Management of Gastric Precancerous Lesions and Early Cancer: Practice-Oriented Answers to Clinical Questions

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a well-structured and insightful review that brilliantly maps out the management of Gastric Precancerous Lesions and Early Cancer. Here are a few comments.

1. Page 4, lines 113-130, while the text provides a wonderful overview of the technical mechanics for conducting high-quality endoscopy, diagnostic tools, imaging techniques, and tissue sampling procedures are missing here.

 

2. The authors should also specify that during First-time diagnostic endoscopy, samples should be tested for Helicobacter pylori, as its abolition is important for pausing the progression of precancerous lesions.

 

3. The text provides an outstanding, evidence-based outline for choosing between EMR and ESD in early gastric neoplasia. However, a few additional details about submucosal fibrosis are missing.

Author Response

Comment 1: Page 4, lines 113-130, while the text provides a wonderful overview of the technical mechanics for conducting high-quality endoscopy, diagnostic tools, imaging techniques, and tissue sampling procedures are missing here.
Response 1: We sincerely thank the Reviewer for this observation. We agree that advanced diagnostic tools (such as HD-WLE and virtual chromoendoscopy) and standardized tissue sampling procedures are fundamental pillars of high-quality endoscopy. However, to maintain a concise, practice-oriented narrative and avoid redundancy, we thoroughly detail these specific imaging techniques and biopsy protocols in the subsequent paragraphs of the manuscript. To clarify this for the reader without unnecessarily repeating information, we have added a brief cross-reference in section 3.1, seamlessly directing them to the upcoming comprehensive discussion (lines 153-156).

Comment 2: The authors should also specify that during First-time diagnostic endoscopy, samples should be tested for Helicobacter pylori, as its abolition is important for pausing the progression of precancerous lesions.
Response 2: We thank the Reviewer for highlighting this fundamental clinical aspect. We completely agree that identifying and treating Helicobacter pylori infection during first-time diagnostic endoscopy is a mandatory step to halt the progression of the gastric precancerous cascade. As suggested, we have modified the manuscript to explicitly state the necessity of H. Pylori testing via biopsy sampling during the first-time diagnostic endoscopy (lines 224-226).

Comment 3: The text provides an outstanding, evidence-based outline for choosing between EMR and ESD in early gastric neoplasia. However, a few additional details about submucosal fibrosis are missing.
Response 3: We sincerely thank the Reviewer for the positive feedback and for highlighting this critical clinical aspect. We completely agree that the presence of submucosal fibrosis is a major determinant in therapeutic decision-making. As suggested, we have expanded Section 3.8 to explicitly discuss how submucosal fibrosis limits the feasibility of EMR and mandates the use of ESD (lines 355-361).

Reviewer 2 Report

Comments and Suggestions for Authors

Dear authors

 The aforementioned paper with title "Management of Gastric Precancerous Lesions and Early Cancer" : Practice-Oriented Answers to Clinical Questions  is reviewed.  The authors provide a comprehensive, clinically-oriented review of the management of gastric precancerous conditions and early gastric cancer. The question-and-answer approach is highly effective for bridging the gap between guidelines and practice. The authors used comprehensive evidence sensitive such as; 2025 ESGE guidelines, 7th Edition JGCA concepts like OLGIMA and FAMISH scoring, Comprehensive management flowchart, balanced presentation of controversies and high-quality figures.

Although, lots of advantageous is existed, there are some suggestions such as;

1-Consider adding a small table comparing OLGA vs OLGIM vs OLGIMA for quick reference in risk strategies.

2-Clear recommendations for Sydney protocol sampling and clear algorithm for managing "dysplasia without visible lesion.

3- The manuscript states the literature search was conducted "up to April 2026." This is either an error (should be 2025) or the authors have somehow incorporated future publications. This needs clarification and correction.

4- There are apparent duplications, Page 7: "3.5 What is the role of virtual chromoendoscopy...”, Page 8: "3.6 What is the role of virtual chromoendoscopy..."
Section 3.6 appears to be about surveillance but has the same title as 3.5. This should be corrected.

5- Breaking table 1 into two tables (diagnosis/risk stratification + treatment/surveillance) because it is very dence.

6- Please check the authors affiliations.

7- It needs more language clarity  ex:

• "Potential cure" vs "curative" - consistently use "curative resection" throughout for clarity
• Some sentences are excessively long (e.g., first paragraph of 3.2) - consider breaking into shorter sentences
• "The eCura system...illustrated in Figure 4" - good cross-reference

8- Figure 2 (A-D) - labels are clear but consider adding arrows or annotations to highlight key features.

