PONE-D-23-03805Adequacy of endoscopic recognition and surveillance of gastric intestinal metaplasia and atrophic gastritis: a multicentre retrospective study in low incidence countriesPLOS ONE Dear Dr. di Pietro,

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Reviewers' comments:

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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: Partly

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: No

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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: Manuscript title:

Adequacy of endoscopic recognition and surveillance of gastric intestinal

metaplasia and atrophic gastritis: a multicentre retrospective study in low

incidence countries (Manuscript ID: PONE-D-23-03805).

Authors:

J.Honing, W.Keith Tan, E. Dieninyte, M.O’Donovan, L.A.A.Brosens, B.L.A.M.Weusten,6 and M. di Pietro.

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GENERAL COMMENTS

This study aims "to evaluate endoscopic recognition and adequacy of surveillance for GA/GIM in countries with low GAC prevalence."

Three centers from Netherlands and UK (years 2012- 2019) were retrospectively involved.

A consistent number of patients (396, with a median follow-up of 57.2 months) with GIM/GA diagnosis at index endoscopy were retrieved through a systematic search of pathology databases.

By assuming histology as the reference standard (?, if so, the histology criteria should be mentioned), endoscopic recognition rates were 48.5 % for GA and 16.3 % for GIM.

According to the ESGE guidelines, surveillance was adequately carried out in 215 out of 396 patients (54.3%).

The Authors (wisely) conclude that in countries with a low GC incidence, the rate of endoscopic recognition of gastric pre-cancerous lesions and adherence to surveillance recommendations are low.

The issue addressed by this study is of primary importance, that's why my personal opinion about the priority of this study. The study, however, includes some major methodological weaknesses that should be carefully addressed to make the Authors' conclusions consistent with an evidence-based approach.

In retrieving the considered patients, the authors regarded the definitions of atrophic gastritis and intestinal metaplasia as equivalent. The two conditions are not biologically nor clinically the same, being IM one of the histological phenotypes included in the Atrophy definition.

The reliability of endoscopy in atrophy detection is considered lower than that of IM (particularly by adopting high-resolution instruments). It is frankly unexpected the higher value of consistency in endoscopic detection of atrophy versus IM (48.5 % for GA versus 16.3 % for IM). This impressive result should be carefully considered and confirmed.

The definition of pangastritis includes heterogeneous clinical and histological situations. According to the Sydney system, the current (ambiguous) definitions of pangastritis includes different conditions associated with different GC risk:

(a) sparse foci of atrophy involving the mucous-secreting antrum and the oxyntic compartment;

(b) extensive atrophic lesions involving both the antrum and body (i.e., Open Type gastritis according to Kimura and Takemoto).

I agree entirely with the author's choice of assuming histology as a reference standard in atrophy assessment. Histology reliability - however - is strongly conditioned by the biopsy sampling protocol. No information about this crucial issue is reported.

All those mentioned above "basic" discrepancies in gastritis classification/definition may result in an equivocal clinical setting which may ultimately affect both the choice of the follow-up strategy and the consistency of the follow-up schedule with the considered ESGE guidelines.

Reviewer #2: The paper titled: "Adequacy of endoscopic recognition and surveillance of gastric intestinal metaplasia and atrophic gastritis: a multicentre retrospective study in low incidence countries" is very interesting regarding the rate of endoscopic recognition of gastric pre-cancerous lesions. Also, the authors state well the limitations of this study. However, I would like to ask the authors to provide more info with regards to the histological confirmation of the cases that they studies. For all the cases did the histological analysis confirm correctly the status of each case? Also, what was the time between the histological analysis and the endoscopy. The authors should provide a comparison between endoscopic and histological confirmation of the cases (as the histological confirmation remains the gold standard). Finally, a further discussion is needed with regards to the AI tools for the confirmation of these cases. For example, I would suggest the authors take into account and discuss the following recent work: "A digital pathology workflow for the segmentation and classification of gastric glands: Study of gastric atrophy and intestinal metaplasia cases".

Generally, I think that this article will certainly be of interest to many readers of PLOS One.

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Reviewer #1: No

Reviewer #2: No

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Adequacy of endoscopic recognition and surveillance of gastric intestinal metaplasia and atrophic gastritis: a multicentre retrospective study in low incidence countries

PONE-D-23-03805R1

Dear Dr. di Pietro,

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,

Ozlem Boybeyi-Turer

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Congratulations for your manuscript since the authors have addressed and clarified all required points. Therefore, I think the revised version of the manuscript is suitable for publication in PLOSONE.

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 #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 #2: Yes

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

Reviewer #2: Yes

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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 #2: Yes

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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 #2: Yes

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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 #2: In the revised manuscript, the authors have provided a more thorough explanation of their methodology, addressing the gaps and clarifying any ambiguities that were present in the initial version. The additional details and clarity have improved the understanding of their research approach.

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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 #2: No

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