Overview

Hepatic malignancies are common, with more than 1 million diagnosed each year worldwide. Tumors can be primary, as with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (IHC), or they can be secondary, as with colorectal liver metastases (CLM), neuroendocrine malignancy, or metastases from other primary cancers, such as those of the breast or lung. Many patients come to medical attention with advanced disease that is not amenable to surgical therapy. Unresectable disease carries a poor prognosis, because systemic chemotherapeutic agents and radiation therapy have limited efficacy in treating many of these diseases. As a result of the limited treatment options in this particular patient population, liver-directed regional therapies have evolved that include selective internal radiation therapy (Cianni et al, 2009), transarterial chemoembolization (TACE) (Rathore et al, 2010), portal vein embolization (PVE) (Manizate et al, 2010), and ablative technologies.

Ablation is not a new concept; it has been used in medicine for more than 100 years, initially as a therapy designed for patients with unresectable lesions (Halsted, 1894); however, advancements in medicine have transformed ablation into an effective locoregional therapy with an improved perioperative profile for morbidity and mortality and options of performing the procedure using an open, laparoscopic, or percutaneous approach. It has evolved from injecting ethanol (Uflacker et al, 1986) to employing different energy sources, such as cryoablation (Iannitti et al, 1998), radiofrequency ablation (RFA) (Iannitti et al, 2002), and microwave ablation (MWA) (Simon et al, 2006) to achieve tumor destruction (see Chapters 85A through 85C). Current ablation therapies also provide the flexibility to perform procedures in an ambulatory setting to allow treatment of patients whose disease is not amenable to resection. The application of ablative technology does not necessarily preclude patients from future operations, nor does it compromise their chance for transplantation (Casaccia et al, 2009); however, complications resulting from ill-advised ablative procedures may complicate subsequent attempts at resection.

The most common thermoablative technologies used clinically are RFA and MWA. Both modalities produce tissue destruction, but the physical properties of the energy sources are different. MWA is a relatively new modality compared with RFA, and it provides important physical advantages over RFA.

Thermoablation is an effective modality, because irreversible thermal destruction of tissue occurs when temperatures above 50° C are maintained for an interval of 4 to 6 minutes (Larson et al, 1996). Vaporization and carbonization occur when tissue temperature is raised rapidly to over 100° C. Effective ablation relies on an adequate margin around the lesion, ideally 1 cm, to ensure complete eradication of microscopic foci. Large ablation volume may require multiple applications of thermal energy.

Physics of Microwave Energy

MWA that achieves heat destruction of tissue involves both active and passive heating. The active heating process of microwave energy requires the presence of dielectric molecules, such as water, to function. MWA is an excellent option for thermal ablation of solid organs, such as the liver (Brace, 2009a, 2009b). Clinical microwave energy operates at a frequency of 900 MHz to 10 GHz (Fig. 85D.1), which is much higher than radiofrequency (460 to 480 kHz). As a dipole molecule, water is affected by the applied electromagnetic field broadcasted by the microwave antenna. This property is called dielectric permittivity (ε). Water molecules orient themselves to the rapidly changing polarity of the electromagnetic field, and vibratory energy generates heat production. This process is called dielectric hysteresis. Microwaves emit nonionizing radiation for heating, and this produces homogeneous heating within the field regardless of the tissue types; this distinguishes MWA from monopolar RFA in terms of mechanism of heating and makes it a clinically superior method for ablation. The passive phase of microwave heating is by conduction of heat beyond the active heating zone and is susceptible to local tissue factors, such as heat and current sinking, which will be discussed later in this chapter.

FIGURE 85D.1 Electromagnetic spectrum.

The MWA systems used in the United States today are 915 MHz, 2.45 GHz, and 9.2 GHz; however, only the 915-MHz and 2.45-GHz systems are commercially available for tumor ablation. The 915-MHz and 2.45-GHz systems are more effective for large tissue destruction than monopolar RFA, and the 915-GHz system is currently under investigation for ablating lesions in the breast. Microwave energy can be generated through a magnetron or solid-state amplifier (Brace, 2009a, 2009b), and the antenna broadcasts the electromagnetic energy to the target tissue. The coaxial cable consists of an inner and outer conductor, and dielectric material is placed between the two layers. At its tip, the outer conductor is stopped to expose the inner conductor for broadcasting the microwave energy (Fig. 85D.2). This inner conductor is covered in a ceramic pointed tip for insertion into the tissue, and microwave energy can pass freely through the ceramic. The power loss is influenced by power output, cable diameter, and antenna design. Given its broadcasting characteristic, the microwave system does not require a grounding pad.

FIGURE 85D.2 A, Left, Microwave antenna as shown; the bracket points to the area from which microwave energy is broadcasted at the ceramic shield just beyond the termination of the outer conductor. B, Computer illustration of the projected microwave field from the microwave antenna.

Large ablative volume can be created by increasing the power and duration of the application. Several factors influence the final ablative size, including water content of the tissue, power output at the generator, power loss at the cable, antenna design, formation of clustered antennae, and the number of applications. Various tissue types exhibit different responses to microwave energy, and liver tissue usually exhibits a noticeable response to MWA (Hines-Peralta et al, 2006). Surgeons must understand the relationship between the different properties of tissue and the energy modality used to achieve successful ablation.

Local Tissue Factors That Affect Thermoablation

Local tissue factors play an important role in the final ablation volume and shape. The tissue’s electric conductivity (σ) and dielectric permittivity (ε) influence the deposition of energy for radiofrequency and microwave, respectively, which explains why MWA is more effective than RFA in depositing energy across vessels and liver parenchyma.

Modalities using radiofrequency rely heavily on the tissue’s electric conductivity, and heat is generated from ionic agitation of the molecules in the tissue. The tip of the monopolar RFA probe and the grounding pad forms a closed circuit, and alternate current passes between them. The current density is higher in the tip, compared with that of the grounding pad, because of the difference in surface area. The transfer of heat to the surrounding tissue is through conduction and is proportional to the amount of current deposited; however, the rate of perfusion to the target tissue could significantly affect the final heat transfer.

Coagulation necrosis of tissue is proportional to energy deposition minus heat loss (Goldberg et al, 2000). Hence, local tissue factors such as blood flow and tissue temperature affect energy deposition. Close proximity to blood vessels causes diversion of the current and decreases the amount of energy generated from the current; this is termed current sinking. The final ablative size is affected, because radiofrequency relies on heat transfer from the tip of the applicator, and the cooling from the vessel shunts the heat energy away; this phenomenon is termed heat sinking. Microwave technology also encounters such limitations but to a much lesser extent (Stauffer et al, 2003), because the propagation of microwave energy relies on the dielectric permittivity of the tissue, and it stays fairly constant along the broadcasted electromagnetic field (Table 85D.1). It can overcome the effect of current and heat sinking within its field and result in deeper heat penetration and more uniform ablative size. Outside the active heating zone, heat is propagated by conduction and is therefore susceptible to local factors such as heat sinking.

Another consideration is tissue desiccation and charring by the applicator during the heating process. Both conditions can significantly decrease the final ablative volume for RFA, because it requires a complete electric circuit to function. Acting as electric insulators, the resultant increase of impedance decreases the amount of current deposition and thereby decreases heat production. Moreover, if the target temperature is reached rapidly, above 100° C, the intracellular content vaporizes and carbonizes. The gas formation acts as an electric insulator that increases the impedance and hinders the heat diffusion (Dadd et al, 1996); both decrease the amount of current deposition and result in a less uniform ablative zone. Unlike radiofrequency, microwaves broadcast energy throughout the electromagnetic field and can achieve high power density uniformly, which results in deeper heat penetration and a more consistent ablative size.

915 MHz Versus 2.45 GHz

MWA, like RFA, can be carried out via three approaches: 1) open, 2) laparoscopic, and 3) percutaneous. The first clinical microwave system, Microtaze (Heiwa Electronics Industry, Tokyo), was developed in the 1990s. Clinical use was limited because of its 1.5-cm ablation zone (Saitsu et al, 1991, 1993), but 915-MHz and 2.45-GHz systems are currently available (Fig. 85D.3). Both systems were introduced to the United States market in 2008: the Viva Wave system (Valleylab, Boulder, CO) and the MTA microwave system (Microsulis Medical, Denmead, UK). Advancements in microwave technology and better antenna design have significantly improved ablative capabilities, and large-volume ablation can be reliably achieved.

FIGURE 85D.3 Commercially available ablation systems. A, Viva Wave system (Valleylab, Boulder, CO). B, Acculis MTA microwave system.

(B Courtesy Microsulis Medical Ltd, Denmead, UK.)

The Viva Wave system uses a 915-MHz generator, and its power output can reach up to 45 W. It carries two different sized antennae for open and laparoscopic/percutaneous use and usually employs a three-antennae cluster design for achieving a 5-cm zone of ablation; it requires three generators firing in a nonsynchronized fashion. A saline-infused cool-shaft antenna is also available to reduce the incidence of skin burn during transcutaneous antenna placement. Another system was approved by the Food and Drug Administration (FDA) in 2008, the MicroTherm X-100 (BSD Medical, Salt Lake City, UT). This is the only system with synchronized power output that uses multiple antennae.

The Acculis MTA (Microsulis Medical) is a 2.45-GHz system that uses a 5-mm antenna for its open application. It produces a 5-cm ablation zone reliably in 4 minutes and up to 8 cm in 8 minutes, with one application by a single antenna at 100 W. Currently under consideration by the FDA for approval is a 1.8-mm cool-shaft antenna for the laparoscopic/percutaneous approach.

The 2.45-GHz system is used more often in Europe and Asia, whereas the 915-mHz system is used in the United States; both are capable of producing an adequate ablation volume. The 2.45-GHz system uses a single antenna, and the 915-mHz employs a multiantenna array powered by separate generators. An advantage of using multiple antennae in different formations is to achieve various shapes and sizes of ablations (Simon et al, 2006). The microwave antenna is not composed of alloy but is coated with polytetrafluoroethylene (PTFE). It is not as rigid as the RFA metal applicator, and care should be taken during manipulation of the microwave antenna to prevent breakage at the tip of the antenna.

Technical Consideration for Performing Microwave Ablation

Three approaches can be used for MWA: 1) open, 2) laparoscopic, and 3) percutaneous. The underlying principles to achieve successful ablation are the same. Each patient represents a unique circumstance, and the chosen approach should be tailored to the patient’s need and the skill level of the practitioner. Lesions that are located anteriorly and not adjacent to a major pedicle can be ablated percutaneously using ultrasound (US), magnetic resonance imaging (MRI), or computed tomographic (CT) guidance. If the lesion is located deep in the liver, at the dome, next to a major pedicle, or adjacent to other structures such as the diaphragm and colon, ablation of these lesions should be performed surgically. The choice of an open or laparoscopic MWA is determined by the patient’s history of celiotomy and the surgeon’s level of advanced laparoscopic skill. If an open approach is used, it is best done through a subcostal or midline laparotomy.

Regardless of the approach, the patient is usually positioned supine on the table. The key of a successful ablative session is adequate exposure of the liver by taking down the suspensory attachments and performing a methodic evaluation of the liver by intraoperative US. All eight segments of the liver must be evaluated to ensure no lesions are missed, and it is helpful to review the preoperative imaging and formulate a table with information regarding the location and size of each lesion.

Once all lesions are identified, the plane of the needle tract should be evaluated to ensure that it does not cross a portal or major hepatic vein pedicle. The antenna is then deployed to treat the lesion. Close attention is paid to ensure no other structure is in the vicinity of the microwave field. Usually, the power and duration of each application is based on the size of the lesion and its proximity to major vessels, and 915 MHz can reliably reproduce a 5-cm ablative zone at 45 W for 10 minutes, and 2.45 GHz can achieve the same result with one antenna at 100 W for 5 minutes. The deepest lesion is usually treated first; in a staged procedure, the most difficult lesion is treated first.

Another consideration for ablating large lesions is how to overlap the zone of ablation. This is clinically challenging, given that the final ablative area is three-dimensional (3D), and the intraoperative US provides two-dimensional (2D) information in real time. Hence, a disciplined approach is needed to achieve adequate overlapping. Usually, the ablation is started at the most central medial portion of the lesion and progresses with the repeat ablations in an upward and outward fashion.

Clinical Results of Microwave Ablation for Hepatocellular Carcinoma (See Chapter 80)

The first open microwave application for tumor destruction was reported in the early 1990s in Japan, when Seki and colleagues (1994) reported a series of 24 patients with HCC with a 92% survival at 3 years. The application of microwave technology has since expanded to treat colorectal liver metastases and metastases from other primary tumors; this will be discussed later in this chapter.

Clinical trials have evaluated the efficacy of MWA for treating HCC. In a Phase I trial that evaluated the safety of MWA, 11 patients underwent hepatoma ablation followed by resection (Simon et al, 2006). The complete destruction of viable tumor cells was confirmed by immunohistochemistry in the ablation zone. The average volume of ablation was 5.5 cm in diameter using three clustered antennae at 45 W for 10 minutes. The Phase II trial enrolled 87 patients for whom MWA was the primary treatment (Iannitti et al, 2007). In 94 ablation sessions, 224 lesions with a mean diameter of 3.6 cm were treated (Fig. 85D.4). The local recurrence rate was 2.7%, and regional recurrence was 43% during 19 months of follow-up; overall mortality rate was 2.3% with no procedure-related deaths. Major complications included two patients with postoperative fluid collections that required a drainage procedure and five patients with minor skin burn at the needle tract. This clinical trial proved that using MWA for hepatic tumors is a safe, effective treatment option with a low complication rate. Multiple series were subsequently published reaffirming the role of MWA in treating liver lesions (Table 85D.2; Kawamoto et al, 2005; Martin et al, 2009).

FIGURE 85D.4 Computer tomography (CT) images of for a large segment VII liver lesion. A, Preablation. B, Postablation. CT images of multiple neuroendocrine lesions in the liver. C, Preablation. Arrows indicate liver lesions. Postablation scans show successful ablation at segment VI (D), segment VII (E), and segment VIII (F).

Microwave Ablation: Specific Complications and Future Applications

MWA heats the entire electromagnetic field, and several potential complications may arise from this modality. Technical advances have made ablation near large vessels possible, which increases the potential for thrombus in the hepatic vein. The true incidence of hepatic vein thrombus (HVT) related to MWA is unknown. We identified three such cases in 122 MWA applications, all without symptoms, and the thrombus resolved after anticoagulation. We have used a porcine model to reproduce HVT, and it appears that puncturing the hepatic vein during MWA is a risk factor (Sindram, 2011). Surprisingly, the proximity of MWA to the hepatic vein is only associated with minimal endothelial damage.

Skin burn at the needle tract during laparoscopic/percutaneous application is an MWA-specific injury that has been reported in the literature (Iannitti et al, 2007). It can occur when the power output is increased, and the outer conductor does not sufficiently shield the microwave energy (Liang et al, 2009). The risk of skin burn can be minimized by reducing the inward angulation of clustered antennae, spacing antennae 1.5 cm apart, and applying an internal cooling tip with running saline to reduce the temperature (Sindram, 2011).

All structures within the microwave field are heated, so it is essential to be aware of critical structures within the field, such as the diaphragm and heart. Further research is ongoing for development of a microwave shield to potentially decrease risks to vital organs.

Another logical extension of microwave technology, similar to radiofrequency, is using the microwave energy to coagulate liver parenchyma before resection. Radiofrequency devices are commercially available for this purpose but require a longer application time.

Microwave technology offers superior physical properties compared with radiofrequency, and it makes ablating larger lesions in the liver possible. One series reported that large-volume ablation can be effectively and safely done with a recurrence rate of 22% for HCC lesions in sizes ranging from 3 to 7 cm (Yin et al, 2009).

Emerging Technologies

The ideal ablation system should be safe, cost effective, and have reproducible ablation results and a tissue-specific applicator design with real-time feedback for dedicated algorithms to achieve optimal ablation size. Although no current system fits these criteria perfectly, new technologies that show great promise are on the horizon.

Real-Time Three-Dimensional Virtual Reality–Guided Targeting

The advancement in ablation technology has proved that large-volume ablation is a reality, but this capacity is useless if the targeting of a lesion is inaccurate. The complete destruction of a lesion requires an adequate margin, and achievement of this margin often requires multiple applications for adequate overlap of the ablation zone. The use of 2D ultrasound has greatly enhanced the ability to identify a target lesion, but deploying the microwave requires complex coordination between interpreting the information on the monitor and positioning the applicator to track the course from the parenchyma into the tumors. This complicated process has a learning curve, and even in the hands of an expert, improper applicator position can occur. So achieving an adequate 3D overlap of the ablative zone is challenging, especially when only 2D information is available. To aid the surgeon in this process, a real-time 3D system was developed by InnerOptic (Hillsborough, NC). Using either an electromagnetic field generator with sensors or stereoscopic infrared cameras with reflectors, real-time 3D information is generated into virtual reality images and projected on a true 3D stereoscopic screen (Fig. 85D.5). This provides valuable information for targeting lesions, especially from an angle that is out of the plane of the US probe. The safety and accuracy of various procedures such as biopsy, venous catheter placement, and percutaneous ablation might be improved once this system is available commercially.

FIGURE 85D.5 Three-dimensional virtual reality image guidance system. Note the computer-generated ablation zone at the tip of the needle.

Future Directions

The future of ablation is exciting, and MWA will likely play a more prominent role in thermoablation. The theoretic advantages of its physical properties make it a reliable choice for ablation of liver lesions, especially for lesions larger than 3 cm or those near blood vessels. The addition of other modalities, such as high-intensity focused US and irreversible electroporation, complements MWA and allows practitioners more treatment choices for liver lesions. The emerging technologies, such as a real-time lesion-guidance systems, will increase the accuracy of ablation and may help define niche applications for various ablative modalities.

The continuing evolution of technologies for tumor destruction and the addition of accurate targeting systems will doubtless allow more surgeons to treat unresectable liver cancers with low morbidity and mortality. It is imperative to create a curriculum for upcoming hepatopancreatobiliary surgeons that will help them master ablative therapy and incorporate similar new technologies into practice.