Study protocol of the HYPER-LIV01 trial: a multicenter phase II, prospective and randomized study comparing simultaneous portal and hepatic vein embolization to portal vein embolization for hypertrophy of the future liver remnant before major hepatectomy for colo-rectal liver metastases

Emmanuel Deshayes, Lauranne Piron, Antoine Bouvier, Bruno Lapuyade, Emilie Lermite, Laurent Vervueren, Christophe Laurent, Jean-Baptiste Pinaquy, Patrick Chevallier, Anthony Dohan, Agnès Rode, Christian Sengel, Chloé Guillot, François Quenet, Boris Guiu, Emmanuel Deshayes, Lauranne Piron, Antoine Bouvier, Bruno Lapuyade, Emilie Lermite, Laurent Vervueren, Christophe Laurent, Jean-Baptiste Pinaquy, Patrick Chevallier, Anthony Dohan, Agnès Rode, Christian Sengel, Chloé Guillot, François Quenet, Boris Guiu

Abstract

Background: In patients undergoing major liver resection, portal vein embolization (PVE) has been widely used to induce hypertrophy of the non-embolized liver in order to prevent post-hepatectomy liver failure. PVE is a safe and effective procedure, but does not always lead to sufficient hypertrophy of the future liver remnant (FLR). Hepatic vein(s) embolization has been proposed to improve FLR regeneration when insufficient after PVE. The sequential right hepatic vein embolization (HVE) after right PVE demonstrated an incremental effect on the FLR but it implies two different procedures with no time gain as compared to PVE alone. We have developed the so-called liver venous deprivation (LVD), a combination of PVE and HVE during the same intervention, to optimize the phase of liver preparation before surgery. The main objective of this randomized phase II trial is to compare the percentage of change in FLR volume at 3 weeks after LVD or PVE.

Methods: Patients eligible to this multicenter prospective randomized phase II study are subjects aged from 18 years old suffering from colo-rectal liver metastases considered as resectable and with non-cirrhotic liver parenchyma. The primary objective is the percentage of change in FLR volume at 3 weeks after LVD or PVE using MRI or CT-Scan. Secondary objectives are assessment of tolerance, post-operative morbidity and mortality, post-hepatectomy liver failure, rate of non-respectability due to insufficient FLR or tumor progression, per-operative difficulties, blood loss, R0 resection rate, post-operative liver volume and overall survival. Objectives of translational research studies are evaluation of pre- and post-operative liver function and determination of biomarkers predictive of liver hypertrophy. Sixty-four patients will be included (randomization ratio 1:1) to detect a difference of 12% at 21 days in FLR volumes between PVE and LVD.

Discussion: Adding HVE to PVE during the same procedure is an innovative and promising approach that may lead to a rapid and major increase in volume and function of the FLR, thereby increasing the rate of resectable patients and limiting the risk of patient's drop-out.

Trial registration: This study was registered on clinicaltrials.gov on 15th February 2019 (NCT03841305).

Keywords: Colo-rectal cancer; Liver metastases; Major hepatectomy; Portal vein embolization; Venous deprivation.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study design of the HYPER-LIV01 trial

References

    1. Yokoyama Y, Nagino M, Nimura Y. Mechanisms of hepatic regeneration following portal vein embolization and partial hepatectomy: a review. World J Surg. 2007;31(2):367–374. doi: 10.1007/s00268-006-0526-2.
    1. Schnitzbauer AA, Lang SA, Goessmann H, Nadalin S, Baumgart J, Farkas SA, et al. Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg. 2012;255(3):405–414. doi: 10.1097/SLA.0b013e31824856f5.
    1. Schadde E, Ardiles V, Robles-Campos R, Malago M, Machado M, Hernandez-Alejandro R, et al. Early survival and safety of ALPPS: first report of the international ALPPS registry. Ann Surg. 2014;260(5):829–836. doi: 10.1097/SLA.0000000000000947.
    1. Hwang S, Lee SG, Ko GY, Kim BS, Sung KB, Kim MH, et al. Sequential preoperative ipsilateral hepatic vein embolization after portal vein embolization to induce further liver regeneration in patients with hepatobiliary malignancy. Ann Surg. 2009;249(4):608–616. doi: 10.1097/SLA.0b013e31819ecc5c.
    1. Guiu B, Chevallier P, Denys A, Delhom E, Pierredon-Foulongne MA, Rouanet P, et al. Simultaneous trans-hepatic portal and hepatic vein embolization before major hepatectomy: the liver venous deprivation technique. Eur Radiol. 2016;26(12):4259–4267. doi: 10.1007/s00330-016-4291-9.
    1. Guiu B, Quenet F, Escal L, Bibeau F, Piron L, Rouanet P, et al. Extended liver venous deprivation before major hepatectomy induces marked and very rapid increase in future liver remnant function. Eur Radiol. 2017;27(8):3343–52.
    1. Guiu B, Quenet F, Panaro F, Piron L, Cassinotto C, Herrerro A, et al. Liver venous deprivation versus portal vein embolization before major hepatectomy: future liver remnant volumetric and functional changes. Hepatobiliary Surg Nutr. 2020. 10.21037/hbsn.2020.02.06.
    1. de Graaf W, van Lienden KP, van Gulik TM, Bennink RJ. (99m)Tc-mebrofenin hepatobiliary scintigraphy with SPECT for the assessment of hepatic function and liver functional volume before partial hepatectomy. J Nucl Med. 2010;51(2):229–236. doi: 10.2967/jnumed.109.069724.
    1. van Lienden KP, van den Esschert JW, de Graaf W, Bipat S, Lameris JS, van Gulik TM, et al. Portal vein embolization before liver resection: a systematic review. Cardiovasc Intervent Radiol. 2013;36(1):25–34. doi: 10.1007/s00270-012-0440-y.
    1. Le Roy B, Perrey A, Fontarensky M, Gagniere J, Abergel A, Pereira B, et al. Combined preoperative portal and hepatic vein embolization (Biembolization) to improve liver regeneration before major liver resection: a preliminary report. World J Surg. 2017;41(7):1848–1856. doi: 10.1007/s00268-017-4016-5.
    1. Panaro F, Giannone F, Riviere B, Sgarbura O, Cusumano C, Deshayes E, et al. Perioperative impact of liver venous deprivation compared with portal venous embolization in patients undergoing right hepatectomy: preliminary results from the pioneer center. Hepatobiliary Surg Nutr. 2019;8(4):329–337. doi: 10.21037/hbsn.2019.07.06.
    1. Hocquelet A, Sotiriadis C, Duran R, Guiu B, Yamaguchi T, Halkic N, et al. Preoperative portal vein embolization alone with biliary drainage compared to a combination of simultaneous portal vein, right hepatic vein embolization and biliary drainage in Klatskin tumor. Cardiovasc Intervent Radiol. 2018;41(12):1885–1891. doi: 10.1007/s00270-018-2075-0.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe