Reply to Sah et al.

10.1055/a-2781-6343

We sincerely thank Drs. Sah and Kumbhalwar for their thoughtful letter and interest in our study [1]. We appreciate their recognition of our approach to capturing post-endoscopic submucosal dissection (ESD) burden across both minor and major post-procedural events.

Regarding residual confounding, we acknowledge that both the age-adjusted Charlson Comorbidity Index (ACCI) and the American Society of Anesthesiologists Physical Status (ASA-PS) classification reflect important aspects of patients' overall condition. However, in our propensity-score model, we deliberately selected ACCI as the primary comorbidity measure because ACCI and ASA-PS represent conceptually distinct constructs that cannot realistically be balanced simultaneously [2]. Enforcing tight balance on both indices would have substantially reduced the number of matched pairs. ACCI incorporates both age and a comprehensive range of comorbidities, and our matching achieved an absolute standardized difference of 0.10, indicating satisfactory balance. While some residual confounding may persist, we believe this represents a reasonable compromise for an exploratory study.

Concerning exposure characterization, we agree that our dichotomous classification of glucocorticoid/immunomodulator (GC/IM) use represents a simplification [3]. Although exploratory subgroup analyses by agent type and GC dose revealed no clear patterns, these analyses were constrained by small sample sizes, especially in the IM-only subgroup. In addition, because of the inherent limitations of a retrospective study design, we were unable to access complete information on cumulative dose, treatment duration, or other treatment-specific variables for all patients. Future studies with prospective data collection will be essential to strengthen the biological plausibility framework and better inform counseling for patients receiving different immunosuppressive regimens.

The concern regarding our composite endpoint is valid. As an exploratory study in a field lacking established evidence, we selected a pragmatic composite endpoint to capture overall post-ESD clinical workload. Minor symptoms such as pain [4] or low-grade fever [5] frequently necessitate bedside assessments, medication administration, and occasionally imaging, thereby contributing to real-world resource utilization. Concurrently, we analyzed major complications—delayed bleeding and perforation—separately as clinically critical outcomes; these remained uncommon and showed no between-group differences. While more stratified burden analyses (e.g., symptom-specific lengths of stay or readmission risk) would provide additional insight, our limited sample size constrained the robustness of such modeling.

Finally, we appreciate the emphasis on the febrile patient subgroup. The overall absence of significant differences in hospitalization duration appears largely attributable to the very small number of febrile cases and the fact that patients with pain alone generally achieved adequate symptom control with analgesics, allowing timely discharge. Although the fever subgroup demonstrated a numerically longer median hospital stay, the sample size was insufficient to determine clinical significance. Only a larger dataset could clarify whether early fever truly signals prolonged recovery risk in GC/IM users undergoing gastric ESD and help refine triage and follow-up strategies.

We appreciate the constructive comments by Drs. Sah and Kumbhalwar, which highlight important methodological and clinical issues for future research. We hope that our study, together with their letter, will contribute to more nuanced risk stratification, informed consent, and postoperative care for immunosuppressed patients undergoing gastric ESD.

Publication note

Letters to the editor do not necessarily represent the opinion of the editor or publisher. The editor and publisher reserve the right to not publish letters to the editor, or to publish them abbreviated or in extracts.

Contributorsʼ Statement

Hiroki Fukuya: Conceptualization, Formal analysis, Writing - original draft. Eikichi Ihara: Supervision, Writing - review & editing. Yoichiro Iboshi: Supervision, Writing - review & editing. Yorinobu Sumida: Resources, Validation, Writing - review & editing. Daisuke Yoshimura: Data curation, Writing - review & editing. Shohei Hamada: Data curation, Writing - review & editing. Taisuke Sasaki: Data curation, Writing - review & editing. Akito Ohkubo: Data curation, Writing - review & editing. Shuichi Itonaga: Data curation, Writing - review & editing. Hitoshi Homma: Data curation, Writing - review & editing. Ryota Okitsu: Data curation, Writing - review & editing. Akihisa Ohno: Formal analysis, Methodology. Mitsuru Esaki: Formal analysis, Methodology. Naohiko Harada: Writing - review & editing.

Conflict of Interest

Eikichi Ihara received lecture fees from Takeda Pharmaceutical Co.Ltd., EA Pharma Co. Ltd., and Viatris Inc. The other authors declare no other conflicts of interest in association with this article.

• References

• 1 Fukuya H, Ihara E, Iboshi Y. et al. Clinical feasibility of gastric endoscopic submucosal dissection in patients on glucocorticoids or immunomodulators: Propensity-score-matched study. Endoscopy International Open 2025; 13
• 2 Lavelle EA, Cheney R, Lavelle WF. Mortality Prediction in a Vertebral Compression Fracture Population: the ASA Physical Status Score versus the Charlson Comorbidity Index. Int J Spine Surg 2015; 9: 63
• 3 Yamamoto S, Kinugasa H, Yamasaki Y. et al. Fever and electrocoagulation syndrome after colorectal endoscopic submucosal dissection for patients with immunosuppressants and steroids. DEN Open 2022; 2: e83
• 4 Jung DH, Youn YH, Kim JH. et al. Factors influencing development of pain after gastric endoscopic submucosal dissection: a randomized controlled trial. Endoscopy 2015; 47: 1119-1123
• 5 Itaba S, Iboshi Y, Nakamura K. et al. Low-frequency of bacteremia after endoscopic submucosal dissection of the stomach. Dig Endosc 2011; 23: 69-72

Publication History

Received: 12 December 2025

Accepted: 21 December 2025

Article published online:
27 January 2026