Reviewer ’s report  
 
Title: The characteristics of nivolumab -induced colitis: an evaluation of three cases and a 
literature review  
 
Version: 1 Date: 18 Jun 2018  
 
Reviewer: Thorsten Brechmann  
 
Reviewer's report:  
 
Topic and design:  
The manusc ript describes three cases of nivolumab -induced colitis and focuses on the 
endoscopic and histological features and treatment options. Due to the increasing use of PD1 - 
and PD -L1-inhibitors these cases are of special interest and worth to publish. However,  the 
article exhibits some important limitations concerning the language and the content.  
 
Case presentation:  
Description of Case 2 does not explain the strategy of nivolumab therapy (cessation? 
continuation?). What kind and dose of corticosteroids was used? Did the symptomatology 
improve „after" or „under" therapy?  
Description of Case 3 does not specify steroid t herapy either.  
Probably it would be handsome to present the cases together and highlight the differences instead 
of repeating similar presentation patterns three times.  
 
Discussion:  
In my point of view the endoscopic image simulates in certain degree (par ticularly image B in 
Figure 1), but does not resemble UC convincingly. Therefore, it would be nice to compare the 
images with UC images meticulously. The same procedure would be appropriate for the 
histology.  
Given the similarity: what is the evidence rega rding PD -1 pathway in UC? Is there an 
immunological link? How do aminosalicylates and steroids act in this situation? What is the role 
of cessation of nivolumab?  
 
Language:  
The article is written in American English; as far as I remember BMC Gastroenterol ogy requires 
British English. Additionally and more importantly, the English sounds inconvenient and needs 
improvement.  
 
Abstract:  
„In this report, we experienced 3 cases of colitis induced by a PD -1 inhibitor nivolumab." - 
better: „In this report, we descr ibe three cases of colitis induced by the PD -1 inhibitor 
nivolumab."  
„Treatment was also applied to the treatment of UC, and a good course was obtained." - better: 
„Treatment was adopted from UC therapy and resulted in beneficial outcome."  
„All three cases  were diagnosed with lung cancer and were treated with nivolumab. Case 1 
reported frequent diarrhea after 15 weeks. Case 2 reported frequent bleeding and diarrhea after 7 
weeks. Case 3 reported mild diarrhea after 3 weeks, which worsened after 43 weeks." - better: 
„Three patients with lung cancer treated with nivolumab presented with diarrhoea with (case 2) 
and without hematochezia (cases 1 and 3), respectively."  
„… which revealed endoscopic findings of UC." This formulation is misleading because this 
particular colitis is drug -induced, not UC. I propose: „… which revealed endoscopic features 
similar to UC"  
 
Discussion:  
Please avoid repetitions like „Similarly, we observed similar clinical findings in the cases 
described herein"  
There are a lot of further exa mples which I do not want to list in detail. Profound revision is 
needed.  
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 t o the authors.  
 
No 
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 any 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.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscrip t: 
 
Not suitable for publication unless extensively edited  
 
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 recei ved 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 do not have any competing interest to declare.  
 
I agree to the open pe er 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 upload will be posted on the website along with the auth ors' 
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 includ ed 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 characteristics of nivolumab -induced colitis: an evaluation of three cases and a 
literature review  
 
Version: 1 Date: 18 Jun 2018  
 
Reviewer: Thorsten Brechmann  
 
Reviewer's report:  
 
Topic and design:  
The manusc ript describes three cases of nivolumab -induced colitis and focuses on the 
endoscopic and histological features and treatment options. Due to the increasing use of PD1 - 
and PD -L1-inhibitors these cases are of special interest and worth to publish. However,  the 
article exhibits some important limitations concerning the language and the content.  
 
Case presentation:  
Description of Case 2 does not explain the strategy of nivolumab therapy (cessation? 
continuation?). What kind and dose of corticosteroids was used? Did the symptomatology 
improve „after" or „under" therapy?  
Description of Case 3 does not specify steroid t herapy either.  
Probably it would be handsome to present the cases together and highlight the differences instead 
of repeating similar presentation patterns three times.  
 
Discussion:  
In my point of view the endoscopic image simulates in certain degree (par ticularly image B in 
Figure 1), but does not resemble UC convincingly. Therefore, it would be nice to compare the 
images with UC images meticulously. The same procedure would be appropriate for the 
histology.  
Given the similarity: what is the evidence rega rding PD -1 pathway in UC? Is there an 
immunological link? How do aminosalicylates and steroids act in this situation? What is the role 
of cessation of nivolumab?  
 
Language:  
The article is written in American English; as far as I remember BMC Gastroenterol ogy requires 
British English. Additionally and more importantly, the English sounds inconvenient and needs 
improvement.  
 
