Reviewer’s report
Title: 
Direct oral anticoagulants increase bleeding risk after endoscopic
sphincterotomy: A retrospective study
Version: 
1 
Date: 
19 May 2021
Reviewer's report:
The authors explored the risk factors for bleeding after EST in patients on
DOAC and evaluated the Japan Gastroenterological Endoscopy Society (JGES)
guidelines in patients undergoing antithrombotic treatment.
They presents DOAC treatment, low platelet count, and old age were significant
predictors of EST bleeding and proved the validity of JGES guidelines.
This is a well written, interesting paper, and useful contributing to clinical
practice.
However, I would like to suggest some issues with several comments and
criticisms as follows;
Comment 1:
All DOACs are affected by renal function.
Could you add the details to Table.1 and Table.5 regarding the presence of renal
dysfunction and the GFR value?
Comment 2:
Page 5, line 100:
In this study, DOAC was typically discontinued for <2 days based on the JGES
guidelines. 
On the other hand, when did the authors restart DOAL after EST or EPLBD?
The authors needs to clarify this point.
Comment 3:
Page 7, line 160-161:
This study also included patients who performed EPLBD as a papillary
procedure.
The authors should describe the detail of EPLBD procedure in the Method
session.
Comment 4:
There were 12 patients (28.6%) adapted Heparin replacement in No-drug group
(Table 2).
These patients should be included in DOAC group.
Moreover, for the 12 patients who indicated Heparin replacement, the APTT
value before EST should be described.
Comment 5:
Page 8, line 184:
Please revise 20.0% (2/15) to 20.0% (3/15).
Comment 6:
Figure 2
The authors showed overall treatment for EST bleeding.
Were there significant difference in the number of Endoscopic treatment for EST
bleeding between the DOAC group and No-drug group?
Could you evaluate the treatments for EST bleeding in the two groups
separately.
Comment 7:
Page 9, line 208-209:
Page 10, line 216-217:
There were 8 (33.3%) and 4 (22.2%) patients who had a combination of
antiplatelet drugs and DOAC in the <2-day group and ≥2-day group, respectively
(Table 5).
Could you add the detail of this point (ex, drug type, cessation period, and
resumption time, etc).
Comment 8:
Table 5
JGES guideline 2017 suggests that DOAC can be cessation on the day of
treatment when performing high-risk of bleeding (EST).
Since the purpose of this study is to evaluate the JGES guidelines for
gastroenterological endoscopy in patients receiving DOAC, how about dividing
the DOAC cessation period into two groups, <1-day group and ≥1-1day group.
Comment 9:
Page 11, line 246-248:
The authors considered that the low platelet count was caused by infection. Is
there any evidence to support that finding? (ex, rate and severity of cholangitis).
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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?
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: 
Direct oral anticoagulants increase bleeding risk after endoscopic
sphincterotomy: A retrospective study
Version: 
1 
Date: 
19 May 2021
Reviewer's report:
The authors explored the risk factors for bleeding after EST in patients on
DOAC and evaluated the Japan Gastroenterological Endoscopy Society (JGES)
guidelines in patients undergoing antithrombotic treatment.
They presents DOAC treatment, low platelet count, and old age were significant
predictors of EST bleeding and proved the validity of JGES guidelines.
This is a well written, interesting paper, and useful contributing to clinical
practice.
However, I would like to suggest some issues with several comments and
criticisms as follows;
Comment 1:
All DOACs are affected by renal function.
Could you add the details to Table.1 and Table.5 regarding the presence of renal
dysfunction and the GFR value?
Comment 2:
Page 5, line 100:
In this study, DOAC was typically discontinued for <2 days based on the JGES
guidelines. 
On the other hand, when did the authors restart DOAL after EST or EPLBD?
The authors needs to clarify this point.
Comment 3:
Page 7, line 160-161:
This study also included patients who performed EPLBD as a papillary
procedure.
The authors should describe the detail of EPLBD procedure in the Method
session.
Comment 4:
There were 12 patients (28.6%) adapted Heparin replacement in No-drug group
(Table 2).
