ABSTRACT
BACKGROUND & AIMS: Dietary therapy is successful in eosinophilic esophagitis (EoE) but requires multiple upper endoscopies. The aim of this study was to determine if food reintroduction in EoE can be directed by minimally-invasive esophageal sponge cytology. METHODS: In this prospective non-blinded trial, 22 responders to 6-food elimination diets underwent sequential food reintroduction guided by esophageal sponge cytology. Foods were reintroduced followed by unsedated esophageal sponge cytology assessment. A food trigger was defined by sponge cytology peak eosinophil count of ≥15 eos/high-powered field (hpf). Symptoms (EoE symptom activity index [EEsAI]), endoscopic score (EoE endoscopic reference score [EREFS]), and biopsy histology (peak eosinophil count) were collected pre-dietary therapy and post-dietary therapy, and then 4 weeks post food reintroduction. RESULTS: The EEsAI and EREFS were similar post-dietary therapy to post-food reintroduction: 12.0 (interquartile range [IQR], 0.0-27.0) vs 16.5 (IQR, 9.0-28.8) (P = .265) and 1.5 (IQR, 0.2-3.0) vs 1.0 (IQR, 0.0-2.0) (P = .185). However, the peak eosinophil count was increased post-food reintroduction compared with post-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 2.0 (IQR, 1.0-4.0) (P < .001), suggesting a failure of identification of all food triggers. The peak eosinophil count was lower post-food reintroduction compared with pre-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 52.0 (IQR, 30.8-76.2) (P = .008). At the post food reintroduction evaluation, sponge cytology and biopsy histology were in agreement in 59% (13/22) of cases using a cutoff of <15 eos/hpf and 68% (15/22) of cases using a cutoff of <6 eos/hpf. CONCLUSIONS: In the first study to evaluate a non-endoscopic technique in the clinical management of EoE, the esophageal sponge was moderately successful at guiding food reintroduction in EoE dietary responders in the outpatient setting. CLINICALTRIALS: gov, Number NCT02599558.
Subject(s)
Eosinophilic Esophagitis , Humans , Biopsy , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/therapy , Eosinophilic Esophagitis/pathology , Eosinophils/pathology , Prospective StudiesABSTRACT
The phenotypic progression to esophageal cancer is driven by an ongoing process of genomic instability constituting a number of clonal variants and leading to outgrowth of the "fittest" abnormal cell clones. Factors contributing to this process include exposure to chronic tissue damage, host susceptibilities, and alterations of molecular circuitries implicated in tissue homeostasis. Characterization of the host modifiers and molecular alterations will likely lead to the discovery of biomarkers useful for constructing stratified models defining cancer risk, allowing early detection, prediction of response to primary or secondary intervention, and prognostic evaluation of the disease. In addition, identification of key biologic pathways driving esophageal tumorigenesis will lead to development of new targeted interventions. The advent of increasingly sophisticated "omics" (ie, genomics, transcriptomics, proteomics, kinomics, pharmacogenomics), integration of systems biology, and expansion of biologic platforms bridging developmental physio-biology to cancer pathology constitute the backbone of novel tumor classifications and tailored therapies based on molecular signatures and profiles. Promising molecular targets, particularly those implicated in tissue homeostasis and stem cell maintenance, and their potential use in predictive models will be discussed.
