Reviewer ’s report  
 
Title: The Effect of Prophylactic Hemoclips on the Risk of Delayed Post -Endoscopic Mucosal  
Resection Bleed for Upper and Lower Gastrointestinal Lesions: A Retrospective Cohort Study  
 
Version: 0 Date: 19 Se p 2019  
 
Reviewer: A Turan  
 
Reviewer's report:  
 
Dear authors,  
 
 
I read your paper titled 'The effect of prophylactic hemoclips on the risk of delayed post -
endoscopic mucosal resection bleed for upper and lower gastrointestinal lesions: a retrospective 
cohort study' with great interest. In addition to RCT's on prophylac tic clipping in high -risk 
groups, I think it is important to analyse and evaluate the current/past clipping practices and learn 
from that. In doing this, you really considered the strengths and drawbacks of your data in your 
statistical approach, and I com plement you on the thorough description of the performed 
analyses.  
 
Nevertheless, after reading your work, I have some questions and recommendations:  
 
 
Methods  
 
1. You have included patients that had an EMR between January 2012 and December 2015. Why 
did you  choose this period, rather than include more recent years as well?  
 
 
2. What was the definition for prophylactic clipping that you used? Was complete closure always 
attempted, or was the placement of 1 clip enough to include the patient in the Clip -group?  
 
 
3. You used a definition for DB determined by symptoms, Hb drop &gt; 1g/dL and/or blood 
transfusions required. Most recent studies use a different definition for significant DB: rectal 
bleeding within 30 days post -EMR requiring hospitalization, a blood tran sfusion, a colonoscopy, 
surgery or any other invasive treatment. In order to better compare your outcomes with other 
papers, I would suggest to you to add a descriptive table with details of de delayed bleeding 
cases, including presentation, treatment nece ssary, duration of hospitalization etc.  
 
 
 
 
 
Results  
 
4. As you described in the paper, your overall DB rate (2.7%) is quite low in comparison to the 
literature. Although similar rates have been reported in mostly Asian studies, most Western 
cohorts report a hi gher DB rate. Do you have any explanation for this in your cohort? Could it 
have something to do with the inclusion of different lesion types?  
 
5. You were able to include approximately the same amount of patient in the clip - and the 
control -group. This mea ns that around half of the patients in your cohort were clipped. Can you 
explain this high number of clipped cases?  
 
6. I would like to have some extra information on the lesions that bled. Were these all adenomas 
in the colon (except for 1 DB in the upper GI tract)? If so, it may be very interesting to conduct a 
subgroup analyses with only the x out of 476 polyps that were located in the colon.  
 
7. You analysed the effect of polyp location on DB and here you chose to dichotomize the 
variable in upper and low er GI. Although I realize that your Power for additional subgroup 
analyses is limited, I think it would be very interesting to also distinguish between lesions in the 
proximal vs distal colon. Previous studies have determined that lesions in the rightsided  colon 
have an increased risk of DB. If there is an effect of clipping in high -risk lesions (rightsided, 
large etc.), this cohort may not be appropriate to find it because it is so heterogeneous.  
 
8. Are your clip - and controlgroup comparable? I would be in terested to see table 1 and 2 
combined. It will give extra insight in the comparability of the two groups if we know which 
lesions exactly were clipped and where in the GI tract they were located.  
 
9. Although I think it is good that you consider cost -effec tiveness, I would advise you to be 
careful with the interpretation. As the number of clips was unclear in many cases, the DB -risk in 
both groups - and therefore the comparability - is not completely clear, and the DB -rate was very 
low, the cost analysis is  a rough estimation. It is also not placed in the context of the overall 
treatment costs.  
 
 
Discussion  
 
10. In line 411 in the first sentence of the discussion you describe an increase in PC for the 
prevention of DB. I would advise you to find a more recent reference for this statement.  
 
11. I strongly recommend to add three recent papers to your discussion. Earlier this year, Pohl et 
al., Albeniz et al. and Feagins et al. all published randomized controlled trials on prophylactic 
clipping. I advise you to pla ce your results in context to their findings as well.  
 
 
 
 
 
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 nece ssary 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 not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess a ny 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.  
 
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 competing interests, considering the following questions:  
 
1. Have you in t he 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 organisatio n 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, fe es, 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  
 
I agree to the open peer review policy of the jou rnal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload 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 included 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: The Effect of Prophylactic Hemoclips on the Risk of Delayed Post -Endoscopic Mucosal  
Resection Bleed for Upper and Lower Gastrointestinal Lesions: A Retrospective Cohort Study  
 
Version: 0 Date: 19 Se p 2019  
 
Reviewer: A Turan  
 
Reviewer's report:  
 
Dear authors,  
 
 
I read your paper titled 'The effect of prophylactic hemoclips on the risk of delayed post -
endoscopic mucosal resection bleed for upper and lower gastrointestinal lesions: a retrospective 
cohort study' with great interest. In addition to RCT's on prophylac tic clipping in high -risk 
groups, I think it is important to analyse and evaluate the current/past clipping practices and learn 
from that. In doing this, you really considered the strengths and drawbacks of your data in your 
statistical approach, and I com plement you on the thorough description of the performed 
analyses.  
 
Nevertheless, after reading your work, I have some questions and recommendations:  
 
 
Methods  
 
1. You have included patients that had an EMR between January 2012 and December 2015. Why 
did you  choose this period, rather than include more recent years as well?  
 
 
2. What was the definition for prophylactic clipping that you used? Was complete closure always 
attempted, or was the placement of 1 clip enough to include the patient in the Clip -group?  
 
 
3. You used a definition for DB determined by symptoms, Hb drop &gt; 1g/dL and/or blood 
transfusions required. Most recent studies use a different definition for significant DB: rectal 
bleeding within 30 days post -EMR requiring hospitalization, a blood tran sfusion, a colonoscopy, 
surgery or any other invasive treatment. In order to better compare your outcomes with other 
papers, I would suggest to you to add a descriptive table with details of de delayed bleeding 
cases, including presentation, treatment nece ssary, duration of hospitalization etc.  
 
 
 
 
 
Results  
 
4. As you described in the paper, your overall DB rate (2.7%) is quite low in comparison to the 
literature. Although similar rates have been reported in mostly Asian studies, most Western 
cohorts report a hi gher DB rate. Do you have any explanation for this in your cohort? Could it 
have something to do with the inclusion of different lesion types?  
 
5. You were able to include approximately the same amount of patient in the clip - and the 
control -group. This mea ns that around half of the patients in your cohort were clipped. Can you 
explain this high number of clipped cases?  
 
6. I would like to have some extra information on the lesions that bled. Were these all adenomas 
in the colon (except for 1 DB in the upper GI tract)? If so, it may be very interesting to conduct a 
subgroup analyses with only the x out of 476 polyps that were located in the colon.  
 
7. You analysed the effect of polyp location on DB and here you chose to dichotomize the 
variable in upper and low er GI. Although I realize that your Power for additional subgroup 
analyses is limited, I think it would be very interesting to also distinguish between lesions in the 
proximal vs distal colon. Previous studies have determined that lesions in the rightsided  colon 
have an increased risk of DB. If there is an effect of clipping in high -risk lesions (rightsided, 
large etc.), this cohort may not be appropriate to find it because it is so heterogeneous.  
 
8. Are your clip - and controlgroup comparable? I would be in terested to see table 1 and 2 
combined. It will give extra insight in the comparability of the two groups if we know which 
lesions exactly were clipped and where in the GI tract they were located.  
 
9. Although I think it is good that you consider cost -effec tiveness, I would advise you to be 
careful with the interpretation. As the number of clips was unclear in many cases, the DB -risk in 
both groups - and therefore the comparability - is not completely clear, and the DB -rate was very 
low, the cost analysis is  a rough estimation. It is also not placed in the context of the overall 
treatment costs.  
 
 
Discussion  
 
10. In line 411 in the first sentence of the discussion you describe an increase in PC for the 
prevention of DB. I would advise you to find a more recent reference for this statement.  
 
11. I strongly recommend to add three recent papers to your discussion. Earlier this year, Pohl et 
al., Albeniz et al. and Feagins et al. all published randomized controlled trials on prophylactic 
clipping. I advise you to pla ce your results in context to their findings as well.  
 
 
 
 
 
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 nece ssary 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 not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess a ny 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.  
 
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 competing interests, considering the following questions:  
 
1. Have you in t he 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 organisatio n 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, fe es, 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  
 
I agree to the open peer review policy of the jou rnal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload 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 included 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: The Effect of Prophylactic Hemoclips on the Risk of Delayed Post -Endoscopic Mucosal  
Resection Bleed for Upper and Lower Gastrointestinal Lesions: A Retrospective Cohort Study  
 
Version: 0 Date: 19 Se p 2019  
 
Reviewer: A Turan  
 
Reviewer's report:  
 
Dear authors,  
 
 
I read your paper titled 'The effect of prophylactic hemoclips on the risk of delayed post -
endoscopic mucosal resection bleed for upper and lower gastrointestinal lesions: a retrospective 
cohort study' with great interest. In addition to RCT's on prophylac tic clipping in high -risk 
groups, I think it is important to analyse and evaluate the current/past clipping practices and learn 
from that. In doing this, you really considered the strengths and drawbacks of your data in your 
statistical approach, and I com plement you on the thorough description of the performed 
analyses.  
 
Nevertheless, after reading your work, I have some questions and recommendations:  
 
 
Methods  
 
1. You have included patients that had an EMR between January 2012 and December 2015. Why 
did you  choose this period, rather than include more recent years as well?  
 
 
2. What was the definition for prophylactic clipping that you used? Was complete closure always 
attempted, or was the placement of 1 clip enough to include the patient in the Clip -group?  
 
 
3. You used a definition for DB determined by symptoms, Hb drop &gt; 1g/dL and/or blood 
transfusions required. Most recent studies use a different definition for significant DB: rectal 
bleeding within 30 days post -EMR requiring hospitalization, a blood tran sfusion, a colonoscopy, 
surgery or any other invasive treatment. In order to better compare your outcomes with other 
papers, I would suggest to you to add a descriptive table with details of de delayed bleeding 
cases, including presentation, treatment nece ssary, duration of hospitalization etc.  
 
 
 
 
 
Results  
 
4. As you described in the paper, your overall DB rate (2.7%) is quite low in comparison to the 
literature. Although similar rates have been reported in mostly Asian studies, most Western 
cohorts report a hi gher DB rate. Do you have any explanation for this in your cohort? Could it 
have something to do with the inclusion of different lesion types?  
 
5. You were able to include approximately the same amount of patient in the clip - and the 
control -group. This mea ns that around half of the patients in your cohort were clipped. Can you 
explain this high number of clipped cases?  
 
6. I would like to have some extra information on the lesions that bled. Were these all adenomas 
in the colon (except for 1 DB in the upper GI tract)? If so, it may be very interesting to conduct a 
subgroup analyses with only the x out of 476 polyps that were located in the colon.  
 
7. You analysed the effect of polyp location on DB and here you chose to dichotomize the 
variable in upper and low er GI. Although I realize that your Power for additional subgroup 
analyses is limited, I think it would be very interesting to also distinguish between lesions in the 
proximal vs distal colon. Previous studies have determined that lesions in the rightsided  colon 
have an increased risk of DB. If there is an effect of clipping in high -risk lesions (rightsided, 
large etc.), this cohort may not be appropriate to find it because it is so heterogeneous.  
 
8. Are your clip - and controlgroup comparable? I would be in terested to see table 1 and 2 
combined. It will give extra insight in the comparability of the two groups if we know which 
lesions exactly were clipped and where in the GI tract they were located.  
 
9. Although I think it is good that you consider cost -effec tiveness, I would advise you to be 
careful with the interpretation. As the number of clips was unclear in many cases, the DB -risk in 
both groups - and therefore the comparability - is not completely clear, and the DB -rate was very 
low, the cost analysis is  a rough estimation. It is also not placed in the context of the overall 
treatment costs.  
 
 
Discussion  
 
10. In line 411 in the first sentence of the discussion you describe an increase in PC for the 
prevention of DB. I would advise you to find a more recent reference for this statement.  
 
11. I strongly recommend to add three recent papers to your discussion. Earlier this year, Pohl et 
al., Albeniz et al. and Feagins et al. all published randomized controlled trials on prophylactic 
clipping. I advise you to pla ce your results in context to their findings as well.  
 
 
 
 
 
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 nece ssary 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 not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess a ny 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.  
 
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 competing interests, considering the following questions:  
 
1. Have you in t he 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 organisatio n 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, fe es, 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  
 
I agree to the open peer review policy of the jou rnal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload 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 included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant