Reviewer ’s report  
 
Title: BMC Gastroenterology A randomised double -blind placebo -controlled trial of probiotics 
in post -surgical colorectal cancer  
 
Version: 1 Date: 11 Jan 2019  
Reviewer: Adrian Cummins  
Reviewer's report:  
Please include all comments for the authors in this box rather than uploading your  report as an 
attachment. Please only upload as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be included in a text format.  
Please overwrite this text when adding your comments to t he authors.  
 
Abstract:  
Background, lines 1: Replace 'effects' with 'effect'.  
Methods (lines 1 -3): Slightly not relevant. How about "Fifty -two subjects with colorectal cancer 
were randomized at 4 weeks after surgery to receive …. "?  
Results: Replace 'most' with 'the majority' but give actual number or percentage. I would not give 
age of individual groups, as they were randomised and so should not a priori be significantly 
different. Line 3. 'none of the cases complained of …' how about replace with "No surgi cal 
infection occurred and no antibiotics were required".  
Line 6: 'were observed in CRC patients received probiotics' add "who received".  
Conclusion: I would state directly: 'We have shown that probiotics are safe to be consumed at 4 
weeks after surgery. a nd have reduce pro -inflammatory cytokines (except for IFN -gamma). I 
wonder in a future study you could investigate faecal markers of inflammation or assess rectal 
biopsy for repair and inflammation.  
 
Background The first paragraph is woffle. How about "Col orectal cancer is the second most 
common cancer in males and the third most common in females in most developed countries 
after discounting non -melanotic skin cancer."?  
Line 2: Replace 'was' with 'is'  
Line 24 Replace 'effects' with 'effect'  
 
Methods line 52: Replace "This study protocol has obtained approval" 'was approved'  
Line 53: Replace 'is also registered' with 'was registered'.  
 
What did the placebo treatment consist of? Was it matched for energy content or other 
components (eg calcium) that could co nceivably influence the nutritional plane,.  
How did you access compliance?  70% seems a little low for compliance, 80% would be better.  
 
Measuring the systemic immune status is a poor reflection of the mucosal immune status. It 
would have been better to as sess follow up colonic/rectal biopsy or faecal markers of 
inflammation (eg calprotectin).  
 
Results  
I would not repeat the same mean and SD and statistically analysis in both text and Figures.    
 
Table 1: You can't do statistics comparing initial parameters at randomisation. You know a priori 
that that these measures are not significantly different, as they have been randomized. The null 
hypothesis cannot be disputed.  OK, you can list the starting  measures, but not statistically 
analyse them. Only the outcomes can be assessed statistically.  
 
Discussion: Overall needs to be considerably shortened. Delete para 1 just repeating elements of 
Introduction. I would summarise the points to be discussed in para 1 eg ' Our study showed that 
probiotics commenced 4 weeks after surgery for colorectal cancer were safe, did not exacerbate 
diarrhoea, and reduced levels of systemic  production of pro -inflammatory cytokines" The 
description of previous studies has to o much description of previous study and not enough 
critical insight eg How many previous studies have examined cytokine production. Do you think 
that the extra energy intake and better nutrition could explain these results? Do you have weight, 
or plasma/s erum albumin at the conclusion of the trial? Discuss the placebo treatment.  
 
Number pages  
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 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 requ ire 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 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 fin ancial 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 detail s below.  
 
I declare that I have no competing interests  
 
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 
includ ing 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 t he journal  
Reviewer ’s report  
 
Title: BMC Gastroenterology A randomised double -blind placebo -controlled trial of probiotics 
in post -surgical colorectal cancer  
 
Version: 1 Date: 11 Jan 2019  
Reviewer: Adrian Cummins  
Reviewer's report:  
Please include all comments for the authors in this box rather than uploading your  report as an 
attachment. Please only upload as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be included in a text format.  
Please overwrite this text when adding your comments to t he authors.  
 
Abstract:  
Background, lines 1: Replace 'effects' with 'effect'.  
Methods (lines 1 -3): Slightly not relevant. How about "Fifty -two subjects with colorectal cancer 
were randomized at 4 weeks after surgery to receive …. "?  
Results: Replace 'most' with 'the majority' but give actual number or percentage. I would not give 
age of individual groups, as they were randomised and so should not a priori be significantly 
different. Line 3. 'none of the cases complained of …' how about replace with "No surgi cal 
infection occurred and no antibiotics were required".  
Line 6: 'were observed in CRC patients received probiotics' add "who received".  
Conclusion: I would state directly: 'We have shown that probiotics are safe to be consumed at 4 
weeks after surgery. a nd have reduce pro -inflammatory cytokines (except for IFN -gamma). I 
wonder in a future study you could investigate faecal markers of inflammation or assess rectal 
biopsy for repair and inflammation.  
 
Background The first paragraph is woffle. How about "Col orectal cancer is the second most 
common cancer in males and the third most common in females in most developed countries 
after discounting non -melanotic skin cancer."?  
Line 2: Replace 'was' with 'is'  
Line 24 Replace 'effects' with 'effect'  
 
Methods line 52: Replace "This study protocol has obtained approval" 'was approved'  
Line 53: Replace 'is also registered' with 'was registered'.  
 
