Changes in the Plasma Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1(APE1/Ref-1) Level during Cancer Surgery: An Observational Study

Round 1

Reviewer 1 Report

Dear Authors, 

Thank you for taking my comments into conseideration 

Good luck with your manuscript 

MS 

Author Response

Thank you very much.

Reviewer 2 Report

All changes are made according to suggestions.

Author Response

Thank you very much.

Reviewer 3 Report

I don't think the authors successfully revised the manuscript.

Author Response

Dear, reviewer.

 The last part of the limitation and conclusion has been re-edited for conciseness. In the word file, the edited part is in blue text. We are sorry for the things you pointed out. However, the data is so valuable to us that we want to publish it. The limitations are described in detail in the manuscript. I think wise readers of 'medicina' will understand the results with this in mind. It is undoubtedly a study that can be helpful to many clinicians.

Thank you.

Sincerely, yours

Dr. Chaeseong Lim

 

Round 2

Reviewer 3 Report

No comments

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Dear Authors. 

Congratulations on the vast amount of work you put into carrying out the study. It is a pity the anaesthesiologists did not follow the study design, because without proper randomization the results may only show the direction for the future studies. 

If I were you, I would also focus on a specific type of cancer rather than include patients with different cancers. 

Best regards, 

MS

 

Author Response

We are also sorry that randomization did not work well, so we switched to observational study. As you pointed out, we will focus on one type of cancer and establish a next research plan. Thank you.

Reviewer 2 Report

The authors presented in their work possible connection between the plasma APE1/Ref-1 level and the used anesthetics.

Author Response

Thank you.

Reviewer 3 Report

I read with interest the manuscript "Anesthetics and Plasma Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1(APE1/Ref-1) during Cancer Surgery ― Total Intravenous versus Volatile Anesthesia: An Observational Study" submitted to the Medicina.

In this study, the authors examined changes in blood levels of APE1/Ref-1 protein measured by ELISA during the perioperative period with anesthesia in 338 patients with various types of cancer.
They concluded that anesthesia had no effect on APE1/Ref-1 protein levels, but that APE1/Ref-1 protein levels increased immediately after tumor resection, and that these levels correlated with the number of infiltrated lymph nodes.

As the authors are well aware, APE1/Ref-1 was first genetically isolated as a nuclear protein.
Subsequent studies have shown that APE1/Ref-1 is also present in extracellular and serum, and some studies using recombinant APE1/Ref-1 have shown that APE1/Ref-1 has anti-inflammatory properties. The authors have published several reviews in this field and have accumulated considerable knowledge on the function of extracellular APE1/Ref-1.

The study and its analysis were conducted in accordance with a solid methodology, and the results of the study itself are considered to be quite reliable.
On the other hand, there are some problems that need to be solved in this study.
The following is a list of the main points.

# Certainty of the ELISA method
As shown in Table 5 of this study, the concentration of APE1/Ref-1 at the control level varied from study to study.
The evidence suggests that there is no standard ELISA method for measuring the concentration of APE1/Ref-1, which raises serious questions about the reliability of this series of studies.

# The title of this manuscript.
The title of this paper is 'Anesthetics and Plasma Apurinic/Apyrimidinic Endonuclease
1/Redox Factor-1 (APE1/Ref-1) during Cancer Surgery - Total Intravenous versus Volatile Anesthesia: An Observational Study'
This title may mislead the reader and should be revised because anesthetics did not impact the concentration of APE1/Ref-1.
The authors described as followings:
Finally, the greatest problem was the hypothesis itself. There were no differences in plasma APE1/Ref-1 levels according to the anesthetic agent used; our hypothesis was rejected, and no further inferences or interpretations could be made. Interpretation of the results of this study was difficult, due to the low specificity of APE1/Ref-1, and we cannot draw definitive conclusions about the effects of anesthetics on cancer 

# Statistical issues
It can be said that the statistical method is appropriate for the application, but the conclusion is drawn from the relatively small number of cases and the fact that the statistical significance is not high.

# Anesthesia method
The description of the anesthesia method is ambiguous.
The total amount of propofol, narcotics, etc. administered should be stated.

# Patients selection
A variety of cancers are included and claims are not specific.

Author Response

Point1 # Certainty of the ELISA method
As shown in Table 5 of this study, the concentration of APE1/Ref-1 at the control level varied from study to study.
The evidence suggests that there is no standard ELISA method for measuring the concentration of APE1/Ref-1, which raises serious questions about the reliability of this series of studies.

Although a standard ELISA method for APE1/Ref-1 has not been established, the results in this study are those using the same kit and same method. Therefore, we believe that the results and comparisons in this study have logical validity.

 

Point2 # The title of this manuscript.
The title of this paper is 'Anesthetics and Plasma Apurinic/Apyrimidinic Endonuclease
1/Redox Factor-1 (APE1/Ref-1) during Cancer Surgery - Total Intravenous versus Volatile Anesthesia: An Observational Study'
This title may mislead the reader and should be revised because anesthetics did not impact the concentration of APE1/Ref-1.
The authors described as followings:
Finally, the greatest problem was the hypothesis itself. There were no differences in plasma APE1/Ref-1 levels according to the anesthetic agent used; our hypothesis was rejected, and no further inferences or interpretations could be made. Interpretation of the results of this study was difficult, due to the low specificity of APE1/Ref-1, and we cannot draw definitive conclusions about the effects of anesthetics on cancer 

As pointed out, the title has been changed as follows to reduce confusion for readers.

'Changes in the Plasma Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1(APE1/Ref-1) Level during Cancer Surgery: An Observational Study'

 

Point3 # Statistical issues
It can be said that the statistical method is appropriate for the application, but the conclusion is drawn from the relatively small number of cases and the fact that the statistical significance is not high.

We agree with you. If we use big data in the future and focus on one cancer type, we can expect statistical significance as well.

Point4 # Anesthesia method
The description of the anesthesia method is ambiguous.
The total amount of propofol, narcotics, etc. administered should be stated.

Operation time, anesthesia time, and amount of propofol and remifentanil used were additionally investigated and described in the manuscript and Table 2.

Point5 # Patients selection
A variety of cancers are included and claims are not specific.

Although the number is small, we also analyzed the results by cancer type.