Reviewer’s report
Title: 
Pneumatosis cystoides intestinalis associated with etoposide in
hematological malignancies: A case report and a literature review
Version: 
0 
Date: 
03 Oct 2021
Reviewer's report:
Thank you for the submission of your manuscript. I have the following
recommendations:
1. Please clarify if your patient was diagnosed with pneumoperitoneum on
presentation. It appears that the patient presented with colonic distension in the
setting of constipation, and underwent exploratory laparoscopic surgery which
revealed PCI, but there is no evidence of pneumoperitoneum on CT imaging. So
PCI resolved with conservative management, but the patient never had
pneumoperitoneum. 
2. The introduction should be more clearly laid out. You introduce the hypothesis
for the mechanism of PCI, but then step back and talk of the two types (primary
vs secondary). However, there is no explanation for what those two types are.
This needs to be clarified. And from your description of the case, this appears to
be primary PCI, which should also be explicitly stated in the discussion.
3. More information regarding the patient's initial presentation would be helpful.
When was his last bowel movement / was he able to pass flatus / where there any
changes to his stool? Also, beyond imaging and surgery, were any other
diagnostic studies sent (such as stool panels for C. diff or other infections given
his stated long term glucocorticoid exposure)?
4. There are some studies that try to use vital signs with laboratory findings
(such as lactic acid) to try and prognosticate PCI; mentioning these would
strengthen the manuscript.
5. Why was etoposide postulated as the primary culprit? Given that PD-1
inhibitors are linked with a variant of colitis also seems like a reasonable
mechanism of injury for primary PCI (and PCI is associated with IBD).
However, if the authors could support that there was no clear history
(mucous/prior bloody bowel movements/inflammatory appearance) more
commonly associated with the adverse effects of PD-1 inhibitors, it would be
beneficial. Similarly, did the other manuscripts that were reviewed with
etoposide present in a similar manner (with abdominal pain and constipation)?
6. For images, I was unable to see the red arrows described in the CT imaging
legend.
Overall, I would recommend significant revisions highlighting the points above.
I would also recommend review/editing for English/language issues.
And again, I would like to thank the authors for submission of the manuscript.
Publons Reviewer Recognition
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for the benefit of Publons and you as a reviewer, carefully considering the
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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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No
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?
Yes
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: 
Pneumatosis cystoides intestinalis associated with etoposide in
hematological malignancies: A case report and a literature review
Version: 
0 
Date: 
03 Oct 2021
Reviewer's report:
Thank you for the submission of your manuscript. I have the following
recommendations:
1. Please clarify if your patient was diagnosed with pneumoperitoneum on
presentation. It appears that the patient presented with colonic distension in the
setting of constipation, and underwent exploratory laparoscopic surgery which
revealed PCI, but there is no evidence of pneumoperitoneum on CT imaging. So
PCI resolved with conservative management, but the patient never had
pneumoperitoneum. 
2. The introduction should be more clearly laid out. You introduce the hypothesis
for the mechanism of PCI, but then step back and talk of the two types (primary
vs secondary). However, there is no explanation for what those two types are.
This needs to be clarified. And from your description of the case, this appears to
be primary PCI, which should also be explicitly stated in the discussion.
3. More information regarding the patient's initial presentation would be helpful.
When was his last bowel movement / was he able to pass flatus / where there any
changes to his stool? Also, beyond imaging and surgery, were any other
diagnostic studies sent (such as stool panels for C. diff or other infections given
his stated long term glucocorticoid exposure)?
4. There are some studies that try to use vital signs with laboratory findings
(such as lactic acid) to try and prognosticate PCI; mentioning these would
strengthen the manuscript.
5. Why was etoposide postulated as the primary culprit? Given that PD-1
inhibitors are linked with a variant of colitis also seems like a reasonable
mechanism of injury for primary PCI (and PCI is associated with IBD).
However, if the authors could support that there was no clear history
(mucous/prior bloody bowel movements/inflammatory appearance) more
commonly associated with the adverse effects of PD-1 inhibitors, it would be
beneficial. Similarly, did the other manuscripts that were reviewed with
etoposide present in a similar manner (with abdominal pain and constipation)?
6. For images, I was unable to see the red arrows described in the CT imaging
legend.
Overall, I would recommend significant revisions highlighting the points above.
I would also recommend review/editing for English/language issues.
And again, I would like to thank the authors for submission of the manuscript.
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
No
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?
Yes
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: 
Pneumatosis cystoides intestinalis associated with etoposide in
hematological malignancies: A case report and a literature review
Version: 
0 
Date: 
03 Oct 2021
Reviewer's report:
Thank you for the submission of your manuscript. I have the following
recommendations:
1. Please clarify if your patient was diagnosed with pneumoperitoneum on
presentation. It appears that the patient presented with colonic distension in the
setting of constipation, and underwent exploratory laparoscopic surgery which
revealed PCI, but there is no evidence of pneumoperitoneum on CT imaging. So
PCI resolved with conservative management, but the patient never had
pneumoperitoneum. 
2. The introduction should be more clearly laid out. You introduce the hypothesis
for the mechanism of PCI, but then step back and talk of the two types (primary
vs secondary). However, there is no explanation for what those two types are.
This needs to be clarified. And from your description of the case, this appears to
be primary PCI, which should also be explicitly stated in the discussion.
3. More information regarding the patient's initial presentation would be helpful.
When was his last bowel movement / was he able to pass flatus / where there any
changes to his stool? Also, beyond imaging and surgery, were any other
diagnostic studies sent (such as stool panels for C. diff or other infections given
his stated long term glucocorticoid exposure)?
4. There are some studies that try to use vital signs with laboratory findings
(such as lactic acid) to try and prognosticate PCI; mentioning these would
strengthen the manuscript.
5. Why was etoposide postulated as the primary culprit? Given that PD-1
inhibitors are linked with a variant of colitis also seems like a reasonable
mechanism of injury for primary PCI (and PCI is associated with IBD).
However, if the authors could support that there was no clear history
(mucous/prior bloody bowel movements/inflammatory appearance) more
commonly associated with the adverse effects of PD-1 inhibitors, it would be
beneficial. Similarly, did the other manuscripts that were reviewed with
etoposide present in a similar manner (with abdominal pain and constipation)?
6. For images, I was unable to see the red arrows described in the CT imaging
legend.
Overall, I would recommend significant revisions highlighting the points above.
I would also recommend review/editing for English/language issues.
And again, I would like to thank the authors for submission of the manuscript.
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
No
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?
Yes
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