The Impact of Gastrectomy on Inflammatory Bowel Disease Risk in Gastric Cancer Patients: A Critical Analysis

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

1. The article synthesizes findings from various studies but does not address the methodological differences between these studies. For example, the studies cited in relation to microbial changes post-gastrectomy do not all use the same surgical procedures, time frames, or patient populations. This heterogeneity is not sufficiently acknowledged, which weakens the generalizability of the conclusions.
2. Much of the article focuses on correlations between gastrectomy and the development of IBD, but it fails to address causality. While it presents microbial changes as risk factors for IBD, it does not explore whether these changes are causal or simply associated with other postoperative factors.
3. The article discusses nutritional deficiencies post-gastrectomy, but it does not offer a detailed exploration of how specific deficiencies (e.g., vitamin B12, iron) contribute to IBD pathogenesis or recovery. The role of nutritional interventions beyond probiotics is also under-explored.
4. The article touches on the long-term effects of gastrectomy, but this discussion remains superficial. For example, how do the changes in microbiota evolve years after surgery, and what are the implications for chronic disease management? The long-term clinical implications for patients are not fully addressed.
5. While the article suggests that probiotics can help restore gut health, the discussion lacks a thorough evaluation of which strains or formulations are most effective. Additionally, it doesn’t critically assess the limitations or challenges of implementing probiotic therapy in clinical practice.

Author Response

Dear reviewer. Thank you for your comments. We took all these into consideration.

1. We delved deeper into the methodological differences and acknowledged the Bias in our study. “Gastrointestinal malignancies… contributing to IBD progression”, “Tumor cells can also…inflammatory 

   Dear reviewer. Thank you for your comments. We took all these into consideration.

   1. We delved deeper into the methodological differences and acknowledged the Bias in our study. “Gastrointestinal malignancies… contributing to IBD progression”, “Tumor cells can also…inflammatory response in IBD”, “Gastric cancer cells, as well…to inflammation and stress in IBD”, “ Our study faces… long-term gut health”
   2. We made many references to the causality and that the changing in the microbiome is caused by the operation and the changing in gastrointestinal route.
   3. We offered a more specific analysis of the effect of the nutritional deficiencies.
   4. Unfortunately there are not many studies in the literature who had a long term follow up. This is one of the points of this review. To turn also the interest to long term affects.
   response in IBD”, “Gastric cancer cells, as well…to inflammation and stress in IBD”, “ Our study faces… long-term gut health”
2. We made many references to the causality and that the changing in the microbiome is caused by the operation and the changing in gastrointestinal route.
3. We offered a more specific analysis of the effect of the nutritional deficiencies.
4. Unfortunately there are not many studies in the literature who had a long term follow up. This is one of the points of this review. To turn also the interest to long term affects.

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript “The Impact of Gastrectomy on Inflammatory Bowel Disease Risk in Gastric Cancer Patients: A Critical Analysis” is a valuable contribution to the field of gastrointestinal surgery and oncology, with a particular focus on the interplay between gastrectomy and IBD. The paper effectively synthesizes a wide range of studies on gastrectomy and its impacts on gut microbiota, emphasizing the role of microbial dysbiosis in IBD development.

Major Limitations:

1.     The paper could benefit from a clearer organization, especially in distinguishing the findings related to gastrectomy for gastric cancer from those related to bariatric surgery. While the procedures share some similarities, the patient populations and clinical outcomes differ significantly. The inclusion of both gastric cancer and bariatric surgery patients, while adding breadth to the review, represents a significant weakness. Both gastric cancer and obesity, which often necessitates bariatric surgery, are associated with distinct pre-existing microbiota alterations. This confounding factor makes it difficult to directly compare the two patient populations and draw clear conclusions about the impact of gastrectomy alone on IBD development. A clearer distinction between these conditions, or a more focused analysis of the twos groups, would enhance the study’s validity and relevance.

2.     Although the paper discusses several mechanisms, such as dysbiosis, immune dysregulation, and nutritional deficiencies, the review lacks a cohesive framework linking these factors. A more structured approach that connects these mechanisms to clinical outcomes would improve clarity. Consider to cite PMID 36933563.

3.     The literature search appears comprehensive, utilizing databases like PubMed and Web of Science. However, the inclusion and exclusion criteria could be better defined.

4.     While the paper covers a wide array of studies, it would benefit from addressing the quality and limitations of the included studies. For instance, many of the referenced studies have small sample sizes or short follow-up periods, which limit the generalizability of the findings. The manuscript does not provide a formal evaluation of the quality of the studies included in the review. Without this, it is difficult to assess the reliability of the conclusions drawn. Incorporating a more rigorous evaluation, such as using established tools like the Cochrane Risk of Bias tool or GRADE (Grading of Recommendations, Assessment, Development, and Evaluation), would strengthen the review and help clarify whether the conclusions are based on high-quality evidence

5.     The discussion around the use of probiotics in ERAS protocols is promising, but the practical application in clinical settings is not thoroughly explored and strong evidence is lacking. More concrete recommendations based on the evidence presented would be useful for clinicians.

6.     The conclusion could benefit from more specific recommendations for future research.

Minor Comments:

1. There are a few minor typographical and grammatical errors throughout the text that should be addressed.
2. The introduction could be more concise, as some information is repeated later in the discussion.

Comments on the Quality of English Language

The manuscript is generally well-written 

Author Response

We would like to thank you for your thoughtful and constructive feedback on our manuscript. We have carefully addressed each of your comments and have made the necessary revisions to enhance the clarity and quality of the paper. Below is a summary of the actions we have taken in response to your suggestions:

1. Clearer Organization and Distinction Between Gastrectomy for Gastric Cancer and Bariatric Surgery:
   We agree with your observation regarding the distinction between the two patient populations. In response, we have reorganized the paper to more clearly differentiate the findings related to gastrectomy for gastric cancer from those related to bariatric surgery. We have also provided a more focused analysis of the distinct microbiota alterations and clinical outcomes in each group, which should clarify the impact of gastrectomy alone on IBD development.
2. Linking Mechanisms to Clinical Outcomes:
   We have restructured the manuscript to provide a more cohesive framework that connects dysbiosis, immune dysregulation, and nutritional deficiencies to clinical outcomes.
3. Inclusion and Exclusion Criteria:
   We have revised the methodology section to provide a clearer definition of the inclusion and exclusion criteria.
4. Evaluation of Study Quality and Limitations:
   We acknowledge the importance of assessing the quality and limitations of the included studies. However, our study is a narrative review with not enough studies related to the patients that underwent gastrectomy for gastric cancer. So we do not this that this is relevant since we already included a paragraph for our Bias.
5. Recommendations for Future Research:
   The conclusion has been revised to include more specific recommendations for future research, particularly regarding the long-term effects of gastrectomy on gut microbiota and IBD development, as well as the need for larger, more comprehensive studies.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The revised manuscript has made significant improvements based on the initial feedback, especially in terms of organization, clarity, and incorporation of more comprehensive references. However, there is still a need for more rigorous quality assessment of the included studies and the introduction of more practical clinical recommendations. There is still no formal evaluation of the quality of the studies included, and this remains a critical limitation. These adjustments would further enhance the impact and reliability of the paper.

Author Response

Thank you for your valuable feedback. In response to your suggestion, we would like to inform you that we have, in fact, applied the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) scoring system to assess the quality of the studies used in the manuscript. The GRADE system allowed us to evaluate the evidence based on the key outcomes of interest, addressing issues such as study design, bias, and precision. We recognize that some studies have limitations, while they are referred to bariatric surgery, or they have small number of patients etc and we have accounted for these factors in our analysis. We also added clearer suggestions according the use of probiotics in our analysis.

Thank you again for your constructive input, and we will work to improve the clarity and strength of our conclusions based on your advice.