Reviewer ’s report  
 
Title: Bile pigment in small -bowel water content may reflect bowel h abits: a retrospective 
analysis of a capsule endoscopy imaging series  
 
Version: 0 Date: 08 Feb 2020  
 
Reviewer:  Martin  Keuchel  
 
Reviewer's report:  
 
This study has an interesting approach looking at bile pigments during small bowel video capsule 
endoscopy in groups of patients with normal bowel habits, diarrhea, and constipation.  
Video capsule endoscopy offers the unique opportunity to study small bowe l content without 
invasive procedures during a physiologic endoscopy.  
However, this study has some relevant limitations.  
The test system has not been evaluated neither in vitro nor in vivo concerning its capability to 
measure bile pigment. A correlation b etween bile pigment concentration, small bowel water 
content and measured light values is yet to be demonstrated.  
Concentration of bile pigments should be influenced by the amount of water intake. The 
differentiation between small bowel water content and bile pigment content (suggested as a 
surrogate marker for bile acids) is not sharp. The absolute amount of bile pigments shifted into 
the small bowel during a certain   time period influences the concentration of pigments in small 
bowel water (presumably m easured as reduced lightness). Nevertheless, the amount of ingested 
water should also influence the concentration. Patients were allowed to drink 2 hours after 
swallowing the capsule. Assuming a gastric transit of approximately 30 mins and an average 
small  bowel transit of 4 hours, the fluid intake during the procedure may significantly have 
influenced the small bowel water content. This should be recorded, and the time correlated with 
transit times. A retrospective study on a small number of patients who w ere not recruited for this 
study aim cannot produce enough evidence.  
There are only three points for measurement chosen in each patient out of multiple thousands. 
Knowledge of variation in results in each segment in a patient is important to better charact erize 
the reliability. Therefore, multiple points for ileal segment need to be analyzed  
 
 
In the areas of interest optics are focusing small bowel liquid and the underlying mucosa. The 
distance between mucosa and capsule is supposed to influence the brightne ss additionally. These 
differences in brightness are used in software tools to measure distance between the capsule and 
a lesion to enable correction of size estimation. The other way round, brightness may not only 
measure pigments or the degree of their d ilution but also the distance between capsule and 
mucosa behind the analyzed liquid volume.  
The effect of FICE 1 on the influence of bile pigments on capsule images should be 
demonstrated in vitro.  
Spectral color selection modes (as FICE) are not recomme nded for better detection of lesions in 
capsule endoscopy as suggested by the authors because they produce more false positive results 
causing decreased specificity.  
The authors present an innovative approach. However, the evidence needs more details as m any 
methods are yet too speculative.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are requir ed in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
 
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 speci fy 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 t he past five years received reimbursements, fees, funding, or salary from an  
1. 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 organisat ion 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 reimbursemen ts, 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 t his 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.  
 
Lecture fees and travel cost reimbursement from Medtronic and Olympus  
 
I agree to the op en 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 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 i ncluded 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: Bile pigment in small -bowel water content may reflect bowel h abits: a retrospective 
analysis of a capsule endoscopy imaging series  
 
Version: 0 Date: 08 Feb 2020  
 
Reviewer:  Martin  Keuchel  
 
Reviewer's report:  
 
This study has an interesting approach looking at bile pigments during small bowel video capsule 
endoscopy in groups of patients with normal bowel habits, diarrhea, and constipation.  
Video capsule endoscopy offers the unique opportunity to study small bowe l content without 
invasive procedures during a physiologic endoscopy.  
However, this study has some relevant limitations.  
The test system has not been evaluated neither in vitro nor in vivo concerning its capability to 
measure bile pigment. A correlation b etween bile pigment concentration, small bowel water 
content and measured light values is yet to be demonstrated.  
Concentration of bile pigments should be influenced by the amount of water intake. The 
differentiation between small bowel water content and bile pigment content (suggested as a 
surrogate marker for bile acids) is not sharp. The absolute amount of bile pigments shifted into 
the small bowel during a certain   time period influences the concentration of pigments in small 
bowel water (presumably m easured as reduced lightness). Nevertheless, the amount of ingested 
water should also influence the concentration. Patients were allowed to drink 2 hours after 
swallowing the capsule. Assuming a gastric transit of approximately 30 mins and an average 
small  bowel transit of 4 hours, the fluid intake during the procedure may significantly have 
influenced the small bowel water content. This should be recorded, and the time correlated with 
transit times. A retrospective study on a small number of patients who w ere not recruited for this 
study aim cannot produce enough evidence.  
There are only three points for measurement chosen in each patient out of multiple thousands. 
Knowledge of variation in results in each segment in a patient is important to better charact erize 
the reliability. Therefore, multiple points for ileal segment need to be analyzed  
 
 
In the areas of interest optics are focusing small bowel liquid and the underlying mucosa. The 
distance between mucosa and capsule is supposed to influence the brightne ss additionally. These 
differences in brightness are used in software tools to measure distance between the capsule and 
a lesion to enable correction of size estimation. The other way round, brightness may not only 
measure pigments or the degree of their d ilution but also the distance between capsule and 
mucosa behind the analyzed liquid volume.  
The effect of FICE 1 on the influence of bile pigments on capsule images should be 
demonstrated in vitro.  
Spectral color selection modes (as FICE) are not recomme nded for better detection of lesions in 
capsule endoscopy as suggested by the authors because they produce more false positive results 
causing decreased specificity.  
The authors present an innovative approach. However, the evidence needs more details as m any 
methods are yet too speculative.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are requir ed in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
 
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 speci fy 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 t he past five years received reimbursements, fees, funding, or salary from an  
1. 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 organisat ion 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 reimbursemen ts, 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 t his 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.  
 
Lecture fees and travel cost reimbursement from Medtronic and Olympus  
 
I agree to the op en 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 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 i ncluded 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: Bile pigment in small -bowel water content may reflect bowel h abits: a retrospective 
analysis of a capsule endoscopy imaging series  
 
Version: 0 Date: 08 Feb 2020  
 
Reviewer:  Martin  Keuchel  
 
Reviewer's report:  
 
This study has an interesting approach looking at bile pigments during small bowel video capsule 
endoscopy in groups of patients with normal bowel habits, diarrhea, and constipation.  
Video capsule endoscopy offers the unique opportunity to study small bowe l content without 
invasive procedures during a physiologic endoscopy.  
However, this study has some relevant limitations.  
The test system has not been evaluated neither in vitro nor in vivo concerning its capability to 
measure bile pigment. A correlation b etween bile pigment concentration, small bowel water 
content and measured light values is yet to be demonstrated.  
Concentration of bile pigments should be influenced by the amount of water intake. The 
differentiation between small bowel water content and bile pigment content (suggested as a 
surrogate marker for bile acids) is not sharp. The absolute amount of bile pigments shifted into 
the small bowel during a certain   time period influences the concentration of pigments in small 
bowel water (presumably m easured as reduced lightness). Nevertheless, the amount of ingested 
water should also influence the concentration. Patients were allowed to drink 2 hours after 
swallowing the capsule. Assuming a gastric transit of approximately 30 mins and an average 
small  bowel transit of 4 hours, the fluid intake during the procedure may significantly have 
influenced the small bowel water content. This should be recorded, and the time correlated with 
transit times. A retrospective study on a small number of patients who w ere not recruited for this 
study aim cannot produce enough evidence.  
There are only three points for measurement chosen in each patient out of multiple thousands. 
Knowledge of variation in results in each segment in a patient is important to better charact erize 
the reliability. Therefore, multiple points for ileal segment need to be analyzed  
 
 
In the areas of interest optics are focusing small bowel liquid and the underlying mucosa. The 
distance between mucosa and capsule is supposed to influence the brightne ss additionally. These 
differences in brightness are used in software tools to measure distance between the capsule and 
a lesion to enable correction of size estimation. The other way round, brightness may not only 
measure pigments or the degree of their d ilution but also the distance between capsule and 
mucosa behind the analyzed liquid volume.  
The effect of FICE 1 on the influence of bile pigments on capsule images should be 
demonstrated in vitro.  
Spectral color selection modes (as FICE) are not recomme nded for better detection of lesions in 
capsule endoscopy as suggested by the authors because they produce more false positive results 
causing decreased specificity.  
The authors present an innovative approach. However, the evidence needs more details as m any 
methods are yet too speculative.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are requir ed in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
 
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 speci fy 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 t he past five years received reimbursements, fees, funding, or salary from an  
1. 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 organisat ion 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 reimbursemen ts, 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 t his 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.  
 
Lecture fees and travel cost reimbursement from Medtronic and Olympus  
 
I agree to the op en 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 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 i ncluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
 
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