1089-2http://d

Departmcer

AddresDepCansofo

“How We Do it”—A Practical Approach to HepaticMetastases Ablation Techniques

Constantinos T. Sofocleous, MD, PhD, Panagiotis Sideras, MD, and Elena N. Petre, MD

516/13/$ - seex.doi.org/10.1

ent of IntervCenter, News reprint reqartment of Incer Center,clec@mskcc.o

Secondary liver malignancies are associated with significant mortality and morbidity ifleft untreated. Colorectal cancer is the most frequent origin of hepatic metastases. Amultidisciplinary approach to the treatment of hepatic metastases includes medical,surgical, radiation and interventional oncology. The role of interventional oncology in themanagement of hepatic malignancies continues to evolve and applies to a large andcontinuous spectrum of metastatic disease, from the relatively small solitary metastasisto larger tumors and multifocal liver disease. Within the past 10 years, severalpublications of percutaneous image-guided ablation indicated the effectiveness andsafety of this minimally invasive therapy for selected patients with limited number(arguably up to 4 metastases) of relatively small (less than 5 cm) hepatic metastases.Different image-guided procedures such radiofrequency, microwave, and laser causethermal ablation and coagulation necrosis or cell death of the target tumor. Cryoablation,causing cell death via cellular freezing, has also been used. Recently, irreversibleelectroporation, a nonthermal modality, has also been used for liver tumor ablation. In thefollowing section, we review the different liver ablation techniques, as well as indicationsfor ablation, specific patient preparations, and different “tricks of the trade” that we useto achieve safe and effective liver tumor ablation. We also discuss appropriate imagingand clinical patient follow-up and potential complications of liver tumor ablation.Tech Vasc Interventional Rad 16:219-229 C 2013 Elsevier Inc. All rights reserved.

KEYWORDS percutaneous ablation, ablation techniques, thermal ablation, radiofrequencyablation, microwave ablation, cryoablation

Patient EvaluationInterventional oncologists have become important mem-bers of a multidisciplinary team managing a patient withcancer. As physicians treating cancer, interventional oncol-ogists perform a thorough evaluation of the patient withcancer in dedicated clinic visits. A typical clinical evalua-tion should include the history of present illness, reviewof systems, medical and surgical history, assessment ofperformance status, family and social history, allergies,medications, physical examination, laboratory review, andimaging review, with a focus on the discussion of interven-tional treatment options and their respective outcomes.1

When obtaining the history of present illness, attention

front matter & 2013 Elsevier Inc. All rights reserved.053/j.tvir.2013.08.005

entional Radiology, Memorial Sloan-Kettering Can-York, NY.uests to Constantinos T. Sofocleous, MD, PhD,terventional Radiology, Memorial Sloan-Kettering1275 York Ave, New York, NY 10065. E-mail:rg

should be paid to prior radiation therapy, chemotherapy,resections, and interventional treatments. An understandingand discussion of the tumor biology, the chronology, andthe status of the disease are essential. Assessment of patientperformance status is an overall evaluation of the ability ofpatients to function and take care for themselves. Perform-ance status is a potent prognostic indicator for overallsurvival.1

The Eastern Cooperative Oncology Group Scale ofPerformance Status is a 6-point scale ranging from 0-5,with 0 representing normal activities without limitationsand 5 indicating death.2

Quality-of-life evaluation is somewhat similar to per-formance status but more directly focuses on the patient'sability to perform activities of daily living (eating, bathing,and dressing) and instrumental activities of daily living(driving, shopping, and paying bills).3

In general, interventional therapies such as ablation arenot indicated for patients with poor performance status(Eastern Cooperative Oncology Group 42). The labora-tory review should start with a complete blood count,

219

C.T. Sofocleous, P. Sideras, and E.N. Petre220

creatinine level, prothrombin time, and internationalnormalized ratio. Additional tests such as a liver functionpanel and relevant tumor markers such as carcinoem-bryonic antigen, chromogranin A, and carbohydrate anti-gen 19-9 should be obtained as needed for the specifictumor to be treated.1

Personal review of cross-sectional imaging (particularly,abdominal dynamic computed tomography [CT]) is crit-ical. Our recommendation is to perform a triple-phase CTwithin 30 days of any liver tumor ablation.4 The triplephase depicts the target organ without contrast, similar towhat is seen on the CT the day of the ablation. The arterialand portal venous phases give valuable informationregarding tumor characteristics that may modify the treat-ment plan. A hypervascular tumor, for example, may bebest treated with a combination of transarterial emboliza-tion and ablation rather than ablation alone. Carefulevaluation of tumor number, size, morphology, location,adjacent structures, and extrahepatic spread aids in thedetermination of treatment modality and feasibility.1

Clinical Indications andContraindications for LiverTumor AblationThe most common indications for image-guided ablationare the following:

1.

Patients with limited number (arguably less than 4) andsmall size (arguably less than 5 cm in largest diameter)of hepatic metastases that cannot undergo or refusesurgery.

2.

