Reviewer ’s report  
 
Title: Mitotic and apoptotic activity in colorectal neoplasia  
 
Version: 0 Date: 17 Nov 2017  
 
Reviewer: Satish Ramalingam  
 
Reviewer's report:  
 
This is an interesting article by Kohoutova et al., attempted to determine the degree of mitotic 
and apoptotic activity at each stage of colorectal neoplasia.  
In this regard, they have collected samples from, patients with non -advanced colorectal 
adenoma, patients with CRC and normal subjects. Performed H&E to determine the mitotic 
activity and immunohistochemistry analysis using activated caspase -3 antibody for 
determination of apoptotic activity.  
Thou gh the studies on colorectal cancer is significant, the current proposal has several major and 
minor issues as given below,  
 
Major  
Figure 2 is presented to show high false positivity in marginal areas of the section, and the 
authors discuss this could pro bably be due to trauma when the biopsy sample was taken, which 
resulted in a rapid activation of apoptotic signaling pathways. However, necrotic cell death is 
always associated with the traumatic cell death caused by injury, as apoptosis is a programmed 
cell death pathway.  
  Figure 3 is presented to show that the upper part of a crypt of Control sample has no mitotic and 
apoptotic activity. However, they have not presented even one complete crypt. The authors 
should provide better image.  
The authors have stated that the current study with human subjects was approved by the Joint 
Ethical Committee (Charles University, Faculty of Medicine in Hradec Kralove, University 
Hospital Hradec Kralove). However, they have not provided any Human ethical committee 
appro val number.  
The authors have a sentence, "Advanced colorectal adenoma is defined as a neoplasia larger than 
10 mm and/or containing villous component and/or containing high grade dysplasia". Actually 
the colon has no villi, the above statement is not corr ect. 
 
Minor  
Typographical errors - "Preeliminary ", "dysplaing"  
Overall, it is very known that dysregulation of mitosis and apotosis contribute to the 
pathogenesis of CRC. In addition, authors have stated that, Preliminary data without controls in 
each group of patients with colorectal neoplasia and without any data on mitosis have been 
published previously by the same group in "Kohoutova D, Pejchal J, Cyrany J et al. Apoptosis in 
the development of colorectal neoplasia. Gastroenterol and Hepatol. 2016; 70(4):313 -318. 
[Article in Czech]". The current manuscript does not add any significant information to the 
available literature in the field. Therefore, the reviewer recommends rejection of this manuscript.  
Are the methods appropriate and well described?  
If not, please spe cify 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 show n? 
If not, please explain in your comments to the authors.  
 
No 
 
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.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
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, fund ing, 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 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, w rite '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 journal. I understand that my name will be include d 
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 A ccess 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: Mitotic and apoptotic activity in colorectal neoplasia  
 
Version: 0 Date: 17 Nov 2017  
 
Reviewer: Satish Ramalingam  
 
Reviewer's report:  
 
This is an interesting article by Kohoutova et al., attempted to determine the degree of mitotic 
and apoptotic activity at each stage of colorectal neoplasia.  
In this regard, they have collected samples from, patients with non -advanced colorectal 
adenoma, patients with CRC and normal subjects. Performed H&E to determine the mitotic 
activity and immunohistochemistry analysis using activated caspase -3 antibody for 
determination of apoptotic activity.  
Thou gh the studies on colorectal cancer is significant, the current proposal has several major and 
minor issues as given below,  
 
Major  
Figure 2 is presented to show high false positivity in marginal areas of the section, and the 
authors discuss this could pro bably be due to trauma when the biopsy sample was taken, which 
resulted in a rapid activation of apoptotic signaling pathways. However, necrotic cell death is 
always associated with the traumatic cell death caused by injury, as apoptosis is a programmed 
cell death pathway.  
  Figure 3 is presented to show that the upper part of a crypt of Control sample has no mitotic and 
apoptotic activity. However, they have not presented even one complete crypt. The authors 
should provide better image.  
The authors have stated that the current study with human subjects was approved by the Joint 
Ethical Committee (Charles University, Faculty of Medicine in Hradec Kralove, University 
Hospital Hradec Kralove). However, they have not provided any Human ethical committee 
appro val number.  
The authors have a sentence, "Advanced colorectal adenoma is defined as a neoplasia larger than 
10 mm and/or containing villous component and/or containing high grade dysplasia". Actually 
the colon has no villi, the above statement is not corr ect. 
 
Minor  
Typographical errors - "Preeliminary ", "dysplaing"  
Overall, it is very known that dysregulation of mitosis and apotosis contribute to the 
pathogenesis of CRC. In addition, authors have stated that, Preliminary data without controls in 
each group of patients with colorectal neoplasia and without any data on mitosis have been 
published previously by the same group in "Kohoutova D, Pejchal J, Cyrany J et al. Apoptosis in 
the development of colorectal neoplasia. Gastroenterol and Hepatol. 2016; 70(4):313 -318. 
[Article in Czech]". The current manuscript does not add any significant information to the 
available literature in the field. Therefore, the reviewer recommends rejection of this manuscript.  
Are the methods appropriate and well described?  
If not, please spe cify 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 show n? 
If not, please explain in your comments to the authors.  
 
No 
 
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.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
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, fund ing, 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 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, w rite '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 journal. I understand that my name will be include d 
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 A ccess 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: Mitotic and apoptotic activity in colorectal neoplasia  
 
Version: 0 Date: 17 Nov 2017  
 
Reviewer: Satish Ramalingam  
 
Reviewer's report:  
 
This is an interesting article by Kohoutova et al., attempted to determine the degree of mitotic 
and apoptotic activity at each stage of colorectal neoplasia.  
In this regard, they have collected samples from, patients with non -advanced colorectal 
adenoma, patients with CRC and normal subjects. Performed H&E to determine the mitotic 
activity and immunohistochemistry analysis using activated caspase -3 antibody for 
determination of apoptotic activity.  
Thou gh the studies on colorectal cancer is significant, the current proposal has several major and 
minor issues as given below,  
 
Major  
Figure 2 is presented to show high false positivity in marginal areas of the section, and the 
authors discuss this could pro bably be due to trauma when the biopsy sample was taken, which 
resulted in a rapid activation of apoptotic signaling pathways. However, necrotic cell death is 
always associated with the traumatic cell death caused by injury, as apoptosis is a programmed 
cell death pathway.  
  Figure 3 is presented to show that the upper part of a crypt of Control sample has no mitotic and 
apoptotic activity. However, they have not presented even one complete crypt. The authors 
should provide better image.  
The authors have stated that the current study with human subjects was approved by the Joint 
Ethical Committee (Charles University, Faculty of Medicine in Hradec Kralove, University 
Hospital Hradec Kralove). However, they have not provided any Human ethical committee 
appro val number.  
The authors have a sentence, "Advanced colorectal adenoma is defined as a neoplasia larger than 
10 mm and/or containing villous component and/or containing high grade dysplasia". Actually 
the colon has no villi, the above statement is not corr ect. 
 
Minor  
Typographical errors - "Preeliminary ", "dysplaing"  
Overall, it is very known that dysregulation of mitosis and apotosis contribute to the 
pathogenesis of CRC. In addition, authors have stated that, Preliminary data without controls in 
each group of patients with colorectal neoplasia and without any data on mitosis have been 
published previously by the same group in "Kohoutova D, Pejchal J, Cyrany J et al. Apoptosis in 
the development of colorectal neoplasia. Gastroenterol and Hepatol. 2016; 70(4):313 -318. 
[Article in Czech]". The current manuscript does not add any significant information to the 
available literature in the field. Therefore, the reviewer recommends rejection of this manuscript.  
Are the methods appropriate and well described?  
If not, please spe cify 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 show n? 
If not, please explain in your comments to the authors.  
 
No 
 
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.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
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, fund ing, 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 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, w rite '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 journal. I understand that my name will be include d 
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 A ccess 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