Reviewer ’s report  
 
Title: Colorectal endoscopic mucosal resection with submucosal injection of epinephrine versus 
hypertonic saline in patients taking antithrombotic agents: propensity -score -matching analysis  
 
Version: 1 Date: 20 Oct 2019  
 
Reviewer: Li-Chun Chang  
 
Reviewer's report:  
 
Yamaguchi et al. conducted this retrospective study to compare the risk of bl eeding between 
using epinephrine and hypertonic saline for submucosal injection. Their study disclosed that the 
risk of immediate bleeding and post -EMR bleeding was not different between injection with 
epinephrine and hypertonic saline in subjects with an antithrombotic agent. This is a well -written 
paper. Although a significant difference developed in many important variates between two 
groups, this was minimized by propensity score. However, the weakness is the prospective 
design. Too many confounders wil l influence the result even after adjustment. The followings 
are my comments:  
  
1. Comorbidity has a massive impact on the risk of bleeding. A comprehensive evaluation 
of comorbidity, such as using Charlson comorbidity score, will minimize this confoun der.  
 
2. Is there any rule to decide which injection solution to use in the endoscopy unit? For 
neoplasm with a higher risk of bleeding, the endoscopists may prefer one epinephrine for 
submucosal injection. This may lead to bias.  
 
3. I am curious abo ut the reason why prophylactic clipping was performed in every EMR.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in you r 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.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If no t, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manus cript 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.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of comp eting interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now  or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 relati ng 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 have no competing interests.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upl oad will be posted on the website along with the authors' 
responses. 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/ ). I understand that any comments 
which I do not  wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Colorectal endoscopic mucosal resection with submucosal injection of epinephrine versus 
hypertonic saline in patients taking antithrombotic agents: propensity -score -matching analysis  
 
Version: 1 Date: 20 Oct 2019  
 
Reviewer: Li-Chun Chang  
 
Reviewer's report:  
 
Yamaguchi et al. conducted this retrospective study to compare the risk of bl eeding between 
using epinephrine and hypertonic saline for submucosal injection. Their study disclosed that the 
risk of immediate bleeding and post -EMR bleeding was not different between injection with 
epinephrine and hypertonic saline in subjects with an antithrombotic agent. This is a well -written 
paper. Although a significant difference developed in many important variates between two 
groups, this was minimized by propensity score. However, the weakness is the prospective 
design. Too many confounders wil l influence the result even after adjustment. The followings 
are my comments:  
  
1. Comorbidity has a massive impact on the risk of bleeding. A comprehensive evaluation 
of comorbidity, such as using Charlson comorbidity score, will minimize this confoun der.  
 
2. Is there any rule to decide which injection solution to use in the endoscopy unit? For 
neoplasm with a higher risk of bleeding, the endoscopists may prefer one epinephrine for 
submucosal injection. This may lead to bias.  
 
3. I am curious abo ut the reason why prophylactic clipping was performed in every EMR.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in you r 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.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If no t, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manus cript 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.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of comp eting interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now  or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 relati ng 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 have no competing interests.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upl oad will be posted on the website along with the authors' 
responses. 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/ ). I understand that any comments 
which I do not  wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Colorectal endoscopic mucosal resection with submucosal injection of epinephrine versus 
hypertonic saline in patients taking antithrombotic agents: propensity -score -matching analysis  
 
Version: 1 Date: 20 Oct 2019  
 
Reviewer: Li-Chun Chang  
 
Reviewer's report:  
 
Yamaguchi et al. conducted this retrospective study to compare the risk of bl eeding between 
using epinephrine and hypertonic saline for submucosal injection. Their study disclosed that the 
risk of immediate bleeding and post -EMR bleeding was not different between injection with 
epinephrine and hypertonic saline in subjects with an antithrombotic agent. This is a well -written 
paper. Although a significant difference developed in many important variates between two 
groups, this was minimized by propensity score. However, the weakness is the prospective 
design. Too many confounders wil l influence the result even after adjustment. The followings 
are my comments:  
  
1. Comorbidity has a massive impact on the risk of bleeding. A comprehensive evaluation 
of comorbidity, such as using Charlson comorbidity score, will minimize this confoun der.  
 
2. Is there any rule to decide which injection solution to use in the endoscopy unit? For 
neoplasm with a higher risk of bleeding, the endoscopists may prefer one epinephrine for 
submucosal injection. This may lead to bias.  
 
3. I am curious abo ut the reason why prophylactic clipping was performed in every EMR.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in you r 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.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If no t, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manus cript 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.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of comp eting interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now  or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 relati ng 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 have no competing interests.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upl oad will be posted on the website along with the authors' 
responses. 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/ ). I understand that any comments 
which I do not  wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant