ReviewESMO gastrointestinal oncology2026
Early-onset adenocarcinomas of the distal esophagus, gastroesophageal junction, and stomach: a systematic review and meta-analysis of 45 studies.
Review in ESMO gastrointestinal oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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11 authors.
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Abstract
Background: The incidence of adenocarcinomas of the distal esophagus, gastroesophageal junction (GEJ), and stomach diagnosed before age 50 years is increasing and early-onset disease may have a distinct phenotype. A comprehensive synthesis of clinicopathological and molecular differences between early-onset and average-onset disease remains lacking. Materials and methods: We carried out a Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020-compliant systematic review and DerSimonian-Laird random-effects meta-analysis of observational studies comparing early-onset (<50 years) and average-onset adenocarcinomas of the distal esophagus, GEJ/cardia, and stomach. Forty-five studies (35 clinicopathological or epidemiological cohorts comprising >650 000 patients and 10 molecular cohorts) were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were computed in molecularly characterized cohorts. Results: Early-onset disease was associated with advanced stage (OR 1.39, 95% CI 1.26-1.54), signet-ring histology (OR 2.52, 95% CI 1.84-3.47), synchronous distant metastasis (OR 1.20, 95% CI 1.04-1.38), high tumor grade (OR 1.61, 95% CI 1.23-2.11), and female sex (OR 1.29, 95% CI 1.14-1.44, Conclusions: Early-onset adenocarcinomas of the distal esophagus, GEJ, and stomach appear to represent a distinct clinicopathological and molecular phenotype characterized by aggressive histopathology, enrichment of a genomically stable/cadherin 1 (E-cadherin gene)-associated profile, and a potentially more frequent inherited predisposition. These findings may inform age-aware diagnostic pathways, germline evaluation, and future therapeutic research.
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