Title: High serum CA19-9 predicts severe cholecystitis in calculous cholecystitis patients
Version: 2 Date: 18 Oct 2024
Reviewer's report:
Dear Author
Major comments
1. Thank you for your detailed comments. I fully understand that this study focuses on tumor
markers and the degree of cholecystitis. I also understood that the number of cases was too small
to differentiate from cancer. I again understood that the severity of cholecystitis is an important
part of this study, but the criteria for determining the severity of cholecystitis are not clearly
described. We believe that the authors need to clearly state what criteria they use to determine
the severity of the calculus cholecystitis.
2. Thank you for your detailed comments. I now understand the background of the participants
in this study. I understand that it is difficult to investigate the timing of the onset of cholecystitis.
Am I correct in assuming that this study is focused on determining the severity of cholecystitis?
However, we believe that we cannot ignore the fact that the degree of inflammation in
cholecystitis varies depending on whether it is acute or chronic. Also, the flow chart of
cholecystitis care may vary staggeredly depending on the region where the care is provided. It
would be helpful to provide treatment guidelines for cholecystitis in the regions where this study
was conducted, or to specify the indications for surgery in each facility, to better understand the
readings. In the comments, it is noted that asymptomatic cases were included. Asymptomatic
would be inconsistent with a pathologic diagnosis of cholecystitis, as many are considered to be
free of inflammation. At the very least, the criteria for indication for surgery.
We believe that it is necessary to state.
3. Thank you for your thoughtful response, I understand that you want to strongly state
the relationship between CA19-9 and cholecystitis, but in general practice, the degree of
inflammation is determined by the white blood cell count and CRP. The author seems to think
that CA19-9 is a marker of inflammation, but please clarify how useful it is compared to CRP.
Also, I am also putting it on the criteria to determine the degree of inflammation. It is not
objective enough to say that it is easy to perform the surgery. In this study, we do not know if it
is acute or chronic cholecystitis. If CRR is a marker of acute inflammatory response, what is the
position of CA19-9? If CRR is a marker of acute inflammation, what is the position of CA19-9?
We believe that the above should be clarified and the text should be corrected.
4. Thank you for your detailed comments. It is difficult to recognize that they are identical cases.
It would be better to present the entire image and show which part was taken out. In this study,
cases are accumulated on the basis of pathological diagnosis. Therefore, we believe there is a
need to ensure the authenticity of this part of the data. Since this also relates to the reliability of
the data that follows, why not reconstruct it?
5. Thank you for your detailed comments. I have also confirmed the results of the re-experiment;
I understand that there was no difference in mRNA expression levels. However, what is the
position of the results of the comprehensive mRNA analysis in this study?
Minor comments
1.  Thank you for your detailed comments.  I agree with you.
2. Thank you for your detailed comments.  I agree with you.
Title: High serum CA19-9 predicts severe cholecystitis in calculous cholecystitis patients
Version: 2 Date: 18 Oct 2024
Reviewer's report:
Dear Author
Major comments
1. Thank you for your detailed comments. I fully understand that this study focuses on tumor
markers and the degree of cholecystitis. I also understood that the number of cases was too small
to differentiate from cancer. I again understood that the severity of cholecystitis is an important
part of this study, but the criteria for determining the severity of cholecystitis are not clearly
described. We believe that the authors need to clearly state what criteria they use to determine
the severity of the calculus cholecystitis.
2. Thank you for your detailed comments. I now understand the background of the participants
in this study. I understand that it is difficult to investigate the timing of the onset of cholecystitis.
Am I correct in assuming that this study is focused on determining the severity of cholecystitis?
However, we believe that we cannot ignore the fact that the degree of inflammation in
cholecystitis varies depending on whether it is acute or chronic. Also, the flow chart of
cholecystitis care may vary staggeredly depending on the region where the care is provided. It
would be helpful to provide treatment guidelines for cholecystitis in the regions where this study
was conducted, or to specify the indications for surgery in each facility, to better understand the
readings. In the comments, it is noted that asymptomatic cases were included. Asymptomatic
would be inconsistent with a pathologic diagnosis of cholecystitis, as many are considered to be
free of inflammation. At the very least, the criteria for indication for surgery.
We believe that it is necessary to state.
3. Thank you for your thoughtful response, I understand that you want to strongly state
the relationship between CA19-9 and cholecystitis, but in general practice, the degree of
inflammation is determined by the white blood cell count and CRP. The author seems to think
that CA19-9 is a marker of inflammation, but please clarify how useful it is compared to CRP.
Also, I am also putting it on the criteria to determine the degree of inflammation. It is not
objective enough to say that it is easy to perform the surgery. In this study, we do not know if it
is acute or chronic cholecystitis. If CRR is a marker of acute inflammatory response, what is the
position of CA19-9? If CRR is a marker of acute inflammation, what is the position of CA19-9?
We believe that the above should be clarified and the text should be corrected.
4. Thank you for your detailed comments. It is difficult to recognize that they are identical cases.
It would be better to present the entire image and show which part was taken out. In this study,
cases are accumulated on the basis of pathological diagnosis. Therefore, we believe there is a
need to ensure the authenticity of this part of the data. Since this also relates to the reliability of
the data that follows, why not reconstruct it?
5. Thank you for your detailed comments. I have also confirmed the results of the re-experiment;
I understand that there was no difference in mRNA expression levels. However, what is the
position of the results of the comprehensive mRNA analysis in this study?
Minor comments
1.  Thank you for your detailed comments.  I agree with you.
2. Thank you for your detailed comments.  I agree with you.
Please review this paper.
user
Title: High serum CA19-9 predicts severe cholecystitis in calculous cholecystitis patients
Version: 2 Date: 18 Oct 2024
Reviewer's report:
Dear Author
Major comments
1. Thank you for your detailed comments. I fully understand that this study focuses on tumor
markers and the degree of cholecystitis. I also understood that the number of cases was too small
to differentiate from cancer. I again understood that the severity of cholecystitis is an important
part of this study, but the criteria for determining the severity of cholecystitis are not clearly
described. We believe that the authors need to clearly state what criteria they use to determine
the severity of the calculus cholecystitis.
2. Thank you for your detailed comments. I now understand the background of the participants
in this study. I understand that it is difficult to investigate the timing of the onset of cholecystitis.
Am I correct in assuming that this study is focused on determining the severity of cholecystitis?
However, we believe that we cannot ignore the fact that the degree of inflammation in
cholecystitis varies depending on whether it is acute or chronic. Also, the flow chart of
cholecystitis care may vary staggeredly depending on the region where the care is provided. It
would be helpful to provide treatment guidelines for cholecystitis in the regions where this study
was conducted, or to specify the indications for surgery in each facility, to better understand the
readings. In the comments, it is noted that asymptomatic cases were included. Asymptomatic
would be inconsistent with a pathologic diagnosis of cholecystitis, as many are considered to be
free of inflammation. At the very least, the criteria for indication for surgery.
We believe that it is necessary to state.
3. Thank you for your thoughtful response, I understand that you want to strongly state
the relationship between CA19-9 and cholecystitis, but in general practice, the degree of
inflammation is determined by the white blood cell count and CRP. The author seems to think
that CA19-9 is a marker of inflammation, but please clarify how useful it is compared to CRP.
Also, I am also putting it on the criteria to determine the degree of inflammation. It is not
objective enough to say that it is easy to perform the surgery. In this study, we do not know if it
is acute or chronic cholecystitis. If CRR is a marker of acute inflammatory response, what is the
position of CA19-9? If CRR is a marker of acute inflammation, what is the position of CA19-9?
We believe that the above should be clarified and the text should be corrected.
4. Thank you for your detailed comments. It is difficult to recognize that they are identical cases.
It would be better to present the entire image and show which part was taken out. In this study,
cases are accumulated on the basis of pathological diagnosis. Therefore, we believe there is a
need to ensure the authenticity of this part of the data. Since this also relates to the reliability of
the data that follows, why not reconstruct it?
5. Thank you for your detailed comments. I have also confirmed the results of the re-experiment;
I understand that there was no difference in mRNA expression levels. However, what is the
position of the results of the comprehensive mRNA analysis in this study?
Minor comments
1.  Thank you for your detailed comments.  I agree with you.
2. Thank you for your detailed comments.  I agree with you.
assistant