Reviewer’s report
Title: 
Radiofrequency ablation versus hepatic resection for recurrent
hepatocellular carcinoma: an updated meta-analysis
Version: 
1 
Date: 
01 Nov 2020
Reviewer's report:
Nov2, 2020
Dear Editors BMCG
Manuscript ID: BMGE-D-20-01219R1
MS. Title: Radiofrequency ablation versus hepatic resection for recurrent
hepatocellular
carcinoma: an updated meta-analysis
Authors: Xiaohua Xie, et al. 
1. Key finding s of this study were The meta-analysis showed that RHR had
superior OS (HR 0.77, 95% CI =0.65-0.92, P=0.004) and PFS (HR 0.81, 95% CI
=0.67-0.98, P=0.027) compared to RFA, whereas major complications may be
less frequent in the RFA group (OR 0.15, 95% CI = 0.06-0.39, P<0.001
2. Population: From 10 studies with 1612 patients (RHR = 654, RFA = 958)
were included in the meta- analysis. The majority of the sample population was
CP-A (98.3%) and CP-B accounted only 28 cases (1.7%).This selective group of
CP-A have effect on the outcome of overall survival esp. hepatic resection.
Previous article showed that Pre-op MELD had effects on the overall survival1.
The 1-, 3-, and 5-year tumor-free survival rates were 68.4%, 57.9%, and 57.9%,
respectively, for SLT; 69.7%, 49.3%, and 49.3%, respectively, for RR; and
40.0%, 19.8%, and 10.6%, respectively, for rRFA (P=0.001)
3. The total number of 1084 from 1612 cases (67%) caused by HBV infection
which may receive anti-viral agent and this treatment may effect on the overall
survival and outcome too. No details of this information and should add on in
the discussion part.
4. Intervention: The overall result of RFA versus RHR are clearly reported,
however the subgroup analysis which focused on the size of tumor < 3 cm and 3-
5 cm are limited due to the small sample size (2-3 studies) and the indication of
RFA use in HCC tumor size of 3-5 cm is not rational. Thus, the author should
explain the reason of using treatment choices. Additionally, HCC patients with
intrahepatic recurrent tumor should consider for liver transplantation, how many
of them had underwent for this procedure1.
5. Other confounders to the overall survival including the progression or
occurrence of cirrhosis, age group, maximal tumor size at recurrent time, the
duration of the procedure and the expertise of care team should be mentioned for
the outcome.2-7
References
1. Chan AC, Chan SC, Chok KS, et al. Treatment strategy for recurrent
hepatocellular carcinoma: salvage transplantation, repeated resection, or
radiofrequency ablation? Liver Transpl 2013;19:411-9.
2. Sun WC, Chen IS, Liang HL, et al. Comparison of repeated surgical resection
and radiofrequency ablation for small recurrent hepatocellular carcinoma after
primary resection. Oncotarget 2017;8:104571-104581.
3. Eisele RM, Chopra SS, Lock JF, et al. Treatment of recurrent hepatocellular
carcinoma confined to the liver with repeated resection and radiofrequency
ablation: a single center experience. Technol Health Care 2013;21:9-18.
4. Fujiwara N, Tateishi R, Kondo M, et al. Cause-specific mortality associated
with aging in patients with hepatocellular carcinoma undergoing percutaneous
radiofrequency ablation. Eur J Gastroenterol Hepatol 2014;26:1039-46.
5. Asaoka Y, Tateishi R, Nakagomi R, et al. Frequency of and predictive factors
for vascular invasion after radiofrequency ablation for hepatocellular carcinoma.
PLoS One 2014;9:e111662.
6. Tateishi R, Shiina S, Akahane M, et al. Frequency, risk factors and survival
associated with an intrasubsegmental recurrence after radiofrequency ablation
for hepatocellular carcinoma. PLoS One 2013;8:e59040.
7. Shiina S, Tateishi R, Arano T, et al. Radiofrequency ablation for
hepatocellular carcinoma: 10-year outcome and prognostic factors. Am J
Gastroenterol 2012;107:569-77; quiz 578.
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) if this manuscript is accepted for
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do not
 publish my name
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Is the study design appropriate to answer the research question (including the use
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presented?
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Are the methods sufficiently described to allow the study to be repeated?
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Is the use of statistics and treatment of uncertainties appropriate?
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Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Radiofrequency ablation versus hepatic resection for recurrent
hepatocellular carcinoma: an updated meta-analysis
Version: 
1 
Date: 
01 Nov 2020
Reviewer's report:
Nov2, 2020
Dear Editors BMCG
Manuscript ID: BMGE-D-20-01219R1
MS. Title: Radiofrequency ablation versus hepatic resection for recurrent
hepatocellular
carcinoma: an updated meta-analysis
Authors: Xiaohua Xie, et al. 
1. Key finding s of this study were The meta-analysis showed that RHR had
superior OS (HR 0.77, 95% CI =0.65-0.92, P=0.004) and PFS (HR 0.81, 95% CI
=0.67-0.98, P=0.027) compared to RFA, whereas major complications may be
less frequent in the RFA group (OR 0.15, 95% CI = 0.06-0.39, P<0.001
2. Population: From 10 studies with 1612 patients (RHR = 654, RFA = 958)
were included in the meta- analysis. The majority of the sample population was
CP-A (98.3%) and CP-B accounted only 28 cases (1.7%).This selective group of
CP-A have effect on the outcome of overall survival esp. hepatic resection.
Previous article showed that Pre-op MELD had effects on the overall survival1.
The 1-, 3-, and 5-year tumor-free survival rates were 68.4%, 57.9%, and 57.9%,
respectively, for SLT; 69.7%, 49.3%, and 49.3%, respectively, for RR; and
40.0%, 19.8%, and 10.6%, respectively, for rRFA (P=0.001)
3. The total number of 1084 from 1612 cases (67%) caused by HBV infection
which may receive anti-viral agent and this treatment may effect on the overall
survival and outcome too. No details of this information and should add on in
the discussion part.
4. Intervention: The overall result of RFA versus RHR are clearly reported,
however the subgroup analysis which focused on the size of tumor < 3 cm and 3-
5 cm are limited due to the small sample size (2-3 studies) and the indication of
RFA use in HCC tumor size of 3-5 cm is not rational. Thus, the author should
explain the reason of using treatment choices. Additionally, HCC patients with
intrahepatic recurrent tumor should consider for liver transplantation, how many
of them had underwent for this procedure1.
5. Other confounders to the overall survival including the progression or
occurrence of cirrhosis, age group, maximal tumor size at recurrent time, the
duration of the procedure and the expertise of care team should be mentioned for
the outcome.2-7
References
1. Chan AC, Chan SC, Chok KS, et al. Treatment strategy for recurrent
hepatocellular carcinoma: salvage transplantation, repeated resection, or
radiofrequency ablation? Liver Transpl 2013;19:411-9.
2. Sun WC, Chen IS, Liang HL, et al. Comparison of repeated surgical resection
and radiofrequency ablation for small recurrent hepatocellular carcinoma after
primary resection. Oncotarget 2017;8:104571-104581.
3. Eisele RM, Chopra SS, Lock JF, et al. Treatment of recurrent hepatocellular
carcinoma confined to the liver with repeated resection and radiofrequency
ablation: a single center experience. Technol Health Care 2013;21:9-18.
4. Fujiwara N, Tateishi R, Kondo M, et al. Cause-specific mortality associated
with aging in patients with hepatocellular carcinoma undergoing percutaneous
radiofrequency ablation. Eur J Gastroenterol Hepatol 2014;26:1039-46.
5. Asaoka Y, Tateishi R, Nakagomi R, et al. Frequency of and predictive factors
for vascular invasion after radiofrequency ablation for hepatocellular carcinoma.
PLoS One 2014;9:e111662.
6. Tateishi R, Shiina S, Akahane M, et al. Frequency, risk factors and survival
associated with an intrasubsegmental recurrence after radiofrequency ablation
for hepatocellular carcinoma. PLoS One 2013;8:e59040.
7. Shiina S, Tateishi R, Arano T, et al. Radiofrequency ablation for
hepatocellular carcinoma: 10-year outcome and prognostic factors. Am J
Gastroenterol 2012;107:569-77; quiz 578.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons upon publication of the manuscript. If you have already registered at
Publons, they will notify you of the receipt of this review and update your profile
as per your settings and their policy. If you are not registered with Publons, you
will receive an email from them asking you to register in order for them to be
able to recognize your review on your new profile page. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help
editors to identify candidate reviewers. Please find the details of processing in
Publons’ privacy policy 
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Yes
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I have no COI as above.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Radiofrequency ablation versus hepatic resection for recurrent
hepatocellular carcinoma: an updated meta-analysis
Version: 
1 
Date: 
01 Nov 2020
Reviewer's report:
Nov2, 2020
Dear Editors BMCG
Manuscript ID: BMGE-D-20-01219R1
MS. Title: Radiofrequency ablation versus hepatic resection for recurrent
hepatocellular
carcinoma: an updated meta-analysis
Authors: Xiaohua Xie, et al. 
1. Key finding s of this study were The meta-analysis showed that RHR had
superior OS (HR 0.77, 95% CI =0.65-0.92, P=0.004) and PFS (HR 0.81, 95% CI
=0.67-0.98, P=0.027) compared to RFA, whereas major complications may be
less frequent in the RFA group (OR 0.15, 95% CI = 0.06-0.39, P<0.001
2. Population: From 10 studies with 1612 patients (RHR = 654, RFA = 958)
were included in the meta- analysis. The majority of the sample population was
CP-A (98.3%) and CP-B accounted only 28 cases (1.7%).This selective group of
CP-A have effect on the outcome of overall survival esp. hepatic resection.
Previous article showed that Pre-op MELD had effects on the overall survival1.
The 1-, 3-, and 5-year tumor-free survival rates were 68.4%, 57.9%, and 57.9%,
respectively, for SLT; 69.7%, 49.3%, and 49.3%, respectively, for RR; and
40.0%, 19.8%, and 10.6%, respectively, for rRFA (P=0.001)
3. The total number of 1084 from 1612 cases (67%) caused by HBV infection
which may receive anti-viral agent and this treatment may effect on the overall
survival and outcome too. No details of this information and should add on in
the discussion part.
4. Intervention: The overall result of RFA versus RHR are clearly reported,
however the subgroup analysis which focused on the size of tumor < 3 cm and 3-
5 cm are limited due to the small sample size (2-3 studies) and the indication of
RFA use in HCC tumor size of 3-5 cm is not rational. Thus, the author should
explain the reason of using treatment choices. Additionally, HCC patients with
intrahepatic recurrent tumor should consider for liver transplantation, how many
of them had underwent for this procedure1.
5. Other confounders to the overall survival including the progression or
occurrence of cirrhosis, age group, maximal tumor size at recurrent time, the
duration of the procedure and the expertise of care team should be mentioned for
the outcome.2-7
References
1. Chan AC, Chan SC, Chok KS, et al. Treatment strategy for recurrent
hepatocellular carcinoma: salvage transplantation, repeated resection, or
radiofrequency ablation? Liver Transpl 2013;19:411-9.
2. Sun WC, Chen IS, Liang HL, et al. Comparison of repeated surgical resection
and radiofrequency ablation for small recurrent hepatocellular carcinoma after
primary resection. Oncotarget 2017;8:104571-104581.
3. Eisele RM, Chopra SS, Lock JF, et al. Treatment of recurrent hepatocellular
carcinoma confined to the liver with repeated resection and radiofrequency
ablation: a single center experience. Technol Health Care 2013;21:9-18.
4. Fujiwara N, Tateishi R, Kondo M, et al. Cause-specific mortality associated
with aging in patients with hepatocellular carcinoma undergoing percutaneous
radiofrequency ablation. Eur J Gastroenterol Hepatol 2014;26:1039-46.
5. Asaoka Y, Tateishi R, Nakagomi R, et al. Frequency of and predictive factors
for vascular invasion after radiofrequency ablation for hepatocellular carcinoma.
PLoS One 2014;9:e111662.
6. Tateishi R, Shiina S, Akahane M, et al. Frequency, risk factors and survival
associated with an intrasubsegmental recurrence after radiofrequency ablation
for hepatocellular carcinoma. PLoS One 2013;8:e59040.
7. Shiina S, Tateishi R, Arano T, et al. Radiofrequency ablation for
hepatocellular carcinoma: 10-year outcome and prognostic factors. Am J
Gastroenterol 2012;107:569-77; quiz 578.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons upon publication of the manuscript. If you have already registered at
Publons, they will notify you of the receipt of this review and update your profile
as per your settings and their policy. If you are not registered with Publons, you
will receive an email from them asking you to register in order for them to be
able to recognize your review on your new profile page. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help
editors to identify candidate reviewers. Please find the details of processing in
Publons’ privacy policy 
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I have no COI as above.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
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