Reviewer’s report
Title: 
Magnifying endoscopic findings of early-stage poorly differentiated
colorectal adenocarcinoma: a case report
Version: 
1 
Date: 
26 Dec 2021
Reviewer: 
Takashi Murakami
Reviewer's report:
Comments to the Author
Thank you for allowing me to review your manuscript, "Magnifying endoscopic
findings of early-stage poorly differentiated colorectal adenocarcinoma: a case
report."
There were some major drawbacks to this study. My comments are as follows:
1. It was concluded that poorly differentiated colorectal adenocarcinomas were
characterized by the lack of staining with crystal violet on magnifying
endoscopy. However, I think it is difficult to endoscopically characterize these
tumors based on a single case. More confirmatory evidence from a greater
number of cases is needed to clarify the endoscopic features of poorly-
differentiated colorectal adenocarcinoma.
2. The authors stated that this lesion presented as a pure poorly-differentiated
colorectal carcinoma. However, histologically, this does not seem to be the case
since Figure 2D reveals poorly-differentiated carcinoma mixed with moderately-
differentiated adenocarcinoma showing irregular crypt-like structures in the
mucosal layer.
3. Furthermore, the authors stated that magnifying endoscopy with crystal violet
staining demonstrated lack of staining with no pit-like structure on the lesion.
However, Figure 1D reveals many micro pit-like structure. These seemed to
reflect not only a few normal crypts surrounded by tumors cells but also
moderately-differentiated adenocarcinoma with irregular crypt-like structures.
4. It was stated that the lesion presented with dense irregular microvessels in
NBI mode (Figure 1B). However, in Figure 1B, it was difficult to identify this
feature. The authors should share a more representative image or more clearly
highlight this feature.
5. The authors misunderstand the meaning of p53 immunohistochemistry
expression. The TP53 gene mutation can be identified as immunohistochemical
overexpression of the p53 protein. Therefore, this lesion, showing complete
absence of p53 expression, appears to lack the TP53 mutation.
6. The authors stated that immunohistochemical staining of the lesion showed
normal Mismatch Repair (MMR), APC, and 
β
-catenin protein expression. The
concept of "normal" is inappropriate in this context. Immunohistochemically, the
presence or absence of protein expressions should be described in detail,
respectively.
7. Which exon of KRAS was examined for the analysis of the gene mutation?
Publons Reviewer Recognition
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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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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 publish my name with my
report.
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?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
No
Reviewer’s report
Title: 
Magnifying endoscopic findings of early-stage poorly differentiated
colorectal adenocarcinoma: a case report
Version: 
1 
Date: 
26 Dec 2021
Reviewer: 
Takashi Murakami
Reviewer's report:
Comments to the Author
Thank you for allowing me to review your manuscript, "Magnifying endoscopic
findings of early-stage poorly differentiated colorectal adenocarcinoma: a case
report."
There were some major drawbacks to this study. My comments are as follows:
1. It was concluded that poorly differentiated colorectal adenocarcinomas were
characterized by the lack of staining with crystal violet on magnifying
endoscopy. However, I think it is difficult to endoscopically characterize these
tumors based on a single case. More confirmatory evidence from a greater
number of cases is needed to clarify the endoscopic features of poorly-
differentiated colorectal adenocarcinoma.
2. The authors stated that this lesion presented as a pure poorly-differentiated
colorectal carcinoma. However, histologically, this does not seem to be the case
since Figure 2D reveals poorly-differentiated carcinoma mixed with moderately-
differentiated adenocarcinoma showing irregular crypt-like structures in the
mucosal layer.
3. Furthermore, the authors stated that magnifying endoscopy with crystal violet
staining demonstrated lack of staining with no pit-like structure on the lesion.
However, Figure 1D reveals many micro pit-like structure. These seemed to
reflect not only a few normal crypts surrounded by tumors cells but also
moderately-differentiated adenocarcinoma with irregular crypt-like structures.
4. It was stated that the lesion presented with dense irregular microvessels in
NBI mode (Figure 1B). However, in Figure 1B, it was difficult to identify this
feature. The authors should share a more representative image or more clearly
highlight this feature.
5. The authors misunderstand the meaning of p53 immunohistochemistry
expression. The TP53 gene mutation can be identified as immunohistochemical
overexpression of the p53 protein. Therefore, this lesion, showing complete
absence of p53 expression, appears to lack the TP53 mutation.
6. The authors stated that immunohistochemical staining of the lesion showed
normal Mismatch Repair (MMR), APC, and 
β
-catenin protein expression. The
concept of "normal" is inappropriate in this context. Immunohistochemically, the
presence or absence of protein expressions should be described in detail,
respectively.
7. Which exon of KRAS was examined for the analysis of the gene mutation?
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 publish my name with my
report.
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?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
No
Please review this paper.
user
Reviewer’s report
Title: 
Magnifying endoscopic findings of early-stage poorly differentiated
colorectal adenocarcinoma: a case report
Version: 
1 
Date: 
26 Dec 2021
Reviewer: 
Takashi Murakami
Reviewer's report:
Comments to the Author
Thank you for allowing me to review your manuscript, "Magnifying endoscopic
findings of early-stage poorly differentiated colorectal adenocarcinoma: a case
report."
There were some major drawbacks to this study. My comments are as follows:
1. It was concluded that poorly differentiated colorectal adenocarcinomas were
characterized by the lack of staining with crystal violet on magnifying
endoscopy. However, I think it is difficult to endoscopically characterize these
tumors based on a single case. More confirmatory evidence from a greater
number of cases is needed to clarify the endoscopic features of poorly-
differentiated colorectal adenocarcinoma.
2. The authors stated that this lesion presented as a pure poorly-differentiated
colorectal carcinoma. However, histologically, this does not seem to be the case
since Figure 2D reveals poorly-differentiated carcinoma mixed with moderately-
differentiated adenocarcinoma showing irregular crypt-like structures in the
mucosal layer.
3. Furthermore, the authors stated that magnifying endoscopy with crystal violet
staining demonstrated lack of staining with no pit-like structure on the lesion.
However, Figure 1D reveals many micro pit-like structure. These seemed to
reflect not only a few normal crypts surrounded by tumors cells but also
moderately-differentiated adenocarcinoma with irregular crypt-like structures.
4. It was stated that the lesion presented with dense irregular microvessels in
NBI mode (Figure 1B). However, in Figure 1B, it was difficult to identify this
feature. The authors should share a more representative image or more clearly
highlight this feature.
5. The authors misunderstand the meaning of p53 immunohistochemistry
expression. The TP53 gene mutation can be identified as immunohistochemical
overexpression of the p53 protein. Therefore, this lesion, showing complete
absence of p53 expression, appears to lack the TP53 mutation.
6. The authors stated that immunohistochemical staining of the lesion showed
normal Mismatch Repair (MMR), APC, and 
β
-catenin protein expression. The
concept of "normal" is inappropriate in this context. Immunohistochemically, the
presence or absence of protein expressions should be described in detail,
respectively.
7. Which exon of KRAS was examined for the analysis of the gene mutation?
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 publish my name with my
report.
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?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
No
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