Reviewer’s report  
 
Title: Is endoscopic treatment beneficial in patients with clini cally suspicious of common bile 
duct stones but no obvious filling defects during the ERCP examination?  
 
Version: 0 Date: 14 Jun 2016  
 
Reviewer: Henning Gerke  
 
Reviewer's report:  
 
The author's investigate the false negative rate of endoscopic cholangiography for common bile 
duct stones.  The study design is retrospective and they include patients with negative 
cholangiograms. They devide patients into high an d intermediate risk categories based on 
clinical signs and symptoms and find that those in the high -risk category are likely to have CBD 
stones and benefit from stone extractions. The study emphasizes the low negative predictive 
value of ERC in patient wit h clinical suspicion for cholelithiasis. This is of clinical importance, 
and published data on this aspect are still limited. However, the study has several methological 
limitations:  
 
 
 
1. Retrospective design  
 
 
2. Patients with s/p cholecystectomy and those wi thout symptomatic gallbladder stones are 
included and the indications for ERC are not presented.  
 
 
3. Patients with positive bile microscopy for microlithiasis are defined as positive for 
choledocholithasis although bile microscopy is not consistently perfor med.  
 
 
 
Point by point:  
 
1. Abstract: Spell out acronyms prior to their first use: CBDS, EST/EPBD  
 
 
2. Regarding the criterium "mildly elevated Bilirubin": Did the authors exclude patients 
with indirect hyperblirubinemia? Please clarify/discuss.  
 
 
3. Results: "Therefore, endoscopic treatment (EST or EPBD) is beneficial and safe for 
patients with high probability of CBDS". This sentence belongs into the discussion, not 
results.  
4. The authors reference a 2010 ASGE guidelines which refers to patients with symptomatic 
cholelithiasis. Thus, the ASGE risk categories only apply to patients with cholelithiasis. 
The authors included patients with s/p cholecystectomy (11%) in their study and only 
77% had gallbladder stones. It may be problematic to apply the ASGE risk criteria.  
Where there for example other clinical signs and symptoms to warrant ERCP in those 
with intermediate risk whose only risk factors were advanced age? Please 
explain/clarify/discuss.  
 
Microscopic bile analysis was not consistently done in  this study and patients with only 
microscopic evidence of gall stones/sludge should therefore not be included in the group 
of patients with a final diagnosis of choledocholithaisis.  
 
 
 
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.  
 
Yes 
 
Are the conclusions drawn adequa tely supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommende d, 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:  
 
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 wa y 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 t he 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 cont ent 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 inte rests.  
 
I agree to the open peer review policy of the journal. 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 uploa d will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Acc ess 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: Is endoscopic treatment beneficial in patients with clini cally suspicious of common bile 
duct stones but no obvious filling defects during the ERCP examination?  
 
Version: 0 Date: 14 Jun 2016  
 
Reviewer: Henning Gerke  
 
Reviewer's report:  
 
The author's investigate the false negative rate of endoscopic cholangiography for common bile 
duct stones.  The study design is retrospective and they include patients with negative 
cholangiograms. They devide patients into high an d intermediate risk categories based on 
clinical signs and symptoms and find that those in the high -risk category are likely to have CBD 
stones and benefit from stone extractions. The study emphasizes the low negative predictive 
value of ERC in patient wit h clinical suspicion for cholelithiasis. This is of clinical importance, 
and published data on this aspect are still limited. However, the study has several methological 
limitations:  
 
 
 
1. Retrospective design  
 
 
2. Patients with s/p cholecystectomy and those wi thout symptomatic gallbladder stones are 
included and the indications for ERC are not presented.  
 
 
3. Patients with positive bile microscopy for microlithiasis are defined as positive for 
choledocholithasis although bile microscopy is not consistently perfor med.  
 
 
 
Point by point:  
 
1. Abstract: Spell out acronyms prior to their first use: CBDS, EST/EPBD  
 
 
2. Regarding the criterium "mildly elevated Bilirubin": Did the authors exclude patients 
with indirect hyperblirubinemia? Please clarify/discuss.  
 
 
3. Results: "Therefore, endoscopic treatment (EST or EPBD) is beneficial and safe for 
patients with high probability of CBDS". This sentence belongs into the discussion, not 
results.  
4. The authors reference a 2010 ASGE guidelines which refers to patients with symptomatic 
cholelithiasis. Thus, the ASGE risk categories only apply to patients with cholelithiasis. 
The authors included patients with s/p cholecystectomy (11%) in their study and only 
77% had gallbladder stones. It may be problematic to apply the ASGE risk criteria.  
Where there for example other clinical signs and symptoms to warrant ERCP in those 
with intermediate risk whose only risk factors were advanced age? Please 
explain/clarify/discuss.  
 
Microscopic bile analysis was not consistently done in  this study and patients with only 
microscopic evidence of gall stones/sludge should therefore not be included in the group 
of patients with a final diagnosis of choledocholithaisis.  
 
 
 
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.  
 
Yes 
 
Are the conclusions drawn adequa tely supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommende d, 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:  
 
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 wa y 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 t he 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 cont ent 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 inte rests.  
 
I agree to the open peer review policy of the journal. 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 uploa d will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Acc ess 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: Is endoscopic treatment beneficial in patients with clini cally suspicious of common bile 
duct stones but no obvious filling defects during the ERCP examination?  
 
Version: 0 Date: 14 Jun 2016  
 
Reviewer: Henning Gerke  
 
Reviewer's report:  
 
The author's investigate the false negative rate of endoscopic cholangiography for common bile 
duct stones.  The study design is retrospective and they include patients with negative 
cholangiograms. They devide patients into high an d intermediate risk categories based on 
clinical signs and symptoms and find that those in the high -risk category are likely to have CBD 
stones and benefit from stone extractions. The study emphasizes the low negative predictive 
value of ERC in patient wit h clinical suspicion for cholelithiasis. This is of clinical importance, 
and published data on this aspect are still limited. However, the study has several methological 
limitations:  
 
 
 
1. Retrospective design  
 
 
2. Patients with s/p cholecystectomy and those wi thout symptomatic gallbladder stones are 
included and the indications for ERC are not presented.  
 
 
3. Patients with positive bile microscopy for microlithiasis are defined as positive for 
choledocholithasis although bile microscopy is not consistently perfor med.  
 
 
 
Point by point:  
 
1. Abstract: Spell out acronyms prior to their first use: CBDS, EST/EPBD  
 
 
2. Regarding the criterium "mildly elevated Bilirubin": Did the authors exclude patients 
with indirect hyperblirubinemia? Please clarify/discuss.  
 
 
3. Results: "Therefore, endoscopic treatment (EST or EPBD) is beneficial and safe for 
patients with high probability of CBDS". This sentence belongs into the discussion, not 
results.  
4. The authors reference a 2010 ASGE guidelines which refers to patients with symptomatic 
cholelithiasis. Thus, the ASGE risk categories only apply to patients with cholelithiasis. 
The authors included patients with s/p cholecystectomy (11%) in their study and only 
77% had gallbladder stones. It may be problematic to apply the ASGE risk criteria.  
Where there for example other clinical signs and symptoms to warrant ERCP in those 
with intermediate risk whose only risk factors were advanced age? Please 
explain/clarify/discuss.  
 
Microscopic bile analysis was not consistently done in  this study and patients with only 
microscopic evidence of gall stones/sludge should therefore not be included in the group 
of patients with a final diagnosis of choledocholithaisis.  
 
 
 
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.  
 
Yes 
 
Are the conclusions drawn adequa tely supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommende d, 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:  
 
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 wa y 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 t he 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 cont ent 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 inte rests.  
 
I agree to the open peer review policy of the journal. 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 uploa d will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Acc ess 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