SynthesisJournal of gastrointestinal cancer2025
The Association Between Proton Pump Inhibitor Use and Gastroenteropancreatic Neuroendocrine Tumors: A Systematic Review.
Synthesis in Journal of gastrointestinal cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThis systematic review evaluated the site-specific association between long-term use of proton pump inhibitors (PPIs) and neuroendocrine tumors (NETs), with a primary focus on gastric and duodenal NETs.
methodsEight non-randomized studies involving about 1273 cases from the USA, Mexico, and Italy were included and reviewed. Definitions of PPI exposure and comparator groups varied across studies, and methodological quality was assessed with the ROBINS-I tool. Due to heterogeneity in design and outcomes, results were narratively synthesized.
resultsThe findings were site-specific. For gastric NETs (G-NETs), an association was noted with indolent tumors-generally small, confined to the mucosa or submucosa, and rarely metastatic. In contrast, for pancreatic and ileal NETs, the main impact of PPIs is related to interference with the diagnostic biomarker chromogranin A (CgA) rather than tumorigenesis. Several studies indicated a biological link between prolonged PPI therapy, enterochromaffin-like (ECL) or parietal cell hyperplasia, and tumor development, whereas others emphasized chronic atrophic or autoimmune gastritis as major contributors. PPIs were also found to elevate circulating CgA, potentially confounding diagnosis, while vasostatin-1 (VS-1) emerged as a more specific biomarker.
conclusionThe association between PPI use and GEP-NETs is site-specific. PPI-associated G-NETs appear to represent a distinct subgroup with low malignant potential, whereas links to non-gastric NETs seem more related to diagnostic confounding. Hypergastrinemia plays a central role in pathogenesis, but co-factors such as atrophic gastritis, autoimmune gastritis, and Helicobacter pylori infection likely contribute. The association is multifactorial, and large prospective studies are needed to establish causality.
Indexed as
Identifiers
41191220What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.