Lesions that are judged to be amenable to completeablation with sufficient margin when using the appro-priate ablation technique.Expanding from these criteria it should be noted that:

The ideal tumor for percutaneous ablation is a solitarylesion with largest diameter up to 3 cm.Tumor size up to 5 cm may be acceptable for ablation

although multiple overlapping ablation will be requiredto achieve complete ablation with a sufficient surround-ing margin (ideally a 1 cm margin all around the tumorshould be created).There is no absolute number of tumor eligibility but

most series agree that patients with more than 4simultaneous liver metastases are not good candidatesfor image-guided percutaneous ablation.

The following are the contraindications:

1.

No safe access of the ablation needle to the tumor. 2. Proximity to a vital structure that would be injured by

the ablation despite protective maneuvers such ashydrodissection.

3.

Uncorrectable coagulopathy. 4. A relative contraindication is the inability of a patient to

undergo general anesthesia.

5. Close proximity to the porta hepatis and large vessels.

Types of Ablation

Radiofrequency Ablation (RFA)RFA involves the administration of energy with frequency ofo900 kHz into tissue via needle electrodes. Ablation causestargeted tissue necrosis or cell death via ionic agitation of watermolecules by elevating tissue temperature to lethal levels.Highest success rates of ablation are achieved in patients

with solitary colorectal liver metastases (CLM) or patientswith small number of metastases o3 cm in the largestdiameter.5

The principles and technical considerations of RFA aredescribed comprehensively in a separate review article inthis issue.

CryoablationCryoablation circulates liquid nitrogen or argon to a probetip, causing rapid cooling of tissue and the formation ofintracellular ice crystals. Subsequent damage to the adja-cent microvasculature disrupts tissue perfusion, leading toischemia. Tissue death occurs by freezing at temperatures�401C or lower.Cryoablation technique is described in detail in a

separate review article.

Microwave Ablation (MWA)MWA uses high-frequency waves in the range of 900 MHzand 2.4 GHz. These high-frequency waves, much like RF,cause water molecules to oscillate creating friction thatgenerates heat and tissue destruction.6

MW technology is described together with the otherablation modalities in a separate review article in this issue.

Irreversible Electroporation(IRE)IRE technology (ie, Nanoknife System, AngioDynamics,Queensbury, NY) is a nonthermal ablation modality.Electroporation involves permeabilization of the cell mem-brane via application of electrical pulses across the cell,which creates permanent cell membrane pores (openings),causing lysis and cell death.7

IRE is presented in a separate review article in this issue.

Procedural Steps—Intraoperative ManagementUse of AnesthesiaA significant number of percutaneous ablation procedurescan be done on an outpatient basis requiring shortpostprocedure observation before discharging the patienthome, provided that patient is clinically stable and feelingwell. As such, image-guided ablation is associated withsignificantly less morbidity and shorter length of hospitalstay when compared with intraoperative interventions,

Hepatic metastases ablation techniques 221

such as laparoscopic resection, intraoperative ablation, orintraoperative resection.Image-guided liver RFA can be performed with con-

scious sedation, the preferred approach in Europe, orgeneral anesthesia, which is generally preferred in the USA.The decision to use conscious sedation or general anes-thesia is variable and is at the discretion of the physicianperforming the procedure. Cryoablation, in contrast toRFA, is relatively painless procedure, and patients may beoffered conscious sedation more often than with RFA orMWA.8 Our clinical practice and recommendation is touse general anesthesia for any type of tumor ablation.Although we understand the possible risks associated withgeneral anesthesia, we have noticed that the use of generalanesthesia has certain advantages and may even be safer.This is in particular the case when extensive imaging isrequired to actually visualize and accurately target thelesion. In such a lengthy process, patient cooperation isessential, and we believe that the risk of patient motionowing to discomfort or pain is higher than that of generalanesthesia. In addition, the presence of the anesthesiologistin the procedure room allows the interventional oncologistto concentrate constantly on tumor eradication withoutbeing concerned about managing patient's discomfort orpain. This is extremely important in particular whenadditional protective maneuvers such as hydrodissection

Figure 1 A 76-year-old female with colorectal cancer was refThe lesion was visible on both contrast-enhanced CT scan (ausing a RITA ablation system was performed with the help otargeting and coverage of the tumor by the ablation zone w

are required to protect adjacent structures from theablation zone.

Ablation Guidance and ProcedureA key component of any ablation procedure is the visual-ization of the target tumor and the accurate targeting ofthe tumor by the ablation needle to create an ablationzone with sufficient margins. The choice of imagingmodality is extremely important. There are geographicdifferences related to the availability of different imagingequipments in different countries. In Asia and Europe, itappears that ultrasound guidance (Fig. 1) is the preferredmethod, whereas in the USA, CT guidance is morecommon. We strongly recommend CT guidance with theavailability of CT fluoroscopy and ultrasound (Fig. 1).CT affords the interventional radiologist a complete viewof the target area, as well as the surrounding organs,whereas ultrasound and CT fluoroscopy provide the toolsfor real-time visualization of electrode placement andmonitoring of the ablation in real time. Recent develop-ments have allowed the use of positron emission tomo-graphy (PET)/CT as a guiding tool for ablation in certaininstitutions (Fig. 2). We are fortunate to have this cap-ability and are currently investigating the added valueof PET/CT not only for improved target localization but

erred for radiofrequency ablation of a liver metastasis.rrow) (A) and ultrasound (B). Radiofrequency ablationf both CT (C) and US (D) guidance to ensure adequateith sufficient margins (E).

