Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
CardioVascular and Interventional Radiology
Published in: CardioVascular and Interventional Radiology 6/2016

Open Access 01-06-2016 | Review/State of the Art

Percutaneous Isolated Hepatic Perfusion for the Treatment of Unresectable Liver Malignancies

Authors: Mark C. Burgmans, Eleonora M. de Leede, Christian H. Martini, Ellen Kapiteijn, Alexander L. Vahrmeijer, Arian R. van Erkel

Published in: CardioVascular and Interventional Radiology | Issue 6/2016

Login to get access

Abstract

Liver malignancies are a major burden of disease worldwide. The long-term prognosis for patients with unresectable tumors remains poor, despite advances in systemic chemotherapy, targeted agents, and minimally invasive therapies such as ablation, chemoembolization, and radioembolization. Thus, the demand for new and better treatments for malignant liver tumors remains high. Surgical isolated hepatic perfusion (IHP) has been shown to be effective in patients with various hepatic malignancies, but is complex, associated with high complication rates and not repeatable. Percutaneous isolated liver perfusion (PHP) is a novel minimally invasive, repeatable, and safer alternative to IHP. PHP is rapidly gaining interest and the number of procedures performed in Europe now exceeds 200. This review discusses the indications, technique and patient management of PHP and provides an overview of the available data.
Literature
1.
European Association for Study of THE Liver, European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. Eur J Cancer. 2012;48(5):599–641.CrossRef
2.
Jovanovic P, Mihajlovic M, Djordjevic-Jocic J, Vlajkovic S, Cekic S, Stefanovic V. Ocular melanoma: an overview of the current status. Int J Clin Exp Pathol. 2013;6(7):1230–44.PubMedPubMedCentral
3.
4.
Schenk WG Jr, McDonald JC, McDonald K, Drapanas T. Direct measurement of hepatic blood flow in surgical patients: with related observations on hepatic flow dynamics in experimental animals. Ann Surg. 1962;156:463–71.CrossRefPubMedPubMedCentral
5.
van de Velde CJ, Kothuis BJ, Barenbrug HW, Jongejan N, Runia RD, de Brauw LM, et al. A successful technique of in vivo isolated liver perfusion in pigs. J Surg Res. 1986;41(6):593–9.CrossRefPubMed
6.
Ausman RK. Development of a technic for isolated perfusion of the liver. N Y State J Med. 1961;61:3993–7.PubMed
7.
Aigner K, Walther H, Tonn J, Wenzl A, Hechtel R, Merker G, et al. First experimental and clinical results of isolated liver perfusion with cytotoxics in metastases from colorectal primary. Recent Results Cancer Res. 1983;86:99–102.CrossRefPubMed
8.
de Brauw LM, Marinelli A, van de Velde CJ, Hermans J, Tjaden UR, Erkelens C, et al. Pharmacological evaluation of experimental isolated liver perfusion and hepatic artery infusion with 5-fluorouracil. Cancer Res. 1991;51(6):1694–700.PubMed
9.
Hafstrom LR, Holmberg SB, Naredi PL, Lindner PG, Bengtsson A, Tidebrant G, et al. Isolated hyperthermic liver perfusion with chemotherapy for liver malignancy. Surg Oncol. 1994;3(2):103–8.CrossRefPubMed
10.
Marinelli A, Vahrmeijer AL, van de Velde CJ. Phase I/II studies of isolated hepatic perfusion with mitomycin C or melphalan in patients with colorectal cancer hepatic metastases. Recent Results Cancer Res. 1998;147:83–94.CrossRefPubMed
11.
van Etten B, de Wilt JH, Brunstein F, Eggermont AM, Verhoef C. Isolated hypoxic hepatic perfusion with melphalan in patients with irresectable ocular melanoma metastases. Eur J Surg Oncol. 2009;35(5):539–45.CrossRefPubMed
12.
Noter SL, Rothbarth J, Pijl ME, Keunen JE, Hartgrink HH, Tijl FG, et al. Isolated hepatic perfusion with high-dose melphalan for the treatment of uveal melanoma metastases confined to the liver. Melanoma Res. 2004;14(1):67–72.CrossRefPubMed
13.
Alexander HR, Libutti SK, Bartlett DL, Puhlmann M, Fraker DL, Bachenheimer LC. A phase I–II study of isolated hepatic perfusion using melphalan with or without tumor necrosis factor for patients with ocular melanoma metastatic to liver. Clin Cancer Res. 2000;6(8):3062–70.PubMed
14.
Alexander HR Jr, Libutti SK, Pingpank JF, Steinberg SM, Bartlett DL, Helsabeck C, et al. Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver. Clin Cancer Res. 2003;9(17):6343–9.PubMed
15.
van Iersel LB, Gelderblom H, Vahrmeijer AL, van Persijn van Meerten EL, Tijl FG, Putter H, et al. Isolated hepatic melphalan perfusion of colorectal liver metastases: outcome and prognostic factors in 154 patients. Ann Oncol. 2008;19(6):1127–34.CrossRefPubMed
16.
Rothbarth J, Pijl ME, Vahrmeijer AL, Hartgrink HH, Tijl FG, Kuppen PJ, et al. Isolated hepatic perfusion with high-dose melphalan for the treatment of colorectal metastasis confined to the liver. Br J Surg. 2003;90(11):1391–7.CrossRefPubMed
17.
Alexander HR Jr, Libutti SK, Pingpank JF, Bartlett DL, Helsabeck C, Beresneva T. Isolated hepatic perfusion for the treatment of patients with colorectal cancer liver metastases after irinotecan-based therapy. Ann Surg Oncol. 2005;12(2):138–44.CrossRefPubMed
18.
de Wilt JH, van Etten B, Verhoef C, Eggermont AM. Isolated hepatic perfusion: experimental evidence and clinical utility. Surg Clin North Am. 2004;84(2):627–41.CrossRefPubMed
19.
Alexander HR Jr, Bartlett DL, Libutti SK, Fraker DL, Moser T, Rosenberg SA. Isolated hepatic perfusion with tumor necrosis factor and melphalan for unresectable cancers confined to the liver. J Clin Oncol. 1998;16(4):1479–89.PubMed
20.
Facy O, Doussot A, Zinzindohoue F, Holl S, Rat P, OrtegaDeballon P. Isolated hepatic perfusion: principles and results. J Visc Surg. 2014;151(Suppl 1):S25–32.CrossRefPubMed
21.
Eggermont AM, van IJken MG, van Etten B, van der Sijp JR, ten Hagen TL, Wiggers T, et al. Isolated hypoxic hepatic perfusion (IHHP) using balloon catheter techniques: from laboratory to the clinic towards a percutaneous procedure. Hepatogastroenterology. 2000;47(33):776–81.PubMed
22.
Burgmans MC, Kao YH, Irani FG, Dames EL, Teo TK, Goh AS, et al. Radioembolization with infusion of yttrium-90 microspheres into a right inferior phrenic artery with hepatic tumor supply is feasible and safe. J Vasc Interv Radiol. 2012;23(10):1294–301.CrossRefPubMed
23.
Kao YH, Hock Tan AE, Burgmans MC, Irani FG, Khoo LS, Gong Lo RH, et al. Image-guided personalized predictive dosimetry by artery-specific SPECT/CT partition modeling for safe and effective 90Y radioembolization. J Nucl Med. 2012;53(4):559–66.CrossRefPubMed
24.
Miyayama S, Yamashiro M, Okuda M, Yoshie Y, Sugimori N, Igarashi S, et al. Usefulness of cone-beam computed tomography during ultraselective transcatheter arterial chemoembolization for small hepatocellular carcinomas that cannot be demonstrated on angiography. Cardiovasc Intervent Radiol. 2009;32(2):255–64.CrossRefPubMed
25.
Miyayama S, Yamashiro M, Hattori Y, Orito N, Matsui K, Tsuji K, et al. Efficacy of cone-beam computed tomography during transcatheter arterial chemoembolization for hepatocellular carcinoma. Jpn J Radiol. 2011;29(6):371–7.CrossRefPubMed
26.
Takayasu K, Muramatsu Y, Maeda T, Iwata R, Furukawa H, Muramatsu Y, et al. Targeted transarterial oily chemoembolization for small foci of hepatocellular carcinoma using a unified helical CT and angiography system: analysis of factors affecting local recurrence and survival rates. AJR Am J Roentgenol. 2001;176(3):681–8.CrossRefPubMed
27.
Spreafico C, Morosi C, Maccauro M, Romito R, Lanocita R, Civelli EM, et al. Intrahepatic flow redistribution in patients treated with radioembolization. Cardiovasc Intervent Radiol. 2015;38(2):322–8.CrossRefPubMed
28.
Dougherty TB, Mikolajek JA, Curley SA. Safe anesthetic management of patients undergoing a novel method of treating human hepatocellular cancer. J Clin Anesth. 1997;9(3):220–7.CrossRefPubMed
29.
Ravikumar TS, Pizzorno G, Bodden W, Marsh J, Strair R, Pollack J, et al. Percutaneous hepatic vein isolation and high-dose hepatic arterial infusion chemotherapy for unresectable liver tumors. J Clin Oncol. 1994;12(12):2723–36.PubMed
30.
Miao N, Pingpank JF, Alexander HR, Steinberg SM, Beresneva T, Quezado ZM. Percutaneous hepatic perfusion in patients with metastatic liver cancer: anesthetic, hemodynamic, and metabolic considerations. Ann Surg Oncol. 2008;15(3):815–23.CrossRefPubMed
31.
Rothbarth J, Koevoets C, Tollenaar RA, Tilby MJ, van de Velde CJ, Mulder GJ, et al. Immunohistochemical detection of melphalan-DNA adducts in colon cancer cells in vitro and human colorectal liver tumours in vivo. Biochem Pharmacol. 2004;67(9):1771–8.CrossRefPubMed
32.
Vahrmeijer AL, van Dierendonck JH, Keizer HJ, Beijnen JH, Tollenaar RA, Pijl ME, et al. Increased local cytostatic drug exposure by isolated hepatic perfusion: a phase I clinical and pharmacologic evaluation of treatment with high dose melphalan in patients with colorectal cancer confined to the liver. Br J Cancer. 2000;82(9):1539–46.CrossRefPubMedPubMedCentral
33.
Rothbarth J, Vahrmeijer AL, Mulder GJ. Modulation of cytostatic efficacy of melphalan by glutathione: mechanisms and efficacy. Chem Biol Interact. 2002;140(2):93–107.CrossRefPubMed
34.
Uzgare RP, Sheets TP, Johnston DS. Evaluation of melphalan, oxaliplatin, and paclitaxel in colon, liver, and gastric cancer cell lines in a short-term exposure model of chemosaturation therapy by percutaneous hepatic perfusion. Anticancer Res. 2013;33(5):1989–2000.PubMed
35.
de Vries MR, Borel Rinkes IH, van de Velde CJ, Wiggers T, Tollenaar RA, Kuppen PJ, et al. Isolated hepatic perfusion with tumor necrosis factor alpha and melphalan: experimental studies in pigs and phase I data from humans. Recent Results Cancer Res. 1998;147:107–19.CrossRefPubMed
36.
Ku Y, Saitoh M, Iwasaki T, Tominaga M, Maekawa Y, Shiki H, et al. Intraarterial infusion of high-dose adriamycin for unresectable hepatocellular carcinoma using direct hemoperfusion under hepatic venous isolation. Eur J Surg Oncol. 1993;19(4):387–92.PubMed
37.
van Iersel LB, de Leede EM, Vahrmeijer AL, Tijl FG, den Hartigh J, Kuppen PJ, et al. Isolated hepatic perfusion with oxaliplatin combined with 100 mg melphalan in patients with metastases confined to the liver: a phase I study. Eur J Surg Oncol. 2014;40(11):1557–63.CrossRefPubMed
38.
Rothbarth J, Tollenaar RA, Schellens JH, Nortier JW, Kool LJ, Kuppen PJ, et al. Isolated hepatic perfusion for the treatment of colorectal metastases confined to the liver: recent trends and perspectives. Eur J Cancer. 2004;40(12):1812–24.CrossRefPubMed
39.
Pingpank JF, Libutti SK, Chang R, Wood BJ, Neeman Z, Kam AW, et al. Phase I study of hepatic arterial melphalan infusion and hepatic venous hemofiltration using percutaneously placed catheters in patients with unresectable hepatic malignancies. J Clin Oncol. 2005;23(15):3465–74.CrossRefPubMedPubMedCentral
40.
Ku Y, Fukumoto T, Iwasaki T, Tominaga M, Samizo M, Nishida T, et al. Clinical pilot study on high-dose intraarterial chemotherapy with direct hemoperfusion under hepatic venous isolation in patients with advanced hepatocellular carcinoma. Surgery. 1995;117(5):510–9.CrossRefPubMed
41.
Ku Y, Iwasaki T, Fukumoto T, Tominaga M, Muramatsu S, Kusunoki N, et al. Induction of long-term remission in advanced hepatocellular carcinoma with percutaneous isolated liver chemoperfusion. Ann Surg. 1998;227(4):519–26.CrossRefPubMedPubMedCentral
42.
Fukumoto T, Tominaga M, Kido M, Takebe A, Tanaka M, Kuramitsu K, et al. Long-term outcomes and prognostic factors with reductive hepatectomy and sequential percutaneous isolated hepatic perfusion for multiple bilobar hepatocellular carcinoma. Ann Surg Oncol. 2014;21(3):971–8.CrossRefPubMed
43.
Ku Y, Fukumoto T, Tominaga M, Iwasaki T, Maeda I, Kusunoki N, et al. Single catheter technique of hepatic venous isolation and extracorporeal charcoal hemoperfusion for malignant liver tumors. Am J Surg. 1997;173(2):103–9.CrossRefPubMed
44.
Chen HS, Gross JF. Intra-arterial infusion of anticancer drugs: theoretic aspects of drug delivery and review of responses. Cancer Treat Rep. 1980;64(1):31–40.PubMed
45.
Christoforidis D, Martinet O, Lejeune FJ, Mosimann F. Isolated liver perfusion for non-resectable liver tumours: a review. Eur J Surg Oncol. 2002;28(8):875–90.CrossRefPubMed
46.
Vogl TJ, Zangos S, Scholtz JE, Schmitt F, Paetzold S, Trojan J, et al. Chemosaturation with percutaneous hepatic perfusions of melphalan for hepatic metastases: experience from two European centers. Rofo. 2014;186(10):937–44.CrossRefPubMed
47.
Moeslein FM, McAndrew EG, Appling WM, Hryniewich NE, Jarvis KD, Markos SM, et al. Evaluation of Delcath Systems’ Generation 2 (GEN 2) melphalan hemofiltration system in a porcine model of percutaneous hepatic perfusion. Cardiovasc Intervent Radiol. 2014;37(3):763–9.CrossRefPubMedPubMedCentral
48.
Savier E, Azoulay D, Huguet E, Lokiec F, Gil-Delgado M, Bismuth H. Percutaneous isolated hepatic perfusion for chemotherapy: a phase 1 study. Arch Surg. 2003;138(3):325–32.CrossRefPubMed
49.
Runia RD, de Brauw LM, Kothuis BJ, Pauwels EK, van de Velde CJ. Continuous measurement of leakage during isolated liver perfusion with a radiotracer. Int J Rad Appl Instrum B. 1987;14(2):113–8.CrossRefPubMed
50.
Rothbarth J, Pijl ME, Tollenaar RA, Tijl F, Ivancev G, Mulder GJ, et al. An experimental minimally invasive perfusion technique for the treatment of liver metastases. Eur J Surg Oncol. 2003;29(9):757–63.CrossRefPubMed
51.
52.
Forster MR, Rashid OM, Perez MC, Choi J, Chaudhry T, Zager JS. Chemosaturation with percutaneous hepatic perfusion for unresectable metastatic melanoma or sarcoma to the liver: a single institution experience. J Surg Oncol. 2014;109(5):434–9.CrossRefPubMedPubMedCentral
53.
Hughes MS, Zager J, Faries M, Alexander HR, Royal RE, Wood B, et al. Results of a randomized controlled multicenter phase III trial of percutaneous hepatic perfusion compared with best available care for patients with melanoma liver metastases. Ann Surg Oncol. 2015. doi:10.​1245/​s10434-015-4968-3.
54.
Ku Y, Saitoh Y. Extracorporeal carbon chemofiltration under hepatic venous isolation for high-dose intraarterial chemotherapy of the liver. Surgery. 1994;116(5):941.PubMed
55.
Ku Y, Saitoh Y. Percutaneous technique of hepatic venous isolation and charcoal hemoperfusion with a dual-balloon vena cava catheter. Surgery. 1996;119(3):360.CrossRefPubMed
56.
Ku Y, Tominaga M, Iwasaki T, Fukumoto T, Muramatsu S, Kusunoki N, et al. Efficacy of repeated percutaneous isolated liver chemoperfusion in local control of unresectable hepatocellular carcinoma. Hepatogastroenterology. 1998;45(24):1961–5.PubMed
57.
Fitzpatrick M, Richard Alexander H, Deshpande SP, Martz DG Jr, McCormick B, Grigore AM. Use of partial venovenous cardiopulmonary bypass in percutaneous hepatic perfusion for patients with diffuse, isolated liver metastases: a case series. J Cardiothorac Vasc Anesth. 2014;28(3):647–51.CrossRefPubMed
58.
Pingpank JF, Royal RE, Kammula US, Kam AW, Wood BJ, Libutti SK, et al. Chemo-saturation with percutaneous hepatic perfusion (CS:PHP) using Melphalan for unresectable neuroendocrine tumor liver metastases (MNET). Abstract CIRSE 2011; FP2109.
59.
Ku Y, Iwasaki T, Tominaga M, Fukumoto T, Takahashi T, Kido M, et al. Reductive surgery plus percutaneous isolated hepatic perfusion for multiple advanced hepatocellular carcinoma. Ann Surg. 2004;239(1):53–60.CrossRefPubMedPubMedCentral
60.
Kawai S, Tani M, Okamura J, Ogawa M, Ohashi Y, Monden M, et al. Prospective and randomized trial of lipiodol-transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: a comparison of epirubicin and doxorubicin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan. Semin Oncol. 1997;24(2 Suppl 6):S6-38–45.
Metadata
Title
Percutaneous Isolated Hepatic Perfusion for the Treatment of Unresectable Liver Malignancies
Authors
Mark C. Burgmans
Eleonora M. de Leede
Christian H. Martini
Ellen Kapiteijn
Alexander L. Vahrmeijer
Arian R. van Erkel
Publication date
01-06-2016
Publisher
Springer US
Published in
CardioVascular and Interventional Radiology / Issue 6/2016
Print ISSN: 0174-1551
Electronic ISSN: 1432-086X
DOI
https://doi.org/10.1007/s00270-015-1276-z

Other articles of this Issue 6/2016

CardioVascular and Interventional Radiology 6/2016 Go to the issue

Clinical Investigation

Comparison of Balloon-Occluded Retrograde Transvenous Obliteration (BRTO) Using Ethanolamine Oleate (EO), BRTO Using Sodium Tetradecyl Sulfate (STS) Foam and Vascular Plug-Assisted Retrograde Transvenous Obliteration (PARTO)

Clinical Investigation

Feasibility of Intraoperative Nerve Monitoring in Preventing Thermal Damage to the “Nerve at Risk” During Image-Guided Ablation of Tumors

Clinical Investigation

PET/MRI of Hepatic 90Y Microsphere Deposition Determines Individual Tumor Response

Clinical Investigation

Long-Term Efficacy of Percutaneous Internal Plastic Stent Placement for Non-anastomotic Biliary Stenosis After Liver Transplantation

Clinical Investigation

Change in Imaging Findings on Angiography-Assisted CT During Balloon-Occluded Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma

Commentary

TAE for HCC: When the Old Way is Better than the New Ones!!!