Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, but they frequently trigger gastrointestinal side effects—diarrhea being among the most common. When such diarrhea occurs, clinicians often measure fecal elastase to gauge pancreatic function. However, a key limitation of this test is that watery stool can dilute elastase concentrations, potentially leading to misdiagnosis of pancreatic insufficiency. Whether low fecal elastase in ICI-treated patients reflects genuine pancreatic dysfunction or merely stool dilution has remained unclear.
A new study made available online on July 16, 2026, in the Journal of Pancreatology set out to answer this question. Researchers at The University of Texas MD Anderson Cancer Center and the Cleveland Clinic retrospectively reviewed 388 patients treated with ICIs who developed diarrhea and underwent fecal elastase testing between 2016 and 2024.
The team found that fecal elastase was low in 168 (43.3%) and normal in 220 patients (56.7%). Crucially, patients with low elastase had significantly higher fecal calprotectin levels (356.0 vs. 124.9 mcg/g), indicating greater gastrointestinal inflammation. Yet on colonoscopy and histology, the rates of active inflammation were similar between the low- and normal-elastase groups.
Most importantly, diarrhea outcomes were similar regardless of elastase status: remission occurred in 74.4% of patients with low elastase and 69.1% of those with normal levels. Baseline pre‑existing pancreatic abnormalities were rare and unrelated to elastase levels, though new ICI‑related pancreatic injury was observed more frequently among patients with low elastase. Together, these findings suggest that in ICI-related diarrhea, low fecal elastase is more likely a dilutional artifact than evidence of true exocrine pancreatic insufficiency.
The authors recommend that when pancreatic disease is genuinely suspected, clinicians should consider confirmatory fecal fat testing before initiating pancreatic enzyme replacement therapy. This highlights the need for comprehensive diagnostic approaches, including fecal fat testing, to confirm exocrine pancreatic insufficiency before starting enzyme therapy.
Reference
Title of original paper: Role of fecal elastase in the context of diarrhea related to immune checkpoint inhibitors
Journal: Journal of Pancreatology
DOI: https://doi.org/10.1097/JP9.0000000000000262
About Dr. Yinghong Wang from The University of Texas, USA
Yinghong Wang, Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
E-mail: ywang59@mdanderson.org
Funding Information
This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.
Journal of Pancreatology
Not applicable
Role of fecal elastase in the context of diarrhea related to immune checkpoint inhibitors
16-Jul-2026
The authors declare no conflicts of interest.