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Abstract

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References

Orthotopic liver transplantation (OLT) can be a definitive treatment for patients with hepatocellular carcinoma (HCC). Prolonged waiting times for cadaveric livers, however, may lead to dropout from the waiting list or worsened post-OLT prognosis as a result of interval tumor progression. Percutaneous radiofrequency ablation (RFA) is widely used for local control of small unresectable HCC, but its pretransplant role remains unclear. We studied the outcome of 52 consecutive patients accepted for OLT bearing 87 HCC nodules and treated with percutaneous RFA. On initial staging, the tumor burden exceeded the Milan criteria in 10 patients. Complete tumor coagulation was observed in 74 of 87 (85.1%) nodules based on postablation imaging. After a mean of 12.7 months (range: 0.3-43.5) on the waiting list, 3 of 52 patients (5.8%) had dropped out due to tumor progression. Forty-one patients had undergone transplantation, with 1- and 3-year post-OLT survival rates of 85% and 76%, respectively. No patient developed HCC recurrence. There were three major complications in 76 RFA procedures (hepatic arterial hemorrhage, small bowel perforation, and liver decompensation salvaged by OLT), without resultant death or dropout. In conclusion, percutaneous RFA is an effective bridge to OLT for patients with compensated liver function and safely accessible tumors. Tumor-related dropout rate and post-OLT outcome compared favorably with published controls of patients with early-stage disease. This can be attributed to the efficacy of RFA in producing local cure or curbing tumor progression during the waiting period. (HEPATOLOGY 2005;41:1130–1137.)

The incidence of hepatocellular carcinoma (HCC) in the United States continues to increase, owing largely to a growing population of patients with chronic hepatitis C virus infection.1 Because few cases are amenable to surgical resection as a consequence of either tumor- or patient-related factors, various locoregional therapies have emerged to allow control of tumors through minimally invasive, liver-sparing treatments. Of these, radiofrequency ablation (RFA) is among the most widely used, with well-established safety and efficacy profiles for selected cases of HCC.2–5 Nevertheless, significant rates of local recurrence for larger lesions and de novo tumorigenesis within the diseased liver are obstacles to achieving long-term control.

Orthotopic liver transplantation (OLT) remains the definitive treatment for patients with HCC burdens within limits established by the Milan criteria (single lesion ≤5 cm, or up to three lesions all ≤3 cm).6 However, limited supply of donor organs prolongs the waiting time for transplantation and causes high dropout rates from tumor progression.7, 8 This pressure has driven the increased use of living and marginal donors as well as split cadaveric transplantations.9–12 Also of concern is whether any increase in tumor burden, even below the current limits warranting removal from transplant candidacy, might adversely affect posttransplantation prognosis.

Transarterial chemoembolization (TACE), a locoregional therapy for HCC, has been investigated as a means of curbing tumor progression in the pretransplant setting, with varying results.13–15 Recently in the United States and abroad, however, RFA has emerged as the first-line treatment for small, nonresectable cases of HCC, such as those fulfilling transplant criteria, with TACE filling a secondary role or reserved for more extensive disease.16–21 Therefore, a potentially beneficial role of RFA while awaiting OLT has been widely discussed,22–26 although it remains unsubstantiated. The present study was undertaken to assess the efficacy of RFA as a bridge to liver transplantation.

Patients and Methods

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References

This retrospective study was approved by the Medical Center Institutional Review Board, with waiver of informed consent.

Patient Population.

At our institution, the strategy for management of HCC has evolved with a multimodality algorithmic approach similar to that adopted in other centers,16–21 incorporating RFA as the primary treatment method. RFA is used as a first-line therapy for single tumors up to 5 cm and three or fewer tumors each up to 3 cm, except in the presence of contraindications including proximity to central bile ducts, bowel, gallbladder, inaccessibility by image guidance, or Child-Turcotte-Pugh class C cirrhosis. Percutaneous ethanol injection therapy (PEI) is then considered in some tumors adjacent to gallbladder or bowel to avoid thermal damage to these structures. Tumors that are not eligible for RFA or PEI, often because of excessive size, are considered for TACE. A few tumor nodules received multiple treatments with different modalities depending on their posttreatment course.

We analyzed the medical records of 52 consecutive patients at our institution that were accepted for liver transplantation and treated with percutaneous RFA (intention-to-treat group) from May 1998 to July 2003. In total, 87 HCC nodules were treated with RFA. Of these, 7 were treated in combination with TACE, and 3 were treated in combination with PEI. Six patients had another separate lesion treated only with TACE or PEI, without RFA. All patients were deemed to have nonresectable HCC based on size, location, or underlying liver dysfunction. Diagnoses of HCC were confirmed on biopsy in 32 of 52 patients. In 6 other patients, a hypervascular tumor was present on computed tomography (CT) or magnetic resonance imaging (MRI) along with elevated alpha-fetoprotein levels. In the remaining 14 patients, a diagnosis of HCC was made based on classical imaging characteristics and/or growth of nodules over time. In cases of multiple lesions, the smaller nodules were deemed to be HCC as long as they showed imaging characteristics similar to those of the dominant lesion. Diagnostic and management decisions were made in consensus fashion by a multidisciplinary team of hepatologists, oncologists, hepatobiliary surgeons, abdominal radiologists, and liver pathologists. Of the 52 patients, 38 were male and 14 were female; the mean age was 57.1 years (range: 33-73).

RFA.

All tumors were treated percutaneously by one of two board-certified abdominal interventional radiologists (D. L. and S. R.) with 7 and 5 years of RFA experience, respectively. A total of 76 sessions were performed: 49 with 2-, 3-, or 3.5-cm LeVeen electrodes (Radiotherapeutics Corporation, Mountain View, CA), 18 with single or cluster cooled-tip electrodes (Radionics, Inc., Cambridge, MA), and 9 with 2- to 3-cm Model 30 and 3-cm Starburst Rita electrodes (Rita Medical, Mountain View, CA). Regardless of the device used, the same guiding technical principles were applied to all ablations: Single or overlapping ablations were performed based on lesion size, geometry, and imaging feedback from sonographic or CT monitoring to target for complete ablation of the visible tumor as well as a 5- to 10-mm margin of surrounding hepatic tissue where feasible.

Ultrasound-guided procedures (n = 63) were performed using HDI 3000 or 5000 (Advanced Technology Laboratories, Bothell, WA). Gray-scale imaging was used for continuous monitoring of sonographic changes at the site of ablation, marked by an area of developing echogenicity, to estimate the size of the ablation zone. Single or multiple overlapping ablations were strategically placed such that the total hyperechoic zone covered the intended volume of ablation without extending to critical structures such as central bile ducts or liver capsule contiguous to gallbladder, bowel, and pericardium. When the index tumor was not adequately visualized by ultrasound, RFA was performed under CT guidance (n = 13) using spiral scanners (High Speed, G. E. Medical Systems, Milwaukee, WI; or Somatom, Siemens Medical Systems, Erlangen, Germany).

Imaging Follow-up and Repeat RFA.

Posttreatment, contrast-enhanced, dual-phase CT or gadolinium-enhanced MRI were obtained within the first month (usually within a few days) and every 3 months thereafter following ablation. At our institution, CT was performed on single or multidetector spiral scanners (CTi, or Lightspeed, G. E. Medical Systems; or Sensation 16, Siemens Medical Systems) with a dual-phase protocol consisting of precontrast images, a hepatic arterial dominant phase, and a portal dominant phase (collimation 5-7 mm, pitch 1-1.5). MRI was performed on 1.5 Tesla scanners (Horizon, G. E. Medical Systems; or Vision, Siemens Medical Systems) consisting of T2-weighted images and fat-saturated, T1-weighted gradient echo acquisitions pre- and dynamically post-intravenous contrast (Omniscan, Nycomed Amersham, Princeton, NJ). Postablation images were analyzed and compared with preablation images. Any pre-existing tumor region not encompassed by the new coagulation zone was considered incomplete treatment, even if distinct nodular enhancement was not clearly seen, prompting repeat ablation when feasible. On the follow-up scans, any new discrete foci of abnormal enhancing tissue within or along the margin of the coagulation zone was considered a residual tumor. In cases of uncertainty, additional follow-up scans were obtained to determine stability, with interval growth of the questionable area considered to represent a residual tumor. Some residual tumors were retreated with a second session if clinically feasible while awaiting transplantation. Final imaging determination of completeness of tumor coagulation was made using the last available follow-up imaging study, after either single or double RFA sessions. For posttransplant follow-up, patients underwent CT or MRI, along with alpha-fetoprotein measurement, every 3 months for 2 years and every 6 months thereafter to assess possible tumor recurrence.

Determination of Tumor Necrosis on Explanted Livers.

All explanted liver specimens were processed by hepatopathologists using routine protocol, consisting of 1 cm or less sections through the entire liver. All lesions and suspicious areas were taken for standard histological (hematoxylin-eosin) staining. For tumors less than 2 cm in diameter, the slides typically encompassed the entire lesion. For larger lesions, representative samples were taken for slide preparation with special attention to areas appearing grossly viable, according to routine practice. For the purpose of this study, slides were retrospectively reviewed by a single liver pathologist (C. L.) to assess the degree of necrosis.

Statistical Analysis.

Analyses of survival and dropout time were performed using the Kaplan-Meier method. For dropout time course, the date of acceptance for transplantation or, for those who developed HCC after listing, the date of HCC diagnosis was taken as time zero. Patients were censored at the time of transplantation or last follow-up. For intention-to-treat survival analysis, all 52 patients were followed from the time of listing to death or last follow-up. Univariate analysis of the dependence of complete tumor coagulation on several variables (tumor size, patient sex and age, operator) was tested using the Fisher exact test for nominal variables and a t test or Mann-Whitney test for continuous variables. A threshold P value of .05 was chosen for statistical significance. All statistical tests were performed using InStat version 3.05 (GraphPad Software, Inc., San Diego, CA) and SPSS for Windows version 11.0.1 (SPSS, Inc., Chicago, IL).

Results

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References

Tumor/Patient Characteristics.

Eighty-seven HCC nodules in 52 liver transplantation candidates were treated with RFA. Thirty-nine patients had documented HCC at the time of listing, and 13 were diagnosed after acceptance. On initial staging, 42 patients fit the Milan criteria for tumor burden, while 10 had more advanced disease (solitary lesion >5 cm, n = 2; at least one of 2 or 3 lesions >3 cm, n = 4; ≥4 lesions, n = 4). The mean maximal tumor diameter was 2.5 cm (range 0.4-5.7). The mean size was greater for tumors treated with TACE (4.1 cm) than for those treated with RFA/PEI alone (2.4 cm) (P < .0001). One patient had a fibrolamellar variant of HCC. The mean alpha-fetoprotein level was 198 ng/mL (range: 2-2,876). Etiology and severity of liver disease are shown in Table 1.

Table 1. Patient Characteristics and Tumor Profile
Patients (n = 52)n (%)
Liver disease 
 Hepatitis C32 (61)
 Hepatitis B13 (25)
 Alcohol3 (6)
 Cryptogenic3 (6)
 Hemochromatosis1 (2)
Child-Turcotte-Pugh class 
 A19 (36)
 B29 (56)
 C4 (8)
HCC (n = 87) 
Number of lesions 
 1/2/3/≥438/7/3/4 patients
Size0.4-5.7 cm (mean 2.5)
RFA only/+TACE/+PEI77/7/3 nodules

RFA Efficacy.

In all, 76 RFA sessions were performed (mean 1.46 sessions/patient). Extra sessions included planned double-session treatments (n = 8), repeat ablation due to locally recurrent tumor (n = 4), and treatment of separate intrahepatic metachronous lesions (n = 12). Based on postablation CT or MRI, radiographic local tumor control was achieved in 74/87 tumors (85.1%) and 69 of 77 (89.6%) treated exclusively with RFA.

For patients who underwent transplantation, the explanted liver showed complete tumor necrosis without histological evidence of viable carcinoma in 46 of 70 lesions (65.7%), including 45 of 64 (70.3%) treated only with RFA. At the time of transplantation, repeat RFA was pending for five lesions with a known residual viable tumor on follow-up imaging. Other recurrences confirmed on histology were either not detected on surveillance imaging (n = 15) or were judged to be unsuitable for further ablation (n = 4).

Using the latest available imaging or pathological follow-up, the mean diameter of completely ablated nodules was 2.19 cm, versus 3.17 cm for those with local recurrence (P < .001). Alternatively, 50 of 64 nodules (78.1%) less than or equal to 3 cm were completely coagulated, versus 9 of 23 (39.1%) of those greater than 3 cm (P = 0.0013). Other factors, including sex, age, interventionist, and alpha-fetoprotein level, were not predictive of treatment efficacy on univariate analysis (Table 2).

Table 2. Univariate Analysis for Dependence of Ablation Efficacy on Selected Variables
 SuccessFailureP Value*
  • Abbreviation: NS, not significant.

  • *

    Fisher exact test was used for nominal variables (tumor size category, sex, and operator), and unpaired t test and Mann-Whitney test were used for age and alpha-fetoprotein, respectively, as continuous variables.

Tumor size   
 ≤3.0 cm50 (78.1%)14 
 >3 cm9 (39.1%)14<.01
Sex   
 Male3924 
 Female204NS
Age57.3 ± 8.456.9 ± 9.7NS
Operator   
 A3119 
 B289NS
Alpha-fetoprotein192.3127.1NS

Transplantation List Status.

Mean time on the transplantation waiting list for all patients was 12.7 months (range: 0.3-43.5). Three patients (5.8%) dropped out because of HCC progression. For all three, dropout occurred relatively late in the waiting period, at a mean of 11.1 months post-RFA. In 1 patient, lung metastasis was discovered after ablation of a 4.9-cm solitary tumor despite no evidence of local recurrence. In the other two, recurrence was noted in local ablation sites in association with lung metastasis or intrahepatic progression. One of these patients had exceeded the Milan criteria, with 1 of 2 nodules exceeding 3 cm on initial staging.

Two additional patients expired on the list from liver decompensation not caused by HCC progression or treatment, and 1 was excluded after discovery of de novo renal cell carcinoma. Cumulatively, 6 dropouts occurred, with a mean time to dropout of 15.2 months (range: 3.1-31.9) from enlisting or diagnosis of HCC (Fig. 1). One patient withdrew from the list in the absence of any medical contraindications. In all, four patients died without receiving transplantation. Four currently remain on the active waiting list. Forty-one patients went on to receive transplantation after a mean of 8.7 months (range: 0.5-34.4) post-RFA. One patient underwent living donor transplantation; all others received cadaveric livers. Repeat transplantation was performed in four cases as because of primary nonfunction.

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Figure 1. Time course of patient dropout from waiting list. Time 0 represents the date of acceptance to the waiting list or, for those diagnosed with hepatocellular carcinoma (HCC) after enlisting, the date of HCC diagnosis. Three dropouts related to tumor progression are marked by asterisks (*). Cross marks (+) denote censoring at the time of transplantation or last follow-up on the waiting list.

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Posttransplantation Outcome and Survival.

On examination of explant specimens, there were incidental small HCC nodules undetected on preoperative imaging in 10 of 41 patients (24%). Intrahepatic lymphovascular invasion was noted in 5 patients, 2 of whom were among the group exceeding the Milan criteria. Three of these patients received postoperative adjuvant chemotherapy. During posttransplantation follow-up of 0.1 to 55.0 months (mean: 14.9, median: 9.4), 6 of 41 patients (14.6%) died. Two of these patients died within 3 days of surgery from perioperative complications. The other 4 deaths were attributed to liver failure from recurrent hepatitis C virus or graft rejection. One-, two-, and three-year survival rates were 85%, 85%, and 76%, respectively (Fig. 2A). Analysis based on intention-to-treat principle from the time of acceptance to the waiting list for the entire cohort yielded 1-, 2-, and 3-year survival rates of 98%, 84%, and 74%, respectively (Fig. 2B). Notably, no patient developed HCC recurrence after transplantation.

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Figure 2. Kaplan-Meier survival analysis. (A) Forty-one patients who received transplantation, including 2 who died perioperatively, were used to analyze postsurgical survival. (B) Survival analysis was performed using all patients (n = 52) based on an intention-to-treat principle from the date of acceptance to the waiting list. Cross marks (+) denote time of censoring.

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Complications of RFA.

In a total of 76 RFA sessions, major complications occurred in 3 cases (3.9%). These included arterial hemorrhage requiring embolization, small bowel perforation requiring operative repair, and liver decompensation requiring transplantation at 15 days postablation in a patient with Child-Turcotte-Pugh class C cirrhosis. No deaths or dropout occurred as a result of these complications. No case of tumor seeding was noted.

Discussion

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References

Initial experiences with OLT for HCC were marred by high rates of tumor recurrence and poor survival compared with groups that underwent transplantation for nonmalignant indications. Subsequently, however, it was found that patients with small HCC lesions discovered incidentally at transplantation fared just as well as those without malignancy on explant specimens. The relationship between tumor burden and OLT outcome is now well documented27–29 and provides a rationale for implementation of the Milan criteria.6

HCC has an approximate median doubling time of 6 months30 and can progress significantly while awaiting transplantation. Even for cases in which a tumor does not progress to the dropout threshold, any growth would increase the risk of microvascular invasion, occult metastasis, and posttransplantation recurrence and death. This growing sense of urgency for timely transplantation has been exacerbated by a shortage of donor livers. According to national data compiled by the United Network for Organ Sharing (UNOS), the proportion of candidates waiting 2 years or more has increased steadily from 15% in 1993 to 46% in 2002, correlating with a near sixfold rise in the number of patients on the waiting list.31

Several strategies have been adopted to address this pressing organ shortage. On the side of supply, many centers are using living and marginal donors,9–11 as well as split-liver transplantation.12 These options may be limited by a paucity of surgical experience or a lack of clinically and ethically sound policy for implementation.32 On the side of demand, some patients are treated first with resection, with OLT reserved for salvage therapy in case of postresection recurrence. The vast majority of patients, however, are unsuitable candidates for resection because of tumor location or severity of liver disease, and even those who qualify may later become unsalvageable.33, 34

For these reasons, significant attention has been devoted to minimally invasive therapies that can provide an effective bridge to transplantation over a prolonged waiting period. Of these, TACE has been investigated most widely, though with varying results. Among the most optimistic of these reports, a European center showed a 5-year survival of 93% in 48 patients receiving TACE, with no dropouts over a mean waiting period of 6 months.14 Others, however, have debated whether pretransplantation TACE yields any survival benefit.13 In the most recent series by Maddala et al., pre-OLT TACE in 54 predominantly early-stage cases yielded a reasonable 5-year post-OLT survival of 74%.15 However, the benefit of TACE could not be inferred given that waiting list dropout and post-OLT recurrence rates were not markedly lower than historical controls.

In RFA, an alternating current is applied through an electrode into adjacent surrounding tissue, causing cell death from heat generated from resulting ionic friction. It has several advantages over TACE, including the possibility of simple percutaneous access, greater amenability as an outpatient procedure, and characteristically less posttreatment discomfort. Furthermore, adequate tumor control using TACE typically requires repeated treatment sessions, raising concern over complication rates and progressive liver failure.18, 21, 35–37 Above all, RFA, when employing the proper technique, is a more reliable means of achieving consistent necrosis given its direct thermal-based tissue destruction, whereas the success of TACE is dependent on a variety of uncontrollable factors associated with tumor vascularity and biology. Therefore, for small (<3-5 cm) unresectable HCC, as is found in OLT candidates selected according to Milan criteria, RFA is now universally emerging as the treatment of choice.2, 16–21

Nevertheless, RFA has not been adequately investigated as an adjunct to transplantation for patients awaiting OLT. One series including 15 patients transplanted after RFA showed a 3-year posttransplantation survival rate of 85%, with two (13%) recurrences.13 Although a useful role of RFA was suggested, the study was limited by a small sample size and no analysis of waiting list dropout from tumor progression, which is a crucial gauge of bridging efficacy. Other published series were even smaller in scale, precluding meaningful analysis of clinical outcomes, or presented only in the context of overall RFA experience without a primary focus on its pretransplant role.24, 38, 39 A somewhat larger study reviewed 33 patients treated with multimodality nonresective therapy while awaiting transplantation, showing 5 (12.2%) dropouts and a 79% 3-year intent-to-treat survival rate.25 In the present study, however, only 3 patients were treated exclusively with RFA, while 16 underwent transarterial chemo-infusion, which is an unproven modality and is not considered a first-line therapy for early-stage HCC.

The benefit of RFA in our cohort may be strongly suggested by comparisons with historical data that serve as relevant controls. First, waiting list dropout secondary to tumor growth is known to occur in excess of 20%, even in early-stage patients.7, 8, 40 One recent study of 54 subjects reported 6 dropouts (11.1%) with a 7-month median waiting time (15% overall cumulative dropout probability at 6 months), even with use of neoadjuvant TACE as an attempt to curb disease progression.15 In our series, only 3 dropouts (5.8%) from tumor progression were noted in 52 patients, comparing favorably against these historical rates. Furthermore, they occurred fairly late into the waiting period, with an RFA dropout time interval of greater than 10 months in each case. Hence, even for these cases, RFA may have contributed toward maximizing the duration of patient retention on the waiting list. Indeed, all-cause cumulative probability of dropout at 12 months was less than 10%.

Second, tumor recurrence rates after transplantation exceeding 20% are not uncommon29, 41 with, at best, 8% to 10% reported even in more recent, well-selected recipients.6, 8, 42–44 Most recently, Ravaioli et al. demonstrated a higher recurrence rate in early patients exceeding versus recent ones fulfilling the Milan criteria (37.5% vs. 12.7%).29 Although these figures highlight marked improvements in outcomes achieved with careful patient selection, they show that recurrence still remains a significant threat. Even with systematic pre-OLT TACE treatment, in the study mentioned above, 5/46 (10.8%) patients died from recurrence.15 No patient in our study had HCC recurrence after mean 14.9 months (median: 9.4, range: 0.5-55.0) follow-up. Although most recurrences occur soon after transplantation (typically within 1-2 years), clearly a longer follow-up will be required to validate this hopeful trend.

Consistent with the absence of tumor recurrence (i.e., all post-OLT deaths were attributable to problems unrelated to HCC), our 3-year post-OLT survival rate of 76% is consistent with those for cases with nonmalignant indications and for groups with incidentally discovered HCC.6, 28, 42 Recent query of the Organ Procurement and Transplantation Network database shows 1- and 3-year posttransplantation survival rates of 82% and 66%, respectively, in the group transplanted from 1996-2001 for the indication of malignancy (based on Organ Procurement and Transplantation Network data as of June 16, 2004). These rates reflect significant improvement over earlier results, most prominently due to a more judicious patient selection based on defined HCC criteria.45

Such favorable dropout, recurrence, and survival rates were observed despite the inclusion of 10 patients whose tumor burden surpassed the Milan criteria. In fact, 9 of the 10 patients were successfully bridged to transplantation. Whether tumor burden criteria could be liberalized to include treatment-responsive advanced-stage patients is unknown. Given the small number of these cases, a statistically meaningful comparison between the groups within and exceeding Milan criteria could not be performed.

The effective role of pretransplant RFA can be directly attributed to its high tumoricidal efficacy. On explant analysis, 45 of 64 (70.3%) nodules treated exclusively with RFA showed complete coagulation, with most of the remaining showing near total necrosis. Explant-based evaluation of RFA found in the literature have been few, small in scale, and in disagreement regarding complete necrosis rates (ranging from 21% to 75%).22, 39, 46 Most recently, a larger study of 50 explants showed 55% (63% for tumors ≤3 cm) complete response rate after RFA treatment prospectively limited to a single session.26 Our result, obtained after multiple-session treatments as needed, is not inconsistent with this finding and, we believe, reflects a local efficacy that can be realistically expected with meticulous technique47 and close posttreatment surveillance, both of which are crucial for optimizing outcome.

Indeed, although many tumors are adequately coagulated with single sessions, the convenient option of repeat sessions, if needed, is a key attribute of RFA as a bridging modality. Residual tumor volumes after ablation will often be small, sometimes microscopic, such that the overestimation of local success rate by imaging—with its limited spatial resolution and tissue contrast—is an expected finding. Many such residuals as well as any de novo tumors would, however, be amenable to repeat treatments once grown to radiographically detectable sizes. Furthermore, although subtotal tumor necrosis is in general considered a failure of RFA, even incomplete control would be a success in the pretransplant setting if waiting list dropout and posttransplant recurrence are prevented. In other words, complete eradication of malignancy in the native liver is not of primary concern in patients for whom OLT is expected to be the definitive treatment.

In the largest study of safety involving 2,320 patients undergoing percutaneous liver RFA, 56 (2.4%) major complications were reported, including 6 (0.3%) deaths, 2 (0.1%) rapid hepatic decompensations, and 12 (0.6%) tumor seedings.48 One of the early patients in our series, with Child-Turcotte-Pugh class C cirrhosis, underwent hepatic decompensation postablation, requiring salvage transplantation. Severely decompensated cirrhosis is now widely viewed as a contraindication to RFA.49 Our series included no cases of tumor seeding, corroborating the low incidence of this oft-feared complication. Overall, these figures support RFA as a generally safe modality with acceptable risk for most patients, including those awaiting liver transplantation.

One confounding factor involved the concurrent use of PEI or TACE in some patients, somewhat diluting the contribution of RFA. Although RFA was undoubtedly the dominant factor in pretransplant tumor control, comprising the only treatment in the majority (37/52 [71%]) of patients, we tended to use combined TACE for larger tumors and PEI for those adjacent to critical structures at risk of thermal damage. Indeed, even though RFA plays a primary role in the treatment of early-stage, unresectable HCC at many institutions, as already discussed, optimal pretransplant management will likely require a multimodal approach. Future randomized controlled studies may help formulation of an authoritative treatment guideline.

In summary, our experience validates percutaneous RFA as a robust bridging therapy for unresectable HCC in liver transplantation candidates, yielding low rates of dropout, posttransplantation recurrence, and mortality despite moderately long waiting times. Good clinical outcomes were supported by direct evidence of effective tumor coagulation based on explant pathology. Nevertheless, potential major complications must be carefully weighed, especially in cases where waiting time is expected to be short. Therefore, the procedure should be limited to patients with Child-Turcotte-Pugh class A or B liver function and safely treatable tumor location. Also, subtotal necrosis achieved in many large tumors underscores the need for further advances in RFA technology and for consideration of other therapies in a multimodal strategy.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References

We thank Wanda Marfori, Myrna Alvarez, Katherine Lee Schwegel, Prest Oshodi, Debra Wafer, Barbara J. Nuesse, Maria Correa, Karyn M. Marks, and Gregg Kunder for their assistance in the UCLA Image-Guided Tumor Ablation Program, Dumont Liver Transplant Center, and Pfleger Liver Institute.

References

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. References
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