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Originally published as Ann Surg Oncol Early Release 10.1245/ASO.2004.08.019 on April 12, 2004

Annals of Surgical Oncology 11:500-505 (2004)
© 2004 Society of Surgical Oncology
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ORIGINAL ARTICLES

Local Recurrences After Intraoperative Radiofrequency Ablation of Liver Metastases: A Comparative Study with Anatomic and Wedge Resections

Dominique Elias, MD, PhD, Olivier Baton, MD, Lucas Sideris, MD, FRCSC, Tadashi Matsuhisa, MD, Marc Pocard, MD, PhD and Philippe Lasser, MD

From the Department of Surgical Oncology, Gustave Roussy Institute, Villejuif, France.

Correspondence: Address correspondence and reprint requests to: Dominique Elias, MD, PhD, Chief, Division of Surgical Oncology, Department of Surgery, Gustave Roussy Institute, 39 Rue Camille Desmoulins, 94805 Villejuif Cedex, France; Fax: 33-1-41-11-52-56; e-mail: elias{at}igr.fr


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Background: The indications and results of intraoperative radiofrequency ablation (RFA) of liver metastases (LMs) are not well defined in the literature and have never been compared with those of hepatectomy. The aim of the study was to appreciate the local recurrence rate of RFA in comparison with anatomic and wedge resection.

Methods: Eighty-eight patients with technically unresectable LMs were treated with curative intent. The LMs were treated by anatomic resection (40 patients, 213 LMs) when large, by wedge resection (64 patients, 99 LMs) when peripheral and small, and by RFA (88 patients, 227 LMs) when central and small. The median follow-up was 27.6 months (range, 15–74 months), and a total of 539 LMs were treated (median of 5 per patient).

Results: The local recurrence rates were 5.7% for the 227 RFAs, 7.1% for the 99 wedge resections, and 12.5% for the 40 anatomic resections (P = .216). Local recurrence rates after RFA were correlated with LMs larger than 30 mm (P < .001) and with LMs in direct contact with large vessels (P < .001).

Conclusions: RFA is as efficient and safe as wedge or anatomic resections in terms of local control.

Key Words: Colorectal cancer • Hepatectomy • Liver metastases • Radiofrequency ablation • Wedge resection


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Radiofrequency ablation (RFA) is a physical treatment able to destroy small liver metastases (LMs) by heat. It is recognized as minimally invasive when used percutaneously, but this approach is possible only in patients with a maximum of three small, well-sited liver metastases.1

RFA during laparotomy is mainly considered when multiple LMs are not totally resectable by anatomic hepatectomy and/or wedge resections. In these cases, the addition of RFA to the partial hepatectomy is the only means that allows performing a treatment with curative intent. Therefore, in our center, the main indication of intraoperative RFA is actually to treat centrally sited small LMs in the remaining part of liver.2

This combined surgical and ablative treatment has a curative objective for patients who have LMs not resectable by surgery alone. Therefore, the considered population is different from the one usually selected to undergo curative hepatectomy, who have more advanced disease and a greater risk of recurrence. For this reason, it is not possible to compare the results of classic hepatectomy with those of hepatectomy plus RFA.

Currently, the indications for using intraoperative RFA are vague for three reasons: (1) a reported rate of local failure ranging from 1.8% to 39% in the literature,3–7 (2) an absence of comparison between surgical resection and RFA for similar tumors, and (3) an unclear and variable definition of unresectability of liver tumors in the literature, although these tumors could possibly be treated by RFA.

This study was mainly aimed at assessing the efficacy of anatomic hepatectomy, wedge resection, and RFA, in order to better define the place of intraoperative RFA destruction of LMs.

Patients
From January 1997 to December 2001, 88 patients underwent a partial hepatectomy associated with RFA for strictly unresectable LMs. Their data were prospectively collected.

Unresectability criteria implied that LMs could not be treated by surgical resection alone and were defined as follows: (1) >5 LMs, distributed in the whole liver, (2) a bilateral location not respecting at least one sector of the liver (one sector corresponding to two vertical Couinaud segments), and (3) tumor proximity to the inferior or superior central major vascular structures, precluding a margin-negative resection. The three classic oncologic criteria of unresectability, i.e., the presence of extrahepatic disease, a future free margin smaller than 10 mm, and a high number of LMs, were not taken into account.

Our criteria of LM unresectability were only and purely technical, not oncological. However, the complete resection of tumorous disease was always our final target. Naturally, all patients were medically fit to undergo a laparotomy.

Inclusion criteria comprised (1) the feasibility of resecting or ablating all LM and extrahepatic tumorous disease,8 (2) the absolute necessity of using RFA in addition to partial hepatectomy to reach this purpose, (3) a relatively small operative risk, with adequate remaining hepatic tissue, and (4) no hepatocellular carcinoma.

The preoperative workup always included helical computed tomography (CT) of the abdomen, pelvis, and thorax and liver ultrasonography. Hepatic magnetic resonance imaging (MRI) was performed when LMs were not easily seen on the previous examinations. Positron emission tomography with 18FDG was not used.

There were 51 men and 37 women, of a mean age of 55 years (range, 21–76 years). The origins of LMs are reported in Table 1. Most of them (72%) came from colorectal adenocarcinomas. A total of 539 LMs were treated in these 88 patients, with a median of 5 per patient (mean, 6.1; range, 3–28).


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  		TABLE 1. Origins of the liver metastases
 
Anatomic hepatectomies were performed for large LMs or multiple clustered LMs sited in one part of the liver. Wedge resections were performed for small (<3 cm) peripheral LMs (Fig. 1). Wedge resections consisted of large craters and nonanatomic resections. RFA was intended to destroy small (<3 cm) centrally sited LMs. Unfortunately, in eight patients, the intraoperative findings included the discovery of larger lesions (>3 cm) than predicted, but these were treatable only with RFA in nonoptimal conditions. Right or wrong, because the laparotomy was already done, we decided to proceed with the RFA destruction of these lesions, and all these patients were included in the analysis. The description of these three different procedures and the characteristics of the LMs are reported in Table 2.



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  		FIG. 1. Partial hepatectomies, excluding radiofrequency ablation (RFA).

 

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  		TABLE 2. Characteristics of the different procedures used to treat the 539 liver metastases (mean number per patient:6.1)
 
Hepatectomies and RFA were performed after mobilization of the liver and ultrasonographic exploration. Intermittent hepatic vascular exclusion was systematically used.9 RFA was done with one of the three following materials: the Cool-tip system (Radionics, Burlington, MA, the expandable (deployed multiple array needles) LeVeen Needle Electrode (Radiotherapeutics, Mountain View, CA), and the Elektrotom perfused needle system (Berchtold, Tuttlingen, Germany), in which the infused saline solution acts as a liquid electrode. RFA was performed according to the manufacturer’s instructions for each apparatus.

For 26 of the 227 RFAs, the LMs were in direct contact with a large vessel (terminal part of the hepatic veins: 12, vena cava: 4, portal bifurcation: 7, primary portal branch: 3). Selective clamping of the hepatic vein(s) and bile duct cooling (to protect the biliary tree from stenosis) were used in such cases.2,10,11

In 32 patients (36%), an extrahepatic tumor resection was associated with the operative treatment of the LMs. The details of these procedures are reported in Table 3. This high rate of extrahepatic disease illustrates, with the high number of LMs, the high risk of recurrence in this population. Finally, 16 patients (18%) who had recurrent disease after this combined treatment underwent surgery again, with a curative intent.


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  		TABLE 3. Details of the 32 extrahepatic resections performed at the same time than the operative treatment of the liver metastases
 
The follow-up consisted of a clinical examination, liver imaging (used on a case-by-case basis; ultrasonography, MRI, or CT), and CEA measurement every 3 months. A thoracic CT scan was obtained every 6 months.

Statistics
Data were prospectively recorded in a specific database. The exact status of each patient was clear at the date of analysis of the series (March 2003). Minimal follow-up was 16 months for each patient. The {chi}2 test or Fisher exact test, when appropriate, was used for univariate comparisons. Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank test. Differences were considered significant at P = .05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
There were no postoperative deaths, and the rate of morbidity (complication requiring a specific treatment or at least 1 week of additional hospitalization) was 27%. There were 6 transient biliary leakages, 8 transient clinical liver failures, 1 hemorrhage, 6 instances of peritonitis or abscesses related to extrahepatic surgery, and 4 miscellaneous complications. There was no postoperative complication directly due to RFA (abscess, hemorrhage, biliary fistula, or stenosis). RFA might have partly contributed to some transient liver insufficiency (not measurable) or right pleural effusion. The median follow-up after hepatectomy plus RFA was 27.6 months (range, 15–74 months).

Comparison of In Situ Recurrence Rates According to the Procedure
In the particular field of this series (classically unresectable multiple LMs), it is important to emphasize that the section margins were unusually small by necessity, especially for anatomic hepatectomies. They were smaller than 2 mm12 in 37% of anatomic hepatectomies (Table 2), versus 9% of wedge resections. Of course, the minimal safety margin was unknown after RFA.

The in situ recurrence rates at 2 years, when the number of procedures was considered, were 5.7% for RFA, 7.1% for wedges, and 12.5% for anatomic resections (P = .216) (Table 4). When the recurrence rates per patient were considered, they were essentially equivalent: 14.8%, 10.9%, and 12.5% for the respective procedures (Fig. 2).


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  		TABLE 4. In situ-recurrence rates in the liver according to the procedure used to treat the liver metastases
 


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  		FIG. 2. Recurrence rates (per patient), according to procedure.

