Symptoms and General Pathology

All Conditions

Neoplasms

Hypertrophy

Neoplasm Metastasis

Neoplastic Processes

Pathological Conditions, Anatomical

Hematinics

All Drugs and Chemicals

Liver Extracts

Liver preparation before major hepatectomy : portal vein embolization (PVE) in patient with liver metastases from colo-rectal origin considered as resectable.

Liver preparation before major hepatectomy : Patients with the liver venous deprivation (LVD) technique that combines both PVE and hepatic vein embolization (HVE) during the same procedure.

Simultaneous portal and hepatic vein embolization versus Portal vein embolization, also called venous deprivation OR portal vein embolization.

Liver preparation before major hepatectomy

Boris GUIU, MD

Antoine Bouvier, MD

Bruno LAPUYADE

Romaric Loffroy, MD

Christian Sengel, MD

Agnès Rode, MD

Charles MASTIER, MD

Patrick Chevallier, MD

Anthony DOHAN

Guillaume Vesselle, MD

Oriana Ciacio, MD

Thierry BAERE

The hypothesis is that liver venous deprivation (LVD) could strongly improve hypertrophy of the future remnant liver (FRL) at 3 weeks, as compared to portal vein embolization (PVE) in patient with liver metastases from colo-rectal origin considered as resectable.

Portal vein embolization (PVE) has been widely used to generate hypertrophy of the nonembolized lobe in patients undergoing major hepatectomy in order to prevent small-for-size remnant liver resulting in post-operative liver insufficiency.

Although PVE is a safe and effective procedure, it does not always induce sufficient hypertrophy of the future remnant liver (FRL) even after a long time. In case of insufficient liver regeneration following PVE, some authors suggested to embolize hepatic vein(s) (Hwang, Ann Surg 2009).

Interestingly, the sequential right hepatic vein embolization (HVE) after right PVE demonstrated an incremental effect on the FRL. Although attractive, this approach requires two different procedures and does not spare time as compared to PVE alone.

To shorten and optimize the phase of liver preparation before surgery,the so-called liver venous deprivation (LVD) technique that combines both PVE and HVE during the same procedure was developed.

The aim of this randomized phase II trial is to compare the percentage of change in FRL volume at 3 weeks after LVD or PVE using MRI or CT-scan.

Simultaneous Portal and Hepatic Vein Versus Portal Vein Embolizations for Hypertrophy of the Future Liver Remnant

Simultaneous Portal and Hepatic Vein Embolization Versus Portal Vein Embolization for Hypertrophy of the Future Liver Remnant Before Major Hepatectomy of Non-cirrhotic Liver : a Multicentric Comparative Randomized Phase II Trial

The primary outcomes is to compare the increase in volume of the future remnant liver (FRL)

Toxicities are evaluated according to NCI-CTCAE version 4.03 published 14 June 2010

Post-operative mortality defined as any death within 90 days after surgery or within the hospital stay

Post-operative morbidity defined as the percentages of grade I/II/III/IV/V complications according to Clavien-Dindo classification within the 90 days after surgery or within the hospital stay.

Post-hepatectomy liver failure defined according to the "50-50" criteria or peak bilirubin \>7mg/dL.

Rate of non-resectability due to insufficient FRL defined as the percentage of patients for whom resection will be not attempted due to insufficient FRL

Rate of non-resectability due to tumor progression defined as the percentage of patients for whom resection will not be attempted due to tumor progression.

Rate of per-operative difficulties defined as the percentage of patients for whom per-operative difficulties are encountered by the surgeon

Blood loss are evaluated in mL. Operating time avec evaluated in minutes and transfusion are evaluated by number of packed red blood cells

Rate of R0 resection defined as no microscopic tumor residual

Rate of R1 resection defined as the percentage of patients resected with margin \<1mm

Pre and post-operative liver volumes will be evaluated through CT or MRI acquisitions by calculating whole liver, tumor and FRL volumes

Recurrence-free survival defined as the time from date of randomization to date of recurrence or death from their tumor. Patients alive will be censored at the date of last news.

Overall survival defined as the time from date of randomization to date of death from any cause. Patients alive will be censored at the date of last news.

Evaluation of pre and post-operative liver function will be evaluated using 99mTc mebrofenine scintigraphy through SPECT/CT acquisitions by calculating mebrofenin clearance in %/min/m² of whole liver and FRL at the same time points as CT/MRI

Biomarkers predictive of liver hypertrophy/regeneration are evaluated by blood samples and liver biopies

Federation Francophone de Cancerologie Digestive

University Hospital, Montpellier

Anti-Infective Agents

Central Nervous System Depressants

Ethanol

3 patients per center over one year approximately 90 patients in total. Patients will undergo portal vein and hepatic vein embolization instead of only portal vein embolization.

Procedure/Surgery: Combined portal vein embolization and hepatic vein embolization (PVE/HVE) • All techniques of PVE allowed (ipsi-lateral, contra-lateral, trans-splenic, all embolization agents except for ethanol alone) • All modifications of HVE allowed (venous occlusion umbrellas; trans-jugular, trans-hepatic, no use of vein glue to avoid lung embolization; staged approach allowed, but first PVE, then HVE and within 48 hours)

Portal and Hepatic Vein Embolization

Ronald M van Dam, MD PhD

Erik Schadde, MD FACS FEBS

Marc AH Bemelmans, MD PhD

Christiaan van der Leij, MD PhD

Christoph A Binkert, Prof.Dr.Med

Brief Summary: Some colorectal liver metastases can only be resected after inducing liver regeneration by portal vein embolization (PVE) to increase size function of the future liver remnant (FLR). While PVE is standard, embolization of portal vein and hepatic veins (PVE/HVE) on one side of the liver may faster and more extensive liver size and function growth. PVE/HVE is a novel procedure and requires a safety and feasibility evaluation in a pretrial (DRAGON1) to then be compared in a randomized controlled trial (RCT) to PVE (DRAGON 2).

Detailed Description: Resection of liver metastases from colorectal cancer (CRLM) improves survival compared to chemotherapy alone and may lead to cure in up to 40% of patients. Surgical resectability is limited by location of metastases and by FLR size and function. Commonly, the volume of the future liver remnant (FLR) should be at least 30% of the functional FLR volume. If this volume criterion is not met, the induction of liver regeneration between a two-stage hepatectomy is performed at many centers, with the aim to render patients resectable and reduce the risk of post hepatectomy liver failure. Gold standard to induce regeneration is the embolization of the portal vein branches to the tumor carrying liver (PVE) to induce regeneration of the FLR. Recently, combined embolization of both portal and hepatic veins (PVE/HVE) has been described as an alternative to portal vein embolization because it accelerates and increases growth of the FLR. PVE/HVE combines simultaneous embolization of the portal main branches into the tumor bearing liver and the hepatic vein draining them. The tissue in the part of the liver treated with PVE/HVE stays viable because the hepatic artery continues to supplies the liver deprived of portal and hepatic veins. Preclinical studies in pigs have demonstrated feasibility of this method and human case series show accelerated and increased liver growth. No multi-center evaluation has been performed so far. DRAGON 1 is an international, prospective, multi-center trial to test enrolment capacity of participants and safety of portal and hepatic vein embolization (PVE/HVE). DRAGON 1 will form the basis of the RCT DRAGON 2 to compare PVE with PVE/HV. DRAGON 2 is expected to start in 2021.

Multicenter, international, prospective, multi-center trial to test enrolment capacity of participants and safety of Portal and Hepatic Vein Embolization (PVE/HVE): DRAGON 1 will form the basis of a planned subsequent trial ("DRAGON 2") that will compare PVE with PVE/HVE. In DRAGON 1 every center has to demonstrate the ability to enroll 3 patients in 12 months safely

DRAGON 1- Training, Accreditation, Implementation and Safety Evaluation of Combined PVE/HVE

DRAGON 1- Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization to Accelerate Future Liver Remnant (FLR) Hypertrophy

upon reasonable request after publication.

Ability of each center to enroll 3 patients for PVE/HVE in 12 months safely and perform the procedure including the liver resection without 90-day mortality after resection due to complications. If this goal is achieved center will be enrolled in DRAGON 2.

Increased of standardized future liver remnant volume between initial imaging and imaging at 1 week, 3 weeks, 6 weeks, degree of hypertrophy based on standard future liver remnant volume, kinetic growth

ion of patients proceeding to complete resection (=resection rate)

90-day complications, general (Clavien-Dindo)

90-day complications, liver specific (FABIB-classification)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Simultaneous Portal and Hepatic Vein Versus Portal Vein Embolizations for Hypertrophy of the Future Liver Remnant	NCT03841305	Liver Metastasi...	Liver preparati...	18 Years -	University Hospital, Montpellier
DRAGON 1- Training, Accreditation, Implementation and Safety Evaluation of Combined PVE/HVE	NCT04272931	Colorectal Canc...	Portal and Hepa...	18 Years -	Maastricht University

Spots Global Cancer Trial Database for portal and hepatic vein embolization