Peer Review History

Original SubmissionJuly 10, 2025
Decision Letter - Yoshihisa Tsuji, Editor

Dear Dr. Honselmann,

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.

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We look forward to receiving your revised manuscript.

Kind regards,

Yoshihisa Tsuji

Academic Editor

PLOS ONE

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When submitting your revision, we need you to address these additional requirements.

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2. Thank you for stating the following financial disclosure: [Parts of the study are currently funded by The Federal Ministry of Education and Research (BMBF) (Funding number: 01KD2412A) and was supported by the Clinician-scientist school Luebeck (project number 413535489) to KCH.]. 

Please state what role the funders took in the study.  If the funders had no role, please state: ""The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.""

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4. Please amend your authorship list in your manuscript file to include authors Dr. Matthias Birth, Louisa Bolm, Ruediger Braun, Ihsan Ekin Demir, Maximilian Denzinger, Beate Drews, Ana Dugic, Thomas Ewers, Josephine-Alisa Grandi, Susanne Haberer, Christoph Ammer-Hermenau, Philip Hildebrandt, Felix Huettner, Katja Janke, Katja Kilani, Georg Lamprecht, Jens Schuette, Jolina Michaelis, Albrecht Neesse, Rene Wilke, Lukas Perkhofer, Sebastian Rasch, Maximilian Reichert, Martina Mueller-Schilling, and Thorben Sauer.

5. One of the noted authors is a group or consortium [the GerPaCyst Study Group]. In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript. Please also indicate clearly a lead author for this group along with a contact email address.

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

Reviewer #1: Yes

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses??>

Reviewer #1: Partly

Reviewer #2: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable??>

Reviewer #1: No

Reviewer #2: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete??>

The PLOS Data policy

Reviewer #1: No

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

Reviewer #1: This is the protocol paper of the prospective, multicenter German Pancreas Club cyst registry.

Minor Comments:

1. Clarification of presumed diagnosis criteria:

The protocol mentions inclusion of patients with a “presumed diagnosis”. However, it is unclear what specific clinical, imaging, or laboratory criteria are used to define this presumed diagnosis. Please clarify the diagnostic criteria and specify how interobserver variation is addressed in such assessments. This information should be explicitly described in the protocol.

2. Handling and evaluation of imaging data:

It is not clear whether the imaging findings are assessed solely based on site-reported entries in the case report forms or whether a central image review is planned. If central review of imaging data is not conducted, this should be explicitly stated. In that case, please describe how consistency across institutions (e.g., interobserver variability) will be managed or minimized. This point should be clearly addressed in the study protocol.

Reviewer #2: Comment

This is a large observational study of the long-term follow-up of pancreatic cystic lesions in Germany. Prospective studies of pancreatic cystic lesions are limited and the findings from this study are expected to be important. Some comments are provided below.

1. Abstract lacks primary endpoints, making it difficult to understand the study summary.

2. Is there a defined objective number of cases?

3. The evaluation items are difficult to understand. For example, the items to be evaluated in blood tests and in imaging tests. Why not list them all in a table?

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Reviewer #1: No

Reviewer #2: No

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https://doi.org/10.1371/journal.pone.0335809.r001
Revision 1
Author Response

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Partly

Reviewer #2: Yes

Answer 2: For Reviewer #1: Since this is not an interventional trial, controls are not described. We have added methodology for building a multi-omics risk stratification model in line 275ff.

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: No

Reviewer #2: Yes

Answer 3: Reviewer#1: We see your concerns. As this is a registry trial, the research questions in the future are not sufficiently foreseeable at this point. However, our primary goal is to generate a multi-omics model for risk stratification of pancreatic cyst progression. For this, we added the detailed methodology and hope to answer your question sufficiently (Line 282ff.

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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

Answer 4: We thank Reviewer #1 and #2 for this comment. As we have described and outlined above, this is a mere study protocol. There is no data available currently as the study is still in its data acquisition phase. There are no concrete data points to be shared at this moment. As our study continues, we will make the outcomes available through publications. We have added a comment regarding publication of our findings in the manuscript line 354f: “Participant-level dataset and statistical codes can be obtained from KCH.”

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

Answer 5: We thank Reviewer #1 and #2 for their comment.

6. Review Comments to the Author

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This is the protocol paper of the prospective, multicenter German Pancreas Club cyst registry.

Minor Comments:

1. Clarification of presumed diagnosis criteria:

The protocol mentions inclusion of patients with a “presumed diagnosis”. However, it is unclear what specific clinical, imaging, or laboratory criteria are used to define this presumed diagnosis. Please clarify the diagnostic criteria and specify how interobserver variation is addressed in such assessments. This information should be explicitly described in the protocol.

Answer 1: We added our criteria for diagnosis of the different pancreatic cysts in the manuscript under “Participants, Eligibility criteria and outcomes” line 199ff.

2. Handling and evaluation of imaging data:

It is not clear whether the imaging findings are assessed solely based on site-reported entries in the case report forms or whether a central image review is planned. If central review of imaging data is not conducted, this should be explicitly stated. In that case, please describe how consistency across institutions (e.g., interobserver variability) will be managed or minimized. This point should be clearly addressed in the study protocol.

Answer 2: We thank Reviewer #1 for this comment. We will perform central image review. We have addressed this in line 205ff.

Reviewer #2: Comment

This is a large observational study of the long-term follow-up of pancreatic cystic lesions in Germany. Prospective studies of pancreatic cystic lesions are limited and the findings from this study are expected to be important. Some comments are provided below.

1. Abstract lacks primary endpoints, making it difficult to understand the study summary.

2. Is there a defined objective number of cases?

3. The evaluation items are difficult to understand. For example, the items to be evaluated in blood tests and in imaging tests. Why not list them all in a table?

Answer: We have addressed 1) in the abstract and have added the necessary information in line 86ff. Regarding 2) we have adjusted the manuscript accordingly in line 434f . Regarding comment 3) we have added a table to the supporting information addressing the items that are being evaluated at the moment. (S4 Table). However, this might change over the course of the 20 year study period.

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.

Answer 7: Yes, please include the peer review.

Attachments
Attachment
Submitted filename: kch edit Rebutal Letter GERPACYST.pdf
https://doi.org/10.1371/journal.pone.0335809.r002
Decision Letter - Yoshihisa Tsuji, Editor

GerPaCyst- The Trial Protocol Of The Prospective, Multicenter, Interdisciplinary German Pancreas Club Cyst Registry

PONE-D-25-34705R1

Dear Dr. Honselmann,

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,

Yoshihisa Tsuji

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

https://doi.org/10.1371/journal.pone.0335809.r003
Formally Accepted
Acceptance Letter - Yoshihisa Tsuji, Editor

PONE-D-25-34705R1

PLOS ONE

Dear Dr. Honselmann,

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on behalf of

Professor Yoshihisa Tsuji

Academic Editor

PLOS ONE

https://doi.org/10.1371/journal.pone.0335809.r004

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