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Long-term outcomes after hepatectomy for recurrences after

prior local ablation for hepatocellular carcinoma
J. Sakata, Y. Shirai*, T. Wakai, K. Kaneko, K. Hatakeyama
Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences,
1e757 Asahimachi-dori, Niigata City 951-8510, Japan
Accepted 20 March 2007

Abstract
Aims: Intrahepatic recurrence is the most common manifestation of failure after local ablation therapy for hepatocellular carcinoma. The
present study evaluates the safety and efficacy of partial hepatectomy for intrahepatic recurrence after prior local ablation.
Methods: A retrospective analysis was conducted of 188 consecutive patients with hepatocellular carcinoma who underwent either partial
hepatectomy for recurrence after prior local ablation (n 13) or partial hepatectomy as initial local treatment (n 175). The 13 patients
with recurrence after prior local ablation were referred to our division after the resectable recurrences were considered to be resistant to
non-surgical treatment modalities.
Results: The incidences of postoperative morbidity and mortality were similar for patients with prior local ablation and patients without
prior local ablation ( p 0.75 and p 0.52, respectively). The overall survival rates after hepatectomy were comparable between patients
with prior local ablation (median survival time of 86 months; cumulative 5-year survival rate of 63%) and patients without prior local ablation (median survival time of 76 months; cumulative 5-year survival rate of 54%; p 0.60). The disease-free survival rates after hepatectomy were significantly worse for patients with prior local ablation based on both univariate ( p 0.01) and multivariate (relative risk,
2.73; p < 0.01) analyses.
Conclusions: Hepatectomy can be performed safely and may be efficacious, in terms of overall survival, for selected patients with intrahepatic recurrence after prior local ablation for hepatocellular carcinoma. On the other hand, prior local ablation appears to increase the
probability of failure after hepatectomy.
2007 Elsevier Ltd. All rights reserved.
Keywords: Hepatocellular carcinoma; Hepatectomy; Catheter ablation; Neoplasm recurrence; Survival rate; Prognosis

Introduction
Local ablation therapy, such as radiofrequency ablation
(RFA), percutaneous ethanol injection (PEI), microwave
coagulation therapy (MCT), or cryoablation, is a widely accepted treatment modality for hepatocellular carcinoma
(HCC).1e5 As local ablation therapy becomes more widely
accepted, the worldwide increase in the number of patients
with local ablation failure becomes a critical problem in the
treatment of HCC.3e5
Intrahepatic recurrence is the most common manifestation of failure after local ablation therapy for HCC.3e8 Therefore, the management of intrahepatic recurrence may prolong
patient survival after local ablation therapy. Although local
* Correspondence author. Tel.: 81 25 227 2228; fax: 81 25 227 0779.
E-mail address: shiray@med.niigata-u.ac.jp (Y. Shirai).

ablation therapy9e12 or repeat hepatectomy13e17 has been reported to be effective for intrahepatic recurrences after initial
hepatectomy, there have been no reports regarding the utility
of hepatectomy for intrahepatic recurrences after prior local
ablation.
The current study was designed to evaluate the safety
and efficacy of partial hepatectomy for intrahepatic recurrence after prior local ablation.
Patients and methods
Patient population
From January 1990 through December 2004, 188 consecutive patients underwent initial partial hepatectomy for
HCC at the Division of Digestive and General Surgery,

0748-7983/$ - see front matter 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.ejso.2007.03.018
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Niigata University Medical and Dental Hospital. These patients formed the basis of this retrospective study. They included 138 men and 50 women with a median age of 65
(range, 16e80) years. All of the patients were Japanese.
In the current series, 13 patients underwent hepatectomy
for recurrences after prior local ablation (RFA, PEI, and
MCT) for HCC, whereas remaining 175 patients underwent
hepatectomy as initial local treatment. The outcomes after
hepatectomy were compared for the two cohorts.
Prior local ablation

Indications for hepatectomy for failure

after prior local ablation
The 13 patients who underwent hepatectomy for recurrence after prior local ablation were referred to our division
after the resectable recurrences were considered to be resistant to non-surgical treatment modalities. In these patients,
hepatectomy was indicated for intrahepatic recurrences
when a potentially curative (R0) resection20 was considered
feasible, even though ten of these patients had multiple
recurrences.
Laboratory evaluation

Prior local ablations were performed at the Division of

Gastroenterology and Hepatology in our hospital, where a
microwave tissue coagulator (Microtaze OT-110M; Alfresa-Pharma Co., Inc., Osaka, Japan) and an RF generator
(Cool-tip RF System; CMI Century Medical Co., Inc., Tokyo,
Japan) were introduced in 1995 and 2000, respectively. At
the time of prior local ablation, all 13 patients were considered to have resectable tumors but were advised by gastroenterologists to undergo local ablation rather than hepatectomy.
In this series, the median interval between prior local
ablation and hepatectomy was 30 (range, 3e97) months.
Failures after prior local ablation were designated as: local
failure (recurrences contiguous to or within the ablated
areas; n 3); new intrahepatic lesions (n 3); and combined local and new lesions (n 7).

The following parameters were measured before hepatectomy: serum aspartate aminotransferase (AST); serum alanine aminotransferase (ALT); serum a-fetoprotein (AFP);
hepatitis B surface antigen (HBsAg); and antibody to hepatitis C virus (anti-HCV). The serum concentrations of AFP
were determined by enzyme immunoassay (Luminomaster
AFP; Sankyo Yell Yakuhin Co., Ltd., Tokyo, Japan), with
a reference range of <21 ng/mL. HBsAg and anti-HCV in
serum samples were detected by radioimmunoassay (Lumipulse II HBsAg; Fujirebio Co., Inc., Tokyo, Japan) and a
second-generation enzyme-linked immunosorbent assay
(Lumipulse II Ortho HCV; Ortho-Clinical Diagnostics
Co., Inc., Tokyo, Japan), respectively.

Hepatectomy procedures

Pathologic evaluation

During the study period, a hepatectomy procedure was

selected for each patient, taking into account the primary tumor status (size, number, and location), hepatic functional
reserve, and general condition of the patient. There was
a tendency to select a more extensive hepatectomy procedure for patients with larger tumors, more deeply located tumors, better hepatic functional reserve, or those in better
general condition. The terminology used regarding hepatectomy procedures is based on The Brisbane 2000 Terminology of Liver Anatomy and Resections.18 The hepatectomy
procedures for this series of patients included non-anatomic
resection (n 59), segmentectomy (n 27), bisegmentectomy (n 38), right hepatectomy (n 34), left hepatectomy (n 10), central bisectionectomy (i.e., resection of
the right anterior and left medial sections) (n 1), right
hepatectomy extended to a medial part of Couinaud segment
4 (n 14), and left hepatectomy extended to a medial part
of the right anterior section (n 5). Extended hepatectomy
(trisectionectomy) was not employed. In the case of combined non-anatomic and anatomic resections in the same patient, the anatomic resection represented the hepatectomy
procedure for that patient.
In this study, right or left hepatectomy, central bisectionectomy, or more extensive hepatectomy was referred to as
major hepatectomy, whereas less extensive resections were
designated as minor hepatectomy.

Resected specimens were submitted to the Department of

Surgical Pathology in our hospital. Each specimen was examined for the presence of cirrhosis, the number of hepatic
tumors, size of the largest hepatic tumor, histologic grade,
and vascular invasion. A median of 12 (range, 2e38) microscopic slides of the resected liver from each patient was
available.
Cirrhosis in the adjacent (non-tumorous) liver was diagnosed microscopically based on the presence of regenerative
nodules surrounded by fibrous septa. Histologic grade was
determined according to the Edmondson-Steiner classification,19 and was based on the areas of the tumor with the
highest grade. Vascular invasion was defined as gross or
microscopic vascular invasion and included both portal
and hepatic venous invasion.
Patient follow-up after resection
Postoperative morbidity was defined as any postoperative complication that lengthened the hospital stay. Postoperative mortality was defined as any death that occurred
during the hospital stay for resection of HCC. After hepatectomy, 19 patients underwent adjuvant chemotherapy,
which consisted of transarterial administration of 20 or
40 mg of doxorubicin combined with lipiodol and none
of the patients received adjuvant radiotherapy.

