Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma

Summary

Here, we present a protocol how to perform an isolated liver perfusion (IHP) with melphalan and we also discuss IHP as a treatment option for liver metastases of uveal melanoma.

Abstract

Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic agent melphalan. Briefly, the procedure starts with the setup of a percutaneous veno-venous bypass from the femoral vein to the external jugular vein. Via a laparotomy, catheters are then inserted into the proper hepatic artery and the caval vein. The portal vein and the caval vein, both supra- and infrahepatically, are then clamped. The arterial and venous catheters are connected to a heart lung machine and the liver is perfused with melphalan (1 mg/kg body weight) for 60 min. This way it is possible to locally perfuse the liver with a high dose of a chemotherapeutic agent, without leakage to the systemic circulation.

In previous studies including patients with isolated liver metastases of uveal melanoma, an overall response rate of 33-100% and a median survival between 9 and 13 months, have been reported. The aim of this protocol is to give a clear description of how to perform the procedure and to discuss IHP as a treatment option for liver metastases of uveal melanoma.

Introduction

Uveal melanoma is the most common primary intraocular malignancy in adults, with the incidence being highest in Caucasian populations ¹. Local treatment consists of enucleation or local plaque radiation therapy ^2,3. Irrespective of local treatment, metastatic disease will ultimately develop in about 35-50% of the patients ^4,5. The liver is the most common site of metastases and approximately 50% of the patients present with isolated liver metastases. The median overall survival (OS) for patients with liver metastases is 6-12 months ⁴. Several different systemic and regional treatment strategies have been explored, but surviv....

Protocol

Patients provided written informed consent and the study was approved by the Regional Ethical Review Board at the University of Gothenburg.

1. Anesthesia

1. Set up all the monitoring (ECG, blood pressure cuff) ¹⁷.
2. Insert an epidural catheter in the lower to mid thoracic level ¹⁷.
3. Induce anesthesia with Propofol 2 mg/kg, 150 µg of Fentanyl, and Rocuronium 0.6 mg/kg through a previously inserted peripheral venous catheter.
4. Preoxygenate and intubate the patient. Maintain anesthesia with Sevoflurane, oxygen and air ¹⁷.
5. Insert a double lumen central ....

Results

An initial report included 22 patients treated with melphalan with or without TNF-alpha. The results showed an overall response rate of 62%, including two patients with CR (10%), and a median overall survival of 11 months ²⁰. A subsequent study reported on the outcome of 29 consecutive patients treated using melphalan alone. The outcome was very similar with a 62% overall response including 10% complete response and a median survival of 12 months ²¹.

In a study by Rizell .......

Discussion

Patients with metastatic uveal melanoma have few therapeutic options. Chemotherapy ⁶, immunotherapy ²³ and targeted therapy ²⁴ have not been able to show improved OS. For patients with few liver metastases, liver resection is an option ¹². Other treatments include hepatic intra-arterial chemotherapy (HIA) ⁹, transarterial chemoembolization (TACE) ²⁵ and selective internal radiation therapy (SIRT) ²⁶.

IHP is a major an.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Wire re-inforced catethers	Medtronic Inc, Minnesota, USA		12-18Fr
Stöckert S5	Sorin Group, Mirandola, Italy		Heart-lung machine
Rotaflow	Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany		Centrifugal pump
HU 35	Maquet cardiopulmonary AG, Hirrlingen, Germany		Heater unit
Flexbumin 200 g/l	Baxter Medical AB, Kista, Sweden
Tribonat	Fresenius Kabi AB, Uppsala, Sweden
Heparin LEO, 5000 IE/ml	LEO Pharma AB, Sweden
Ringer Acetate	Baxter Medical AB, Kista, Sweden
Vasculosis	Cis-Bio International, Gif-Sur-Yvette, France		99mTc-albumin
MedicView	SystemData AB, Gothenburg, Sweden		Leakage monitoring system
Alkeran	Aspen Europe GmbH, Bad Oldesloe, Germany		melphalan