9- Remove duplicate reference (72 = 14)

10- Add brief discussion of implementation challenges/training needs

11- Include a "Future Directions" section (AI beyond detection, biomarkers, molecular risk stratification)

 

In the final, I recommend this paper for publication ofter revisison.

Regards 

Comments on the Quality of English Language

It needs more language clarity ex:

• "Potential cure" vs "curative" - consistently use "curative resection" throughout for clarity
• Some sentences are excessively long (e.g., first paragraph of 3.2) - consider breaking into shorter sentences
• "The eCura system...illustrated in Figure 4" - good cross-reference

Author Response

Comment 1: Consider adding a small table comparing OLGA vs OLGIM vs OLGIMA for quick reference in risk strategies.
Response 1: We thank the Reviewer for this excellent suggestion, which greatly enhances the practical utility and readability of our manuscript. As requested, we have added a new table (Table 2) that provides a concise comparison of the OLGA, OLGIM, and OLGIMA staging systems to serve as a quick reference for risk stratification strategies.

Comment 2: Clear recommendations for Sydney protocol sampling and clear algorithm for managing "dysplasia without visible lesion."
Response 2: We thank the Reviewer for highlighting these important clinical aspects. Regarding the first point, we have included clear recommendations for the Sydney protocol sampling in the revised text (lines 224-226). As for the management of "dysplasia without visible lesion," while this topic was already addressed in the manuscript (lines 311-314), we have enhanced this section by integrating further clarifications specifically detailing the management of High-Grade Dysplasia (HGD) to provide clearer guidance.

Comment 3: The manuscript states the literature search was conducted "up to April 2026." This is either an error (should be 2025) or the authors have somehow incorporated future publications. This needs clarification and correction.
Response 3: We thank the Reviewer for this observation, but we confirm that there is no typographical error. Our comprehensive literature search was indeed updated and finalized in April 2026, just prior to the submission of this manuscript, to ensure the inclusion of the most up-to-date evidence. Therefore, we have retained 'April 2026' in the text to accurately reflect our methodology.

Comment 4: There are apparent duplications, Page 7: "3.5 What is the role of virtual chromoendoscopy...”, Page 8: "3.6 What is the role of virtual chromoendoscopy..."
Section 3.6 appears to be about surveillance but has the same title as 3.5. This should be corrected.
Response 4: We thank the Reviewer for catching this oversight. We apologize for the duplication error in the section heading. We have now corrected the title of Section 3.6 to reflect its content regarding surveillance. The heading has been updated to read: "3.6 When is endoscopic surveillance appropriate for precancerous conditions?"

Comment 5: Breaking table 1 into two tables (diagnosis/risk stratification + treatment/surveillance) because it is very dense.
Response 5: We thank the Reviewer for this practical observation regarding the density of Table 1. To improve readability while keeping all related information conveniently consolidated, we have clearly separated the two topics (diagnosis/risk stratification and treatment/surveillance) into two distinct sections within the same table.

Comment 6: Please check the authors affiliations.
Response 6: We have reviewed and corrected the authors' names and affiliations section in the revised manuscript.

Comment 7: It needs more language clarity  ex: "Potential cure" vs "curative" - consistently use "curative resection" throughout for clarity Some sentences are excessively long (e.g., first paragraph of 3.2) - consider breaking into shorter sentences
Response 7: We thank the Reviewer for these constructive suggestions, which have significantly improved the readability and clarity of our manuscript. We agree with the observation regarding terminology and have carefully reviewed the entire text, consistently replacing terms such as "potential cure" with "curative resection." Furthermore, we have revised the sentence structure; specifically, the excessively long sentences in the first paragraph of Section 3.2 have been broken down into shorter, clearer statements..

Comment 8: Figure 2 (A-D) - labels are clear but consider adding arrows or annotations to highlight key features”.
Response 8: We thank the Reviewer for this helpful suggestion, which significantly improves the visual clarity of our manuscript. We agree that highlighting the key features makes the images much more intuitive for the reader. Accordingly, we have modified Figure 2 (A-D) by adding explicit arrows and annotations to clearly identify the relevant endoscopic findings.

Comment 9: "Remove duplicate reference (72 = 14)".
Response 9: We apologize for this oversight. We have removed the duplicate reference (former Reference 72) and carefully updated the numbering throughout the text and the bibliography accordingly. We thank the Reviewer for catching this error.

Comment 10: "Add brief discussion of implementation challenges/training needs".
Response 10: We thank the Reviewer for highlighting this important aspect. We completely agree that addressing practical implementation and specific training requirements provides a much more comprehensive overview of the topic. Accordingly, we have expanded our discussion to include these points (lines 555-565).

Comment 11: "Include a "Future Directions" section (AI beyond detection, biomarkers, molecular risk stratification)".
Response 11: We thank the Reviewer for this forward-looking suggestion. We fully agree that outlining these upcoming advancements provides a valuable perspective for the field. As requested, we have added a dedicated "Future Directions" section (section 6) to the revised manuscript, which explicitly addresses the evolution of artificial intelligence beyond simple detection, the application of novel biomarkers, and the potential of molecular risk stratification.

Reviewer 3 Report

Comments and Suggestions for Authors

Our research colleagues have produced a study whose goal is to summarize current evidence and provide practice-oriented, question-based guidance for the management of gastric precancerous lesions and early gastric cancer. The title is well-crafted, and the abstract provides a good summary of the entire study. In the next section, we agree with what is stated regarding Helicobacter pylori, but it is now well established that diet plays a fundamental role in all gastrointestinal malignancies. While we completely agree with what is stated subsequently, I would add that in cases of chronic atrophic gastritis, it is always advisable to also test for HBV. As the authors write, a deep biopsy performed in multiple locations is essential because the tumor may be multifocal. Their comments regarding endoscopic resection are also correct. The materials and methods are described with great care and are reproducible in any high-volume tertiary care hospital, based on experience gained in the field. Furthermore, this is a comprehensive review based on independent literature research, which requires discerning articles of particular significance. Therefore, the work is well conducted. The findings begin by considering diagnostics as the cornerstone of the oncology process. Even what is written subsequently is accurate and acceptable, including the relatively close follow-up for those who require it based on clinical experience. The description of the lesions and subsequent endoscopic interventions, which in 25% of cases are followed by major surgery, is very thorough. We also appreciated the considerations regarding metachronous neoplasms and the collection of all the evidence that, where necessary, was submitted to the multidisciplinary discussion, although in our experience, it is good practice to bring all committee members to a decision. In conclusion, this paragraph is well written, characterized by the numerous tables and further clarified for the reader, although it could be shortened where concepts are repeated. The discussion is well-described, and congratulations to the authors for their writing about their study. We can only recommend, as they mentioned in the results, introducing the use of artificial intelligence, which is rapidly emerging in clinical practice (doi.org/10.3390/jcm15062208, to be read and cited in the bibliography). The weaknesses are well-introduced. The sentence "The management of gastric precancerous lesions and early-stage gastric cancer is increasingly based on a structured and individualized approach" is excellent. Congratulations to the authors, because this is truly one of the first comprehensive studies on this topic. Good English, good bibliography, and excellent illustrations.

Author Response

We sincerely thank the Reviewer for the thorough evaluation of our manuscript and for the highly positive and encouraging remarks. We are delighted that the practice-oriented approach, the methodology, and the comprehensiveness of our review were appreciated.

Comment 1: While we completely agree with what is stated subsequently, I would add that in cases of chronic atrophic gastritis, it is always advisable to also test for HBV.

Response 1: We thank the Reviewer for this suggestion. While we acknowledge the importance of a comprehensive clinical evaluation of the patient, current international guidelines—such as the ESGE MAPS III guidelines—focus primarily on Helicobacter pylori eradication and do not currently recommend routine screening for the Hepatitis B Virus (HBV) as part of the standard diagnostic and surveillance pathways for chronic atrophic gastritis. To maintain the manuscript's strict focus on established, guideline-driven gastroenterological and endoscopic risk factors directly implicated in the Correa cascade, we have opted not to include this specific recommendation in the revised text. We hope the Reviewer will understand our rationale for keeping the scope strictly aligned with current endoscopic guidelines.

Comment 2: We can only recommend, as they mentioned in the results, introducing the use of artificial intelligence, which is rapidly emerging in clinical practice (doi.org/10.3390/jcm15062208, to be read and cited in the bibliography).

Response: We completely agree with the Reviewer on the transformative impact of artificial intelligence in this field. As suggested, we have updated the Results section to highlight its emerging role in clinical practice and have gladly incorporated the recommended reference, which provides excellent insights into this topic (row 143-146).

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Dear authors

All the comments in the first review are replied or corrected only minor revision are needed:

1- line 218: revise the name of bacteria to Helicobacter pylori.

2- Line 398- 399:  The main sentence divided to short  sentences.

Regards

Author Response

Thank you for pointing this out. We corrected the manuscript accordingly.

Reviewer 3 Report

Comments and Suggestions for Authors

Our colleagues have revised their study according to the reviewers' recommendations. Some parts of the original paper have been modified. The work is more precise than the previous version and is an enjoyable and informative read, especially the final section, where the authors describe future treatment options for this disease. We support the editor so that this study can be published and thus opened to a wider audience of colleagues who can benefit from it in terms of knowledge and thus improve their work. Good English, good bibliography, excellent illustrations.

Author Response

Thank you for your appreciation.