Reviewer’s report
Title: 
Pneumatosis cystoides intestinalis associated with etoposide in
hematological malignancies: A case report and a literature review
Version: 
0 
Date: 
02 Jan 2022
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses a
testable research question(s) (brief or other article types: is there a clear
objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work
technically sound? If not, can revisions be made to make the work technically
sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: 
My overall impression is very good with good description and interpretation of
the report and clearly outlined novelty.
Relevance: This report contributes to medical knowledge.
Case Description: Please kindly provide the details of the laboratory tests with
complete blood count, CRP/ESR or other inflammatory markers if available.
Diagnosis/Interpretation: The work described is medically sound.
Case Discussion: If possible and feasible detailed operative findings with areas
of colon or mesocolon predominantly involved such as right and transverse
colon in earlier reported cases and add laparoscopy as potential modality for
therapeutic approach at least for initial diagnostic and assessment of the extent of
the disease and gastrointestinal endoscopy may aggravate the PI/PCI due to
increased intraluminal pressure. As recently described in a similar case report
given below:
Patel RV, Sutton PA, Colliver D, Stewart R: Pneumoperitoneum and
pneumatosis cystoides intestinalis (PCI) following chemotherapy in an
adolescent with Hodgkin's lymphoma. BMJ Case Reports 23 February 2014;
doi:10.1136/bcr-2013-203433
REQUESTED REVISIONS: 
The pathogenesis of PCI in this case is secondary and remains to be explored
involving following possible major hypotheses: mechanical theory (by increased
intraluminal colonic gas and pressure due to adynamic febrile or septic ileus
increasing the colonic luminal pressure leading to relative ischemia on the
mesocolon side of the lumen allowing leakage of air), bacterial theory (bacterial
transudation via relative ischemic zone and reduced immunity by chemotherapy
medications) and chemical theory (toxic effects of chemotherapy on the cell
adhesion and apoptosis) or nutritional deficiency theory (depletion of
micronutrients in these debilitated patients).
1. Title, abstract and introduction is very good.
2. In the case report if possible and feasible complete blood counts and
inflammatory markers at admission may be added and the operative detailed
findings as to what areas were exactly involved as most cases happens in
pediatric and geriatric cases and most cases part of the colon and terminal ileum
is involved possible due to temporary ileocecal reflux and more lesions are seen
involving right and transverse colon and mesocolon and even in the review cases
these details if available will provide a definite pattern and possible ileus
involving left colon as more cases are seen in neurotoxicity chemotherapy
agents.
3. In the discussion, possible pathogenesis mechanism in this case, role of
laparoscopy and addition of one more recent reference will do.
ADDITIONAL REQUESTS/SUGGESTIONS: 
Overall the case report and review of literature is very good except for minor
revisions indicated.
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
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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.
This reviewer has been recruited by a partner organization, Research Square.
Reviewers with declared or apparent competing interests are not utilized for
these reviews. This reviewer has agreed to publication of their comments online
under a Creative Commons Attribution License attributed to Research Square
and was paid a small honorarium for completing the review within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
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?
No
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
Reviewer’s report
Title: 
Pneumatosis cystoides intestinalis associated with etoposide in
hematological malignancies: A case report and a literature review
Version: 
0 
Date: 
02 Jan 2022
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses a
testable research question(s) (brief or other article types: is there a clear
objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work
technically sound? If not, can revisions be made to make the work technically
sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: 
My overall impression is very good with good description and interpretation of
the report and clearly outlined novelty.
Relevance: This report contributes to medical knowledge.
Case Description: Please kindly provide the details of the laboratory tests with
complete blood count, CRP/ESR or other inflammatory markers if available.
Diagnosis/Interpretation: The work described is medically sound.
Case Discussion: If possible and feasible detailed operative findings with areas
of colon or mesocolon predominantly involved such as right and transverse
colon in earlier reported cases and add laparoscopy as potential modality for
therapeutic approach at least for initial diagnostic and assessment of the extent of
the disease and gastrointestinal endoscopy may aggravate the PI/PCI due to
increased intraluminal pressure. As recently described in a similar case report
given below:
Patel RV, Sutton PA, Colliver D, Stewart R: Pneumoperitoneum and
pneumatosis cystoides intestinalis (PCI) following chemotherapy in an
adolescent with Hodgkin's lymphoma. BMJ Case Reports 23 February 2014;
doi:10.1136/bcr-2013-203433
REQUESTED REVISIONS: 
The pathogenesis of PCI in this case is secondary and remains to be explored
involving following possible major hypotheses: mechanical theory (by increased
intraluminal colonic gas and pressure due to adynamic febrile or septic ileus
increasing the colonic luminal pressure leading to relative ischemia on the
mesocolon side of the lumen allowing leakage of air), bacterial theory (bacterial
transudation via relative ischemic zone and reduced immunity by chemotherapy
medications) and chemical theory (toxic effects of chemotherapy on the cell
adhesion and apoptosis) or nutritional deficiency theory (depletion of
micronutrients in these debilitated patients).
1. Title, abstract and introduction is very good.
2. In the case report if possible and feasible complete blood counts and
inflammatory markers at admission may be added and the operative detailed
findings as to what areas were exactly involved as most cases happens in
pediatric and geriatric cases and most cases part of the colon and terminal ileum
is involved possible due to temporary ileocecal reflux and more lesions are seen
involving right and transverse colon and mesocolon and even in the review cases
these details if available will provide a definite pattern and possible ileus
involving left colon as more cases are seen in neurotoxicity chemotherapy
agents.
3. In the discussion, possible pathogenesis mechanism in this case, role of
laparoscopy and addition of one more recent reference will do.
ADDITIONAL REQUESTS/SUGGESTIONS: 
Overall the case report and review of literature is very good except for minor
revisions indicated.
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.
This reviewer has been recruited by a partner organization, Research Square.
Reviewers with declared or apparent competing interests are not utilized for
these reviews. This reviewer has agreed to publication of their comments online
under a Creative Commons Attribution License attributed to Research Square
and was paid a small honorarium for completing the review within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
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?
No
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: 
Pneumatosis cystoides intestinalis associated with etoposide in
hematological malignancies: A case report and a literature review
Version: 
0 
Date: 
02 Jan 2022
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses a
testable research question(s) (brief or other article types: is there a clear
objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work
technically sound? If not, can revisions be made to make the work technically
sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: 
My overall impression is very good with good description and interpretation of
the report and clearly outlined novelty.
Relevance: This report contributes to medical knowledge.
Case Description: Please kindly provide the details of the laboratory tests with
complete blood count, CRP/ESR or other inflammatory markers if available.
Diagnosis/Interpretation: The work described is medically sound.
Case Discussion: If possible and feasible detailed operative findings with areas
of colon or mesocolon predominantly involved such as right and transverse
colon in earlier reported cases and add laparoscopy as potential modality for
therapeutic approach at least for initial diagnostic and assessment of the extent of
the disease and gastrointestinal endoscopy may aggravate the PI/PCI due to
increased intraluminal pressure. As recently described in a similar case report
given below:
Patel RV, Sutton PA, Colliver D, Stewart R: Pneumoperitoneum and
pneumatosis cystoides intestinalis (PCI) following chemotherapy in an
adolescent with Hodgkin's lymphoma. BMJ Case Reports 23 February 2014;
doi:10.1136/bcr-2013-203433
REQUESTED REVISIONS: 
The pathogenesis of PCI in this case is secondary and remains to be explored
involving following possible major hypotheses: mechanical theory (by increased
intraluminal colonic gas and pressure due to adynamic febrile or septic ileus
increasing the colonic luminal pressure leading to relative ischemia on the
mesocolon side of the lumen allowing leakage of air), bacterial theory (bacterial
transudation via relative ischemic zone and reduced immunity by chemotherapy
medications) and chemical theory (toxic effects of chemotherapy on the cell
adhesion and apoptosis) or nutritional deficiency theory (depletion of
micronutrients in these debilitated patients).
1. Title, abstract and introduction is very good.
2. In the case report if possible and feasible complete blood counts and
inflammatory markers at admission may be added and the operative detailed
findings as to what areas were exactly involved as most cases happens in
pediatric and geriatric cases and most cases part of the colon and terminal ileum
is involved possible due to temporary ileocecal reflux and more lesions are seen
involving right and transverse colon and mesocolon and even in the review cases
these details if available will provide a definite pattern and possible ileus
involving left colon as more cases are seen in neurotoxicity chemotherapy
agents.
3. In the discussion, possible pathogenesis mechanism in this case, role of
laparoscopy and addition of one more recent reference will do.
ADDITIONAL REQUESTS/SUGGESTIONS: 
Overall the case report and review of literature is very good except for minor
revisions indicated.
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.
This reviewer has been recruited by a partner organization, Research Square.
Reviewers with declared or apparent competing interests are not utilized for
these reviews. This reviewer has agreed to publication of their comments online
under a Creative Commons Attribution License attributed to Research Square
and was paid a small honorarium for completing the review within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
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?
No
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
assistant