Reviewer’s report
Title: 
Diaphragmatic Perforation after Transcatheter Arterial
Chemoembolization of Hepatocellular Carcinoma via Inferior Phrenic Artery: A
Case Report
Version: 
1 
Date: 
07 Jan 2022
Reviewer's report:
SPECIFIC COMMENTS
This manuscript is pleasurable and flowing, in general; no major issues are
appreciable. 
Although language used is appropriate, I recommend to Editorial staff to check
the final version because I am not a native English speaker. 
TITLE
The title is very interesting. 
ABSTRACT
The abstract appears clear. I believe that the authors could make the conclusions
more attractive. 
KEYWORDS
Authors did not correctly report all keywords from MeSH Browser. In particular,
for example, I checked "chemoembolization" on MeSH Browser and I did not
find this KW. This is important, in my personal opinion, in order to increase the
traceability of this paper (and consequently the possibility of the Journal to be
cited by Readers and Stakeholders). I suggest the check of the all KWs. 
SECTION: Background
Please, could the authors introduce the theme of chemoembolization performed
via extrahepatic feeding vessels? Is this procedure rare? Or not? Please, refer to
different papers that analyze this theme that is vary important because this
procedure is performed via extrahepatic vessel about in ¼ - 1/3 of cases/nodules.
In the background and in discussion section, the authors stated that: "However,
irreversible diaphragmatic injury after TACE without radiofrequency ablation is
an extremely rare complication.". Please, could the authors reports a percentage
of extremely rare? Obviously, referring to some series.
SECTION: Case presentation
Please, describe better the BCLC classification of the patient to justify the TACE
procedures.
To obtain results that are comparable from different studies, it is essential to
report the type of chemo-embolization that has been performed by the Authors.
In particular, according to [Ann Hepatol. 2021;22:100278.
doi:10.1016/j.aohep.2020.10.006], what kind of chemo-embolization is used:
Water-in-oil (Wio) or chemotherapeutic-in-oil (Cio)? DEB-TACE? Other ftypes
of TACE? The authors could discuss this theme.
In my opinion, this section should be expanded with comments regarding the
strategy the authors adopted for re-treatment. They used the scheduled strategy?
Or on-demand strategy? This point is very important and the authors must
discuss this point. In fact, it is well known that the decision on whether a HCC
patient needs a re-treatment after treatment may vary among different
radiologists, especially in case of a non-specifically trained radiologist and,
therefore, regardless of the adopted criteria, patients should be evaluated by
experienced radiologists to minimize variability in this critical instance [Eur
Radiol. 2018;28(9):3611-3620. doi:10.1007/s00330-018-5393-3]. Please, could
the Authors report that it is important that experienced radiologists evaluate
imaging prior to a re-treatment, and that one or more experienced radiologists
must evaluated imaging according to mRECIST. Please, cite the aforementioned
paper [Eur Radiol. 2018;28(9):3611-3620. doi:10.1007/s00330-018-5393-3].
Furthermore, during the execution of the TACE procedures there is an amount of
absorbed radiant dose. In my opinion a correct standardization of the procedures,
including TACE, it is also possible to reduce the number of rays absorbed for
both patients and radiologists and reduce possible stochastic effects [Med Phys.
2012;39(5):2491-2498. doi:10.1118/1.3702457]. in my opinion, the
interventional radiologists who performed TACE should be necessary expert
radiologists in order to reduce the dose in patients that received these treatments
[cite the paper: Med Phys. 2012;39(5):2491-2498. doi:10.1118/1.3702457].
according to the aforementioned paper, could the authors report if the
interventional radiologist who performed these procedures were expert, to reduce
the risks of x-ray exposure particularly if the treatments were performed via
extrahepatic vessels? In my opinion, this theme could be briefly analyzed in this
section, highlighting that in non dedicated centers without expert interventional
radiologist, the possibility to use a systemic therapy would be considered.
Finally, linked to the above theme, did the interventional radiologist performed
the TACE as selective as possible also in non-hepatic vessels to reduce the risks?
SECTION: Discussion
Please, in my opinion the authors must discuss an important theme: the theme of
associating a systemic therapy with TACE. There are many papers concerning
the associations of systemic and trans.arterial therapies. Please, the authors must
write some lines about this theme. Furthermore, it is necessary that
Interventional radiological procedures are performed by experienced
inteventional radiologists to reduce stochastic and non-stochastic risks from x-
ray exposure [Med Phys. 2012;39(5):2491-2498. doi:10.1118/1.3702457] and to
reduce these complications.
Please, could the authors discuss the possible roule in these procedure of cone-
beam CT, citing this paper: 
Bannangkoon K, Hongsakul K, Tubtawee T. Impact of cone-beam computed
tomography with automated feeder detection software on the survival outcome
of patients with hepatocellular carcinoma during treatment with conventional
transarterial chemoembolization. BMC Gastroenterol. 2021;21(1):419. Published
2021 Nov 8. doi:10.1186/s12876-021-02004-z
SECTION: Conclusion
I believe that the authors could make the conclusions more attractive.
Figures
OK.
Publons Reviewer Recognition
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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 declare that I have no competing interests'
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?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Diaphragmatic Perforation after Transcatheter Arterial
Chemoembolization of Hepatocellular Carcinoma via Inferior Phrenic Artery: A
Case Report
Version: 
1 
Date: 
07 Jan 2022
Reviewer's report:
SPECIFIC COMMENTS
This manuscript is pleasurable and flowing, in general; no major issues are
appreciable. 
Although language used is appropriate, I recommend to Editorial staff to check
the final version because I am not a native English speaker. 
TITLE
The title is very interesting. 
ABSTRACT
The abstract appears clear. I believe that the authors could make the conclusions
more attractive. 
KEYWORDS
Authors did not correctly report all keywords from MeSH Browser. In particular,
for example, I checked "chemoembolization" on MeSH Browser and I did not
find this KW. This is important, in my personal opinion, in order to increase the
traceability of this paper (and consequently the possibility of the Journal to be
cited by Readers and Stakeholders). I suggest the check of the all KWs. 
SECTION: Background
Please, could the authors introduce the theme of chemoembolization performed
via extrahepatic feeding vessels? Is this procedure rare? Or not? Please, refer to
different papers that analyze this theme that is vary important because this
procedure is performed via extrahepatic vessel about in ¼ - 1/3 of cases/nodules.
In the background and in discussion section, the authors stated that: "However,
irreversible diaphragmatic injury after TACE without radiofrequency ablation is
an extremely rare complication.". Please, could the authors reports a percentage
of extremely rare? Obviously, referring to some series.
SECTION: Case presentation
Please, describe better the BCLC classification of the patient to justify the TACE
procedures.
To obtain results that are comparable from different studies, it is essential to
report the type of chemo-embolization that has been performed by the Authors.
In particular, according to [Ann Hepatol. 2021;22:100278.
doi:10.1016/j.aohep.2020.10.006], what kind of chemo-embolization is used:
Water-in-oil (Wio) or chemotherapeutic-in-oil (Cio)? DEB-TACE? Other ftypes
of TACE? The authors could discuss this theme.
In my opinion, this section should be expanded with comments regarding the
strategy the authors adopted for re-treatment. They used the scheduled strategy?
Or on-demand strategy? This point is very important and the authors must
discuss this point. In fact, it is well known that the decision on whether a HCC
patient needs a re-treatment after treatment may vary among different
radiologists, especially in case of a non-specifically trained radiologist and,
therefore, regardless of the adopted criteria, patients should be evaluated by
experienced radiologists to minimize variability in this critical instance [Eur
Radiol. 2018;28(9):3611-3620. doi:10.1007/s00330-018-5393-3]. Please, could
the Authors report that it is important that experienced radiologists evaluate
imaging prior to a re-treatment, and that one or more experienced radiologists
must evaluated imaging according to mRECIST. Please, cite the aforementioned
paper [Eur Radiol. 2018;28(9):3611-3620. doi:10.1007/s00330-018-5393-3].
Furthermore, during the execution of the TACE procedures there is an amount of
absorbed radiant dose. In my opinion a correct standardization of the procedures,
including TACE, it is also possible to reduce the number of rays absorbed for
both patients and radiologists and reduce possible stochastic effects [Med Phys.
2012;39(5):2491-2498. doi:10.1118/1.3702457]. in my opinion, the
interventional radiologists who performed TACE should be necessary expert
radiologists in order to reduce the dose in patients that received these treatments
[cite the paper: Med Phys. 2012;39(5):2491-2498. doi:10.1118/1.3702457].
according to the aforementioned paper, could the authors report if the
interventional radiologist who performed these procedures were expert, to reduce
the risks of x-ray exposure particularly if the treatments were performed via
extrahepatic vessels? In my opinion, this theme could be briefly analyzed in this
section, highlighting that in non dedicated centers without expert interventional
radiologist, the possibility to use a systemic therapy would be considered.
Finally, linked to the above theme, did the interventional radiologist performed
the TACE as selective as possible also in non-hepatic vessels to reduce the risks?
SECTION: Discussion
Please, in my opinion the authors must discuss an important theme: the theme of
associating a systemic therapy with TACE. There are many papers concerning
the associations of systemic and trans.arterial therapies. Please, the authors must
write some lines about this theme. Furthermore, it is necessary that
Interventional radiological procedures are performed by experienced
inteventional radiologists to reduce stochastic and non-stochastic risks from x-
ray exposure [Med Phys. 2012;39(5):2491-2498. doi:10.1118/1.3702457] and to
reduce these complications.
Please, could the authors discuss the possible roule in these procedure of cone-
beam CT, citing this paper: 
Bannangkoon K, Hongsakul K, Tubtawee T. Impact of cone-beam computed
tomography with automated feeder detection software on the survival outcome
of patients with hepatocellular carcinoma during treatment with conventional
transarterial chemoembolization. BMC Gastroenterol. 2021;21(1):419. Published
2021 Nov 8. doi:10.1186/s12876-021-02004-z
SECTION: Conclusion
I believe that the authors could make the conclusions more attractive.
Figures
OK.
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 after the final decision on the manuscript has been made. 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 declare that I have no competing interests'
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?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
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: 
Diaphragmatic Perforation after Transcatheter Arterial
Chemoembolization of Hepatocellular Carcinoma via Inferior Phrenic Artery: A
Case Report
Version: 
1 
Date: 
07 Jan 2022
Reviewer's report:
SPECIFIC COMMENTS
This manuscript is pleasurable and flowing, in general; no major issues are
appreciable. 
Although language used is appropriate, I recommend to Editorial staff to check
the final version because I am not a native English speaker. 
TITLE
The title is very interesting. 
ABSTRACT
The abstract appears clear. I believe that the authors could make the conclusions
more attractive. 
KEYWORDS
Authors did not correctly report all keywords from MeSH Browser. In particular,
for example, I checked "chemoembolization" on MeSH Browser and I did not
find this KW. This is important, in my personal opinion, in order to increase the
traceability of this paper (and consequently the possibility of the Journal to be
cited by Readers and Stakeholders). I suggest the check of the all KWs. 
SECTION: Background
Please, could the authors introduce the theme of chemoembolization performed
via extrahepatic feeding vessels? Is this procedure rare? Or not? Please, refer to
different papers that analyze this theme that is vary important because this
procedure is performed via extrahepatic vessel about in ¼ - 1/3 of cases/nodules.
In the background and in discussion section, the authors stated that: "However,
irreversible diaphragmatic injury after TACE without radiofrequency ablation is
an extremely rare complication.". Please, could the authors reports a percentage
of extremely rare? Obviously, referring to some series.
SECTION: Case presentation
Please, describe better the BCLC classification of the patient to justify the TACE
procedures.
To obtain results that are comparable from different studies, it is essential to
report the type of chemo-embolization that has been performed by the Authors.
In particular, according to [Ann Hepatol. 2021;22:100278.
doi:10.1016/j.aohep.2020.10.006], what kind of chemo-embolization is used:
Water-in-oil (Wio) or chemotherapeutic-in-oil (Cio)? DEB-TACE? Other ftypes
of TACE? The authors could discuss this theme.
In my opinion, this section should be expanded with comments regarding the
strategy the authors adopted for re-treatment. They used the scheduled strategy?
Or on-demand strategy? This point is very important and the authors must
discuss this point. In fact, it is well known that the decision on whether a HCC
patient needs a re-treatment after treatment may vary among different
radiologists, especially in case of a non-specifically trained radiologist and,
therefore, regardless of the adopted criteria, patients should be evaluated by
experienced radiologists to minimize variability in this critical instance [Eur
Radiol. 2018;28(9):3611-3620. doi:10.1007/s00330-018-5393-3]. Please, could
the Authors report that it is important that experienced radiologists evaluate
imaging prior to a re-treatment, and that one or more experienced radiologists
must evaluated imaging according to mRECIST. Please, cite the aforementioned
paper [Eur Radiol. 2018;28(9):3611-3620. doi:10.1007/s00330-018-5393-3].
Furthermore, during the execution of the TACE procedures there is an amount of
absorbed radiant dose. In my opinion a correct standardization of the procedures,
including TACE, it is also possible to reduce the number of rays absorbed for
both patients and radiologists and reduce possible stochastic effects [Med Phys.
2012;39(5):2491-2498. doi:10.1118/1.3702457]. in my opinion, the
interventional radiologists who performed TACE should be necessary expert
radiologists in order to reduce the dose in patients that received these treatments
[cite the paper: Med Phys. 2012;39(5):2491-2498. doi:10.1118/1.3702457].
according to the aforementioned paper, could the authors report if the
interventional radiologist who performed these procedures were expert, to reduce
the risks of x-ray exposure particularly if the treatments were performed via
extrahepatic vessels? In my opinion, this theme could be briefly analyzed in this
section, highlighting that in non dedicated centers without expert interventional
radiologist, the possibility to use a systemic therapy would be considered.
Finally, linked to the above theme, did the interventional radiologist performed
the TACE as selective as possible also in non-hepatic vessels to reduce the risks?
SECTION: Discussion
Please, in my opinion the authors must discuss an important theme: the theme of
associating a systemic therapy with TACE. There are many papers concerning
the associations of systemic and trans.arterial therapies. Please, the authors must
write some lines about this theme. Furthermore, it is necessary that
Interventional radiological procedures are performed by experienced
inteventional radiologists to reduce stochastic and non-stochastic risks from x-
ray exposure [Med Phys. 2012;39(5):2491-2498. doi:10.1118/1.3702457] and to
reduce these complications.
Please, could the authors discuss the possible roule in these procedure of cone-
beam CT, citing this paper: 
Bannangkoon K, Hongsakul K, Tubtawee T. Impact of cone-beam computed
tomography with automated feeder detection software on the survival outcome
of patients with hepatocellular carcinoma during treatment with conventional
transarterial chemoembolization. BMC Gastroenterol. 2021;21(1):419. Published
2021 Nov 8. doi:10.1186/s12876-021-02004-z
SECTION: Conclusion
I believe that the authors could make the conclusions more attractive.
Figures
OK.
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 after the final decision on the manuscript has been made. 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 declare that I have no competing interests'
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?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant