PONE-D-21-14973

Use of Gentamicin-Collagen Sponge (Collatamp® G) in laparoscopic colorectal cancer surgery: A propensity score-matched study

PLOS ONE

Dear Dr. Lee,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please address the issues and revise accordingly.

Please submit your revised manuscript by Jul 23 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Authors aim to determine the effectiveness of a gentamicin-collagen sponge to reduce surgical site infections in minimally invasive surgery for colorectal cancer in a single institution between December 1, 2018 and February 28, 2021. After propensity score matching, 130 patients were allocated to each group. No differences in clinical characteristics existed between the two groups. Surgical site infection occurred in 2 (1.5%) patients and 3 (2.3%) patients in the gentamicin-collagen sponge group and the control group, respectively (p<0.999). After analyzing factors that affect surgical site infection, the following factors were found to be statistically significant: body mass index >25 kg/m2 (odds ratio, 39.0; 95% confidence interval, 1.90-802.21; p=0.018), liver disease (odds ratio, 254.8; 95% confidence interval, 10.43-6222.61; p=0.001), and right hemicolectomy (odds ratio, 36.22; 95% confidence interval, 2.37-554.63; p=0.010). In summary, the present study indicated that applying a gentamicin-collagen sponge to mini-laparotomy wound could not reduce the frequency of surgical site infection. Further studies should be conducted regarding whether the selective use of gentamicin-collagen sponges may help reduce surgical site infection in high-risk patients. The results seems informative and appealing; however, there are a lot of criticisms and have several issues that the authors need to address before the manuscript is suitable for publication.

Major Compulsory Revisions:

1. The major flaw of the current study was that authors included only 260 patients divided into 2 groups (130 patients in each group), and the relatively low incidence of SSI (1.5% vs 2.3%); therefore, an estimated sample size analysis is warranted before authors conducting this study to prevent small sample size study bias.

2. In Patients paragraph: The inclusion criteria were laparoscopic or robotic operations for biopsy-proven colorectal cancer and specimen extraction via minilaparotomy wounds. However, the title of the manuscript is Use of Gentamicin-Collagen Sponge (Collatamp® G) in laparoscopic colorectal cancer surgery: A propensity score-matched study. The title needs to be amended.

3. In Statistical analysis paragraph: For multivariable analysis of factors affecting SSI, a logistic regression test was used for factors with a p-value <0.2 in univariable analysis. Authors have to elucidate why set a p-value <0.2 not < 0.05 to reduce false positives.

4. Another major flaw was that authors define body mass index >25 kg/m2 (overweight) as a variable for further analysis, of which it was relatively lower threshold compared to the common definition of obesity was BMI > 30 kg/m2. It would be better to re-analyze by using BMI > 30 kg/m2in the subsequent study.

5. Body mass index >25 kg/m2 (p=0.018), liver disease (p=0.001), and right hemicolectomy (p=0.010) were independent factors affecting SSI. The definitions of liver disease should be clarified with more detailed information, and how about uremia patients undergoing hemodialysis?

6. In Table 2: Total patients with surgical site infection was 5; however, there were 8 SSI in Table 3. The inconsistent data within the manuscript rise a serious concern.

7. Obviously, dual-ring wound protector has been widely used to significantly reduce SSI after elective surgery for colorectal cancer, e.g. Impact of a Dual-Ring Wound Protector on Outcome after Elective Surgery for Colorectal Cancer. J Surg Res 2019;244:136-145. There were no relevant references in the Discussion section.

8. In Discussion, right hemicolectomy was an independent factors affecting SSI should be described in more details with references.

9. In Conclusion paragraph: We demonstrated that in patients with colon cancer or rectal cancer who undergo laparoscopic resection, applying a gentamicin-collage sponge to the mini-laparotomy wound could not reduce the frequency of SSI. However, our findings confirmed that the gentamicin collagen sponge lowered the frequency of SSI among patients at high risk for SSI, although this difference was not statistically significant. The above statements must be extensively revised based on a negative results and no powerful data to demonstrate it.

Minor Essential Revisions:

1. Please correct the typo and grammatical error with an expert good at English-editing.

2. The term of operation name in tables 1-4 that is advised to be substituted with operation methods. .

Reviewer #2: The aim of the manuscript focus on the effect of Gentamicin-Collagen Sponge (Collatamp® G) in the SSI of laparoscopic colorectal surgery. It is interesting and important issue although the result of the study was limited due to small sample size. I have some comments for the authors.

1. What is the definition of the SSI in the study?

2.In methods, for multivariable analysis of factors affecting SSI, a logistic regression test was used for factors with a p-value <0.2 in univariable analysis. But Table 4 didn't show the multivariable analysis result of Hypertension and hemoglobin with p-value< 0.2 in univariable analysis.

3. In discussion, authors thought small sample size was the limitation for less SSI in this study than other previously published data. Please explain why subgroup analysis can compensate for the limitation.

4.Please explain the sentences "In particular, in the subgroup analysis, when the Collatamp was used in the BMI>25 kg/m 2 group, SSI was lowered by an OR of 0.29 (95% CI, 0.03-2.68; p=0.375), compared with that in patients with a BMI<25 kg/m2" in discussion. The data didn't show in result. Table 5 only showed Collatamp decrease SSI rate in BMI>25 kg/m2 (p=0.375).

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Reviewer #1: No

Reviewer #2: No

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PONE-D-21-14973R1Use of Gentamicin-Collagen Sponge (Collatamp® G) in minimally invasive colorectal cancer surgery: A propensity score-matched studyPLOS ONE

Dear Dr. Lee,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please revise.

Please submit your revised manuscript by Jan 28 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Major Compulsory Revisions:

1. The major flaw of the current study was that authors included only 260 patients

divided into 2 groups (130 patients in each group), and the relatively low incidence of

SSI (1.5% vs 2.3%); therefore, an estimated sample size analysis is warranted before

authors conducting this study to prevent small sample size study bias.

Reply: We sincerely appreciate the reviewer’s valuable comments. As mentioned in the

discussion of the study’s limitations, the sample size required was calculated at about

1134 patients in each group, which is practically impossible to achieve with a single

center retrospective design. In addition, since the purpose of this study was to conduct

a randomized control study using Collatamp, a subsequent multicenter study will be

conducted based on this study.

Query: Authors should mention in the limitations as the inadequate sample size might lead to min-interpretation of results.

Conclusion paragraph: We demonstrated that, in patients with colon or rectal cancer who undergo laparoscopic

resection, applying a gentamicin-collage sponge to the mini-laparotomy wound did not reduce

the frequency of SSIs, even in high-risk patients.

Authors were suggested to correct "who undergo laparoscopic resection" to "who undergo minimally invasive surgery".

Reviewer #2: The authors have responded to all previous comments appropriately. Small sample size is still be concerned.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Use of Gentamicin-Collagen Sponge (Collatamp® G) in minimally invasive colorectal cancer surgery: A propensity score-matched study

PONE-D-21-14973R2

Dear Dr. Lee,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No