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The serum concentration of AFP was measured and abdominal ultrasonography and/or contrast-enhanced computed tomography scan was performed approximately
1 month after resection for all patients. Thereafter, the patients were followed-up every 3 months in outpatient clinics
and monitored for disease recurrence by measurement of serum concentrations of AFP and/or imaging studies. When intrahepatic recurrences were detected, they were treated with
interventional radiological techniques, repeat hepatectomy,
or systemic chemotherapy. Patients with disseminated recurrences and those in a debilitated state received supportive
care. The median follow-up period after hepatectomy was
81 (range, 8e190) months.
At the time of disease status assessment, 77 patients had
died of tumor recurrence. Sixteen patients had died of other
causes with no evidence of disease. Forty-one patients were
alive with recurrent disease and the remaining 54 patients
were alive with no evidence of disease.
Prognostic factors
To determine the factors that influence long-term outcomes after hepatectomy, 17 conventional variables20e22
together with the presence or absence of prior ablative therapy were tested in all 188 patients: age (65 years vs.
>65 years), gender, Child-Pugh classification (A vs. B C),
cirrhosis (absent vs. present), serum AST level (50 IU/L vs.
>50 IU/L), serum ALT level (50 IU/L vs. >50 IU/L),
serum AFP level (20 ng/mL vs. >20 ng/mL), HBsAg
status (negative vs. positive), anti-HCV status (negative vs.
positive), type of hepatic resection (minor vs. major), number
of hepatic tumors (solitary vs. multiple), size of the largest
hepatic tumor (3 cm vs. >3 cm), Edmondson-Steiner grade
(IeII vs. IIIeIV), vascular invasion (negative vs. positive),
operating time (300 min vs. >300 min), estimated blood
loss (1000 mL vs. >1000 mL), adjuvant chemotherapy
(absent vs. present), and prior local ablation (absent vs.
present).
Statistical analysis
Medical records and survival data were obtained for all
patients. Categoric variables were compared using the
Fisher exact test, whereas continuous variables were compared with the ManneWhitney test. The causes of death
were determined from the medical records and autopsy records. Deaths from other causes were treated as uncensored
cases. The KaplaneMeier method was used to estimate the
cumulative incidences of events, and differences in these
incidences were evaluated using the log rank test. The
Cox proportional hazards regression model using a stepbackward fitting procedure was performed to identify factors that were independently associated with survival and
disease-free survival. In this model, a stepwise selection
was used for variable selection with entry and removal
limits of p < 0.1 and p > 0.15, respectively. All the

statistical evaluations were performed using the SPSS

11.5J software package (SPSS Japan Inc., Tokyo, Japan).
All tests were two-sided and p values of <0.05 were considered to be statistically significant.
Results
For all 188 patients, the incidences of posthepatectomy
morbidity and mortality were 27% and 5%, respectively;
overall survival rates were 54% at 5 years and 36% at
10 years with a median survival period of 80 months; disease-free survival rates were 34% at 5 years and 23% at
10 years with a median disease-free survival period of
23 months.
Patients with prior local ablation had a greater number
of hepatic tumors ( p < 0.01) and lower serum AFP levels
( p 0.04) compared with patients without prior local ablation. The remaining factors, which included operating time
and estimated blood loss, were comparable between the
two groups.
Impact of prior local ablation on morbidity/mortality
after hepatectomy
The incidence of postoperative morbidity was 31% (4/13
patients) for patients with prior local ablation and 26% (46/
175 patients) for patients without prior local ablation
( p 0.75). The incidence of postoperative mortality was
8% (1/13 patient) for patients with prior local ablation
compared with 5% (9/175 patients) for patients without prior
local ablation ( p 0.52). Thus, the incidences of postoperative morbidity and mortality were comparable between the
two groups.
Factors influencing overall survival after hepatectomy
Univariate analysis revealed that Child-Pugh classification ( p 0.04), cirrhosis ( p 0.03), serum AST level
( p < 0.01), serum AFP level ( p < 0.01), number of hepatic
tumors ( p < 0.01), size of the largest hepatic tumor
( p 0.02), Edmondson-Steiner grade ( p < 0.01), vascular
invasion ( p < 0.01), and estimated blood loss ( p < 0.01)
were significant factors for overall survival. The presence
or absence of prior local ablation did not affect overall survival after hepatectomy (Fig. 1).
The variables that were found to be significant in the
univariate analyses were entered into multivariate analyses,
which revealed that serum AST level (relative risk, 1.57;
95% confidence interval, 1.03e2.37; p 0.04), number
of hepatic tumors (relative risk, 1.68; 95% confidence interval, 1.08e2.61; p 0.02), and Edmondson-Steiner grade
(relative risk, 2.29; 95% confidence interval, 1.40e3.74;
p < 0.01) were significantly independent factors for overall
survival.

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p < 0.05), Edmondson-Steiner grade (relative risk, 3.33;

95% confidence interval, 2.13e5.19; p < 0.01), and prior
local ablation (relative risk, 2.73; 95% confidence interval,
1.42e5.23; p < 0.01) were significantly independent factors for disease-free survival.
Discussion

Figure 1. KaplaneMeier survival estimates. Overall survival after hepatectomy was comparable between patients with prior local ablation (median
survival period of 86 months; cumulative 5-year survival rate of 63%)
and patients without prior local ablation (median survival period of
76 months; cumulative 5-year survival rate of 54%; p 0.60).

Factors influencing disease-free survival

after hepatectomy
Univariate analysis revealed that cirrhosis ( p 0.04),
serum AST level ( p < 0.01), serum ALT level ( p < 0.01),
serum AFP level ( p < 0.01), number of hepatic tumors
( p < 0.01), size of the largest hepatic tumor ( p < 0.01),
Edmondson-Steiner grade ( p < 0.01), vascular invasion
( p 0.03), and prior local ablation ( p 0.01) were significant factors for disease-free survival. Prior local ablation
was associated with decreased disease-free survival (Fig. 2).
The variables that were found to be significant in the
univariate analyses were entered into multivariate analyses,
which revealed that serum ALT level (relative risk, 1.71;
95% confidence interval, 1.17e2.50; p < 0.01), serum
AFP level (relative risk, 1.65; 95% confidence interval,
1.10e2.48; p 0.02), size of the largest hepatic tumor (relative risk, 1.49; 95% confidence interval, 1.01e2.20;

Local ablation therapy is a widely accepted treatment modality for small HCCs;1e5 intrahepatic recurrences are frequently seen following this type of treatment.3e8 In recent
years, increasing numbers of patients with such failure after
local ablation therapy have been referred to our division for
hepatectomy. However, the role of partial hepatectomy in
the management of failure after local ablation was largely unknown. This spurred us to conduct the current study, in which
we discovered that the operating time, estimated blood loss,
and postoperative morbidity/mortality were similar between
patients with prior local ablation and patients without prior
local ablation. Furthermore, prior local ablation did not affect
the overall survival rates after hepatectomy (Fig. 1). Taken
together, these observations indicate that hepatectomy can
be performed safely and may be efficacious, in terms of overall survival, for selected patients with intrahepatic recurrence
after prior local ablation for HCC. In these situations, surgeons should not hesitate to perform hepatectomy, provided
that the patient is considered fit for the operation.
In contrast, prior local ablation was associated with decreased disease-free survival (Fig. 2), which suggests that
failure after hepatectomy is more frequently seen in patients with prior local ablation than in patients without prior
local ablation. The predominance of multiple tumors in
patients with prior local ablation may partly explain this
observation. Therefore, recurrences should be monitored
closely in patients who undergo hepatectomy for failure after prior local ablation.
Tumor dissemination associated with
local ablation therapy

Figure 2. KaplaneMeier survival estimates. Disease-free survival after

hepatectomy was worse for patients with prior local ablation (median disease-free survival period of 12 months; cumulative 5-year disease-free survival rate of 10%) than for patients without prior local ablation (median
disease-free survival period of 26 months; cumulative 5-year disease-free
survival rate of 35%; p 0.01).

Intrahepatic recurrence is a critical problem following

local ablation therapy for HCC.3e8 In this study, multiple
hepatic recurrences around the ablated area were commonly observed in patients with prior local ablation, which
raises the possibility that local ablation disseminates tumor
cells into the adjacent liver. Recently, RFA has been reported to facilitate the spread of HCC via the portal
vein,23e26 probably due to elevated intratumoral pressure
during ablation,23e25 the occurrence of an arterioportal fistula after RFA,23,26 and puncture of the portal venous
branch(es) with a contaminated needle.23,25 In addition,
percutaneous local ablation for HCC may result in peritoneal seeding.27e29 These observations suggest that local ablation therapy facilitates the spread of HCC, which may
partly explain the predominance of multiple tumors in patients with prior local ablation.

