The most common indications for locoregional hepatic intervention are hepatocellular carcinoma (HCC) and liver metastatic disease. HCC—the most common primary liver malignancy—is ranked as the third leading cause of cancer-related deaths worldwide,(1) and its incidence is rising in the United States and other countries. Additionally, the liver is often the first site of metastasis from gastrointestinal tract malignancies. Use of imaging has helped to improve diagnosis, decrease complications, and ultimately improve the overall survival of patients with HCC and other neoplastic liver diseases.
HCC can be evaluated by ultrasound (US), contrast-enhanced ultrasound (CEUS), computed tomography (CT), and magnetic resonance imaging (MRI). Triple-phase CT and contrast-enhanced MRI are routinely used in the diagnosis of HCC and to assess extent of the disease.
Although the diagnosis of HCC can be achieved with imaging alone, percutaneous image-guided needle biopsy may be indicated in cases where imaging criteria are not met. (2) The diagnostic accuracy of liver biopsy results depends on size and location of the lesion, and on the operator’s experience. On-site cytological evaluation has a high diagnostic accuracy for malignancy and can be extremely helpful. (3)
At Memorial Sloan Kettering Cancer Center (MSK), an on-site cytopathology technologist is available for every biopsy to determine the adequacy of the sample. Although rare, post-biopsy complications include bleeding and tumor seeding along the tract. In a meta-analysis by Silva et al, tumor seeding in the puncture tract was found after 2.7 percent of biopsies. (4)
Several guidelines are available for the noninvasive diagnosis of HCC, including those from the American Association for the Study of Liver Disease (AASLD), the European Association for the Study of the Liver (EASL), and the American College of Radiology (ACR). The guidelines have multiple similarities and often rely on tumor hypervascularity on arterial phase, and washout on portal venous and later phases of contrast enhancement. Both AASLD and EASL guidelines indicate biopsy for lesions that do not fit imaging criteria.
Recently, the Liver Imaging Reporting and Data System (LI-RADS) was introduced by an ACR committee with the goal of standardizing terminology and criteria for liver imaging report. This system is designed to categorize lesions in patients with cirrhosis or who are otherwise at risk for HCC. LI-RADS has five main categories ranging from L1 to L5, with increasing probability of HCC (L1, definitely benign; L2, probably benign; L3, intermediate probability of HCC or benignity; L4, probably HCC; and L5, definitely HCC). In 2014, LI-RADS was updated to be congruent with both AASLD and OPTN (Organ Procurement and Transplantation Network) criteria. The latter is supported by the United Network for Organ Sharing (UNOS).Back to top
Interventional oncology is an important part of the multidisciplinary approach in managing patients with liver masses. The Barcelona Clinic Liver Cancer (BCLC) staging system is the widely accepted system in treatment and management of patients with HCC (5) (Figure 1).
Resection remains the first option for patients with optimal clinical profile, very early stage (stage 0) in the BCLC system. Patients with early stage (A) and intermediate stage (B) should undergo locoregional treatment. These are patients with either single or up to 3 nodules (≤3 cm), or patients with multiple nodules/masses.
The most favorable outcome of percutaneous image-guided ablation depends on accurate targeting of the lesion. Ultrasound, CT, CT fluoroscopy (CTF), MRI, PET, or a combination of these modalities can be used. Success of treatment is intimately linked to the volumetric spatial relationship of the mass to the ablated lesion margins.
CT fluoroscopy provides excellent three-dimensional anatomic visualization and guidance in real time for a variety of CT-guided interventions. At MSK, we have developed a robotic guidance system for interventional procedures. (6) This system allows precise and accurate procedural planning, holding and moving the instruments with negligible radiation exposure to the physicians (Figure 2). (6), (7) Image-guided locoregional therapies available at MSK include ablations using ethanol, radiofrequency, and microwave, as well as cryoablation and irreversible electroporation. For more diffuse disease, hepatic artery embolization and radioembolization are available.
Radiofrequency ablation (RFA) involves administration of energy (˂900 kHz) into the mass via needle electrodes to induce frictional heating, leading to tissue necrosis and cell death. At MSK, we use RFA mainly to treat small HCCs, up to 3 cm in diameter. Additionally, we use RFA to treat liver metastases from colorectal cancer, lung cancer, breast cancer, neuroendocrine tumors, ovarian malignancies, duodenal cancer, round cell tumors, and leiomyosarcoma. The highest success rates and low recurrence rates are achieved in patients with solitary tumors or with small numbers of metastases (<3 cm in the largest diameter). (8)Patients with HCC ≥3 cm should be treated with transarterial embolization followed by ablation. The major limitation of RFA is evident when the lesion is adjacent to a blood vessel, as blood flow prevents increases in tissue temperature—a phenomenon known as the “heat sink” effect.
Microwave ablation (MWA) uses high-frequency waves (900 MHz - 2.4 GHz). Similar to RFA, the high frequency causes water molecules to oscillate, leading to frictional heating and tissue necrosis. This technique is faster than RFA and theoretically is not diminished by the “heat sink” effect. At MSK, we use MWA for treatment of both HCC and metastatic liver disease. Most recently, we used MWA in treating chemorefractory solitary testicular liver metastases.
With cryoablation, argon or liquid nitrogen is circulated in a probe, causing rapid cooling of surrounding tissue. Tissue death occurs by freezing (-40ºC or lower). This technique is used to treat HCC and metastatic liver masses.
Irreversible electroporation (IRE) is a nonthermal ablation modality. Electrical pulses are applied across the cell to create permanent cell membrane pores, leading to cell lysis and death. At MSK, IRE is used for metastatic liver disease where the tumor is adjacent to a large (>3 mm) blood vessel or major bile duct.
Hepatic artery embolization (HAE) and radioembolization (TARE) are acceptable locoregional therapies for unresectable HCC, BCLC stages A and B. HAE can improve survival in patients with metastatic neuroendocrine tumor from pancreas or lung and metastatic renal cell carcinoma. There is level 1, phase III evidence that radioembolization improves survival in patients with metastatic colorectal disease. At MSK, radioembolization is used to treat patients with metastatic liver disease from colorectal, breast, and lung cancers. TARE is also used in patients that do not respond to HAE.
Accurate detection of the entire tumor feeding vessels by intraprocedural imaging is essential for the technical success of embolization procedures. Two-dimensional angiography provides valuable information in identifying tumor figures accurately.Back to top
Recent progress in imaging technology, including advances in C-arm cone-beam technology, has enabled the visualization of three-dimensional vascular anatomy with a single acquisition using nonselective C-arm computed tomography (CBCT). (9) Such capability allows the interventionist to visualize the vascular tree associated with the target tumor from multiple projections during the procedure.
At MSK, we currently use a computer software program designed to assist in selective liver tumor embolization. This software, FlightPlan for Liver (GE Healthcare, Waukesha, WI, USA), was specifically designed to detect tumor feeders using three-dimensional CBCT data. (10) When the catheter entry site and the target tumor are chosen on multiplanar reformatted (MPR) C-arm CT images, the software automatically predicts feeder vessels by displaying a color-coded image on the workstation screen (Figure 3).