Comment on the study by Fukuya et al. (2025)

10.1055/a-2733-1229

Dear Editor,

We read with great interest the retrospective propensity score-matched study by Fukuya et al., which evaluated clinical feasibility of gastric endoscopic submucosal dissection (ESD) in patients receiving glucocorticoids or immunomodulators [1]. Use of a composite primary endpoint integrating both minor and major post-procedural events, along with granular data on analgesic and antipyretic use, reflects an important step toward operationalizing the post-ESD resource burden as a pragmatic outcome. Although the findings support the procedural feasibility in immunosuppressed individuals, several aspects merit deeper consideration regarding causal inference, exposure characterization, and post-procedure care implications.

Although the matching strategy was carefully constructed, it did not fully balance the age-adjusted Charlson Comorbidity Index (absolute standardized difference = 0.100) or the American Society of Anesthesiologists Physical Status classification, both of which are critical proxies for procedural resilience [2]. This partial imbalance may introduce residual confounding, particularly given the established interaction between systemic immunosuppression and host inflammatory thresholds. Clinically, this limits generalizability of the safety signal, especially when extrapolating to patients with higher functional vulnerability or complex multimorbidity.

The study defined exposure based on a dichotomous classification of glucocorticoid or immunomodulator use; however, agent-specific and dose-stratified effects remain unclear. The data revealed that no adverse events (AEs) occurred in the small immunomodulator-only subgroup, whereas higher glucocorticoid doses were paradoxically associated with fewer complications. However, the limited sample size precluded meaningful interpretation. Absence of cumulative dose, treatment duration, or immunologic biomarker data weakens the biological plausibility framework [3]. From a clinical standpoint, this raises uncertainty when counseling patients regarding procedural risk stratification for varying immunosuppressive regimens.

Interpretively, the composite endpoint, although pragmatic, aggregates fever and pain with delayed bleeding and perforation without weighting their clinical relevance. Although this reflects total resource utilization, it may overstate the impact of low-grade symptoms that resolve with conservative management [4]. Notably, only one major event (delayed bleeding) occurred in the glucocorticoid and immunomodulator groups. A stratified burden analysis, such as symptom-specific lengths of stay or readmission risk, could offer more nuanced insights into which events truly disrupt care pathways.

The authors noted that symptom-directed management resulted in complications without prolonging hospitalization in most cases. However, the fever subgroup had a median stay of 18 days, more than double that of asymptomatic patients, suggesting that early minor symptoms may sometimes herald protracted recovery in immunosuppressed individuals [5]. Clarifying which baseline features predict escalation from manageable symptoms to extended hospital care could refine triage protocols and inform pre-procedure risk disclosure.

We commend the authors for integrating symptom-driven management metrics into a procedural outcome framework and for operationalizing real-world feasibility through resource-based endpoints rather than binary AEs. Clarifying these analytical and clinical dimensions may improve procedural decision-making for this growing patient population and ensure more tailored consent and monitoring protocols in the setting of gastric endoscopic submucosal dissection.

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Contributorsʼ Statement

Shyam Sundar Sah: Conceptualization, Methodology, Writing - original draft, Writing - review & editing. Abhishek Kumbhalwar: Project administration, Supervision, Validation, Writing - original draft, Writing - review & editing.

Conflict of Interest

The authors declare that they have no conflict of interest.

• References

• 1 Fukuya H, Ihara E, Iboshi Y. et al. Clinical feasibility of gastric endoscopic submucosal dissection in patients on glucocorticoids or immunomodulators: a propensity-score-matched study. Endosc Int Open Published 2025; 13: a27331229
• 2 Kılıç M, Bombacı E, Çevik B. The comparison of ASA, SORT, CCI and CACI indexes to predict postoperative intensive care requirement in patients with gastrointestinal malignancy surgery. Bakirkoy Tip Dergisi/Medical Journal of Bakirkoy 2019; 15: 142-149
• 3 Bantia S, Choradia N. Treatment duration with immune-based therapies in Cancer: an enigma. J Immunother Cancer 2018; 6: 143
• 4 Leung DY. End points in clinical trials: are they moving the goalposts?. Heart 2006; 92: 870-872
• 5 Lamb HM, Goa KL. Management of febrile episodes in neutropenic patients. Disease Management Health Outcomes 1999; 5: 101-115

Publication History

Received: 08 November 2025

Accepted: 05 January 2026

Article published online:
27 January 2026