j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 5 ( 2 0 1 5 ) 1 6 6 e1 7 4
Available online at www.sciencedirect.com
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Radiofrequency ablation versus surgical resection for intrahepatic hepatocellular carcinoma recurrence: a meta-analysis Xuxiao Chen, MS, Yongjun Chen, MD, PhD,* Qinyu Li, MD, PhD, Di Ma, MS, Baiyong Shen, MD, PhD, and Chenghong Peng, MD, PhD Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
article info
abstract
Article history:
Background: To compare the clinical efficacy and safety of radiofrequency ablation (RFA)
Received 30 November 2014
versus surgical resection (SR) for intrahepatic hepatocellular carcinoma (HCC) recurrence
Received in revised form
by meta-analytical techniques.
7 January 2015
Methods: Literature documenting a comparison of RFA and SR for intrahepatic HCC recur-
Accepted 23 January 2015
rence was identified by searching PubMed, Embase, Cochrane Library, and Web of Science
Available online 30 January 2015
databases, for those from inception to July 2014 with no limits. The heterogeneity was tested by the Cochrane Q statistic; the pooled estimates were measured using either fixed
Keywords:
or random effect model. Furthermore, subgroup and sensitivity analyses were conducted
Hepatocellular carcinoma
to explore heterogeneity between studies and to assess the efficacy of different studies.
Recurrence
Results: Seven studies were included with a total of 718 patients (359 treated with RFA and
Radiofrequency ablation
359 treated with SR). Our meta-analysis showed that the 1-, 3-, and 5-y overall survival rate
Surgical resection
and procedure-related mortality rate were similar in patients treated with RFA or SR.
Meta-analysis
Meanwhile, SR was associated with significantly higher 1-, 3-, and 5-y re-recurrence-free survival rate and procedure-related morbidity rate compared with RFA. In the subgroup analysis of patients in China, the results concerning overall and re-recurrence-free survival were similar to the outcomes of the meta-analysis without regional restriction. In the subgroup analysis of intrahepatic recurrent HCC 3 cm, the 1-, 3-, and 5-y overall survival rate did not differ significantly in the comparison of RFA and SR. Conclusions: Although RFA was associated with lower re-recurrence-free survival, it seems to be as effective as SR for the treatment of intrahepatic HCC recurrence owing to comparable overall survival benefits. The advantages of being less invasive, highly targetselective, and repeatable may render RFA a preferred treatment option for selected patients. ª 2015 Elsevier Inc. All rights reserved.
1.
Introduction
Although liver transplantation is the best option for patients with hepatocellular carcinoma (HCC), surgical resection (SR) is
always considered as the first-line treatment for HCC because of the donor shortage [1,2]. After the primary treatment, a major problem is intrahepatic HCC recurrence with a 5-y recurrence rate of more than 77% [3,4]. Nonetheless, there is
* Corresponding author. Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. Tel.: þ86 13818607707; fax: þ86 021 54660106. E-mail address: [email protected] (Y. Chen). 0022-4804/$ e see front matter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2015.01.042
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 5 ( 2 0 1 5 ) 1 6 6 e1 7 4
no clearly elucidated coherent algorithm for treating intrahepatic HCC recurrence so far. Considering the recurrent nature of HCC, how to manage the intrahepatic HCC recurrence merits further attention. SR for recurrent HCC, first reported in 1986 by Nagasue et al., has been now established as a feasible and effective treatment option for intrahepatic HCC recurrence with a 5-y survival rate comparable with that of primary hepatectomy [5,6]. However, only a small proportion of patients with intrahepatic HCC recurrence are eligible candidates for SR because of either small liver remnant or poor liver function reserve [7,8]. Radiofrequency ablation (RFA), as one of the nonsurgical ablative therapeutic approaches for HCC, has been investigated for decades. Because of its minimal invasiveness and little deterioration of liver function, RFA attracted great attention in clinical application [9]. Numerous large series have demonstrated that RFA is a safe and effective therapy for small HCC with similar overall survival benefits to SR [10e13]. Moreover, some centers recently tried to apply RFA in the treatment of recurrent HCC after primary hepatectomy, which achieved a comparable 3-y survival rate to SR [11,14,15]. However, there is still no study of large series or randomized controlled trial comparing the efficacy of RFA with SR for intrahepatic HCC recurrence after primary treatment. To evaluate the exact role of RFA and SR in the treatment of intrahepatic HCC recurrence, we conducted the current metaanalysis to investigate the clinical efficacy and safety of RFA versus SR for intrahepatic HCC recurrence.
2.
Methods
2.1.
Literature search strategy
A comprehensive literature search was performed using PubMed, Embase, Cochrane Library, and Web of Science databases for those from inception to July 2014 with no limits. The key words used in this search strategy were as the following Mesh headings: “radiofrequency ablation,” “repeat hepatectomy,” “second hepatectomy,” “repeat liver resection,” “repeat hepatic resection,” “surgical resection,” “recurrence,” “recurrent,” “hepatocellular carcinoma,” “liver cancer,” “hepatic cancer,” and we also used both free text and “related articles” function for literature search. The reference list of all retrieved articles was searched manually to identify other relevant articles.
2.2.
Study selection criteria
The inclusion criteria for the present meta-analysis were as follows: (1) patients involved in studies were diagnosed as intrahepatic HCC recurrence without extrahepatic metastasis; (2) the primary therapeutic method was hepatectomy or RFA with curative intent; (3) none of the patients had contraindication for SR and/or RFA; (4) SR or RFA was conducted without any antecedent treatment for intrahepatic HCC recurrence; (5) comparing the outcomes of SR and RFA for intrahepatic HCC recurrence; (6) reporting at least one of the following outcomes: the overall and re-recurrence-free survival rate at 1, 3, and 5 y, recurrence rate, and treatment complications; (7) if
167
dual or multiple studies were reported by the same institution or authors, the one of higher quality was included in the metaanalysis; and (8) full-text of the articles was available, and at least 10 patients were included in both groups of RFA and SR. The exclusion criteria were as follows: (1) nonhuman studies, abstracts, editorials, letters, case reports, expert opinions, reviews, and studies lacking control group; (2) studies in which patients were diagnosed as other malignant liver tumors instead of HCC, such as cholangiocellular carcinomas or liver metastases; and (3) studies not clearly reporting the outcomes of interest attributed to each specific intervention (e.g., RFA versus SR).
2.3.
Data extraction and quality assessment
The eligibility of studies was appraised by reviewers X.C. and Q.L. independently and critically; data were independently extracted by reviewers X.C. and D.M. in duplicate. Any discrepancy in the process was resolved by mutual discussion or consulting the corresponding author (Y.C.). The extracted data included first author, publication year, patient demographics, disease characteristics, overall survival data, re-recurrence-free survival data, procedurerelated morbidity, and mortality data. The quality of nonrandom controlled studies was assessed by a modification of the NewcastleeOttawa scale [16].
2.4.
Data synthesis and analysis
The meta-analysis was performed by Review Manager (version 5.2), provided by the Cochrane Collaboration (The Nordic Cochrane Centre, Copenhagen). Medians reported in some studies were converted to means using the method described by Hozo et al. [17]. Continuous outcomes and dichotomous outcomes were analyzed by calculating mean difference and odds ratio (OR) with 95% confidence interval (95% CI). The heterogeneity across each included study was explored by the chi square (c2) and I2 statistic. I2 50% was considered to reflect high heterogeneity. Heterogeneity was considered substantially significant when the Cochrane Q test P < 0.10, and random effect model was applied for metaanalysis; otherwise, fixed effect model was used. P < 0.05 was considered statistically significant. Unlike other regions in the world, in China more than 85% of patients with HCC were related with hepatitis B virus infection. Therefore, we performed subgroup analyses to identify the efficacy of RFA versus SR for intrahepatic HCC recurrence in the Chinese population. Moreover, another subgroup analysis was performed in intrahepatic recurrent HCC 3 cm. When significant heterogeneity was considered across the identified studies, sensitivity analysis was performed by eliminating each study in turn to test the influence of individual study on the pooled estimates.
2.5.
Publication bias
Potential publication bias was evaluated by visually inspecting of the funnel plots.
168
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 5 ( 2 0 1 5 ) 1 6 6 e1 7 4
359 patients treated with SR. As a coincidence, the number of patients in each pooled group is exactly the same. The baseline characteristics of these patients are summarized in Table 1.
3.2.
Quality of the included studies
3.
Results
For the quality assessment of the seven included studies, a modification of the NewcastleeOttawa scale was used. Fulltext of all the seven articles was downloaded and reviewed scrupulously. Both RFA and SR groups of each study were from the same center during the same period. Exposure ascertainment and outcome assessment were confirmed by operation records and record linkage, respectively. The comparability between RFA and SR groups was matched in the following nine aspects: demographic data, tumor size of primary tumor, disease-free interval, HBs-Ag positive, ChildePugh class, presence and degree of cirrhosis, tumor size of recurrent tumor, number of recurrent tumor, and serum alpha fetoprotein level. Description of missing data was not adequate in most studies. Table 2 lists the detail assessment results of the seven included studies. Figure 2 illustrates a symmetrical funnel plot of the included studies, which suggested no obvious publication bias exist in the present meta-analysis.
3.1.
Characteristics of identified studies
3.3.
Fig. 1 e Flowchart of searching strategy for meta-analysis study selection.
Figure 1 presents the flowchart of the study screening and the detailed selection process. Based on the inclusion and exclusion criteria, we ultimately identified a total of seven nonrandomized comparative studies comparing RFA and SR as a therapeutic method for intrahepatic HCC recurrence [18e24]. All these eligible studies were single-center retrospective research, which involved 359 patients treated with RFA and
Overall survival rates
All the seven included studies reported 1-, 3-, and 5-y overall survival data. No significant difference was observed between RFA group and SR group (OR 1.01, 95% CI 0.61e1.67, P ¼ 0.97 for the first year; OR 1.05, 95% CI 0.76e1.45, P ¼ 0.78 for the third year; and OR 0.96, 95% CI 0.70e1.33, P ¼ 0.82 for the fifth year). No heterogeneity was detected in the analysis of the effects of overall survival rates (Fig. 3).
Table 1 e Baseline characteristics of the patients in the seven included studies. First author (y)
Liang (2008) Ren (2008) Shen (2008) Umeda (2011)
Country
Treatment
Cases
Age (y)
Gender (M/F)
HBsAg ()
Tumor size (cm)
Tumor size (3 cm)
Tumor number (single/ multiple)
Childe Pugh (A/B/C)
China
RFA SR RFA SR RFA SR RFA SR TACE RFA SR RFA SR TACE ST RFA SR
66 44 68 145 45 31 58 29 38 45 29 50 54 254 77 27 27
54.6 10.8 48.8 12.0 52.0 51.0 56.8 1.7 51.3 2.2 NA NA NA 59.0 11.0 52.0 10.3 61.0 11.1 56.3 12.3 59.4 11.6 57.2 12.3 68.0 7.0 60.0 17.0
54/12 39/5 64/4 127/18 37/8 25/6 NA NA NA NA NA 39/11 40/14 198/56 60/17 20/7 15/12
60/6 41/3 57/11 127/18 40/5 29/2 11/47 8/21 4/34 40/5 26/3 27/23 39/15 160/94 56/21 NA NA
NA NA 2.0 2.0 2.9 0.1 3.2 0.2 2.1 0.3 3.2 0.57 2.9 1.0 2.2 1.3 2.1 1.1 2.3 1.9 2.9 1.8 3.0 2.1 5.2 4.3 2.8 1.1 4.0 2.3
44 26 68 145 30 15 NA NA NA NA NA 45 52 157 36 NA NA
48/18 34/10 53/15 126/19 25/20 22/9 NA NA NA 29/16 21/8 NA NA NA NA 15/12 16/11
64/2/0 44/0/0 68/0/0 145/0/0 37/8/0 29/2/0 51/7/0 29/0/0 31/7/0 40/5/0 29/0/0 50/0/0 51/2/1 239/15/0 44/23/10 19/7/1 27/0/0
[18] China [19] China [20] Japan [21]
Chan (2012) [22] Ho (2012) [23]
China (Hong Kong) China (Taiwan)
Eisele (2013) [24]
Germany
cm ¼ centimeter; F ¼ female; M ¼ male; NA ¼ not applicant; ST ¼ supportive treatment; TACE ¼ transarterial chemoembolization.
