Reviewer ’s report  
 
Title:  Prognostic value of microvessel density in stage II and III colon cancer patients: a 
retrospective cohort study  
 
Version: 0 Date: 19 Jun 2019 
 
Reviewer:  Andrzej  Wincewicz  
 
Reviewer’s report:  
 
In BMG E-D-19-00377 the authors investigated microvessel density between stage III compared 
to stage II colon cancers to draw a bit unexpected conclusions conclude that High MVD in stage 
II patients was linked with poor disease free survival (DFS) while on contra ry high MVD in5FU -
treated stage III patients was accompanied with better DFS. I do think that such results merit 
publication as they inspire reflection, repetition of MVD studies on larger and different 
populations of colon cancer etc.  Such a finding coul d appear a bit confusing for enthusiasts of 
anti-angiogenic therapy, which has been shown very beneficiary in aspect of use of bevacizumab 
and related factors. The study was well designed, the methodology is fine and the study is 
conducted with care. The a uthors are very concise in the light of  obtained results which could be 
intriguing. The study groups are not huge but they comprise enough cases ( each over 50 
patients) to conduct this sort of study. The authors sincerely admitted that  further validatio n may 
be needed and the numbers of investigated cases in this study actually calls for further 
verification of the results and conclusions on large groups of colon cancers but the topic and 
findings are so important and interesting for even the philosophy of therapeutic approach that it 
is worth to publish this paper even in preliminary form. I do also think that authors should state 
in the paper if the histological type of colon cancer was identical in both of groups ( thus this 
would emphasize uniformity of groups): were they all been conventional adenocarcinoma or 
were they all been mucinous adenocarcinomas? Any explanation of such findings can appear a 
bit speculative and is included in the text of the paper e.g. that higher MVD in stage III cancers 
can provide better exposition to chemotherapeutic agent and better distribution of curative agent 
in tumor vasculature in course of neoadjuvant  therapy and consequently contribute to longer 
DFS. Therefore I do think that they need a bit longer commentary in d iscussion section. The 
authors are recommended to consider referring to other reports on HIF1a expression in  
colorectal cancer e.g. Wincewicz A, Koda M, Sulkowski S, Kanczuga -Koda L, Sulkowska M. 
Comparison of beta -catenin with TGF -beta1, HIF -1alpha and p atients' disease -free survival in 
human colorectal cancer. Pathol Oncol Res. 2010 Sep;16(3):311 -8. doi: 10.1007/s12253 -009-
9217 -2.  Wincewicz A, Sulkowska M, Koda M, Sulkowski S. Cumulative expression of HIF -1-
alpha, Bax, Bcl -xL and P53 in human colorectal  cancer. Pathology. 2007 Jun;39(3):334 -
8.Wincewicz A, Sulkowska M, Koda M, Sulkowski S. Clinicopathological significance and 
linkage of the distribution of HIF -1alpha and GLUT -1 in human primary colorectal cancer. 
Pathol Oncol Res. 2007;13(1):15 -20. Epub 2 007 Mar 27.  
 
 
with compliments,  
 
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 as sess 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 manuscript:  
 
Acceptable  
 
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 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 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 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my repo rt 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 nam ed 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:  Prognostic value of microvessel density in stage II and III colon cancer patients: a 
retrospective cohort study  
 
Version: 0 Date: 19 Jun 2019 
 
Reviewer:  Andrzej  Wincewicz  
 
Reviewer’s report:  
 
In BMG E-D-19-00377 the authors investigated microvessel density between stage III compared 
to stage II colon cancers to draw a bit unexpected conclusions conclude that High MVD in stage 
II patients was linked with poor disease free survival (DFS) while on contra ry high MVD in5FU -
treated stage III patients was accompanied with better DFS. I do think that such results merit 
publication as they inspire reflection, repetition of MVD studies on larger and different 
populations of colon cancer etc.  Such a finding coul d appear a bit confusing for enthusiasts of 
anti-angiogenic therapy, which has been shown very beneficiary in aspect of use of bevacizumab 
and related factors. The study was well designed, the methodology is fine and the study is 
conducted with care. The a uthors are very concise in the light of  obtained results which could be 
intriguing. The study groups are not huge but they comprise enough cases ( each over 50 
patients) to conduct this sort of study. The authors sincerely admitted that  further validatio n may 
be needed and the numbers of investigated cases in this study actually calls for further 
verification of the results and conclusions on large groups of colon cancers but the topic and 
findings are so important and interesting for even the philosophy of therapeutic approach that it 
is worth to publish this paper even in preliminary form. I do also think that authors should state 
in the paper if the histological type of colon cancer was identical in both of groups ( thus this 
would emphasize uniformity of groups): were they all been conventional adenocarcinoma or 
were they all been mucinous adenocarcinomas? Any explanation of such findings can appear a 
bit speculative and is included in the text of the paper e.g. that higher MVD in stage III cancers 
can provide better exposition to chemotherapeutic agent and better distribution of curative agent 
in tumor vasculature in course of neoadjuvant  therapy and consequently contribute to longer 
DFS. Therefore I do think that they need a bit longer commentary in d iscussion section. The 
authors are recommended to consider referring to other reports on HIF1a expression in  
colorectal cancer e.g. Wincewicz A, Koda M, Sulkowski S, Kanczuga -Koda L, Sulkowska M. 
Comparison of beta -catenin with TGF -beta1, HIF -1alpha and p atients' disease -free survival in 
human colorectal cancer. Pathol Oncol Res. 2010 Sep;16(3):311 -8. doi: 10.1007/s12253 -009-
9217 -2.  Wincewicz A, Sulkowska M, Koda M, Sulkowski S. Cumulative expression of HIF -1-
alpha, Bax, Bcl -xL and P53 in human colorectal  cancer. Pathology. 2007 Jun;39(3):334 -
8.Wincewicz A, Sulkowska M, Koda M, Sulkowski S. Clinicopathological significance and 
linkage of the distribution of HIF -1alpha and GLUT -1 in human primary colorectal cancer. 
Pathol Oncol Res. 2007;13(1):15 -20. Epub 2 007 Mar 27.  
 
 
with compliments,  
 
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 as sess 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 manuscript:  
 
Acceptable  
 
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 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 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 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my repo rt 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 nam ed 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:  Prognostic value of microvessel density in stage II and III colon cancer patients: a 
retrospective cohort study  
 
Version: 0 Date: 19 Jun 2019 
 
Reviewer:  Andrzej  Wincewicz  
 
Reviewer’s report:  
 
In BMG E-D-19-00377 the authors investigated microvessel density between stage III compared 
to stage II colon cancers to draw a bit unexpected conclusions conclude that High MVD in stage 
II patients was linked with poor disease free survival (DFS) while on contra ry high MVD in5FU -
treated stage III patients was accompanied with better DFS. I do think that such results merit 
publication as they inspire reflection, repetition of MVD studies on larger and different 
populations of colon cancer etc.  Such a finding coul d appear a bit confusing for enthusiasts of 
anti-angiogenic therapy, which has been shown very beneficiary in aspect of use of bevacizumab 
and related factors. The study was well designed, the methodology is fine and the study is 
conducted with care. The a uthors are very concise in the light of  obtained results which could be 
intriguing. The study groups are not huge but they comprise enough cases ( each over 50 
patients) to conduct this sort of study. The authors sincerely admitted that  further validatio n may 
be needed and the numbers of investigated cases in this study actually calls for further 
verification of the results and conclusions on large groups of colon cancers but the topic and 
findings are so important and interesting for even the philosophy of therapeutic approach that it 
is worth to publish this paper even in preliminary form. I do also think that authors should state 
in the paper if the histological type of colon cancer was identical in both of groups ( thus this 
would emphasize uniformity of groups): were they all been conventional adenocarcinoma or 
were they all been mucinous adenocarcinomas? Any explanation of such findings can appear a 
bit speculative and is included in the text of the paper e.g. that higher MVD in stage III cancers 
can provide better exposition to chemotherapeutic agent and better distribution of curative agent 
in tumor vasculature in course of neoadjuvant  therapy and consequently contribute to longer 
DFS. Therefore I do think that they need a bit longer commentary in d iscussion section. The 
authors are recommended to consider referring to other reports on HIF1a expression in  
colorectal cancer e.g. Wincewicz A, Koda M, Sulkowski S, Kanczuga -Koda L, Sulkowska M. 
Comparison of beta -catenin with TGF -beta1, HIF -1alpha and p atients' disease -free survival in 
human colorectal cancer. Pathol Oncol Res. 2010 Sep;16(3):311 -8. doi: 10.1007/s12253 -009-
9217 -2.  Wincewicz A, Sulkowska M, Koda M, Sulkowski S. Cumulative expression of HIF -1-
alpha, Bax, Bcl -xL and P53 in human colorectal  cancer. Pathology. 2007 Jun;39(3):334 -
8.Wincewicz A, Sulkowska M, Koda M, Sulkowski S. Clinicopathological significance and 
linkage of the distribution of HIF -1alpha and GLUT -1 in human primary colorectal cancer. 
Pathol Oncol Res. 2007;13(1):15 -20. Epub 2 007 Mar 27.  
 
 
with compliments,  
 
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 as sess 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 manuscript:  
 
Acceptable  
 
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 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 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 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my repo rt 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 nam ed 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