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Patterns of failure after local ablation therapy

Intrahepatic recurrence after local ablation includes local failure, intrahepatic metastasis, and multicentric new lesions.2e8 Early recurrences (within 2 years after local
treatment) may include all the patterns of failure, whereas
late recurrences (more than 2 years after local treatment)
are predominantly of multicentric origin.22,30,31 The interval between prior local ablation and hepatectomy ranged
from 3 to 97 months, which suggests that intrahepatic recurrences after local ablation occurred via all three patterns
of failure in our patients. Although it is very likely that the
role of hepatectomy in the management of failure after
local ablation differs according to the patterns of failure,
the small number of patients in the present study precluded
this type of analysis. Further investigations using a greater
number of patients are warranted to explore this idea.
Liver transplantation for failure after
local ablation therapy
Among the 13 patients with failure after prior local ablation, four met the Milan criteria at the time of recurrence
(data not shown) and subsequently underwent partial hepatectomy; the initial site of recurrence following partial hepatectomy was the remnant liver alone in all four patients.
This observation implies that some patients with isolated
intrahepatic recurrences after local ablation therapy may
be candidates for liver transplantation provided that they
meet the Milan criteria.32,33
Limitations
There are two main limitations to the current study.
First, it constitutes a retrospective analysis of a small group
of patients who underwent prior local ablation. Second, the
median follow-up time was short for some of the patients.
Despite these limitations, we have first clarified the role
of partial hepatectomy in the management of failure after
prior local ablation for HCC.
Conclusions
Hepatectomy can be performed safely and may be efficacious, in terms of overall survival, for selected patients
with intrahepatic recurrence after prior local ablation for
HCC. On the other hand, prior local ablation appears to increase the probability of failure after hepatectomy.
References
1. Arii S, Yamaoka Y, Futagawa S, et al. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. Hepatology 2000;32:12249.
2. Lencioni R, Cioni D, Crocetti L, Bartolozzi C. Percutaneous ablation
of hepatocellular carcinoma: state-of-the-art. Liver Transpl 2004;10:
S917.

3. Poon RT, Fan ST, Tsang FH, Wong J. Locoregional therapies for hepatocellular carcinoma: a critical review from the surgeons perspective. Ann Surg 2002;235:46686.
4. Lau WY, Leung TW, Yu SC, Ho SK. Percutaneous local ablative therapy for hepatocellular carcinoma: a review and look into the future.
Ann Surg 2003;237:1719.
5. Omata M, Tateishi R, Yoshida H, Shiina S. Treatment of hepatocellular carcinoma by percutaneous tumor ablation methods: ethanol injection therapy and radiofrequency ablation. Gastroenterology 2004;127:
S15966.
6. Sala M, Llovet JM, Vilana R, et al. Initial response to percutaneous
ablation predicts survival in patients with hepatocellular carcinoma.
Hepatology 2004;40:135260.
7. Lencioni R, Cioni D, Crocetti L, et al. Early-stage hepatocellular
carcinoma in patients with cirrhosis: long-term results of percutaneous
image-guided radiofrequency ablation. Radiology 2005;234:9617.
8. Raut CP, Izzo F, Marra P, et al. Significant long-term survival after radiofrequency ablation of unresectable hepatocellular carcinoma in patients with cirrhosis. Ann Surg Oncol 2005;12:61628.
9. Nicoli N, Casaril A, Marchiori L, Mangiante G, Hasheminia AR.
Treatment of recurrent hepatocellular carcinoma by radiofrequency
thermal ablation. J Hepatobiliary Pancreat Surg 2001;8:41721.
10. Itamoto T, Katayama K, Fukuda S, et al. Percutaneous microwave coagulation therapy for primary or recurrent hepatocellular carcinoma:
long-term results. Hepatogastroenterology 2001;48:14015.
11. Choi D, Lim HK, Kim MJ, et al. Recurrent hepatocellular carcinoma:
percutaneous radiofrequency ablation after hepatectomy. Radiology
2004;230:13541.
12. Lu MD, Yin XY, Xie XY, et al. Percutaneous thermal ablation for recurrent hepatocellular carcinoma after hepatectomy. Br J Surg 2005;
92:13938.
13. Nagasue N, Kohno H, Hayashi T, et al. Repeat hepatectomy for recurrent hepatocellular carcinoma. Br J Surg 1996;83:12731.
14. Shimada M, Takenaka K, Taguchi K, et al. Prognostic factors after repeat hepatectomy for recurrent hepatocellular carcinoma. Ann Surg
1998;227:805.
15. Poon RT, Fan ST, Lo CM, Liu CL Wong J. Intrahepatic recurrence
after curative resection of hepatocellular carcinoma: long-term
results of treatment and prognostic factors. Ann Surg 1999;229:
21622.
16. Nakajima Y, Ko S, Kanamura T, et al. Repeat liver resection for hepatocellular carcinoma. J Am Coll Surg 2001;192:33944.
17. Minagawa M, Makuuchi M, Takayama T, Kokudo N. Selection criteria
for repeat hepatectomy in patients with recurrent hepatocellular carcinoma. Ann Surg 2003;238:70310.
18. Terminology Committee of the International Hepato-Pancreato-Biliary
Association. The Brisbane 2000 terminology of liver anatomy and resections. HPB Surg 2000;2:3339.
19. Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of
100 cases among 48,900 necropsies. Cancer 1954;7:462503.
20. Greene FL, Page DL, Fleming ID, et al. AJCC cancer staging manual.
6th ed. New York: Springer-Verlag; 2002, p. 1318.
21. Cruz PV, Wakai T, Shirai Y, Yokoyama N, Hatakeyama K. Loss of carcinoembryonic antigen-related cell adhesion molecule 1 expression is
an adverse prognostic factor in hepatocellular carcinoma. Cancer
2005;104:35460.
22. Wakai T, Shirai Y, Suda T, et al. Long-term outcomes of hepatectomy
vs percutaneous ablation for treatment of hepatocellular carcinoma <
or 4 cm. World J Gastroenterol 2006;12:54652.
23. Ruzzenente A, Manzoni GD, Molfetta M, et al. Rapid progression of
hepatocellular carcinoma after radiofrequency ablation. World J Gastroenterol 2004;10:113740.
24. Kotoh K, Enjoji M, Arimura E, et al. Scattered and rapid intrahepatic
recurrences after radio frequency ablation for hepatocellular carcinoma. World J Gastroenterol 2005;11:682832.
25. Takada Y, Kurata M, Ohkohchi N. Rapid and aggressive recurrence accompanied by portal tumor thrombus after radiofrequency

Please cite this article in press as: Sakata J et al., Long-term outcomes after hepatectomy for recurrences after prior local ablation for hepatocellular carcinoma, Eur J Surg Oncol (2007), doi:10.1016/j.ejso.2007.03.018

ARTICLE IN PRESS
J. Sakata et al. / EJSO xx (2007) 1e6

26.

27.

28.

29.

ablation for hepatocellular carcinoma. Int J Clin Oncol 2003;8:

3325.
Nicoli N, Casaril A, Hilal MA, et al. A case of rapid intrahepatic dissemination of hepatocellular carcinoma after radiofrequency thermal
ablation. Am J Surg 2004;188:1657.
Llovet JM, Vilana R, Bru C, et al. Increased risk of tumor seeding after
percutaneous radiofrequency ablation for single hepatocellular carcinoma. Hepatology 2001;33:11249.
Livraghi T, Lazzaroni S, Meloni F, Solbiati L. Risk of tumour seeding
after percutaneous radiofrequency ablation for hepatocellular carcinoma. Br J Surg 2005;92:8568.
Ishii H, Okada S, Okusaka T, et al. Needle tract implantation of hepatocellular carcinoma after percutaneous ethanol injection. Cancer
1998;82:163842.

30. Sakon M, Umeshita K, Nagano H, et al. Clinical significance of hepatic resection in hepatocellular carcinoma: analysis by disease-free
survival curves. Arch Surg 2000;135:14569.
31. Wakai T, Shirai Y, Sakata J, et al. Anatomic resection independently
improves long-term survival in patients with T1eT2 hepatocellular
carcinoma. Ann Surg Oncol 2007;14:135665.
32. Brillet PY, Paradis V, Brancatelli G, et al. Percutaneous radiofrequency ablation for hepatocellular carcinoma before liver transplantation: a prospective study with histopathologic comparison. Am J
Roentgenol 2006;186:S296305.
33. Mazzaferro V, Battiston C, Perrone S, et al. Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients awaiting liver transplantation: a prospective study. Ann Surg 2004;240:
9009.

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