Operation records Operation records Operation records
Operation records
Yes/same; patient base. Yes/same; patient base. Yes/same; patient base.
Yes/same; patient base.
Umeda [21] (2011) Chan [22] (2012) Ho [23] (2012)
Eisele [24] (2013)
cm ¼ centimeter; No. ¼ number; NOS ¼ NewcastleeOttawa scale; US ¼ ultrasound; AFP ¼ alpha fetoprotein. * The controls SR for recurrent HCC. y Matched in: 1, demographic data; 2, tumor size of primary tumor; 3, disease-free interval; 4, HBs-Ag positive; 5, ChildePugh class; 6, cirrhosis; 7, tumor size of recurrent tumor; 8, number of recurrent tumor; and 9, serum AFP level. z Articles published in Chinese.
Unclear Details provided Record linkage
Unclear Unclear Unclear Details not available Details not available Details provided Record linkage Record linkage Record linkage
Unclear Operation records Yes/same; patient base. Shen [20] (2008)
z
Operation records z
Ren [19] (2008)
Yes/same; patient base.
Restricted in no major portal vein cancer metastasis. Matched in 1, 3e5, 7e9 No restriction. Matched in 1e5, 8, 9 Restriction in
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofSurgicalResearch.com
Radiofrequency ablation versus surgical resection for intrahepatic hepatocellular carcinoma recurrence: a meta-analysis Xuxiao Chen, MS, Yongjun Chen, MD, PhD,* Qinyu Li, MD, PhD, Di Ma, MS, Baiyong Shen, MD, PhD, and Chenghong Peng, MD, PhD Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
article info
abstract
Article history:
Background: To compare the clinical efficacy and safety of radiofrequency ablation (RFA)
Received 30 November 2014
versus surgical resection (SR) for intrahepatic hepatocellular carcinoma (HCC) recurrence
Received in revised form
by meta-analytical techniques.
7 January 2015
Methods: Literature documenting a comparison of RFA and SR for intrahepatic HCC recur-
Accepted 23 January 2015
rence was identified by searching PubMed, Embase, Cochrane Library, and Web of Science
Available online 30 January 2015
databases, for those from inception to July 2014 with no limits. The heterogeneity was tested by the Cochrane Q statistic; the pooled estimates were measured using either fixed
Keywords:
or random effect model. Furthermore, subgroup and sensitivity analyses were conducted
Hepatocellular carcinoma
to explore heterogeneity between studies and to assess the efficacy of different studies.
Recurrence
Results: Seven studies were included with a total of 718 patients (359 treated with RFA and
Radiofrequency ablation
359 treated with SR). Our meta-analysis showed that the 1-, 3-, and 5-y overall survival rate
Surgical resection
and procedure-related mortality rate were similar in patients treated with RFA or SR.
Meta-analysis
Meanwhile, SR was associated with significantly higher 1-, 3-, and 5-y re-recurrence-free survival rate and procedure-related morbidity rate compared with RFA. In the subgroup analysis of patients in China, the results concerning overall and re-recurrence-free survival were similar to the outcomes of the meta-analysis without regional restriction. In the subgroup analysis of intrahepatic recurrent HCC 3 cm, the 1-, 3-, and 5-y overall survival rate did not differ significantly in the comparison of RFA and SR. Conclusions: Although RFA was associated with lower re-recurrence-free survival, it seems to be as effective as SR for the treatment of intrahepatic HCC recurrence owing to comparable overall survival benefits. The advantages of being less invasive, highly targetselective, and repeatable may render RFA a preferred treatment option for selected patients. ª 2015 Elsevier Inc. All rights reserved.
1.
Introduction
Although liver transplantation is the best option for patients with hepatocellular carcinoma (HCC), surgical resection (SR) is
always considered as the first-line treatment for HCC because of the donor shortage [1,2]. After the primary treatment, a major problem is intrahepatic HCC recurrence with a 5-y recurrence rate of more than 77% [3,4]. Nonetheless, there is
* Corresponding author. Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. Tel.: þ86 13818607707; fax: þ86 021 54660106. E-mail address: [email protected] (Y. Chen). 0022-4804/$ e see front matter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2015.01.042
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 5 ( 2 0 1 5 ) 1 6 6 e1 7 4
no clearly elucidated coherent algorithm for treating intrahepatic HCC recurrence so far. Considering the recurrent nature of HCC, how to manage the intrahepatic HCC recurrence merits further attention. SR for recurrent HCC, first reported in 1986 by Nagasue et al., has been now established as a feasible and effective treatment option for intrahepatic HCC recurrence with a 5-y survival rate comparable with that of primary hepatectomy [5,6]. However, only a small proportion of patients with intrahepatic HCC recurrence are eligible candidates for SR because of either small liver remnant or poor liver function reserve [7,8]. Radiofrequency ablation (RFA), as one of the nonsurgical ablative therapeutic approaches for HCC, has been investigated for decades. Because of its minimal invasiveness and little deterioration of liver function, RFA attracted great attention in clinical application [9]. Numerous large series have demonstrated that RFA is a safe and effective therapy for small HCC with similar overall survival benefits to SR [10e13]. Moreover, some centers recently tried to apply RFA in the treatment of recurrent HCC after primary hepatectomy, which achieved a comparable 3-y survival rate to SR [11,14,15]. However, there is still no study of large series or randomized controlled trial comparing the efficacy of RFA with SR for intrahepatic HCC recurrence after primary treatment. To evaluate the exact role of RFA and SR in the treatment of intrahepatic HCC recurrence, we conducted the current metaanalysis to investigate the clinical efficacy and safety of RFA versus SR for intrahepatic HCC recurrence.
2.
Methods
2.1.
Literature search strategy
A comprehensive literature search was performed using PubMed, Embase, Cochrane Library, and Web of Science databases for those from inception to July 2014 with no limits. The key words used in this search strategy were as the following Mesh headings: “radiofrequency ablation,” “repeat hepatectomy,” “second hepatectomy,” “repeat liver resection,” “repeat hepatic resection,” “surgical resection,” “recurrence,” “recurrent,” “hepatocellular carcinoma,” “liver cancer,” “hepatic cancer,” and we also used both free text and “related articles” function for literature search. The reference list of all retrieved articles was searched manually to identify other relevant articles.
2.2.
Study selection criteria
The inclusion criteria for the present meta-analysis were as follows: (1) patients involved in studies were diagnosed as intrahepatic HCC recurrence without extrahepatic metastasis; (2) the primary therapeutic method was hepatectomy or RFA with curative intent; (3) none of the patients had contraindication for SR and/or RFA; (4) SR or RFA was conducted without any antecedent treatment for intrahepatic HCC recurrence; (5) comparing the outcomes of SR and RFA for intrahepatic HCC recurrence; (6) reporting at least one of the following outcomes: the overall and re-recurrence-free survival rate at 1, 3, and 5 y, recurrence rate, and treatment complications; (7) if
167
dual or multiple studies were reported by the same institution or authors, the one of higher quality was included in the metaanalysis; and (8) full-text of the articles was available, and at least 10 patients were included in both groups of RFA and SR. The exclusion criteria were as follows: (1) nonhuman studies, abstracts, editorials, letters, case reports, expert opinions, reviews, and studies lacking control group; (2) studies in which patients were diagnosed as other malignant liver tumors instead of HCC, such as cholangiocellular carcinomas or liver metastases; and (3) studies not clearly reporting the outcomes of interest attributed to each specific intervention (e.g., RFA versus SR).