Figure 2 Radiofrequency ablation using PET/CT guidance. (A) Fused FDG PET/CT imaging before ablation showsliver metastasis (arrow). (B) Insertion of LeVeen needle electrode is performed using PET/CT guidance. (Colorversion of figure is available online.)

C.T. Sofocleous, P. Sideras, and E.N. Petre222

also as surrogate imaging biomarker of complete ablation(Fig. 3).9

Immediate Postprocedure ManagementPostprocedure care should focus on pain and nausea reliefas well as monitoring for complications. For cases thatrequired transthoracic passage of the electrode, as may bethe case for dome lesions, attention should be paid to thedetection and prompt treatment of pneumothorax. Thisoften is done during the procedure and allows the con-tinuation and safe completion of the ablation (Fig. 4).

Figure 3 PET/CT as a tool for both guidance and evaluatioallows for accurate target identification (arrow). (B) Placablation. (C) Fused PET/CT immediately after ablation shversion of figure is available online.)

Similar to lung ablation, the interventional oncologistshould be familiar with the management of growing, largeor symptomatic pneumothorax with thoracostomy. Forpatients with stable small pneumothorax, we recommendchest radiographs immediately on completion of theablation and then again 2 hours later. Stable patients,without pneumothorax, or those with small asymptomaticand stable pneumothorax who do not require any intra-venous medication for pain or nausea may be able to gohome the same day after ablation, provided they are able tokeep oral intake and can urinate. Postablation pain andlow-grade fever can usually be managed with ibuprofen

n of treatment effectiveness. (A) Fused FDG PET/CTement of three Covidien Cool-tip electrodes for RFows the photopenic ablation defect (arrows). (Color

Figure 4 Pneumothorax developing during microwave ablation of a colorectal liver metastasis located in the domeof the liver using a transthoracic approach (A). Insertion of a thoracostomy catheter permitted safe completion ofthe ablation (B).

Hepatic metastases ablation techniques 223

administered orally; however, some patients may requirenarcotic analgesic medications, especially for subcapsularor dome lesions.

Technical Challenges or ProtectiveManeuversThere are several technical challenges that a practicinginterventional radiologist may face while performingablation of liver tumors. Most of these challenges originatefrom the goal to create a safe and effective ablation zonethat encompasses the target lesion with clear margins (atleast 5 and ideally 10 mm all around the tumor) while

Figure 5 A transthoracic route is the only approach for sulesions (arrows) (A). An artifical pneumothorax is performe

taking the appropriate steps to minimize injury to thesurrounding normal liver and adjacent organs. Particularlychallenging are tumors located in subcapsular locations, inthe dome or adjacent to a bowel loop. Similarly, lesionsin the central liver near a major bile duct or vascularstructure pose a challenge in terms of achieving ablationwith clear margins without injuring the adjacent structure.A careful review of the preprocedure diagnostic imagesidentifies the tumor location and its relation to structuresthat need protection. The operator determines the safestand shortest pathway from the skin surface to the tumorwhile avoiding crossing structures that could be injured, asmuch as possible. There would be instances when technical

ccessful radiofrequency ablation of the dome-locatedd to protect the normal lung during ablation (B).

Figure 6 Protective hydrodissection needed to protect the adjacent colon during radiofrequency ablation of asegment 6 liver metastasis (A). Multiplanar reconstruction before (B) and after (C) confirms the creation of a buffer.

C.T. Sofocleous, P. Sideras, and E.N. Petre224

steps such as air dissection or artificial pneumothorax arecreated to protect the normal lung when the needle needsto reach a dome lesion and a transpulmonary approachis necessary (Fig. 5). In other instances, hydrodissectionwith the instillation of sterile water or 5% dextrose createsan artificial space (ascites), buffering the liver surface fromadjacent organs to protect them from thermal injuryduring ablation (Fig. 6). When we contemplate ablationclose to the gastrointenstinal tract, body wall, diaphragm,or other organs such as the pancreas or the stomach, weuse infusion of 5% dextrose or sterile water to createartificial ascites and protect against nontarget thermalinjury and decrease intraprocedure and postprocedurepain.10 The type and number of probes and number of

ablations are planned to achieve a total ablation zone of atleast 5 mm circumferentially larger than the tumor. Thisadditional circumferential margin of ablation mitigateslocal recurrence. Tumor diameters equal to or larger thanthe size of a single ablation zone require multiple over-lapping ablations to create a sufficient margin.1 Geometricmodeling assuming spherical target and ablation zonespredicts that 8 perfectly overlapped ablations would beneeded to cover a tumor 1 cm larger than the probe. This,in practice, is very difficult, and it may account for the highlocal failure rate, especially for tumors larger than 3 cm.Another technical consideration is perfusion-mediatedcooling by adjacent vessels (the ‘‘heat-sink’’ effect). Bloodvessels as small as 3 mm have sufficient flow to provide

Hepatic metastases ablation techniques 225

convective cooling that limits the size of the ablation zone.Placement of a balloon occlusion catheter into the hepaticvein or inferior vena cava during the ablation may help toprevent this effect.11

At the conclusion of the procedure, most thermalsystems allow for ablation along the needle track todecrease the risk of bleeding and tumor seeding. Werecommend such track ablation when withdrawing theneedle from relatively deep-seated lesions; however, wewould like to indicate that the track should not becauterized all the way to the liver surface to preventburning the capsule or the adjacent chest or abdominalwall.Triple-phase enhanced CT should be performed at the

conclusion of every liver tumor ablation to evaluate forcompleteness of the ablation, recognizing that the intenseinflammatory reaction to thermal ablation may result insubstantial perilesional enhancement and abnormal perfu-sion patterns in the surrounding liver. The ablation zoneshould not enhance and should be larger than the targettumor accounting for the desired margin. The nonen-hanced phase of the scan is important to identify newperilesional bleeding or collection or demonstrate thebaseline appearance of iatrogenic ascites in those casesthat required hydrodissection. Small amount of hyper-density in the ablation zone depicted during the non-contrast phase of the CT is common and represents smallamount of blood.

Complications and TheirManagementHemorrhageClinically significant bleeding is extremely rare especiallyafter RF or MWA. Catastrophic bleeding was reported inearly series of intraoperative cryoablation and was attrib-uted to the thawing cycles causing liver fracture. Even inthat scenario, the well-aware interventional radiologist,using current imaging modalities, would detect bleedingthat could be managed with hepatic arterial emboliza-tion.12 The standard continuous electrophysiological mon-itoring of the patient during the procedure is anothermeans for the early detection of possible clinically signifi-cant side effects or complications, including hemodynami-cally significant bleeding.

Tumor Lysis Syndrome (Cryoshock)This was also described after early series of cryoablation.Tumor lysis syndrome was attributed to a severe systemicreaction resulting in thrombocytopenia and disseminatedintravascular coagulopathy or even hepatic, renal, ormultiorgan failure.13 When this was reported, it wasrelated to larger ablation volumes caused by the earliestgeneration of cryoablation devices. Such complicationshave not been reported with heat-generating ablationmodalities. This was thought to be because of thecoagulation caused in surrounding small blood vessels,

preventing entrance of necrotic substances in the systemiccirculation and thus diminishing the incidence of ageneralized immune response.

AbscessesPostablation abscesses are extremely rare. However, aswith other liver interventions, they have been observed at arelatively high frequencies in patients who have undergonebiliary interventions including sphincterotomy, biliaryenteric anastomoses, or biliary catheterization that resultedin prior contamination of the biliary tree by entericcontents. The use of biliary excreted antibiotics in theperiablative period and for the following 5-10 days cansignificantly reduce this risk.14-16 We routinely use thesame antibiotic prophylaxis (intravenous Piperacillin-Tazobactam for 5 days) as we do with the same high-riskpopulation when undergoing hepatic embolotherapies.The highest risk and the likelihood of abscess formationrequiring drainage should be discussed with the suscep-tible patients and their referral oncologist.

Tumor SeedingThe risk is increased with subcapsular lesions requiringmultiple capsular punctures and larger applicators. Forsuch lesions, we recommend access via a route that lets theneedle pass through normal liver allowing track ablationupon electrode withdrawal.

Postablation SyndromeThis is a very mild form of tumor lysis syndrome andpresents with malaise and low-grade fevers. This syndromeis milder than the well-described postembolization syn-drome and can often be managed with nonsteroidalantiinflammatory drugs orally. It is very rare that post-ablation syndrome requires hospitalization.

Biliary ComplicationsThis usually occurs when ablating a centrally located lesionin proximity to a relatively large bile duct, especially whentreating tumors near the porta hepatis. Of note, bilomashave been recently shown to occur more frequently thanpreviously reported after percutaneous RF ablation ofhepatocellular carcinoma (HCC). In most cases, theyappeared to be a minor complication and resolved withoutany treatment. The use of the newest nonthermal ablationmethod of IRE can prevent the occurrence of complica-tions related to bile duct injury.17

Liver FailureThis severe complication can be fatal; however, it isextremely rare after ablation when patient selectionadheres to the guidelines and indications.18 Patients withlimited or compromised hepatic reserve and the treatmentof large tumors requiring large ablation volumes are

C.T. Sofocleous, P. Sideras, and E.N. Petre226

obvious risk factors and should be taken into consider-ation when planning the treatment.

PneumothoraxIt can occur when treating lesions near the diaphragmaticdome. Similar to lung ablation, thoracostomy manages thepneumothorax and allows the completion of the ablationtreatment in the vast majority of patients.A summary of the most common complications19,20 ispresented in Table 1.

