Dear Editor,
We have read your recent article titled “Immediate and long-term efficacy of persistent throat symptoms to gastric inlet patch ablation.”1 This study provides important real-world efficacy data for the ablation treatment of gastric inlet gastric inlet patch (GIP), and we commend it highly.
The study results indicate that 50 per cent (18/36) of patients responded to argon plasma coagulation (APC) ablation in the short term. Furthermore, during long-term follow-up (median, 4.5 years), 75 per cent (9/12) of initial responders maintained their therapeutic response. These data not only confirm the enduring benefits of ablation for some patients but also highlight a critical clinical conundrum: Why does the treatment prove effective only for certain patients, and why does its long-term efficacy diminish over time?
As discussed in the article, the heterogeneity in therapeutic efficacy may be related to factors such as whether GIP is completely ablated, its histological subtype (e.g., presence of acid-secreting cells) and the presence of concomitant Helicobacter pylori infection. These observations suggest that GIP is not a homogeneous “acid patch,” but may exhibit significant functional differences.
Based on this, we propose an integrated conceptual framework for discussion: GIP/esophagogastric mucosal ectopia (EGHM) may be redefined as a functionally active “foregut microenvironment hub.” As an ectopic intact gastric mucosa, it functions as an active unit with a diverse “secretory proteome”: it secretes pepsin (capable of driving inflammation and visceral hypersensitivity even at non-optimal pH),2 releases neuroendocrine substances (such as 5-hydroxytryptamine)3 and actively shapes the local immune and microbial microenvironment through secretion of factors like human β-defensin-2, Trefoil factor 3 and cytokines (e.g., interleukin [IL]-8), actively shaping the local immune and microbial microenvironment. This constitutes a complex local signalling network.4–6
From this perspective, several findings in your paper can be interpreted further:
Mechanisms underlying therapeutic efficacy differences: Variations in ablation response rates may stem from differing functional activities of the GIP “hub” across patients (e.g., variations in pepsin secretion levels or local immune activation states). This provides a pathophysiological explanation for the article’s assertion that “not all GIP triggers symptoms.”
Impact of co-morbidities: Some patients with concomitant hiatal hernia or Barrett’s oesophagus demonstrated poor treatment outcomes in the study, suggesting their symptoms may primarily stem from typical distal gastroesophageal reflux disease (GORD) rather than local “pivot points.” This underscores the importance of identifying the primary symptom driver prior to ablation.
Long-term efficacy decline: During extended follow-up, some patients experienced diminished therapeutic response. This may be attributed not only to incomplete ablation of lesions but also to long-term remodelling of the local microenvironment (e.g., immune system, microbiome) following ablation.
Therefore, we fully concur with your paper’s conclusion that “future research should focus on patient selection.” We further suggest that future selection criteria could extend beyond morphology to functional activity. For instance, could targeted biopsies prior to ablation enable histological subtype analysis, pepsinogen immunohistochemistry or Helicobacter pylori testing to assess the activity of this “hub”? For patients with “high activity” and highly symptomatic presentations, ablation may represent precise resection. Conversely, for patients with low activity or multifactorial symptom origins, non-destructive targeted therapies (e.g., pepsin inhibitors) or enhanced anti-reflux management may be prioritised.
We believe that advancing treatment decisions from “whether to ablate” to “for whom to ablate,” and implementing risk stratification based on “functional activity,” represents a crucial step towards achieving truly personalised and precision-based therapy in this field.
Thank you for publishing this thought-provoking and important research.
Sincerely,
Lijuan Fan
Availability of supporting data
Data sharing is not applicable to this article as no new datasets were generated or analysed during the current study.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. The authors have no competing financial interests to declare. No specific funding was received for the preparation of this manuscript.
Competing interests
The authors declare that they have no competing interests.
Ethical approval and consent to participate
Not applicable. No new human or animal subjects were involved.
Acknowledgements
The authors thank all colleagues involved in this work and acknowledge the editorial team for the opportunity to contribute this correspondence.
Human ethics
Not applicable. This manuscript does not contain any new studies with human participants performed by any of the authors.
Consent for publication
Not applicable.
Authors’ contributions
This work was conceptualised and supervised by Lijuan Fan (Corresponding Author). The original draft was written equally by Ruifang Hu and Zongyao Liu. All authors reviewed and approved the final manuscript.
