Reviewer’ s report
Title: Peritumoral ductular reaction can be a prognostic factor for intrahepatic cholangiocellular
carcinoma
Version: 1Date: 04 Jun 2020
Reviewer's report:
The reviewer suggests that the abbreviations should be coherent with the literature, for example,
intrahepatic cholangiocarcinoma as iCCA[1]. The word 'significant' should be reserved for thedescription of statistical hypothesis testing; otherwise, readers may misunderstand what theauthors states. Is it possible to change the term 'significant DR' to other terms to avoid this issue?
There are too many abbreviations in the text, some of them are used rarely, for example, ECC: two
times and CHC: 4 times. The reviewer suggests decreased the number of abbreviations.
In the methods subsection 'Histological and immunohistochemical analysis', line 45-50, the word
'blindly' should be changed to 'independently'. The author also needs to state how they deal withthe results when the scores of two independent pathologists are inconsistent.
In the results subsection: 'Peritumoral DR was related to local inflammation and fibrosis', the
reviewer supposes the authors were using Pearson's correlation coefficient (r). It will be more clearif the author states the 95% confidence interval of the correlation coefficient explicitly.
In the results subsection: 'Peritumoral DR was related to the prognosis of ICC' line 47-53, the p-
value is 0.058, therefore, the null hypothesis that the recurrence rates are the same between
significant or mild DR cannot be rejected by the preset level of significance (0.05).
In the result subsection: 'Different proliferation of peritumoral ductular cells' lines 17-18, the
author stated:
'The percentage of high PI...'However, the reviewer cannot find the definition of 'high PI' in the methods. The corresponding y-
label of figure 4b should be changed to avoid readers intemperate as the absolute value of PIbetween different groups.
In the results subsection 'Different grade of peritumor, DR was related to different
microenvironments', the author utilized immunofluorescent of CK19, alpha-SMA, and DAPI. Thereviewer cannot identify the abbreviation of DAPI from the text, and the author should stateexplicitly.
As a clinician, the reviewer interested in the impact of survival of different grades of ductal
reaction. The TNM stages of the non-mucinous iCCA should also be considered as a factor of
overall or disease-free survival. The reviewer wants to know whether it is possible or for survival
analysis for combining DR grade and TNM in the limited samples. If it is difficult for inferences,
the author should state this as a limitation of the study.
figure 2: The lines and rectangles for median and quantiles should be canceled because the size of
each group is small; therefore, direct presentation by dots is enough. The presentation of barplotwith error bars is not suitable comparing the tumor part and non-tumor part; the reviewer suggestsboxplots with individual observations or present individual observations as the rest of the subplotsin the same figure.
The reviewer suggests the figures comparing tumor and non-tumor results to be presented in
another figure because the sample size is different (n=30) to avoiding confusion with othersubplots.
In figure 3, the x-axis and y-axis should be adjusted. The reviewer suggests the maximum of the y-
axis is 100% because the survival curve started from (0, 1) and steps down toward the x-axis.Also, the reviewer found that the scales of x-axises of the two sub-plots are different ( max 150and 100 months) which will confuse readers when comparing the disease-free and overall survival.
The presentation of figure 5b is quite different from that of figure 4b. if the author want showed
the different immunohistochemical staining results in different groups of ductal reactions thefigure should plot with x-axis showing different groups of DR and y-axis reveal the grades ofalpha-SMA.
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.
Unable to assessAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
YesAre 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 furtherassessment 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 publishedDeclaration 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
Reviewer Publication Consent. 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) if this manu-script is accepted for publication. Any comments that I do not wish to be included in the publishedreport have been included as confidential comments to the editor, which will not be published.Ifyou are not happy for us to publish this report, please contact the editorial office before completingthe review.If you wish, you can include your name in your published report. Please note you mustdecide whether to include your name at the start of the process and confirm this decision wheneverprompted. If you change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report.
(default)
Reviewer’ s report
Title: Peritumoral ductular reaction can be a prognostic factor for intrahepatic cholangiocellular
carcinoma
Version: 1Date: 04 Jun 2020
Reviewer's report:
The reviewer suggests that the abbreviations should be coherent with the literature, for example,
intrahepatic cholangiocarcinoma as iCCA[1]. The word 'significant' should be reserved for thedescription of statistical hypothesis testing; otherwise, readers may misunderstand what theauthors states. Is it possible to change the term 'significant DR' to other terms to avoid this issue?
There are too many abbreviations in the text, some of them are used rarely, for example, ECC: two
times and CHC: 4 times. The reviewer suggests decreased the number of abbreviations.
In the methods subsection 'Histological and immunohistochemical analysis', line 45-50, the word
'blindly' should be changed to 'independently'. The author also needs to state how they deal withthe results when the scores of two independent pathologists are inconsistent.
In the results subsection: 'Peritumoral DR was related to local inflammation and fibrosis', the
reviewer supposes the authors were using Pearson's correlation coefficient (r). It will be more clearif the author states the 95% confidence interval of the correlation coefficient explicitly.
In the results subsection: 'Peritumoral DR was related to the prognosis of ICC' line 47-53, the p-
value is 0.058, therefore, the null hypothesis that the recurrence rates are the same between
significant or mild DR cannot be rejected by the preset level of significance (0.05).
In the result subsection: 'Different proliferation of peritumoral ductular cells' lines 17-18, the
author stated:
'The percentage of high PI...'However, the reviewer cannot find the definition of 'high PI' in the methods. The corresponding y-
label of figure 4b should be changed to avoid readers intemperate as the absolute value of PIbetween different groups.
In the results subsection 'Different grade of peritumor, DR was related to different
microenvironments', the author utilized immunofluorescent of CK19, alpha-SMA, and DAPI. Thereviewer cannot identify the abbreviation of DAPI from the text, and the author should stateexplicitly.
As a clinician, the reviewer interested in the impact of survival of different grades of ductal
reaction. The TNM stages of the non-mucinous iCCA should also be considered as a factor of
overall or disease-free survival. The reviewer wants to know whether it is possible or for survival
analysis for combining DR grade and TNM in the limited samples. If it is difficult for inferences,
the author should state this as a limitation of the study.
figure 2: The lines and rectangles for median and quantiles should be canceled because the size of
each group is small; therefore, direct presentation by dots is enough. The presentation of barplotwith error bars is not suitable comparing the tumor part and non-tumor part; the reviewer suggestsboxplots with individual observations or present individual observations as the rest of the subplotsin the same figure.
The reviewer suggests the figures comparing tumor and non-tumor results to be presented in
another figure because the sample size is different (n=30) to avoiding confusion with othersubplots.
In figure 3, the x-axis and y-axis should be adjusted. The reviewer suggests the maximum of the y-
axis is 100% because the survival curve started from (0, 1) and steps down toward the x-axis.Also, the reviewer found that the scales of x-axises of the two sub-plots are different ( max 150and 100 months) which will confuse readers when comparing the disease-free and overall survival.
The presentation of figure 5b is quite different from that of figure 4b. if the author want showed
the different immunohistochemical staining results in different groups of ductal reactions thefigure should plot with x-axis showing different groups of DR and y-axis reveal the grades ofalpha-SMA.
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.
Unable to assessAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
YesAre 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 furtherassessment 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 publishedDeclaration 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
Reviewer Publication Consent. 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) if this manu-script is accepted for publication. Any comments that I do not wish to be included in the publishedreport have been included as confidential comments to the editor, which will not be published.Ifyou are not happy for us to publish this report, please contact the editorial office before completingthe review.If you wish, you can include your name in your published report. Please note you mustdecide whether to include your name at the start of the process and confirm this decision wheneverprompted. If you change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report.
(default)
Please review this paper.
user
Reviewer’ s report
Title: Peritumoral ductular reaction can be a prognostic factor for intrahepatic cholangiocellular
carcinoma
Version: 1Date: 04 Jun 2020
Reviewer's report:
The reviewer suggests that the abbreviations should be coherent with the literature, for example,
intrahepatic cholangiocarcinoma as iCCA[1]. The word 'significant' should be reserved for thedescription of statistical hypothesis testing; otherwise, readers may misunderstand what theauthors states. Is it possible to change the term 'significant DR' to other terms to avoid this issue?
There are too many abbreviations in the text, some of them are used rarely, for example, ECC: two
times and CHC: 4 times. The reviewer suggests decreased the number of abbreviations.
In the methods subsection 'Histological and immunohistochemical analysis', line 45-50, the word
'blindly' should be changed to 'independently'. The author also needs to state how they deal withthe results when the scores of two independent pathologists are inconsistent.
In the results subsection: 'Peritumoral DR was related to local inflammation and fibrosis', the
reviewer supposes the authors were using Pearson's correlation coefficient (r). It will be more clearif the author states the 95% confidence interval of the correlation coefficient explicitly.
In the results subsection: 'Peritumoral DR was related to the prognosis of ICC' line 47-53, the p-
value is 0.058, therefore, the null hypothesis that the recurrence rates are the same between
significant or mild DR cannot be rejected by the preset level of significance (0.05).
In the result subsection: 'Different proliferation of peritumoral ductular cells' lines 17-18, the
author stated:
'The percentage of high PI...'However, the reviewer cannot find the definition of 'high PI' in the methods. The corresponding y-
label of figure 4b should be changed to avoid readers intemperate as the absolute value of PIbetween different groups.
In the results subsection 'Different grade of peritumor, DR was related to different
microenvironments', the author utilized immunofluorescent of CK19, alpha-SMA, and DAPI. Thereviewer cannot identify the abbreviation of DAPI from the text, and the author should stateexplicitly.
As a clinician, the reviewer interested in the impact of survival of different grades of ductal
reaction. The TNM stages of the non-mucinous iCCA should also be considered as a factor of
overall or disease-free survival. The reviewer wants to know whether it is possible or for survival
analysis for combining DR grade and TNM in the limited samples. If it is difficult for inferences,
the author should state this as a limitation of the study.
figure 2: The lines and rectangles for median and quantiles should be canceled because the size of
each group is small; therefore, direct presentation by dots is enough. The presentation of barplotwith error bars is not suitable comparing the tumor part and non-tumor part; the reviewer suggestsboxplots with individual observations or present individual observations as the rest of the subplotsin the same figure.
The reviewer suggests the figures comparing tumor and non-tumor results to be presented in
another figure because the sample size is different (n=30) to avoiding confusion with othersubplots.
In figure 3, the x-axis and y-axis should be adjusted. The reviewer suggests the maximum of the y-
axis is 100% because the survival curve started from (0, 1) and steps down toward the x-axis.Also, the reviewer found that the scales of x-axises of the two sub-plots are different ( max 150and 100 months) which will confuse readers when comparing the disease-free and overall survival.
The presentation of figure 5b is quite different from that of figure 4b. if the author want showed
the different immunohistochemical staining results in different groups of ductal reactions thefigure should plot with x-axis showing different groups of DR and y-axis reveal the grades ofalpha-SMA.
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.
Unable to assessAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
YesAre 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 furtherassessment 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 publishedDeclaration 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
Reviewer Publication Consent. 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) if this manu-script is accepted for publication. Any comments that I do not wish to be included in the publishedreport have been included as confidential comments to the editor, which will not be published.Ifyou are not happy for us to publish this report, please contact the editorial office before completingthe review.If you wish, you can include your name in your published report. Please note you mustdecide whether to include your name at the start of the process and confirm this decision wheneverprompted. If you change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report.
(default)
assistant