What did the placebo treatment consist of? Was it matched for energy content or other 
components (eg calcium) that could co nceivably influence the nutritional plane,.  
How did you access compliance?  70% seems a little low for compliance, 80% would be better.  
 
Measuring the systemic immune status is a poor reflection of the mucosal immune status. It 
would have been better to as sess follow up colonic/rectal biopsy or faecal markers of 
inflammation (eg calprotectin).  
 
Results  
I would not repeat the same mean and SD and statistically analysis in both text and Figures.    
 
Table 1: You can't do statistics comparing initial parameters at randomisation. You know a priori 
that that these measures are not significantly different, as they have been randomized. The null 
hypothesis cannot be disputed.  OK, you can list the starting  measures, but not statistically 
analyse them. Only the outcomes can be assessed statistically.  
 
Discussion: Overall needs to be considerably shortened. Delete para 1 just repeating elements of 
Introduction. I would summarise the points to be discussed in para 1 eg ' Our study showed that 
probiotics commenced 4 weeks after surgery for colorectal cancer were safe, did not exacerbate 
diarrhoea, and reduced levels of systemic  production of pro -inflammatory cytokines" The 
description of previous studies has to o much description of previous study and not enough 
critical insight eg How many previous studies have examined cytokine production. Do you think 
that the extra energy intake and better nutrition could explain these results? Do you have weight, 
or plasma/s erum albumin at the conclusion of the trial? Discuss the placebo treatment.  
 
Number pages  
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 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 requ ire 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 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 fin ancial 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 detail s below.  
 
I declare that I have no competing interests  
 
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 
includ ing 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 t he journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: BMC Gastroenterology A randomised double -blind placebo -controlled trial of probiotics 
in post -surgical colorectal cancer  
 
Version: 1 Date: 11 Jan 2019  
Reviewer: Adrian Cummins  
Reviewer's report:  
Please include all comments for the authors in this box rather than uploading your  report as an 
attachment. Please only upload as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be included in a text format.  
Please overwrite this text when adding your comments to t he authors.  
 
Abstract:  
Background, lines 1: Replace 'effects' with 'effect'.  
Methods (lines 1 -3): Slightly not relevant. How about "Fifty -two subjects with colorectal cancer 
were randomized at 4 weeks after surgery to receive …. "?  
Results: Replace 'most' with 'the majority' but give actual number or percentage. I would not give 
age of individual groups, as they were randomised and so should not a priori be significantly 
different. Line 3. 'none of the cases complained of …' how about replace with "No surgi cal 
infection occurred and no antibiotics were required".  
Line 6: 'were observed in CRC patients received probiotics' add "who received".  
Conclusion: I would state directly: 'We have shown that probiotics are safe to be consumed at 4 
weeks after surgery. a nd have reduce pro -inflammatory cytokines (except for IFN -gamma). I 
wonder in a future study you could investigate faecal markers of inflammation or assess rectal 
biopsy for repair and inflammation.  
 
Background The first paragraph is woffle. How about "Col orectal cancer is the second most 
common cancer in males and the third most common in females in most developed countries 
after discounting non -melanotic skin cancer."?  
Line 2: Replace 'was' with 'is'  
Line 24 Replace 'effects' with 'effect'  
 
Methods line 52: Replace "This study protocol has obtained approval" 'was approved'  
Line 53: Replace 'is also registered' with 'was registered'.  
 
What did the placebo treatment consist of? Was it matched for energy content or other 
components (eg calcium) that could co nceivably influence the nutritional plane,.  
How did you access compliance?  70% seems a little low for compliance, 80% would be better.  
 
Measuring the systemic immune status is a poor reflection of the mucosal immune status. It 
would have been better to as sess follow up colonic/rectal biopsy or faecal markers of 
inflammation (eg calprotectin).  
 
Results  
I would not repeat the same mean and SD and statistically analysis in both text and Figures.    
 
Table 1: You can't do statistics comparing initial parameters at randomisation. You know a priori 
that that these measures are not significantly different, as they have been randomized. The null 
hypothesis cannot be disputed.  OK, you can list the starting  measures, but not statistically 
analyse them. Only the outcomes can be assessed statistically.  
 
Discussion: Overall needs to be considerably shortened. Delete para 1 just repeating elements of 
Introduction. I would summarise the points to be discussed in para 1 eg ' Our study showed that 
probiotics commenced 4 weeks after surgery for colorectal cancer were safe, did not exacerbate 
diarrhoea, and reduced levels of systemic  production of pro -inflammatory cytokines" The 
description of previous studies has to o much description of previous study and not enough 
critical insight eg How many previous studies have examined cytokine production. Do you think 
that the extra energy intake and better nutrition could explain these results? Do you have weight, 
or plasma/s erum albumin at the conclusion of the trial? Discuss the placebo treatment.  
 
Number pages  
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 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 requ ire 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 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 fin ancial 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 detail s below.  
 
I declare that I have no competing interests  
 
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 
includ ing 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 t he journal  
assistant