These patients should be included in DOAC group.
Moreover, for the 12 patients who indicated Heparin replacement, the APTT
value before EST should be described.
Comment 5:
Page 8, line 184:
Please revise 20.0% (2/15) to 20.0% (3/15).
Comment 6:
Figure 2
The authors showed overall treatment for EST bleeding.
Were there significant difference in the number of Endoscopic treatment for EST
bleeding between the DOAC group and No-drug group?
Could you evaluate the treatments for EST bleeding in the two groups
separately.
Comment 7:
Page 9, line 208-209:
Page 10, line 216-217:
There were 8 (33.3%) and 4 (22.2%) patients who had a combination of
antiplatelet drugs and DOAC in the <2-day group and ≥2-day group, respectively
(Table 5).
Could you add the detail of this point (ex, drug type, cessation period, and
resumption time, etc).
Comment 8:
Table 5
JGES guideline 2017 suggests that DOAC can be cessation on the day of
treatment when performing high-risk of bleeding (EST).
Since the purpose of this study is to evaluate the JGES guidelines for
gastroenterological endoscopy in patients receiving DOAC, how about dividing
the DOAC cessation period into two groups, <1-day group and ≥1-1day group.
Comment 9:
Page 11, line 246-248:
The authors considered that the low platelet count was caused by infection. Is
there any evidence to support that finding? (ex, rate and severity of cholangitis).
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?
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: 
Direct oral anticoagulants increase bleeding risk after endoscopic
sphincterotomy: A retrospective study
Version: 
1 
Date: 
19 May 2021
Reviewer's report:
The authors explored the risk factors for bleeding after EST in patients on
DOAC and evaluated the Japan Gastroenterological Endoscopy Society (JGES)
guidelines in patients undergoing antithrombotic treatment.
They presents DOAC treatment, low platelet count, and old age were significant
predictors of EST bleeding and proved the validity of JGES guidelines.
This is a well written, interesting paper, and useful contributing to clinical
practice.
However, I would like to suggest some issues with several comments and
criticisms as follows;
Comment 1:
All DOACs are affected by renal function.
Could you add the details to Table.1 and Table.5 regarding the presence of renal
dysfunction and the GFR value?
Comment 2:
Page 5, line 100:
In this study, DOAC was typically discontinued for <2 days based on the JGES
guidelines. 
On the other hand, when did the authors restart DOAL after EST or EPLBD?
The authors needs to clarify this point.
Comment 3:
Page 7, line 160-161:
This study also included patients who performed EPLBD as a papillary
procedure.
The authors should describe the detail of EPLBD procedure in the Method
session.
Comment 4:
There were 12 patients (28.6%) adapted Heparin replacement in No-drug group
(Table 2).
These patients should be included in DOAC group.
Moreover, for the 12 patients who indicated Heparin replacement, the APTT
value before EST should be described.
Comment 5:
Page 8, line 184:
Please revise 20.0% (2/15) to 20.0% (3/15).
Comment 6:
Figure 2
The authors showed overall treatment for EST bleeding.
Were there significant difference in the number of Endoscopic treatment for EST
bleeding between the DOAC group and No-drug group?
Could you evaluate the treatments for EST bleeding in the two groups
separately.
Comment 7:
Page 9, line 208-209:
Page 10, line 216-217:
There were 8 (33.3%) and 4 (22.2%) patients who had a combination of
antiplatelet drugs and DOAC in the <2-day group and ≥2-day group, respectively
(Table 5).
Could you add the detail of this point (ex, drug type, cessation period, and
resumption time, etc).
Comment 8:
Table 5
JGES guideline 2017 suggests that DOAC can be cessation on the day of
treatment when performing high-risk of bleeding (EST).
Since the purpose of this study is to evaluate the JGES guidelines for
gastroenterological endoscopy in patients receiving DOAC, how about dividing
the DOAC cessation period into two groups, <1-day group and ≥1-1day group.
Comment 9:
Page 11, line 246-248:
The authors considered that the low platelet count was caused by infection. Is
there any evidence to support that finding? (ex, rate and severity of cholangitis).
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?
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