Complementary Use of Resection and Radiofrequency Ablationfor the Treatment of Colorectal Liver Metastases: An Analysisof 395 Patients

Orhan Agcaoglu • Shamil Aliyev • Koray Karabulut • Galal El-Gazzaz •

Federico Aucejo • Robert Pelley • Allan E. Siperstein • Eren Berber

Published online: 5 March 2013

� Societe Internationale de Chirurgie 2013

Abstract

Background Liver resection and radiofrequency ablation

(RFA) are two surgical options in the treatment of patients with

colorectal liver metastases (CLM). The aim of this study was to

analyze patient characteristics and outcomes after resection and

RFA for CLM from a single center.

Methods Between 2000 and 2010, 395 patients with CLM

undergoing RFA (n = 295), liver resection (n = 94) or

both (n = 6) were identified from a prospective IRB-

approved database. Demographic, clinical and survival data

were analyzed using univariate and multivariate analyses.

Results RFA patients had more comorbidities, number of

liver tumors and a higher incidence of extrahepatic disease

compared to the Resection patients. The 5-year overall

actual survival was 17 % in the RFA, 58 % in the Resec-

tion group (p = 0.001). On multivariate analysis, multiple

liver tumors, dominant lesion[3 cm, and CEA[10 ng/ml

were independent predictors of overall survival. Patients

were followed for a median of 20 ± 1 months. Liver and

extrahepatic recurrences were seen in 69 %, and 29 % of

the patients in the RFA, and 40 %, and 19 % of the patients

in the Resection group, respectively.

Conclusions In this large surgical series, we described the

characteristics and oncologic outcomes of patients under-

going resection or RFA for CLM. By having both options

available, we were able to surgically treat a large number

of patients presenting with different degrees of liver tumor

burden and co-morbidities, and also manage liver recur-

rences in follow-up.

Introduction

Liver resection is the ‘‘gold standard’’ for treatment of

patients with colorectal liver metastases (CLM). However,

the majority of patients are not candidates for resection,

because of either extensive disease or patient co-morbidi-

ties, or both [1–7]. Despite the improvement in chemo-

therapy regimens over the last decade, the median survival

of patients treated with chemotherapy is approximately

18 months, and few patients survive beyond 3 years [8].

We and other groups have previously reported on

radiofrequency thermal ablation (RFA) as a minimally

invasive modality providing an acceptable local tumor

control rate with minimal morbidity, and therefore repre-

senting a treatment alternative for patients with unresec-

table colorectal liver metastasis. There has been a tendency

to look at RFA and liver resection as competing modalities

in the literature. Nevertheless, we have been using these

options complementary to each other as part of a multi-

disciplinary approach to treat colorectal cancer liver

metastasis. The aim of this article is to report a surgical

series from a single center and analyze patient character-

istics and outcomes after resection and RFA for CLM.

Materials and methods

Between 2000 and 2010, 389 patients with colorectal liver

metastases who underwent RFA (n = 295) or liver

This study was reported as an oral presentation at the annual meeting

of the American College of Surgeons, October 25–28, 2011 in San

Francisco, CA.

O. Agcaoglu � S. Aliyev � K. Karabulut � G. El-Gazzaz �F. Aucejo � R. Pelley � A. E. Siperstein � E. Berber (&)

Department of General Surgery, and Hematology and Oncology,

Cleveland Clinic, 9500 Euclid Avenue/F20, Cleveland, OH

44195, USA

e-mail: berbere@ccf.org

123

World J Surg (2013) 37:1333–1339

DOI 10.1007/s00268-013-1981-1

resection (n = 94) were identified from a prospectively

maintained, Institutional Review Board-approved database.

Six additional patients underwent combined liver resection

and RFA simultaneously at the same setting. Patients were

evaluated in a multidisciplinary fashion and challenged to

RFA in case of unresectable disease or patient decision.

All patients were followed under a prospective protocol

with quarterly liver computed tomography (CT) scans and

blood work, including carcinoembryonic antigen (CEA)

levels quarterly for the first 2 years and then biannually at

the Cleveland Clinic.

The indications for RFA included (1) unresectable dis-

ease, determined by inadequate liver remnant after a plan-

ned resection; (2) the presence of extrahepatic disease

(EHD); (3) patient co-morbidities predicting high morbidity

and mortality after liver resection; (4) and patient decision.

Summaries of continuous variables are represented in

the form of the mean ± standard error (SEM). Demo-

graphic, clinical, and survival data were assessed with the

t test, v2 test and univariate Kaplan–Meier analysis. Those

parameters with a significance of p \ 0.1 on Kaplan–Meier

survival analyses were entered into a multivariate Cox

proportional hazards model. Statistical significance was

reached at the level of p \ 0.05.

Technique

Our approaches to laparoscopic RFA and liver resection

have been reported elsewhere [9, 10]. All RFA procedures

were performed laparoscopically under general anesthesia.

Two 12 mm trocars were used in the right upper quadrant,

1 for the laparoscope and the other for the ultrasound

probe. All lesions were ablated in every patient. Ablation

equipment consisted of various Angiodynamics Inc. and

R.I.T.A. Medical Systems, Inc. 2, 5, and 7 cm catheters

that were used with 50–200 W generators at different time

points in the study.

Open resections were performed with a combination of

clamp-crush technique, the Cavitron Ultrasonic Surgical

Aspirator (CUSA), and the Aquamantys bipolar sealer,

with or without inflow (Pringle) occlusion. Laparoscopic

liver resections were performed after 2006 for lesions

located in segments II, III, IVB, V, and VI. Techniques for

laparoscopic resection included a combination of radio-

frequency pre-coagulation, Harmonic Scalpel, Tissue-Link

dissecting sealer, and linear staplers. The Pringle maneuver

was not used for laparoscopic resections.

Results

Although the groups were similar regarding age, gender,

and CEA levels, RFA patients had more co-morbidities, a

higher American Society of Anesthesiologists (ASA) score,

a greater number of liver tumors, and a higher incidence of

EHD compared to the Resection patients. The size of the

dominant liver metastasis was larger for the Resection

group (Table 1). The primary indication for RFA was

unresectability due to extrahepatic disease (EHD) (19 %),

inadequate liver remnant (32 %), co-morbidities (22 %),

and patient choice (27 %).

Table 2 shows details of chemotherapy exposure in the

treatment groups. Overall, a larger percentage of patients

had received preoperative chemotherapy in the RFA group

(87 vs. 77 %; p = 0.021).

The mean operative time for the Resection group was

169 ± 25 versus 118 ± 8 min for the RFA group

(p = 0.001). The median length of hospitalization was

5 days (range 1–15 days) for the Resection group and

1 day (range 1–3 days) for the RFA group (p = 0.001). A

total of 265 patients (90 %) underwent a single-session

RFA, and 30 patients (10 %) repeat RFA sessions (range

2–4) for recurrent disease in follow-up.

The types of liver resection included hemihepatectomy

in 14 patients (16 %), segmentectomy in 27 (29 %), wedge

resection in 48 (51 %), extended hemihepatectomy in 2

(2 %), and trisegmentectomy in 3 patients (2 %). Twelve

patients (13 %) underwent portal vein embolization before

the liver resection. Four of them underwent staged hepa-

tectomy. Hepatectomy was done laparoscopically in 31

Table 1 Demographic and clinical data in the study groups

Variables Resection

(n = 94)

RFA

(n = 295)

p value

Age (years) 61.7 ± 1.2 63.4 ± 0.7 0.109

Gender

Male 50 (53 %) 196 (66 %) 0.057

Female 44 (47 %) 99 (34 %)

Co-morbidities 53 (56 %) 214 (73 %) 0.233

ASA status 2.7 ± 0.1 2.9 ± 0.1 \0.001

Preoperative EHD 0 63 (22%) \0.001

Tumor size (cm) 3.7 ± 0.2 3.4 ± 0.1 0.327

Number of tumors

(range)

1.8 ± 0.2 (1–8) 3.0 ± 0.1

(1–11)

\0.001

CEA level (ng/ml) 115 ± 36.2 133 ± 19.8 0.687

Type of metastasis

Synchronous 32 (34 %) 109 (37 %) 0.504

Metachronous 62 (66 %) 186 (63 %)

Follow-up (months) 17.1 ± 1.8 20.0 ± 1.0 0.153

Data regarding 6 patients who underwent concomitant liver resection

and RFA are excluded

RFA radiofrequency ablation, ASA American Society of Anesthesi-

ologists score, CEA carcinoembryogenic antigen, EHD extrahepatic

disease

1334 World J Surg (2013) 37:1333–1339

123

(32 %) patients. In 8 (9 %) patients, the resection margin

was microscopically positive.

Two patients (2 %) in the Resection group died intra-

operatively, one from bleeding who had open resection and

one patient in the RFA group died postoperatively from an

acute myocardial infarction. The 30-day morbidity was

12 % (n = 11) in the Resection group and 4 % (n = 13) in

the RFA group. Morbidity in the Resection group included

pulmonary (n = 2), biliary (n = 2), wound-related

(n = 2), intestinal (n = 1), hemorrhagic (n = 1), cardiac

(n = 2), and renal (n = 1) complications. Complications in

the RFA group were bleeding (n = 3), liver abscess

(n = 2), pulmonary (n = 5), and renal (n = 3).

The median follow up was 21 months (range

6–96 months). The Kaplan–Meier median OS from the

date of surgery was 60 months for Resection patients, and

31 months for RFA patients (p \ 0.001). The 5-year actual

survival rates for the same groups were 58 and 17 %,

respectively (Fig. 1). The median survival of six patients

who had concomitant liver resection and RFA was

47 months.

After excluding RFA patients with EHD, the Kaplan–

Meier median disease-free survival (DFS) was 15 months

for the Resection group and 10 months for RFA group

(p = 0.185). The 5-year DFS rates for the same groups

were 21 and 8 %, respectively (p \ 0.0001) (Fig. 2).

Disease recurrence occurred in 38 (40 %) patients in

Resection group, including recurrence at the resection line

in eight patients (9 %) and in the new liver in 36 patients

(34 %); recurrence was extrahepatic in another 18 patients

(19 %). In 2 (25 %) of 8 patients who developed recur-

rence along the resection margin during follow-up, the

resection margin was microscopically positive at the time

of original hepatectomy. In the RFA group, local liver

recurrence at the site of ablation was seen in 133 patients

(45 %), new liver lesions in 180 patients (61 %), and new

extrahepatic disease in 86 (29 %) patients. The local liver

recurrence per lesion was 31 %. Radiofrequency ablation

was used to treat liver recurrences after an initial hepa-

tectomy in 24 patients, and resection was performed for

either downstaged or recurrent liver disease after RFA in

17 patients.

On univariate analysis, parameters found to affect OS

were bilobar versus unilobar location, number of liver

metastases, dominant tumor size, CEA level, and type of

surgical intervention (Table 3). On multivariate analysis,

independent predictors of OS were the number of tumors,

dominant tumor size, and CEA level (Table 4). For DFS,

parameters significant on univariate analysis were age,

Table 2 Details of chemotherapy exposure in the study patients

Variables Resection

(n = 94)

RFA

(n = 295)

p value

5-FU/leucovorin 64 (68 %) 229

(77 %)

0.333

Oxaliplatin 50 (53 %) 159

(54 %)

0.634

Irinotecan 38 (41 %) 108

(37 %)

0.394

Cetuximab 30 (32 %) 106

(36 %)

0.640

Bevacizumab 35 (37 %) 115

(40 %)

0.743

Preoperative chemotherapy 72 (77 %) 257

(87 %)

0.021

Postoperative chemotherapy 51 (54 %) 103

(35 %)

0.320

Both preoperative and

postoperative chemotherapy

42 (44 %) 83 (28 %) 0.254

5-FU 5-fluorouracil

Fig. 1 Kaplan–Meier overall survival of study patients. The 5-year

actual survival was 58 % for Resection (bold line), and 17 % for

Radiofrequency ablation (RFA) (p \ 0.001)

Fig. 2 Kaplan–Meier disease-free survival (DFS) of study patients

without extrahepatic disease. The median DFS was 15 months for

Resection (bold line) and 10 months for RFA (p = 0.185)

World J Surg (2013) 37:1333–1339 1335

123

bilobar versus unilobar location, number of liver metasta-

ses, size of dominant liver metastasis and CEA level

(Table 5). The number of tumors, age, dominant tumor

size, and CEA level were independent predictors of DFS on

multivariate analysis (Table 6).

The cause of death was known for 75 % of patients in

the RFA group and 69 % in the Resection group. The cause

of death was due to progression of liver disease, EHD

disease, and unrelated in 61 (37 %), 75 (46 %), and 27

patients (17 %), respectively, in the RFA group, and 8

(36 %), 11 (50 %), and 3 patients (14 %), respectively, in

the Resection group.

Discussion

In this large surgical series, we described the characteristics

and oncologic outcomes of patients with CLM undergoing

resection or RFA of CLM. Overall, we used the two

modalities complementary to each other and thus the

groups differed in regards to co-morbidities, tumor burden,

and extrahepatic disease. We reported the recurrence pat-

terns and survival to be expected when each modality is

used within this concept.

Approximately one-quarter of colorectal cancer patients

present with synchronous liver metastases, and an addi-

tional 35–45 % develop hepatic metastases during the

course of their disease [11]. Of those who present with

metastases confined to the liver, only 8–27 % are eligible

for surgical resection, whereas, the remaining majority of

patients rarely survive 5 years [1–3]. For patients with

disease confined to the liver, hepatic resection has clearly

been established as standard treatment, with mortality rates

of \5 % in high-volume centers [12–14]. However, most

patients with liver-only metastases are not candidates for

resection because of bilobar disease that is not amenable to

complete resection. Novel approaches such as neoadju-

vant chemotherapy, preoperative portal vein embolization,

and two-stage hepatectomy have been used in an attempt

to increase respectability [15]. Complete resection has

Table 3 Univariate Kaplan–Meier analysis of overall survival

Variable No. of

patients

Median survival

(months)

p value

Age (years)

B65 208 35 0.619

[65 181 35

Gender

Female 143 40 0.090

Male 246 32

ASA status

I–II 49 44 0.066

III–IV 240 32

Primary tumor

Colon 260 40 0.993

Rectal 129 37

Type of metastases

Metachronous 247 35 0.683

Synchronous 142 32

Location of liver metastases

Bilobar 119 27 0.030

Unilobar 270 39

Number of metastases

B3 294 39 \0.001

[3 95 24

Dominant liver tumor size (cm)

\3 169 46 \0.001

3–5 165 29

[5 55 24

EHD

Present 63 27 0.111

Absent 326 36

Chemotherapy

Yes 359 35 0.874

No 30 36

CEA (ng/ml)

B10 144 49 \0.001

[10 245 28

Type of intervention

RFA 295 31 0.001

Resection 94 60

Table 4 Cox proportional hazards model for overall survival

Variable Hazard ratio (95 % CI) p value

Gender

Male versus female 1.1 (0.9–1.5) 0.394

RFA versus resection 1.4 (1.0–2.2) 0.078

Number of tumors

[3 versus B3 1.6 (1.2–2.1) 0.002

Dominant tumor size

[5 versus \3 cm 2.1 (1.4–3.1) \0.001

Dominant tumor size

3–5 versus \3 cm 1.5 (1.2–2.0) 0.003

Dominant tumor size

[5 versus 3–5 cm 1.4 (0.9–1.9) 0.096

Extrahepatic disease

Present vs absent 1.2 (0.9–1.7) 0.391

ASA status

3–4 versus 1–2 1.3 (0.9–2.1) 0.249

CEA level

[10 versus B10 ng/ml 1.6 (1.2–2.1) 0.001

1336 World J Surg (2013) 37:1333–1339

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resulted in median survival of [40 months, a 5-year sur-

vival of 30–55 % [16, 17], and cure in 20–25 % of patients

[16, 18].

As these patients continue to have a poor prognosis,

with a median survival of 21 months at best with mul-

timodality therapy, the management of colorectal cancer

metastatic to the liver continues to be a therapeutic chal-

lenge for both oncologists and surgeons [8]. Even with all

improvements in systemic therapies, few patients with

hepatic metastases are ever cured with chemotherapy and/

or biologic therapies [19, 20]. Because it is widely accepted

that the most common cause of death is liver failure after

progression of hepatic involvement, aggressive treatment

of the liver tumor burden is necessary [3, 9, 12, 21, 22]. We

have been using both resection and surgeon-performed

laparoscopic RFA for this purpose at our institution. With

the exception of a subgroup of patients with resectable

disease requesting RFA as the first line of treatment,

patients with resectable disease were treated surgically and

those with unresectable disease had RFA. In line with this

selection bias, RFA patients had a larger liver tumor bur-

den, higher CEA levels, more co-morbidities, and a greater

incidence of EHD than Resection patients did. The other

reports in the literature have also demonstrated this dif-

ference between RFA and resection patients regarding

co-morbidities, EHD, and liver tumor volume [1–3], and

therefore attempts to compare RFA with resection, in terms

of oncologic outcomes, have been unsuccessful. This series

reinforces the realization that the two groups of patients

are, in general, not comparable, and therefore the oncologic

outcomes can be best evaluated when the two modalities

are seen as complementary, and not as competing options.

A number of retrospective studies have tried to answer

the question of whether RFA is equivalent to resection in

patients with resectable disease. Carrying the limitations

summarized above, only one report showed equivalent

median survival (41 vs. 37 months) and 3-year survival

rates (55 vs. 53 %) between resection patients and RFA

patients [9], whereas, other studies reported better 5-year

survival (71 vs. 27 %) [6], (48 vs. 15 %) [23], and median

OS (56 vs. 36 months) [5, 9], as well as DFS (15 vs.

8 months) [17] for resection versus RFA.

Table 5 Univariate Kaplan–Meier analysis of disease-free survival

Variable No. of

patients

Median survival

(months)

p value

Age (years)

B65 174 9.5 0.007

[65 152 15

Gender

Female 119 13 0.083

Male 207 11

ASA status

I–II 44 16 0.085

III–IV 283 11

Primary tumor

Colon 197 11 0.614

Rectal 129 11

Type of metastases

Metachronous 207 13 0.261

Synchronous 119 9

Location of liver metastases

Bilobar 101 8 0.008

Unilobar 225 14

Number of metastases

B3 245 14 \0.001

[3 81 7

Dominant liver tumor size (cm)

\3 146 16 \0.001

3–5 133 9

[5 47 8

Chemotherapy

Yes 291 11 0.144

No 35 17

CEA (ng/ml)

B10 117 14 0.008

[10 209 10

Type of intervention

RFA 232 10 0.185

Resection 94 15

RFA patients with EHD were excluded from this analysis

Table 6 Cox proportional hazards model for disease free survival

Variable Hazard ratio (95 % CI) p value

Age 1 (0.9–1.0) 0.046

Gender

Male versus female 1.1 (0.9–1.5) 0.372

RFA vs Resection 1.4 (1.0–2.2) 0.088

Number of tumors

[3 versus B3 1.5 (1.1–2.0) 0.014

Dominant tumor size

[5 versus \3 cm 2.4 (1.6–3.7) \ 0.001

Dominant tumor size

3–5 versus \3 cm 1.6 (1.1–2.1) 0.006

Dominant tumor size

[5 versus 3–5 cm 1.6 (1.1–2.3) 0.029

ASA status

3–4 versus 1–2 1.4 (0.9–2.3) 0.165

CEA level

[10 versus B10 ng/ml 1.7 (1.2–2.3) 0.001

For this analysis, RFA patients without EHD (n = 232) and Resection

patients (n = 94) were used

World J Surg (2013) 37:1333–1339 1337

123

With the surgical RFA and resection program illustrated

in this study, high-risk patients were triaged to RFA,

resulting in a group of patients enjoying a very favorable

long-term survival after resection (5-year, 58 %), whereas,

a lower long-term survival was still achieved in sicker

patients with more aggressive tumors (5-year survival,

17 %). By using both modalities, we were able to surgi-

cally treat patients presenting in a wide spectrum and also

manage recurrences in follow-up. Overall, 47 patients were

treated with both resection and RFA, either simultaneously

or at different time points to achieve liver tumor control in

our study. There are other reports in the literature about the

concomitant use of hepatectomy and RFA [24, 25] to

increase the number of patients eligible for liver resection,

as well as about the utility of RFA to treat recurrent liver

metastases after a partial hepatectomy [26].

A recent study showed that if patients are followed long-

term with strict protocols, recurrence in the liver can be

identified in 70 % of the patients after a liver resection

[27]. In our study recurrence in the liver was seen in 40 %

of the patients after resection and 69 % after RFA. Fur-

thermore, extrahepatic recurrence was seen in 19 % of the

Resection and 29 % of the RFA patients. This study also

documents the incidence of local recurrence along the

resection line after hepatectomy in addition to local

recurrence at the ablation site.

In this study, tumor size [3 cm, multiple liver tumors,

and pretreatment CEA level [10 ng/ml were independent

predictors of mortality. The type of surgical treatment

(RFA vs. resection) did not affect survival. Parameters

reported to be associated with poor prognosis after resec-

tion of colorectal liver metastases include positive margin,

extrahepatic disease, node-positive primary, disease-free

interval from primary to metastases \12 months, number

of tumors more than 1, largest tumor size[5 cm, and CEA

level [200 ng/ml [28], as well as presence and extent of

mesenteric lymph node involvement, grade 3 or 4 primary

tumor, synchronous diagnosis of metastases, satellite

metastases, limited resection margins, and non-anatomic

procedures [29].

In our study, there was no effect of chemotherapy on OS

or DFS. In a study comparing adjuvant 5-fluorouracil and

leucovorin after resection with no adjuvant chemotherapy

[30], there was a difference in DFS (34 vs. 27 %;

p = 0.03), but not in OS (51 vs. 41 %; p = 0.1) for met-

astatic colorectal cancer. In a randomized study of peri-

operative FOLFOX and surgery versus surgery alone, DFS

was found to be better with perioperative chemotherapy,

although perioperative complications were increased [31].

In conclusion, we presented a contemporary series of

CLM treated with resection and RFA based on patient

presentation and choice. We used both modalities for cyto-

reduction of recurrences in follow-up as well. We suggest

that until prospective randomized studies comparing the

two techniques in treatment of colorectal liver metastasis

are available, RFA and resection should be used adjunctive

to each other and not as a replacement for each other.

References

1. McKay A, Dixon E, Taylor M (2006) Current role of radiofre-

quency ablation for the treatment of colorectal liver metastases.

Br J Surg 93:1192–1201

2. Wood TF, Rose DM, Chung M et al (2000) Radiofrequency

ablation of 231 unresectable hepatic tumors: indications, limita-

tions, and complications. Ann Surg Oncol 7:593–600

3. Siperstein AE, Berber E, Ballem N et al (2007) Survival after

radiofrequency ablation of colorectal liver metastases: 10-year

experience. Ann Surg 246:559–565 discussion 565–567

4. Abdalla EK, Vauthey JN, Ellis LM et al (2004) Recurrence and

outcomes following hepatic resection, radiofrequency ablation,

and combined resection/ablation for colorectal liver metastases.

Ann Surg 239:818–825 discussion 825–827

5. White RR, Avital I, Sofocleous CT et al (2007) Rates and pat-

terns of recurrence for percutaneous radiofrequency ablation and

open wedge resection for solitary colorectal liver metastasis.

J Gastrointest Surg 11:256–263

6. Aloia TA, Vauthey JN, Loyer EM et al (2006) Solitary colorectal

liver metastasis: resection determines outcome. Arch Surg

141:460–466 discussion 466–467

7. Belghiti J, Hiramatsu K, Benoist S et al (2000) Seven hundred

forty-seven hepatectomies in the 1990s: an update to evaluate the

actual risk of liver resection. J Am Coll Surg 191:38–46

8. Biasco G, Derenzini E, Grazi G et al (2006) Treatment of hepatic

metastases from colorectal cancer: many doubts, some certain-

ties. Cancer Treat Rev 32:214–228

9. Berber E, Tsinberg M, Tellioglu G (2008) Resection versus

laparoscopic radiofrequency thermal ablation of solitary colo-

rectal liver metastasis. J Gastrointest Surg 12:1967–1972

10. Tsinberg M, Tellioglu G, Simpfendorfer CH et al (2009) Com-

parison of laparoscopic versus open liver tumor resection: a case-

controlled study. Surg Endosc 23:847–853

11. Jemal A, Murray T, Ward E et al (2005) Cancer statistics (2005)

CA Cancer J Clin 55:10–30 [published correction appears in CA

Cancer J Clin 55:259]

12. Berber E, Pelley R, Siperstein AE (2005) Predictors of survival

after radiofrequency thermal ablation of colorectal cancer metas-

tases to the liver: a prospective study. J Clin Oncol 23:1358–1364

13. Jaeck D, Bachellier P, Guiguet M et al (1997) Long-term survival

following resection of colorectal hepatic metastases. Association

Francaise de Chirurgie. Br J Surg 84:977–980

14. Minagawa M, Makuuchi M, Torzilli G et al (2000) Extension of

the frontiers of surgical indications in the treatment of liver

metastases from colorectal cancer: long-term results. Ann Surg

231:487–499

15. Kornprat P, Jarnagin WR, DeMatteo RP et al (2007) Role of

intraoperative thermoablation combined with resection in the

treatment of hepatic metastasis from colorectal cancer. Arch Surg

142:1087–1092

16. Wong SL, Mangu PB, Choti MA et al (2010) American Society

of Clinical Oncology 2009 clinical evidence review on radio-

frequency ablation of hepatic metastases from colorectal cancer.

J Clin Oncol 28:493–508

17. Park IJ, Kim HC, Yu CS et al (2007) Radiofrequency ablation for

metachronous liver metastasis from colorectal cancer after cura-

tive surgery. Ann Surg Oncol 15:227–232

1338 World J Surg (2013) 37:1333–1339

123

18. Greene FL, Sobin LH (2002) The TNM system: our language for

cancer care. J Surg Oncol 80:119–120

19. Saltz LB, Cox JV, Blanke C et al (2000) Irinotecan Study Group.

Irinotecan plus fluorouracil and leucovorin for metastatic colo-

rectal cancer. N Engl J Med 343:905–914

20. Saltz LB, Clarke S, Az-Rubio E et al (2008) Bevacizumab in

combination with oxaliplatin-based chemotherapy as first-line

therapy in metastatic colorectal cancer: a randomized phase III

study. J Clin Oncol 26:2013–2019

21. Livraghi T, Solbiati L, Meloni F et al (2003) Percutaneous

radiofrequency ablation of liver metastases in potential candidates

for resection: the ‘‘test-of-time approach’’. Cancer 97:3027–3035

22. Berber E, Rogers S, Siperstein A (2005) Predictors of survival

after laparoscopic radiofrequency thermal ablation of hepatocel-

lular cancer: a prospective study. Surg Endosc 19:710–714

23. McKay A, Fradette K, Lipschitz J (2009) Long-term outcomes

following hepatic resection and radiofrequency ablation of

colorectal liver metastases. HPB Surg 2009:346863

24. Popescu I, Alexandrescu S, Croitoru A et al (2009) Strategies to

convert to resectability the initially unresectable colorectal liver

metastases. Hepatogastroenterology 56(91–92):739–744

25. Leung EY, Roxburgh CS, Leen E et al (2010) Combined resec-

tion and radiofrequency ablation for bilobar colorectal cancer

liver metastases. Hepatogastroenterology 57:41–46

26. Van der Pool AE, Lalmahomed ZS, de Wilt JH et al (2009) Local

treatment for recurrent colorectal hepatic metastases after partial

hepatectomy. J Gastrointest Surg 13:890–895

27. Vigano L, Ferrero A, Lo Tesoriere R et al (2008) Liver surgery

for colorectal metastases: results after 10 years of follow-up.

Long-term survivors, late recurrences, and prognostic role of

morbidity. Ann Surg Oncol 15:2458–2464

28. Fong Y, Fortner J, Sun R et al (1999) Clinical score for predicting

recurrence after hepatic resection for metastatic colorectal cancer:

analysis of 1001 consecutive cases. Ann Surg 230:309–318

29. Scheele J, Stangl R, Altendorf-Hofmann A et al (1991) Indicators

of prognosis after hepatic resection for colorectal secondaries.

Surgery 110:13–29

30. Portier G, Elias D, Bouche O et al (2006) Multicenter randomized

trial of adjuvant fluorouracil and folinic acid compared with

surgery alone after resection of colorectal liver metastases: FFCD

ACHBTH AURC 9002 trial. J Clin Oncol 24:4976–4982

31. Nordlinger B, Sorbye H, Glimelius B et al (2008) Perioperative

chemotherapy with FOLFOX4 and surgery versus surgery alone

for resectable liver metastases from colorectal cancer (EORTC

Intergroup trial 40983): a randomised controlled trial. Lancet

371(9617):1007–1016

World J Surg (2013) 37:1333–1339 1339

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