2.3.
Data extraction and quality assessment
The eligibility of studies was appraised by reviewers X.C. and Q.L. independently and critically; data were independently extracted by reviewers X.C. and D.M. in duplicate. Any discrepancy in the process was resolved by mutual discussion or consulting the corresponding author (Y.C.). The extracted data included first author, publication year, patient demographics, disease characteristics, overall survival data, re-recurrence-free survival data, procedurerelated morbidity, and mortality data. The quality of nonrandom controlled studies was assessed by a modification of the NewcastleeOttawa scale [16].
2.4.
Data synthesis and analysis
The meta-analysis was performed by Review Manager (version 5.2), provided by the Cochrane Collaboration (The Nordic Cochrane Centre, Copenhagen). Medians reported in some studies were converted to means using the method described by Hozo et al. [17]. Continuous outcomes and dichotomous outcomes were analyzed by calculating mean difference and odds ratio (OR) with 95% confidence interval (95% CI). The heterogeneity across each included study was explored by the chi square (c2) and I2 statistic. I2 50% was considered to reflect high heterogeneity. Heterogeneity was considered substantially significant when the Cochrane Q test P < 0.10, and random effect model was applied for metaanalysis; otherwise, fixed effect model was used. P < 0.05 was considered statistically significant. Unlike other regions in the world, in China more than 85% of patients with HCC were related with hepatitis B virus infection. Therefore, we performed subgroup analyses to identify the efficacy of RFA versus SR for intrahepatic HCC recurrence in the Chinese population. Moreover, another subgroup analysis was performed in intrahepatic recurrent HCC 3 cm. When significant heterogeneity was considered across the identified studies, sensitivity analysis was performed by eliminating each study in turn to test the influence of individual study on the pooled estimates.
2.5.
Publication bias
Potential publication bias was evaluated by visually inspecting of the funnel plots.
168
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 5 ( 2 0 1 5 ) 1 6 6 e1 7 4
359 patients treated with SR. As a coincidence, the number of patients in each pooled group is exactly the same. The baseline characteristics of these patients are summarized in Table 1.
3.2.
Quality of the included studies
3.
Results
For the quality assessment of the seven included studies, a modification of the NewcastleeOttawa scale was used. Fulltext of all the seven articles was downloaded and reviewed scrupulously. Both RFA and SR groups of each study were from the same center during the same period. Exposure ascertainment and outcome assessment were confirmed by operation records and record linkage, respectively. The comparability between RFA and SR groups was matched in the following nine aspects: demographic data, tumor size of primary tumor, disease-free interval, HBs-Ag positive, ChildePugh class, presence and degree of cirrhosis, tumor size of recurrent tumor, number of recurrent tumor, and serum alpha fetoprotein level. Description of missing data was not adequate in most studies. Table 2 lists the detail assessment results of the seven included studies. Figure 2 illustrates a symmetrical funnel plot of the included studies, which suggested no obvious publication bias exist in the present meta-analysis.
3.1.
Characteristics of identified studies
3.3.
Fig. 1 e Flowchart of searching strategy for meta-analysis study selection.
Figure 1 presents the flowchart of the study screening and the detailed selection process. Based on the inclusion and exclusion criteria, we ultimately identified a total of seven nonrandomized comparative studies comparing RFA and SR as a therapeutic method for intrahepatic HCC recurrence [18e24]. All these eligible studies were single-center retrospective research, which involved 359 patients treated with RFA and
Overall survival rates
All the seven included studies reported 1-, 3-, and 5-y overall survival data. No significant difference was observed between RFA group and SR group (OR 1.01, 95% CI 0.61e1.67, P ¼ 0.97 for the first year; OR 1.05, 95% CI 0.76e1.45, P ¼ 0.78 for the third year; and OR 0.96, 95% CI 0.70e1.33, P ¼ 0.82 for the fifth year). No heterogeneity was detected in the analysis of the effects of overall survival rates (Fig. 3).
Table 1 e Baseline characteristics of the patients in the seven included studies. First author (y)
Liang (2008) Ren (2008) Shen (2008) Umeda (2011)
Country
Treatment
Cases
Age (y)
Gender (M/F)
HBsAg ()
Tumor size (cm)
Tumor size (3 cm)
Tumor number (single/ multiple)
Childe Pugh (A/B/C)
China
RFA SR RFA SR RFA SR RFA SR TACE RFA SR RFA SR TACE ST RFA SR
66 44 68 145 45 31 58 29 38 45 29 50 54 254 77 27 27
54.6 10.8 48.8 12.0 52.0 51.0 56.8 1.7 51.3 2.2 NA NA NA 59.0 11.0 52.0 10.3 61.0 11.1 56.3 12.3 59.4 11.6 57.2 12.3 68.0 7.0 60.0 17.0
54/12 39/5 64/4 127/18 37/8 25/6 NA NA NA NA NA 39/11 40/14 198/56 60/17 20/7 15/12
60/6 41/3 57/11 127/18 40/5 29/2 11/47 8/21 4/34 40/5 26/3 27/23 39/15 160/94 56/21 NA NA
NA NA 2.0 2.0 2.9 0.1 3.2 0.2 2.1 0.3 3.2 0.57 2.9 1.0 2.2 1.3 2.1 1.1 2.3 1.9 2.9 1.8 3.0 2.1 5.2 4.3 2.8 1.1 4.0 2.3
44 26 68 145 30 15 NA NA NA NA NA 45 52 157 36 NA NA
48/18 34/10 53/15 126/19 25/20 22/9 NA NA NA 29/16 21/8 NA NA NA NA 15/12 16/11
64/2/0 44/0/0 68/0/0 145/0/0 37/8/0 29/2/0 51/7/0 29/0/0 31/7/0 40/5/0 29/0/0 50/0/0 51/2/1 239/15/0 44/23/10 19/7/1 27/0/0
[18] China [19] China [20] Japan [21]
Chan (2012) [22] Ho (2012) [23]
China (Hong Kong) China (Taiwan)
Eisele (2013) [24]
Germany
cm ¼ centimeter; F ¼ female; M ¼ male; NA ¼ not applicant; ST ¼ supportive treatment; TACE ¼ transarterial chemoembolization.
Operation records Operation records Operation records
Operation records
Yes/same; patient base. Yes/same; patient base. Yes/same; patient base.
Yes/same; patient base.
Umeda [21] (2011) Chan [22] (2012) Ho [23] (2012)
Eisele [24] (2013)
cm ¼ centimeter; No. ¼ number; NOS ¼ NewcastleeOttawa scale; US ¼ ultrasound; AFP ¼ alpha fetoprotein. * The controls SR for recurrent HCC. y Matched in: 1, demographic data; 2, tumor size of primary tumor; 3, disease-free interval; 4, HBs-Ag positive; 5, ChildePugh class; 6, cirrhosis; 7, tumor size of recurrent tumor; 8, number of recurrent tumor; and 9, serum AFP level. z Articles published in Chinese.
Unclear Details provided Record linkage
Unclear Unclear Unclear Details not available Details not available Details provided Record linkage Record linkage Record linkage
Unclear Operation records Yes/same; patient base. Shen [20] (2008)
z
Operation records z
Ren [19] (2008)
Yes/same; patient base.
Restricted in no major portal vein cancer metastasis. Matched in 1, 3e5, 7e9 No restriction. Matched in 1e5, 8, 9 Restriction in
