessed both by analyzing the volumetric increase (by computer tomography scans) and by functional increase (by 99mTc-mebrofenin scintigraphy). Functional assessment of the liver hypertrophy seems to be of crucial importance, as some of the previous studies suggest that there might be a significant discrepancy in the increase of size comparing to the increase of function.

This is a prospective, interventional randomized study. The study group (154 patients) will consist of patients being considered as candidates for major hepatic resection, after inducing hypertrophy of the future remnant liver.

The primary study hypothesis is greater efficacy of ALPPS in preparing patients for large hepatic resection by inducing hypertrophy of the future remnant liver, as compared both to PVE and LVD.

In case of unsuccessful induction of hypertrophy by the embolization techniques, patients may be qualified to rescue ALPPS procedure.

Primary end-point:

Percentage of patients with successful resection (patients, who gained sufficient increase of the FRL to proceed to the liver resection) with no post-surgical 90-day mortality.

Secondary end-points:

1. the rate and degree of volume increase in different groups
2. the rate and degree of functional increase in different groups
3. CCI index and complication rate \>=3 degree according to the Clavien-Dindo classification after the first stage of treatment
4. CCI index and complication rate \>=3 degree according to the Clavien-Dindo classification after the second stage of treatment
5. overall duration of hospital stay

Patient will be randomly assigned to the three study groups. All patients will undergo an abdominal contrast enhanced computed tomography and 99mTc-mebrofenin scintigraphy prior to the first stage of treatment. During the first stage of treatment, patients will undergo, according to their group:

1. Embolization of portal vein branch (PVE, portal vein embolization)
2. Embolization of both portal vein branch and hepatic vein (LVD, liver venous deprivation)
3. Partial ALPPS (Associating Liver Partition and Portal vein Ligation for Staged hepatectomy) - ligation of portal vein branch with partial liver transection, preferentially by laparoscopic technique Computed tomography scans and scintigraphy will be repeated at day 7, 14 and 21 after the first stage of treatment. The second stage of treatment, the liver resection, will be performed after achievement of sufficient mebrofenin clearance rate (\>=2,69%/min/m2). In case of failure to reach the desired clearance rate, the measurements will be continued every 7 days up to day 42. In case of uncertainty and discrepancy between the volumetric assessment in the computed tomography scan and the mebrofenin scintigraphy, it will be allowed to proceed to stage two (partial hepatectomy) after joint consultation of at least 3 hepatobiliary surgeons, 1 radiologist and 1 nuclear medicine specialist. Routine blood tests will be performed according to the standard procedure in the Department, depending on the patient clinical status. An additional blood sample will be collected from patients (after receiving and additional informed consent from the patient) and will be stored in the biobank.

All patients will be monitored for surgical and 90-day complications. The volume increase after first stage of treatment, the functional increase after first stage of treatment, percentage of patients successfully proceeding to the second stage of treatment and complication rate will be calculated.

The percentage of patients with complications \>= 3 degree in Clavien-Dindo classification and CCI index for each patient will be calculated.

Furthermore, the blood test results will be assessed to search for associations with patients' outcomes. Any possible differences in terms of baseline patients characteristics between groups will be addressed.

Statistical analysis will be performed using U Mann-Whitney test, exact Fisher's test, logistic regression, general linear models, Kaplan-Meier method and log-rank test. All three groups will be assessed in terms of occurrence of primary and secondary end-points.

Liver resection is the treatment of choice in patients with malignant liver lesions. Unfortunately, the surgery is not always an option, as in same patients the future remnant liver (FRL) is too small to supply all the functions. Therefore, some additional methods have been proposed to increase the size of the FRL. Among the most widely used ones are: Portal Vein Embolization (PVE) - embolization of one of the portal branches; Liver Vein Deprivation (LVD) - embolization both of the portal branch as well as the hepatic vein and partial ALPPS (Associating Liver Partition and Portal vein Ligation for Staged hepatectomy) - ligation of portal vein branch with partial liver transection.

However, for the time being none of this methods has been proven to provide superior results in comparison to other, and all of them are widely used in different centers. Most of the previously published papers were retrospective in nature and as for now there was no randomized trial conducted to compare all three of them. What is more, most of the previously published papers focused on the volumetric increase, based solely on the computed tomography analysis. The most important is however the functional increase, not the increase in size. The functional increase can be assessed in the 99mTc-mebrofenin scintigraphy, which enables to assess the liver function in a chosen part of the liver.

Some of the previously published papers indicate that there might be a significant discrepancy in the increase of size comparing to the increase of function, which is critically important in the clinical practice.

The aim of this study is to compare the efficacy and safety of three methods of increasing the future remnant liver - PVE, LVD and ALPPS in patients in whom liver resection is considered.

METHODS:

This is a prospective, interventional randomized study. Patients will be randomly assigned to three groups in a 12:71:71 ratio: PVE, LVD and ALPPS groups, respectively.

Randomization will be performed directly after recruitment. The study group will consist of patients being considered as candidates for major hepatic resection, after inducing hypertrophy of the future remnant liver.

Inclusion criteria:

1. age \>= 18 years
2. patients qualified for liver resection
3. future remnant liver \<30% of standard liver volume
4. written informed consent

Exclusion criteria:

1. liver cirrhosis
2. pregnancy
3. poor general health status or comorbidities excluding general anesthesia or hepatic resection
4. contraindications to iodine contrast agents

Hypothesis and study group:

The primary study hypothesis is greater efficacy of ALPPS in preparing patients for large hepatic resection by inducing hypertrophy of the future remnant liver, as compared both to PVE and LVD. Basing on previously published studies following success rates (as percentage of patients completing the second stage of treatment, the hepatic resection) have been assumed: 57% for PVE, 73% for LVD and 91% for ALPPS.

Assuming the thresholds for type I and type II error of 5% and 20% respectively, the calculated size of the study group should be 154 patients, more specifically 12 in the PVE group, 71 in the LVD group and 71 in the ALPPS group.

Special surveillance will be applied to patients in the PVE group and in case of low efficacy (\<50%) in the first 6 patients, randomization to this group will be withheld.

Moreover, in case of unsuccessful induction of hypertrophy by the embolization techniques, patients may be qualified to rescue ALPPS procedure.

Primary end-point:

Percentage of patients with successful resection (patients, who gained sufficient increase of the FRL to proceed to the liver resection) with no post-surgical 90-day mortality.

Secondary end-points:

1. the rate and degree of volume increase in different groups
2. the rate and degree of functional increase in different groups
3. CCI index and complication rate \>=3 degree according to the Clavien-Dindo classification after the first stage of treatment
4. CCI index and complication rate \>=3 degree according to the Clavien-Dindo classification after the second stage of treatment
5. overall duration of hospital stay

Patient will be randomly assigned to the three study groups. All patients will undergo an abdominal contrast enhanced computed tomography and 99mTc-mebrofenin scintigraphy prior to the first stage of treatment. During the first stage of treatment, patients will undergo, according to their group:

1. Embolization of portal vein branch (PVE, portal vein embolization)
2. Embolization of both portal vein branch and hepatic vein (LVD, liver venous deprivation)
3. Partial ALPPS (Associating Liver Partition and Portal vein Ligation for Staged hepatectomy) - ligation of portal vein branch with partial liver transection, preferentially by laparoscopic technique

Computed tomography scans and scintigraphy will be repeated at day 7, 14 and 21 after the first stage of treatment. The second stage of treatment, the liver resection, will be performed after achievement of sufficient mebrofenin clearance rate (\>=2,69%/min/m2). In case of failure to reach the desired clearance rate, the measurements will be continued every 7 days up to date 42. In case of uncertainty and discrepancy between the volumetric assessment in the computed tomography scan and the mebrofenin scintigraphy, it will be allowed to proceed to stage two (partial hepatectomy) after joint consultation of at least 3 hepatobiliary surgeons, 1 radiologist and 1 nuclear medicine specialist.

Routine blood tests such as morphology, serum bilirubin and creatinine concentration, transaminase activity, gamma-glutamyltranspeptidase or INR will be performed according to the standard procedure in the Department of Liver, Transplant and General Surgery, namely at day 0 and 1 and every 2-3 days or more frequent in the next days, depending on the patient clinical status. An additional blood sample will be collected from patients (after receiving and additional informed consent from the patient) and will be stored in the biobank (according to "Quality Standards for Polish Biobanks" v.2.00). The samples will be stored at the LBBK biobank at Medical University of Warsaw.

All patients will be monitored for surgical and 90-day complications. The volume increase after first stage of treatment, the functional increase after first stage of treatment, percentage of patients successfully proceeding to the second stage of treatment and complication rate will be calculated.

The percentage of patients with complications \>= 3 degree in Clavien-Dindo classification and CCI index for each patient will be calculated.

Furthermore, the blood test results will be assessed to search for associations with patients' outcomes. Any possible differences in terms of baseline patients characteristics between groups will be addressed.

Statistical analysis will be performed using U Mann-Whitney test, exact Fisher's test, logistic regression, general linear models, Kaplan-Meier method and log-rank test. All three groups will be assessed in terms of occurrence of primary and secondary end-points.

The study is designed to last 6 years, from 1st June 2023 to 31st May 2029. The firsts four months are planned for the initiation of the study, the following months for recruitment, intervention and observation and the last two months for analyzing the results.

After discharge from the hospital, 2 control visit will be scheduled for each patient, 30 and 90 days after the liver resection. Further treatment will be continued in local oncological centers.

This is a prospective, interventional randomized study. Patients will be randomly assigned to three groups in a 12:71:71 ratio: PVE, LVD and ALPPS groups, respectively.

Randomization will be performed directly after recruitment.

The Investigator performing statistical analysis will blinded to which study group the patient was assigned to.

The patient will not be aware which of the two radiological methods (PVE or LVD) was performed.

TANGO-LIVER Three Arm Nuclear Growth Observation in Liver Surgery

Comparison of Three Methods of Inducing Liver Hypertrophy Before Resection - a Randomized Controlled Trial

Individual participant data (IPD) will be shared by the principal Investigator upon reasonable request.

Percentage of patients with successful resection (patients, who gained sufficient increase of the FRL to proceed to the liver resection) with no post-surgical 90-day mortality.

The rate of future liver remnant volume change (cm3/day) in different groups, assessed on computed tomography scans

The degree (%) of volume increase in different groups, assessed on computed tomography scans

The rate of functional increase (%/min/m2/day) in different groups, assessed on 99mTc-mebrofenin scintigraphy

The degree (%) of functional increase in different groups, assessed on 99mTc-mebrofenin scintigraphy

Development of any complication \>=3 degree according to the Clavien-Dindo classification after the first stage of treatment (censored at completion of the second stage or 90days)

Comprehensive Complication Index after the first stage of treatment (censored at completion of the second stage or 90days)

Development of any complication \>=3 degree according to the Clavien-Dindo classification after the second stage of treatment

Comprehensive Complication Index after the second stage of treatment

Medical Research Agency, Poland

Medical University of Warsaw

Infections

Carcinoma

Carcinoma, Hepatocellular

Hepatitis A

Hepatitis

Hepatitis B

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Hepatitis, Viral, Human

Virus Diseases

Communicable Diseases

Adenocarcinoma

Blood-Borne Infections

Hepadnaviridae Infections

DNA Virus Infections

Chlorotrianisene

TACE

Feng Shen, MD

A primary hepatocellular carcinoma (HCC) is generally regarded as unresectable if the future liver remnant (FLR)≤40％ of total liver volume in patient with underlying liver disease, such as hepatitis B. In China, TACE is the most common treatment for these unresectable HCC. Recently, PVE has been employed to enlarge the FLR of the patients so as to increase the resectability and surgical safety of major hepatectomies. In order to shut the arterio-portal shunt in the liver and control the tumor progress TACE sometimes is performed before PVE. In this study we design a randomized control trial to investigate the efficacy of sequential TACE and PVE on increasing the resectability of hepatitis B related HCC compared with TACE alone.

In China, primary hepatocellular carcinoma (HCC) is mostly a hepatitis B related disease. The liver function of these patients has been damaged, which often limit the execution of major hepatectomy. A tumor is generally regarded as unresectable if the future liver remnant (FLR)≤40％ of total liver volume in patient with underlying liver disease. In China, TACE is the most common treatment for these unresectable HCC. TACE can slow down tumor progress but has little effect on enlarging FLR. Recently, PVE has been employed to enlarge the FLR of the patients so as to increase the resectability and surgical safety of major hepatectomies. But the intrahepatic arterioportal shunt and the tumor progress has decreased the effect of PVE. In order to shut the arterioportal shunt and control the tumor progress TACE sometimes is performed before PVE. In this study we design a randomized control trial to investigate the efficacy of sequential TACE and PVE on increasing the resectability of hepatitis B related HCC compared with TACE alone.

Efficacy of Sequential TACE and PVE on the Resectability of Hepatitis B Related HCC

Efficacy of Sequential Arterial and Portal Vein Embolizations on Increasing the Resectability of Hepatitis B Related Primary Hepatocellular Carcinoma

Eastern Hepatobiliary Surgery Hospital

vice president of the Eastern Hepatobiliary Surgery Hospotal

Liver Failure

Hepatic Insufficiency

Experimental arm with PVE combined with RFA to induce accelerated liver hypertrophy.

In a previous experimental study on rats, the investigators have shown that PVE combined with radiofrequency ablation (RFA), hereafter called Associated Radiofrequency Ablation and Portal Vein Ligation for Staged Hepatectomy (ARAPS), can induce accelerated growth of the FLR

ARAPS

Anders Knudsen, PhD

Anders Riegels Knudsen, MD, PhD

Liver resection is the golden standard in the treatment of hepatic malignancies. The size and function of the remnant liver is a major concern. If the future liver remnant (FLR) is below 30 % of the initial liver volume, the risk of post hepatectomy liver insufficiency rises. Several techniques have been developed to increase the size of FLR before liver resection. In this study a new technique ARAPS (portal vein embolization with radio frequency ablation) is compared to portal vein embolization alone for accelerated liver growth in the FLR. This is done in a randomized controlled trial.

Curative intent liver resection is the gold standard for treatment of hepatic malignancies, including metastases from colorectal cancer (CRLM), but liver resection can only be performed if future liver remnant (FLR) volume is at least 25 %. Unfortunately, many cancer patients have multiple liver lesions at the time of diagnosis, rendering radical resection impossible due to a marginal FLR, thereby increasing the risk of posthepatectomy liver failure and subsequent death.

Several techniques have been designed to increase the size of the FLR, allowing more patients to undergo surgery. These techniques include portal vein embolization (PVE), portal vein ligation (PVL), two-stage partial hepatectomy, and the associating liver partition with PVL for staged hepatectomy (ALPPS). The ALPPS procedure seems to be superior to the other techniques for achieving increased size and accelerated growth of the FLR. Especially the kinetic growth rate (KGR) is superior to what has been previously described. The major drawback of ALPPS is, however, that the patient is subjected to two open procedures that are associated with high morbidity and mortality.

In a previous experimental study on rats, The investigators have shown that PVE combined with radiofrequency ablation (RFA), hereafter called Associated Radiofrequency Ablation and Portal Vein Ligation for Staged Hepatectomy (ARAPS), can induce accelerated growth of the FLR as potent as that seen after ALPPS. In humans, the ARAPS procedure can (the first step), in contrast to the two-stage ALPPS procedure, be performed percutaneously, and the investigators expect this to reduce the high morbidity and mortality associated with the ALPPS. In the present study, the investigators want to examine the effect of ARAPS compared with PVE alone on liver regeneration and function of the FLR.

Study rationale In order to allow more patients to undergo radical surgery for CRLM, implementation of new methods to enhance liver regeneration is vital.

Aim In the present study, the investigators test the hypothesis that the ARAPS approach is superior to PVE alone in achieving growth of the FLR in patients with CRLM.

Hypothesis the investigators expect to see higher growth of the FLR in the ARAPS arm compared with the PVE arm one week after intervention.

Study design The study is an investigator-initiated prospective, randomized study. Any patient eligible for this study will be offered enrollment. Patients enrolled in the study will be randomized (1:1) to either the intervention (ARAPS) or control (PVE) as

Recruitment of study subjects Potential study subjects will be given the option to participate after the study is presented during their first visit to the outpatient clinic. The visit will take place in a consultation room, where the surgeon will provide verbal and written information regarding the study prior to enrollment. Patients are allowed a companion for this interview. At least 24 hours are given before an informed consent is obtained. Patient consent can be withdrawn at any time, and all data collected for the project, will be destroyed without any consequence for their subsequent treatment.

Data analysis plan Power calculations Total liver volume is \~1500 mL. Assuming that FLR is 20 % of the total liver volume, FLR comprises 300 mL. Based on previous literature, the investigators expect a growth in the FLR of 10 % (30 mL, KGR ≈ 4.3 ml/day) in the PVE arm and 50 % (150 mL, KGR ≈ 21.4 ml/day) in the ARAPS arm. At alpha=0.05, power 80 %, and a standard deviation of 200 mL, 12 patients in each arm is needed to show a statistically significant difference between the two interventions. In order to be able to deal with potential dropout of up to 20%, the investigators aim to include 15 patients in each arm; 30 patients in total.

Statistical methods Liver regeneration will be measured as the increase in anatomical (CT) and functional (PET) liver volume seven and thirteen days following intervention (quantified in milliliters). Further, the KGR will be calculated as volume increase per day (ml/day). Differences in the two arms will be expressed as means or medians with associated standard deviations or interquartile ranges (depending on the distribution of data). Differences between the two arms will be analyzed using a t-test or non-parametric test where appropriate. P\<0.05 will be considered statistically significant.

Data on patients Data on age, diagnosis, comorbidity, and tumor imaging material will be passed on from the medical records in order to assess if the patient is eligible for inclusion in the study. Information on sex, tumor size, tumor histology, number and size of metastases, medications, tobacco/alcohol exposure, and blood sample results will be retrieved on from the patient's medical records. Radiological, biochemical, and pathological reports will also be retrieved for use in the statistical analyses.

Study procedures Intervention Portal vein embolization The standard-of-care procedure, which would be offered to the patients regardless of this study, is PVE. PVE will be used to redirect portal flow to segments of the FLR: The portal venous system is assessed through the tumor-bearing part of the liver (i.e. the part that is later going to be removed). The portal vein is assessed under guidance by ultrasonography, and a catheter is then advanced under fluoroscopic guidance for subsequent embolization. In the case of a planned extended right hepatectomy, the portal branches to segment 4 should be selectively embolized. As embolization material plugs are preferred.

Radio-frequency ablation Under guidance of ultrasonography a single-electrode RFA-needle is placed in the part of the liver that has just been deportalized. The needle is placed in normal parenchyma, and within a period of ten minutes a necrosis of approx. 3 cm is created. In literature, complication rates following RFA treatment are low, making it a feasible procedure.

Both treatments will be performed in general anesthesia. Patients will be equipped with two bandages, which they have to wear until after the second PET/CT scan in order to blind them to the treatment received.

PET/CT scanning Accurate liver volume estimation relies on precise segmentation of the liver by multi-phase CT images according to the Couinaud classification. A thicknesses of ≥ 1 mm will be used to ensure accurate results. Total liver volume, volume of the deportalized part of the liver, and volume of the FLR will be estimated before and after intervention. Positron emission tomography (PET) with the radioactively labelled galactose analogue 2-\[18F\]fluoro-2-deoxy-D-galactose (FDGal) can be used to quantify whole-liver and regional hepatic metabolic function as well as to measure functional liver volume. The method is validated, simple and with insignificant day-to-day variation. The PET scan is performed after a 4h fast, but the patient is allowed to drink water. In Aarhus, the scanner is a 64-slice Siemens Biograph TruePoint PET/CT camera (Siemens AG, Erlangen, Germany). FDGal (100 MBq) is injected intravenously and a low-dose CT scan (50 effective mAs with CAREDose4D, 120 kV, pitch 0.8, slice thickness 5 mm) is performed for attenuation correction of the PET data and anatomical co-registration. A static PET scan of the mean tissue radioactivity concentration is performed from 10-20 minutes after tracer injection (12). The PET data are corrected for radioactive decay back to injection time and reconstructed with resolution modeling (4 iterations, 21 subsets and 2 mm (18F-FDGal) or 3 mm (18F-FDG) Gaussian filter) and 336 x 336 matrix. The standardized uptake value (SUV; unit-less) is calculated dividing tissue radioactivity concentration (kBq/mL tissue) with the ratio between injected dose (kBq) and body weight (mL tissue, assuming an average tissue density of 1 g/mL tissue). Whole-liver and regional hepatic FDGal-SUVs as well as the functional liver volume are estimated.

Potential benefits, risks, and side-effects Potential benefits As the potential impact of this study is extensive, including the possibility for more patients with CRLM to undergo curative-intent resection, it is our opinion that the benefits by far outweigh the few potential side effects. Only two PET and two CT scans with minimal radiation will be conducted. The blood samples drawn is part of the standard work-up procedure. No additional blood samples will be drawn on the basis of participation in this study.