 
Types of Recurrences
Unfortunately, other kinds of recurrences also occurred in these high-risk patients. The intrahepatic and extrahepatic recurrence rates at 3 years were 47% and 15%, respectively, and the intrahepatic and extrahepatic recurrence rates were both 25% (Fig. 3). Sixteen patients with a recurrence could be retreated with curative intent.



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  		FIG. 3. Incidence of recurrences inside and outside the liver.

 
When considering the liver only, it is important to differentiate recurrences occurring at the site of RFA or at the section margin of any type of liver resection (that are in situ recurrences) (10%), from newborn LMs (32%) and the association of both (16%) (Fig. 4).



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  		FIG. 4. Types of recurrence in the liver.

 
Analysis of In Situ Recurrences After RFA
Two parameters had a significant impact on in situ recurrence rates: (1) the LM diameter (8 [21.6%] of the 37 LMs >=30 mm recurred, versus 5 [2.6%] of the 190 LMs <30 mm [P < .001]) and (2) the contact of the LMs with a large vessel (6 [23%] of these 26 LMs recurred, versus 7 [3%] of the 201 other LMs [P < .001]). Conversely, the total number of LMs, the tumor origin, and the device used had no significant impact on in situ recurrences.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
This study had only one objective: to define more precisely the indications of intraoperative RFA by assessing the efficacy of the three different types of treatment (RFA destruction, wedge resection, and anatomic hepatectomy), even if the indications to use each of them were not similar. All our patients sustained a good general status, and unresectability criteria were based solely on strictly technical, not oncologic, considerations, in order to have clearer criteria than those used in the literature in recent years. The aim was to obtain an R0 status after resection, whatever the number of LMs and whether or not extrahepatic tumorous disease (resectable) was present.8,13

The safety of RFA appears to be good in this series, with an in situ recurrence rate of only 6%. It has ranged from 1.8% to 39% in other published series3–7,14 (Table 5). However, the patients’ characteristics (median of 5 LMs per patient in our series), the route for RFA achievement (100% of laparotomy in our series), and the mean follow-up are very different in these series. In our experience, the two main factors of failure were the size of LMs (when >30 mm) and their close contact with a large vessel. These two factors are currently well defined and emphasized in other studies.4,6,7,14 At the same time, we did not observe any severe postoperative complication caused by RFA.


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  		TABLE 5. Characteristics and results of the main series of the literature about RF ablations of liver tumors
 
It is even more interesting to compare the in situ recurrence rates of the three kinds of procedures used to treat the LMs with a curative intent (even if they had, very logically, different indications in this series). There are very few data in the literature about posthepatectomy margin recurrences, and the incidence is generally considered to be zero by principle. This statement is not the truth.

First of all, the poor results of anatomic segmental hepatectomies in our series (12.5% of in situ recurrences) cannot be compared with the results in other series. Contrary to the usual circumstances in series of resectable LMs, in which the number of LMs is low and the predicted security margin is large, sufficient remaining liver parenchyma had to be meticulously saved in our patients with unresectable numerous and bilateral LMs. For this reason, our results are far from the 2% rate of in situ recurrence after 148 anatomic segmental resections recently reported by the Memorial-Sloan Kettering Cancer Center, where 80% of patients had only one LM.15 Since 1992, this center’s philosophy favored segmental over wedge resections,15 although it was reported that for patients with tumors smaller than 4 cm, the 5-year survival rate after wedge resection was 31%, compared with 52% after anatomic resection.16

Our conclusion after analyzing our results is that we must be more careful with the security margins when performing anatomic segmental resections for this kind of patients. An anatomic resection is necessary when treating large or badly sited LMs and cannot be compared with or replaced by RFA.

In the same study from the Memorial, the percentage of positive margins was 16% after 119 wedge resections.15 Our results showed 7.1% of in situ recurrences after 99 wedge resections of peripheral LMs, very close to the 5.7% obtained after 227 RFAs of more centrally sited LMs. At the same time, we established, like others,4,6,7,14 that the risk of local recurrence after RFA was significantly higher when LMs were larger than 3 cm and when they were close to a large vessel. A more strict use of RFA for small LMs will reduce this rate.

Thus, we conclude that well-used RFA is at least as efficient as wedge resections to treat LMs smaller than 3 cm. At the same time, it is clear to us that RFA is better tolerated than wedge resections, is less invasive, is less hemorrhagic, and does not necessitate vascular clamping. For these reasons, we think that RFA can replace some wedge resections advantageously in the future, especially when the use of an RFA electrode is already necessary to treat a central LM.

Furthermore, RFA resulted in local control rates similar to those with anatomic hepatectomies or wedge resections, when used for LMs measuring <30 mm in diameter. It could thus be currently considered a valid tool in the arsenal of intraoperative procedures to treat LMs. For strictly unresectable LMs (median of 5 LMs and extrahepatic disease in 36% of patients in our series), the association of anatomic segmental hepatic resection, RFA, and chemotherapy allows treating many patients with curative intent.

Only a study comparing the survival of similar patients treated classically with systemic chemotherapy with those undergoing combined medical and surgical treatment will allow us, in the future, to determine whether this new approach is advantageous.


   CONCLUSIONS
TOP
 ABSTRACT
 INTRODUCTION
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
The local recurrence rate of hepatic RFA is 6% of treated LMs and 15% of treated patients, but these rates can be improved in the future if RFA is not used to treat LMs >30 mm in diameter. These results are at least as good as those obtained with anatomic and wedge resections, which are more invasive. RFA is very useful to destroy central and eventually peripheral small LMs, and it could replace wedge resections in this latter situation, especially if an RFA electrode has already been used to treat a central LM.


   FOOTNOTES
 
Intraoperative radiofrequency ablation of unresectable liver metastases measuring <30 mm in diameter results in the same local recurrence rates as anatomic and wedge resections.

Received for publication August 27, 2003. Accepted for publication January 13, 2004.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Parikh AA, Curley SA, Fornage BD, Ellis LM. Radiofrequency ablation of hepatic metastases. Seminin Oncol 2002; 29: 168–82.
  2. Elias D, De Baere T, Mutillo I, Cavalcanti A, Coyle C, Roche A. Intra-operative use of radiofrequency allows an increase in the rate of curative liver resection. J Surg Oncol 1998; 67: 190–4.[CrossRef][Medline]
  3. Curley SA, Izzo F, Derio P, et al. Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies. Ann Surg 1999; 230: 1–8.[CrossRef][Medline]
  4. De Baere T, Elias D, Dromain C, et al. Radiofrequency ablation of 100 hepatic metastases with a mean follow-up of more than 1 year. AJR 2000; 175: 1619–25.[Abstract/Free Full Text]
  5. Bowles BJ, Machi J, Limm WL, et al. Safety and efficacy of radiofrequency thermal ablation in advanced liver tumors. Arch Surg 2001; 136: 864–9.[Abstract/Free Full Text]
  6. Bleicher RJ, Allegra DP, Nora DT, Wood TF, Foshag LJ, Bilchick AJ. Radiofrequency ablation in 447 complex unresectable liver tumors: lessons learned. Ann Surg Oncol 2003; 10: 52–8.[Abstract/Free Full Text]
  7. Solbiati L, Livraghi T, Golberg N, et al. Percutaneous radiofrequency ablation of hepatic metastases from colorectal cancer: long-term results in 117 patients. Radiology 2001; 221: 159–66.[Abstract/Free Full Text]
  8. Elias D, Ouellet JF, Bellon N, Pignon JP, Pocard M, Lasser P. Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases. Br J Surg 2003; 90: 567–74.[CrossRef][Medline]
  9. Elias D, Lasser P, Debaene B, et al. Intermittent exclusion of the liver without vena cava clamping during major hepatectomy. Br J Surg 1995; 82: 1535–9.[Medline]
  10. Denys AL, De Baere T, Mahe C, et al. Radiofrequency tissue ablation of the liver: effects of vascular exclusion on the diameter and biliary and portal damages in a pig model. Eur Radiol 2001; 11: 2102–8.[CrossRef][Medline]
  11. Elias D, El Otmany A, Goharin A, Attalah D, De Baere T. Intraductal cooling of the main bile ducts during intraoperative radiofrequency ablation. J Surg Oncol 2001; 76: 297–300.[CrossRef][Medline]
  12. Kokudo N, Miki Y, Sugai S, et al. Genetic and histological assessment of surgical margins in resected liver metastases from colorectal carcinoma. Arch Surg 2002; 137: 833–40.[Abstract/Free Full Text]
  13. Elias D, Sideris L, Pocard M, et al. Results of R0 resection for colorectal liver metastases associated with extrahepatic disease. Ann Surg Oncol2004 (in press).
  14. Siperstein A, Garland A, Engle K, et al. Local recurrence after laparoscopic radiofrequency thermal ablation of hepatic tumors. Ann Surg Oncol 2000; 7: 106–13.[Abstract]
  15. DeMatteo RP, Palese C, Jarnagin WR, Sun RL, Blumgart LH, Fong Y. Anatomic segmental hepatic resection is superior to wedge resection as oncologic operation for colorectal liver metastases. J Gastrointest Surg 2000; 4: 178–84.[CrossRef][Medline]
  16. Hughes K, Scheele J, Sugarbaker PH. Surgery for colorectal cancer metastatic to the liver. Optimizing the results of treatment. Surg Clin North Am 1989; 69: 339–59.[Medline]



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