Follow-upFor the proper evaluation of response to treatment and theearly detection of local tumor progression, a postablationscan at 4-8 weeks is considered the new baseline for futurecomparisons. By definition, the ablation defect is largerthan the treated tumor, and any future comparisons todetect local tumor progression are made to this firstpostablation scan. Subsequent scans at 2-4 months arerecommended to detect local, near-local, and distantdisease progression. Despite the use of PET/CT andimplementation of the new PET response in solid tumorscriteria,21-23 assessment of treatment response with imag-ing modalities still remains suboptimal. It appears veryappealing to create a new set of criteria such as those thatexist for the assessment of HCC in the arterial phase of CT.Because CLM are in general enhancing less than classichypervascular tumors such as HCC or GIST, a postulationonly can be made by assessing response by measuringchanges in Hounsfield units during contrast enhancementof the target tumor before and after ablation. In general theablation zone should have no enhancement. An increase inenhancement of part of the ablation zone in subsequentCT should raise suspicion for tumor progression.

Discussion and Outcomes ofAblationA key concept when managing liver metastases withablation is the “test-of-time’’ approach.24 Within thisconcept, patients who were candidates for liver resection

Table 1 Complications, Risks, and Factors Associated With Their

Type of Complication Risk (%)

Death o1 Liver failure, hemorrhLiver failure 1-2 Related to liver reservHemorrhage 2-4 Abnormal coagulationInfection or abscess o5 Vast majority related

Sphincter of OddiIntercostal nerve injury o1 Posterior superficial tBowel-gallbladder-biliaryinjury

�1 Adjacent to tumor

Tumor lysis syndrome(Cryoshock)

o1 Large ablation volum

Pneumothorax o5 Transpleural approac

underwent liver RFA instead. The patients in the trial wereclosely monitored with imaging to detect local, intra-hepatic, or any other progression. This close observationallowed time for biology of the disease to express itselfwhile the identified tumor was treated by ablation. Duringthe follow-up period of this study, 98% of the patientswho had successful ablation were spared unnecessarysurgery either because RFA completely treated the targettumor or owing to the development of multifocal diseaseprogression during the follow-up period, rendering thepatients noneligible for surgery. This latter group, devel-oping multifocal disease within a short time after ablation,was spared unnecessary and morbid surgery. Thisapproach afforded observation of the patient for a fewmonths, allowing for the disease to express its naturalcourse and without jeopardizing surgery. The patientswho had local-only progression at the site of the priorablation were treated with repeat ablation or resection. Inour opinion, this approach is very useful at the initialmanagement of liver metastasis, if ablation with sufficientmargins can be created. It provides local control of thetarget tumor while allowing time for the tumor to expressits biology. This spares several patients unnecessarysurgery.The exact role of ablation in the management of

metastatic liver disease remains unclear and differs amonginstitutions. There is consensus that ablation is indicatedin the management of tumors in patients who cannotundergo surgery and have liver-only disease or in thosewith disease progression in the liver in the face ofotherwise controlled oligometastatic disease.25 The roleof ablation as a salvage therapy for postsurgical recurrencesis also recognized.26,27 There are preliminary data tosuggest that percutaneous ablation may have outcomessimilar to those seen after surgery, especially when itcomes to overall patient survival.25,27-29 This is despite thefact that most ablation series included the patients whowere rejected for surgery owing to comorbitidies.Although survival data between ablation and surgical seriesare comparable, the relatively high rates of local progres-sion in the image-guided ablation series make it hard tosuggest ablation instead of surgery at this point. This couldbe partially explained by a key advantage of surgery whencompared with ablation and specifically the ability to

Development.

Risk Factor(s)

age, or recalcitrant abscesse and ablation volume as well as underlying hepatic reserveprofileto prior biliary intervention with manipulation of the

umor

e

h

Hepatic metastases ablation techniques 227

evaluate margins by histopathology until all the tumors areremoved and sufficient margins are created whenever safeand possible. This shortfall of image-guided ablation hasbeen demonstrated by studies that evaluated the correla-tion between tumor cells30 that were found to beviable30,31 or prolific32 and local tumor progression32,33

as well as overall patient survival34 after liver tumorablation. Further research in this field is very importantto further understand and develop biomarkers and surro-gate imaging biomarkers that could detect early, residualtumor in the ablation zone. Ideally, such biomarkerswould allow detection of residual tumor at the end ofeach ablation so that extension of the ablation zone to theuntreated areas could be achieved before the completion ofthe procedure. Despite this significant limitation, one canuse ablation as the first line of treatment within the “test-of-time” concept and with the understanding that closeimaging and clinical follow-up would be implemented forthe early detection of local recurrence that can be resectedat a later stage. Within this same concept, it would be verydesirable to design randomized controlled trials comparingsurgery with ablation for selected patients with smalltumors that could be ablated completely with clearmargins. We do recognize that such trial would requiremulti-institutional cooperation, and as many similar trialsin oncology, it may be extremely difficult if not impossibleto complete with sufficient accrual to address whetherindeed ablation is comparable to surgery for selectedpatients.In the following paragraphs, we present a brief review of

current experience with percutaneous thermal ablation invarious metastatic settings.

Colorectal Cancer MetastasesIn the past few years, there has been a shift in paradigm insurgical resectability of CLM regarding the number oflesions and preservation of R0 resection yielding good5-year overall survival rates.35 The most challenging ques-tion is not only limited to the creation of sufficient (over10 mm) surgical margins but also in the determination ofthe amount of healthy liver needed to be preserved foradequate liver function. This requirement for residual livervolume can be different for patients receiving intensivechemotherapy. Although at least 20% of total liver volumeshould be preserved for a healthy liver, it is recommendedthat at least 30%-60% should be preserved for liversimpaired by chemotherapy-associated steatosis.36

RF ablation has been used to control liver metastasessuccessfully in selected patients with nonresectable diseaseand relatively small and limited number of tumors.5,28,32

In a series with good selection criteria, 1-, 3-, and 5-yearsurvival rates of 86%, 80%, and 24%, respectively, havebeen reported.28 More recently, long-term (10 year)survival was reported by the same authors.28,37 In thisupdated report, 1-, 3-, 5-, 7- and 10-year survival rateswere 98%, 69%, 48%, 25%, and 18%, respectively and themedian survival time was 53 months.28 Although there hasbeen no randomized controlled trial conducted to

compare surgery vs RFA for CLM, retrospective studiesthat compared the 2 treatments demonstrated comparableoutcomes.38,39

One of the advantages of percutaneous ablation is that itcan be repeated if necessary and can be used to salvagerecurrences after resection26 or prior ablation. Yet anotheradvantage is that chemotherapy interruption (unlike6-week interruption often required with surgery) is notnecessary for ablation.40 In an attempt to demonstrate anysurvival benefit of the addition of ablation to chemo-therapy in the management of unresectable disease, astudy compared outcomes of RFA plus chemotherapy vschemotherapy alone.41 There was a significant improve-ment in 3-year progression-free survival of 27.6% for RFAplus chemotherapy when compared with a 10.7% forchemotherapy alone (P ¼ 0.025), but 30-month overallsurvival was similar amongst the 2 groups (63.8% for RFAplus chemotherapy and 58.6% for the chemotherapy-alone arm).

Breast Cancer MetastasesThe liver is involved in most patients who develop breastcancer metastases, but only 5%-18% of patients havedisease confined only to the liver at the time of presenta-tion.42 In metastatic liver breast cancer, local control withRFA as well as assessment of intermediate- and long-termsurvival was performed.43-45 Although direct compa-risons are impossible, it appears that survival was com-parable to what it has been reported after surgery46 or laserablation.47 Inclusion criteria were as follows: fewer than5 tumors, maximum tumor diameter not larger than 5 cm,and disease confined to the liver or stable extrahepaticdisease controlled by systemic therapy. Patients withtumors 2.5 cm in diameter or larger had a worse prog-nosis than those with smaller tumors. Local tumorprogression occurred in 25% of patients, and new intra-hepatic metastases developed in 53%. Overall mediansurvival time, from the time the first liver metastasiswas diagnosed, was 42 months and 5-year survival was32%.44 Presence of extrahepatic disease, with the excep-tion of skeletal metastases, is associated with shortersurvival after RFA of breast cancer liver metastases.45 Thisfinding highlights the concept that in the setting ofmetastatic disease, every tumor site has to be consideredseparately.

Other MetastasesTheoretically, ablation technologies offer several benefitsover the surgical approaches, including lower complica-tion rate, shorter hospital stay, and a generally favorablesafety profile regardless of tumor pathology. There is,however, a paucity of data to support the use of ablationfor treatment of metastatic liver disease from otherprimaries, in which, sometimes, even the role of liverresection remains controversial.48 Although more scarcethan the data for CLM, there is some evidence that ablationis useful in treating neuroendocrine liver metastases,

C.T. Sofocleous, P. Sideras, and E.N. Petre228

especially in nonresectable patients and patients withsymptoms refractory to medical care.49 Most literaturethat reports on thermal ablation of noncolorectal, non-neuroendocrine liver metastases, such as renal cell carci-noma, sarcoma, cholangiocarcinoma, ocular melanoma,and others is comprised of case reports and small numberseries.50-52 Further investigations may help determine therole of ablative therapies in the treatment of less commonhepatic metastases.In summary, we described the main modalities of tumor

ablation to date and have offered a rationale for the bestuse of ablation in the clinical setting. Technical researchand developments would further advance the field ofablation and would expand the indications for its use.We strongly believe that in the near future, a much largernumber of patients would be candidates and would benefitfor image-guided tumor ablation.

References1. McCarley JR, Soulen MC: Percutaneous ablation of hepatic tumors.

Semin Intervent Radiol 27:255-260, 20102. Sorensen JB, Klee M, Palshof T, et al: Performance status assessment

in cancer patients. An inter-observer variability study. Br J Cancer67:773-775, 1993

3. Gomaa AI, Khan SA, Leen EL, et al: Diagnosis of hepatocellularcarcinoma. World J Gastroenterol 15:1301-1314, 2009

4. Pua BB, Sofocleous CT: Imaging to optimize liver tumor ablation.Imaging Med 2:433-443, 2010

5. Gillams AR, Lees WR: Radio-frequency ablation of colorectal livermetastases in 167 patients. Eur Radiol 14:2261-2267, 2004

6. Izzo F: Other thermal ablation techniques: Microwave and interstitiallaser ablation of liver tumors. Ann Surg Oncol 10:491-497, 2003

7. Lee EW, Chen C, Prieto VE, et al: Advanced hepatic ablationtechnique for creating complete cell death: Irreversible electro-poration. Radiology 255:426-433, 2010

8. Allaf ME, Varkarakis IM, Bhayani SB, et al: Pain control requirementsfor percutaneous ablation of renal tumors: Cryoablation versus radio-frequency ablation—Initial observations. Radiology 237:366-370, 2005

9. Ryan ER, Sofocleous CT, Schoder H, et al.: “Split-dose” technique forFDG PET-CT guided percutaneous ablation: A method to facilitatelesion targeting and to provide immediate assessment of treatmenteffectiveness. Radiology 268:288-295, 2013 doi: 10.1148/radiol.13121462. Epub 2013 Apr 5.

10. Hinshaw JL, Laeseke PF, Winter TC 3rd, et al: Radiofrequencyablation of peripheral liver tumors: Intraperitoneal 5% dextrose inwater decreases postprocedural pain. AJR Am J Roentgenol 186:S306-S310, 2006

11. de Baere T, Bessoud B, Dromain C, et al: Percutaneous radio-frequency ablation of hepatic tumors during temporary venousocclusion. AJR Am J Roentgenol 178:53-59, 2002

12. Ross WB, Horton M, Bertolino P, et al: Cryotherapy of liver tumours—A practical guide. HPB Surg 8:167-173, 1995

13. Seifert JK, Stewart GJ, Hewitt PM, et al: Interleukin-6 and tumornecrosis factor-alpha levels following hepatic cryotherapy: Associa-tion with volume and duration of freezing. World J Surg 23:1019-1026, 1999

14. Deodhar A, Brody LA, Brown KT, et al: Management of sepsis andrecurrent abscess formation complicating radiofrequency ablation ofpancreatic cancer liver metastasis and whipple resection. J InterventOncol 3:17-22, 2010

15. Shibata T, Yamamoto Y, Yamamoto N, et al: Cholangitis and liverabscess after percutaneous ablation therapy for liver tumors: Incidenceand risk factors. J Vasc Intervent Radiol 14:1535-1542, 2003

16. Hoffmann R, Rempp H, Schmidt D, et al: Prolonged antibioticprophylaxis in patients with bilioenteric anastomosis undergoing

percutaneous radiofrequency ablation. J Vasc Intervent Radiol23:545-551, 2012

17. Chang IS, Rhim H, Kim SH, et al: Biloma formation after radio-frequency ablation of hepatocellular carcinoma: Incidence, imagingfeatures, and clinical significance. AJR Am J Roentgenol 195:1131-1136, 2010

18. Fox JP, Gustafson J, Desai MM, et al: Short-term outcomes ofablation therapy for hepatic tumors: Evidence from the 2006-2009nationwide inpatient sample. Ann Surg Oncol 19:3677-3686, 2012

19. Livraghi T, Solbiati L, Meloni MF, et al: Treatment of focal livertumors with percutaneous radio-frequency ablation: Complicationsencountered in a multicenter study. Radiology 226:441-451, 2003

20. Takaki H, Yamakado K, Nakatsuka A, et al: Frequency of and riskfactors for complications after liver radiofrequency ablation underCT fluoroscopic guidance in 1500 sessions: Single-center experi-ence. AJR Am J Roentgenol 200:658-664, 2013

21. Miller AB, Hoogstraten B, Staquet M, et al: Reporting results ofcancer treatment. Cancer 47:207-214, 1981

22. Jain RK, Lee JJ, Ng C, et al: Change in tumor size by RECISTcorrelates linearly with overall survival in phase i oncology studies.J Clin Oncol 30:2684-2690, 2012

23. Wahl RL, Jacene H, Kasamon Y, et al: From RECIST to PERCIST:Evolving considerations for PET response criteria in solid tumors.J Nucl Med 50:122S-150S, 2009 (suppl 1)

24. Livraghi T, Solbiati L, Meloni F, et al: Percutaneous radiofrequencyablation of liver metastases in potential candidates for resection: the“test-of-time approach”. Cancer 97:3027-3035, 2003

25. Mulier S, Ni Y, Jamart J, et al: Radiofrequency ablation versusresection for resectable colorectal liver metastases: Time for arandomized trial? Ann Surg Oncol 15:144-157, 2007

26. Sofocleous CT, Petre EN, Gonen M, et al: CT-guided radiofrequencyablation as a salvage treatment of colorectal cancer hepatic meta-stases developing after hepatectomy. J Vasc Intervent Radiol22:755-761, 2011

27. Umeda Y, Matsuda H, Sadamori H, et al: A prognostic model andtreatment strategy for intrahepatic recurrence of hepatocellularcarcinoma after curative resection. World J Surg 35:170-177, 2011

28. Solbiati L, Livraghi T, Goldberg SN, et al: Percutaneous radio-frequency ablation of hepatic metastases from colorectal cancer:Long-term results in 117 patients. Radiology 221:159-166, 2001

29. Lencioni R, Crocetti L, Cioni D, et al: Percutaneous radiofrequencyablation of hepatic colorectal metastases: Technique, indications,results, and new promises. Invest Radiol 39:689-697, 2004

30. Sofocleous CT, Klein KM, Hubbi B, et al: Histopathologic evaluation oftissue extracted on the radiofrequency probe after ablation of livertumors: Preliminary findings. AJR Am J Roentgenol 183:209-213, 2004

31. Snoeren N, Jansen MC, Rijken AM, et al: Assessment of viabletumour tissue attached to needle applicators after local ablation ofliver tumours. Dig Surg 26:56-62, 2009

32. Sofocleous CT, Nascimento RG, Petrovic LM, et al: Histopathologicand immunohistochemical features of tissue adherent to multitinedelectrodes after RF ablation of liver malignancies can help predictlocal tumor progression: Initial results. Radiology 249:364-374,2008

33. Snoeren N, Huiskens J, Rijken AM, et al: Viable tumor tissueadherent to needle applicators after local ablation: A risk factor forlocal tumor progression. Ann Surg Oncol 18:3702-3710, 2011

34. Sofocleous CT, Garg S, Petrovic LM, et al: Ki-67 is a prognosticbiomarker of survival after radiofrequency ablation of liver malig-nancies. Ann Surg Oncol 2012

35. Malik HZ, Hamady ZZ, Adair R, et al: Prognostic influence ofmultiple hepatic metastases from colorectal cancer. Eur J Surg Oncol33:468-473, 2007

36. Pawlik TM, Schulick RD, Choti MA: Expanding criteria for resect-ability of colorectal liver metastases. Oncologist 13:51-64, 2008

37. Solbiati L, Ahmed M, Cova L, et al: Small liver colorectal metastasestreated with percutaneous radiofrequency ablation: Local responserate and long-term survival with up to 10-year follow-up. Radiology265:958-968, 2012

Hepatic metastases ablation techniques 229

38. Oshowo A, Gillams A, Harrison E, et al: Comparison of resectionand radiofrequency ablation for treatment of solitary colorectal livermetastases. Br J Surg 90:1240-1243, 2003

39. Hur H, Ko YT, Min BS, et al: Comparative study of resection andradiofrequency ablation in the treatment of solitary colorectal livermetastases. Am J Surg 197:728-736, 2009

40. Erinjeri JP, Fong AJ, Kemeny NE, et al: Timing of administration ofbevacizumab chemotherapy affects wound healing after chest wallport placement. Cancer 117:1296-1301, 2011

41. Pathak S, Jones R, Tang JM, et al: Ablative therapies for colorectalliver metastases: A systematic review. Colorectal Dis 13:e252-e265,2011

42. Atalay G, Biganzoli L, Renard F, et al: Clinical outcome of breastcancer patients with liver metastases alone in the anthracycline-taxane era: A retrospective analysis of two prospective, randomisedmetastatic breast cancer trials. Eur J Cancer 39:2439-2449, 2003

43. Sofocleous CT, Nascimento RG, Gonen M, et al: Radiofrequencyablation in the management of liver metastases from breast cancer.AJR Am J Roentgenol 189:883-889, 2007

44. Meloni MF, Andreano A, Laeseke PF, et al: Breast cancer livermetastases: US-guided percutaneous radiofrequency ablation—Inter-mediate and long-term survival rates. Radiology 253:861-869, 2009

45. Jakobs TF, Hoffmann RT, Schrader A, et al: CT-guided radio-frequency ablation in patients with hepatic metastases from breastcancer. Cardiovasc Intervent Radiol 32:38-46, 2009

46. Bergenfeldt M, Jensen BV, Skjoldbye B, et al: Liver resection andlocal ablation of breast cancer liver metastases—A systematic review.Eur J Surg Oncol 37:549-557, 2011

47. Vogl TJ, Farshid P, Naguib NN, et al: Thermal ablation therapies inpatients with breast cancer liver metastases: A review. Eur Radiol23:797-804, 2013

48. Rohde D, Albers C, Mahnken A, et al: Regional thermoablation of localor metastatic renal cell carcinoma. Oncol Rep 10:753-757, 2003

49. Mazzaglia PJ, Berber E, Milas M, et al: Laparoscopic radio-frequency ablation of neuroendocrine liver metastases: A10-year experience evaluating predictors of survival. Surgery142:10-19, 2007

50. Berber E, Ari E, Herceg N, et al: Laparoscopic radiofrequencythermal ablation for unusual hepatic tumors: Operative indicationsand outcomes. Surg Endosc 19:1613-1617, 2005

51. Derek E, Matsuoka L, Alexopoulos S, et al: Combined surgicalresection and radiofrequency ablation as treatment for metastaticocular melanoma. Surg Today 43:367-371, 2013

52. Langan RC, Ripley RT, Davis JL, et al: Liver directed therapy for renalcell carcinoma. J Cancer 3:184-190, 2012