Radiation dose from PET/CT scans Patients participating in the present study are not sustained to more radiation from imaging modalities than patients not participating. From the low-dose CT-scans, the patient receives an irradiation dose of up to 1 mSv. For FDGal the effective radiation dose is 0.032 mSv/MBq, the administration of 100 MBq FDGal thus gives a dose of 3.2 mSv. The total irradiation dose that each patient receives from two PET and two CT scans is approximately 8.4 mSv which equals three times the average yearly background dose in Denmark. This presents an estimated risk of 1:10.000 for cancer development due to participation in the study. These doses should be seen in connection with the potential benefit for the patient in participating in the study, as mentioned above.

Interventions Potential risks related to the RFA treatment are extremely sparse, and include bleeding, hepatic abscesses, hepatic infarcts, and bile duct injuries. PVE is a safe procedure that causes few adverse effects and can be performed in an outpatient setting. Most large series report 0 % procedure related mortality. Risks include bleeding, infection and displacement of the embolization material. Especially the latest is extremely rare.

Further patient treatment Following calculation of KGR and increase in FLR, patients are re-evaluated with regard to the timing of the second-stage partial hepatectomy. Some patients, especially in the PVE arm, are expected to need further liver hypertrophy before advancing to the partial hepatectomy. Further hypertrophy in a period of 1-3 weeks and a new CT evaluation might be necessary. In some patients, the hypertrophy might be impaired or absent. These patients will be evaluated with regard to other treatment options including salvage ALPPS, which have previously been used in patients with impaired hypertrophy following PVE. The resection rate in each arm will be reported as a secondary endpoint.

Time schedule This study will commence on 1. November 2019. Total study duration is expected to be 24 months for subject recruitment, and an additional six months for data analysis. The investigators expect to finalize the data analysis and present our findings during 2021. The project will begin at Aarhus University Hospital, while the other participating centers will be enrolled as appropriate.

Publications Both positive, negative, and inconclusive results will be published, and presented at scientific meetings. Results will be presented at international scientific congresses, and the investigators will aim for publications in high-impact journals with focus on oncology, radiology, and liver surgery. The study will be registered at www.clinicaltrials.gov.

Financial aspects This study is investigator-initiated, and supported by several Danish foundations (Vissing Fonden \[322.000 DKK (Danish Kroner)\], Knud \& Edith Eriksens Mindefond \[50.000 DKK\], Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis' Legat \[148.000 DKK\], Familien Erichsens Mindefond \[98.000 DKK\], Tømmerhandler Vilhelm Bangs Fond \[98.000 DKK\], Riisfort Fonden \[198.000 DKK\], and Neye Fonden \[98.000 DKK\]). Grants from these foundations are given to the principal investigator Prof. Frank Viborg Mortensen, and are administered by Aarhus University Hospital. The grants support running costs related to the project (CT/PET scans, blood samples, RFA needles, etc). The researchers participating in this study are independent from any financial interests. No fee will be paid to the study subjects. Salaries for the scientific staff are already financed by their respective employers.

Ethical considerations The study will be conducted according to the Helsinki Declaration, and following approval by the local ethics committee. The project is registered at the Danish Data Protection Agency in accordance with the Central Denmark Region common registration system. No patient will be included before these permissions are granted. All information involving patients will be handled according to national law on personal data information. The study is covered by the Danish Patient Compensation Authority.

ARAPS Study on Accelerated Liver Regeneration

ARAPS Study: Comparison of Portal Vein Embolization With Radiofrequency Ablation Versus Portal Vein Embolization Alone for Accelerated Liver Regeneration: A Randomized Controlled Trial

FDGal-PET to quantify whole-liver and FLR hepatic metabolic function. The standardized uptake value SUV (unit-less) is calculated for whole liver and FLR.

Number of patients resected following the interventions

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
TANGO-LIVER Three Arm Nuclear Growth Observation in Liver Surgery	NCT06050200	Liver Metastase... Liver Cancer Liver Neoplasms Liver Metastasi...	PVE LVD ALPPS	18 Years - 80 Years	Medical University of Warsaw
Efficacy of Sequential TACE and PVE on the Resectability of Hepatitis B Related HCC	NCT00834158	Hepatocellular ...	TACE PVE	20 Years - 65 Years	Eastern Hepatobiliary Surgery Hospital
ARAPS Study on Accelerated Liver Regeneration	NCT04107324	Liver Regenerat... Liver Cancer Liver Metastase... Liver Failure	ARAPS PVE	18 Years -	University of Aarhus

Spots Global Cancer Trial Database for pve

Every month we try and update this database with for pve cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pve

Every month we try and update this database with for pve cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pve cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.