Abstract:  
„In this report, we experienced 3 cases of colitis induced by a PD -1 inhibitor nivolumab." - 
better: „In this report, we descr ibe three cases of colitis induced by the PD -1 inhibitor 
nivolumab."  
„Treatment was also applied to the treatment of UC, and a good course was obtained." - better: 
„Treatment was adopted from UC therapy and resulted in beneficial outcome."  
„All three cases  were diagnosed with lung cancer and were treated with nivolumab. Case 1 
reported frequent diarrhea after 15 weeks. Case 2 reported frequent bleeding and diarrhea after 7 
weeks. Case 3 reported mild diarrhea after 3 weeks, which worsened after 43 weeks." - better: 
„Three patients with lung cancer treated with nivolumab presented with diarrhoea with (case 2) 
and without hematochezia (cases 1 and 3), respectively."  
„… which revealed endoscopic findings of UC." This formulation is misleading because this 
particular colitis is drug -induced, not UC. I propose: „… which revealed endoscopic features 
similar to UC"  
 
Discussion:  
Please avoid repetitions like „Similarly, we observed similar clinical findings in the cases 
described herein"  
There are a lot of further exa mples which I do not want to list in detail. Profound revision is 
needed.  
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 t o the authors.  
 
No 
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 any 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.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscrip t: 
 
Not suitable for publication unless extensively edited  
 
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 recei ved 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 do not have any competing interest to declare.  
 
I agree to the open pe er 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 upload will be posted on the website along with the auth ors' 
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 includ ed 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 characteristics of nivolumab -induced colitis: an evaluation of three cases and a 
literature review  
 
Version: 1 Date: 18 Jun 2018  
 
Reviewer: Thorsten Brechmann  
 
Reviewer's report:  
 
Topic and design:  
The manusc ript describes three cases of nivolumab -induced colitis and focuses on the 
endoscopic and histological features and treatment options. Due to the increasing use of PD1 - 
and PD -L1-inhibitors these cases are of special interest and worth to publish. However,  the 
article exhibits some important limitations concerning the language and the content.  
 
Case presentation:  
Description of Case 2 does not explain the strategy of nivolumab therapy (cessation? 
continuation?). What kind and dose of corticosteroids was used? Did the symptomatology 
improve „after" or „under" therapy?  
Description of Case 3 does not specify steroid t herapy either.  
Probably it would be handsome to present the cases together and highlight the differences instead 
of repeating similar presentation patterns three times.  
 
Discussion:  
In my point of view the endoscopic image simulates in certain degree (par ticularly image B in 
Figure 1), but does not resemble UC convincingly. Therefore, it would be nice to compare the 
images with UC images meticulously. The same procedure would be appropriate for the 
histology.  
Given the similarity: what is the evidence rega rding PD -1 pathway in UC? Is there an 
immunological link? How do aminosalicylates and steroids act in this situation? What is the role 
of cessation of nivolumab?  
 
Language:  
The article is written in American English; as far as I remember BMC Gastroenterol ogy requires 
British English. Additionally and more importantly, the English sounds inconvenient and needs 
improvement.  
 
Abstract:  
„In this report, we experienced 3 cases of colitis induced by a PD -1 inhibitor nivolumab." - 
better: „In this report, we descr ibe three cases of colitis induced by the PD -1 inhibitor 
nivolumab."  
„Treatment was also applied to the treatment of UC, and a good course was obtained." - better: 
„Treatment was adopted from UC therapy and resulted in beneficial outcome."  
„All three cases  were diagnosed with lung cancer and were treated with nivolumab. Case 1 
reported frequent diarrhea after 15 weeks. Case 2 reported frequent bleeding and diarrhea after 7 
weeks. Case 3 reported mild diarrhea after 3 weeks, which worsened after 43 weeks." - better: 
„Three patients with lung cancer treated with nivolumab presented with diarrhoea with (case 2) 
and without hematochezia (cases 1 and 3), respectively."  
„… which revealed endoscopic findings of UC." This formulation is misleading because this 
particular colitis is drug -induced, not UC. I propose: „… which revealed endoscopic features 
similar to UC"  
 
Discussion:  
Please avoid repetitions like „Similarly, we observed similar clinical findings in the cases 
described herein"  
There are a lot of further exa mples which I do not want to list in detail. Profound revision is 
needed.  
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 t o the authors.  
 
No 
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 any 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.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscrip t: 
 
Not suitable for publication unless extensively edited  
 
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 recei ved 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 do not have any competing interest to declare.  
 
I agree to the open pe er 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 upload will be posted on the website along with the auth ors' 
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 includ ed as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant