Reviewer’s report
Title: 
Small intestinal mucosal injury and its risk factors in patients with
gastrointestinal cancer who developed complicated fluoropyrimidine-induced
diarrhea
Version: 
2 
Date: 
20 May 2020
Reviewer's report:
This is an interesting study but it claims more than it should. It is largely
descriptive.
It is useful to do a study using capsule endoscopy to inspect the small intestine
after chemotherapy injury.
However, the CE was done during the recovery phase and so may not have been
as useful as if it had been done at the time of acute injury. Particularly the lower
grades of injury would be expected to have largely recovered macroscopically by
the time of the CE
Furthermore, only 12 patients actually underwent the procedure, from a possible
32. This is a very small sample size so conclusions need to be cautious.
My major issue is with the conclusions. Firstly, fever and sepsis are part of the
definition of complicated diarrhoea, so developing them was almost a condition
for entering the study, although only 3 of the 10 patients had fever or sepsis. But
it is the next sentence that really has no place: "Bacterial translocation secondary
to small intestinal mucosal injury should therefore be considered in the
management of complicated fluoropyrimidine-induced diarrhea". No evidence
was presented to back this up. The CE findings were of erosions and ulcers and
these were not correlated in the paper with the infections. Why would the
presence of fever/sepsis in 30% of a sample patients lead you to this conclusion?
The paper doesn't address the issue of bacterial translocation in any explanatory
way.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Unable to assess
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
Not relevant to this manuscript
Quality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
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 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)
Reviewer’s report
Title: 
Small intestinal mucosal injury and its risk factors in patients with
gastrointestinal cancer who developed complicated fluoropyrimidine-induced
diarrhea
Version: 
2 
Date: 
20 May 2020
Reviewer's report:
This is an interesting study but it claims more than it should. It is largely
descriptive.
It is useful to do a study using capsule endoscopy to inspect the small intestine
after chemotherapy injury.
However, the CE was done during the recovery phase and so may not have been
as useful as if it had been done at the time of acute injury. Particularly the lower
grades of injury would be expected to have largely recovered macroscopically by
the time of the CE
Furthermore, only 12 patients actually underwent the procedure, from a possible
32. This is a very small sample size so conclusions need to be cautious.
My major issue is with the conclusions. Firstly, fever and sepsis are part of the
definition of complicated diarrhoea, so developing them was almost a condition
for entering the study, although only 3 of the 10 patients had fever or sepsis. But
it is the next sentence that really has no place: "Bacterial translocation secondary
to small intestinal mucosal injury should therefore be considered in the
management of complicated fluoropyrimidine-induced diarrhea". No evidence
was presented to back this up. The CE findings were of erosions and ulcers and
these were not correlated in the paper with the infections. Why would the
presence of fever/sepsis in 30% of a sample patients lead you to this conclusion?
The paper doesn't address the issue of bacterial translocation in any explanatory
way.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Unable to assess
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
Not relevant to this manuscript
Quality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
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 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)
Please review this paper.
user
Reviewer’s report
Title: 
Small intestinal mucosal injury and its risk factors in patients with
gastrointestinal cancer who developed complicated fluoropyrimidine-induced
diarrhea
Version: 
2 
Date: 
20 May 2020
Reviewer's report:
This is an interesting study but it claims more than it should. It is largely
descriptive.
It is useful to do a study using capsule endoscopy to inspect the small intestine
after chemotherapy injury.
However, the CE was done during the recovery phase and so may not have been
as useful as if it had been done at the time of acute injury. Particularly the lower
grades of injury would be expected to have largely recovered macroscopically by
the time of the CE
Furthermore, only 12 patients actually underwent the procedure, from a possible
32. This is a very small sample size so conclusions need to be cautious.
My major issue is with the conclusions. Firstly, fever and sepsis are part of the
definition of complicated diarrhoea, so developing them was almost a condition
for entering the study, although only 3 of the 10 patients had fever or sepsis. But
it is the next sentence that really has no place: "Bacterial translocation secondary
to small intestinal mucosal injury should therefore be considered in the
management of complicated fluoropyrimidine-induced diarrhea". No evidence
was presented to back this up. The CE findings were of erosions and ulcers and
these were not correlated in the paper with the infections. Why would the
presence of fever/sepsis in 30% of a sample patients lead you to this conclusion?
The paper doesn't address the issue of bacterial translocation in any explanatory
way.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Unable to assess
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
Not relevant to this manuscript
Quality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
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 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)
assistant