Use of Partial Venovenous Cardiopulmonary Bypass in Percutaneous Hepatic Perfusion for Patients with Diffuse, Isolated Liver Metastases: A Case Series

Cardiovasc Intervent Radiol

Martini

et al. 2015

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.

Section: Patient Selectionmentioning

confidence: 99%

Percutaneous Isolated Hepatic Perfusion for the Treatment of Unresectable Liver Malignancies

Cardiovasc Intervent Radiol

Martini

et al. 2015

“…A recent phase III trial, comparing PHP to best alternative care (BAC) for patients with hepatic metastases of uveal melanoma, reports improved hepatic progression free survival of 7 months compared to 1.6 months for the group that received BAC (p< 0.0001). 17 In the PHP group 36% of patients had a partial response and another 52% had a stable disease. No significant difference in median overall survival was observed (10 months), probably because patients in the BAC group could crossover to the PHP treatment.…”

Section: Representative Resultsmentioning

confidence: 94%

“…Studies using the first generation filter also report grade 3 and 4 coagulopathy, possibly related to consumption of clotting factors by the filters. 17,22 Based on these findings, a 2 nd generation filter was developed, which is available since April 2012. In pre-clinical studies the filter efficacy was 98%.…”

Section: Postoperative Carementioning

confidence: 99%

“…14 A second period of hypotension occurs after the flow is diverted through the charcoal-activated filters. 17,23 This hypotension is of short duration and responds well to administration of fluids and sympatico-mimetics.…”

mentioning

confidence: 99%

“…This has been reported in the majority of cases in literature, is of transient nature and well manageable with GCSF growth factor and/or blood products, mostly on an outpatient basis. 16,17,19 The nadir of cytopenia is generally reached 10-14 days after PHP. Therefore, regular blood tests in the first two weeks after PHP are mandatory.…”

mentioning

confidence: 99%

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Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver

Martini

et al. 2016

JoVE

Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn unresectable metastases into resectable ones. Some patients however, suffer from side effects or progression under systemic treatment. For patients with metastasized uveal melanoma there are no standard systemic therapy options. For patients without extrahepatic disease, isolated liver perfusion (IHP) may enable local disease control with limited systemic side effects. Previously, this was performed during open surgery with satisfying results, but morbidity and mortality related to the open procedure, prohibited a widespread application. Therefore, percutaneous hepatic perfusion (PHP) with simultaneous chemofiltration was developed. Besides decreasing morbidity and mortality, this procedure can be repeated, hopefully leading to a higher response rate and improved survival (by local control of disease). During PHP, catheters are placed in the proper hepatic artery, to infuse the chemotherapeutic agent, and in the inferior caval vein to aspirate the chemosaturated blood returning through the hepatic veins. The caval vein catheter is a double balloon catheter that prohibits leakage into the systemic circulation. The blood returning from the hepatic veins is aspirated through the catheter fenestrations and then perfused through an extra-corporeal filtration system. After filtration, the blood is returned to the patient by a third catheter in the right internal jugular vein. During PHP a high dose of melphalan is infused into the liver, which is toxic and would lead to life threatening complications when administered systemically. Because of the significant hemodynamic instability resulting from the combination of caval vein occlusion and chemofiltration, hemodynamic monitoring and hemodynamic support is of paramount importance during this complex procedure.

Prospective Clinical and Pharmacological Evaluation of the Delcath System’s Second-Generation (GEN2) Hemofiltration System in Patients Undergoing Percutaneous Hepatic Perfusion with Melphalan

Cardiovasc Intervent Radiol

Meijer

et al. 2017

IntroductionPercutaneous hepatic perfusion (PHP) with melphalan is an effective treatment for patients with hepatic metastases, but associated with high rates of bone marrow depression. To reduce systemic toxicity, improvements have been made to the filtration system. In pre-clinical studies, the Delcath System’s GEN2 filter was superior to the first-generation filters. In this clinical study, we analysed the pharmacokinetics and toxicity of PHP using the new GEN2 filter.Methods and MaterialsStarting February 2014, two prospective phase II studies were initiated in patients with hepatic metastases from ocular melanoma or colorectal cancer. In 10 PHP procedures performed in the first 7 enrolled patients, blood samples were obtained to determine filter efficiency and systemic drug exposure. PHP was performed with melphalan 3 mg/kg with a maximum of 220 mg. Complications were assessed according to CTCAE v4.03. Response was assessed according to RECIST 1.1.ResultsPharmacokinetic analysis of blood samples showed an overall filter efficiency of 86% (range 71.1–95.5%). The mean filter efficiency decreased from 95.4% 10 min after the start of melphalan infusion to 77.5% at the end of the procedure (p = 0.051). Bone marrow depression was seen after up to 80.0% of 10 procedures, but was self-limiting and mostly asymptomatic. No hypotension-related complications or procedure-related mortality occurred.ConclusionThe GEN2 filter has a higher melphalan filter efficiency compared to the first-generation filters and a more consistent performance. PHP with the GEN2 filter appears to have an acceptable safety profile, but this needs further validation in larger studies.