Gone but not forgotten: expanding the spectrum of ORISE (submucosal lifting agent) associated diagnostic pitfalls and complications.

Aims: A synthetic lifting agent, ORISE, used for endoscopic mucosal resections, has been recalled from the market since November 2022 due to clinical complications. Despite this, the impact of ORISE-associated complications is expected to persist in the foreseeable future. We present a large single institutional series of therapeutic resections from patients for whom ORISE was used for initial endoscopic procedures, highlighting the pitfalls and complications associated with its use.

Methods: All specimens showing lifting agent granulomata (LAGs) associated with the use of ORISE were identified. The H&E slides were reviewed to define the morphological characteristics and extent of LAG in the intestinal wall and other organs. The clinical impression and gross findings were compared with the final pathological diagnosis.

Results: 34 cases (28 resections and 6 repeat endoscopic mucosal resection specimens) showed LAG. On microscopy, 20.5% showed no residual disease, 64.7% also showed residual precursor lesion and 14.7% also showed malignancy. In 64.2% of cases, a mass lesion was seen grossly but no malignancy was identified microscopically. ORISE was present in vascular spaces (n=9), lymph nodes (n=2), other organs such as appendix (n=1) and omentum/peritoneum (n=1). The major discordance between clinical impression (mass/neoplasm) and final pathology (no residual malignancy) was seen in 4/34 (11.8%) cases. LAGs were seen up to 10 months after the use of ORISE in the prior endoscopic procedure.

Conclusion: ORISE deposits may mimic residual/disseminated neoplasm and prompt inadvertent changes in surgical decisions. Awareness of this pitfall is essential to prevent unwarranted surgical resections in patients undergoing follow-up for endoscopically resected lesions.