P-184PERSISTENCE OF GENETIC MUTATIONS IN THE NEOSQUAMOUS EPITHELIUM AFTER ABLATION THERAPY FOR BARRETT’S OESOPHAGUS AND OESOPHAGEAL DYSPLASIA
Bibliographic record
Abstract
Objectives: The incidence of Barrett’s oesophagus (BE) and dysplastic oesophageal mucosal changes has increased over the last few decades and is associated with development of oesophageal adenocarcinoma. Novel therapies that destroy (ablate) the epithelium can eradicate BE and dysplastic mucosal changes, resulting in regeneration of a neosquamous epithelium. However, recent literature suggests that both BE and squamous epithelium may be derived from the same progenitor stem cell. If this is true then neosquamous epithelium that develops following ablation may still harbor genetic changes that were present in the original BE. Persistence of genetic mutations in the neo-squamous epithelium may impose a higher risk for disease recurrence and progression. Thus, we aimed to determine if mutations present in BE and dysplasia are present in neo-squamous epithelium that develops following ablation therapy. Methods: Archived biopsy specimens were retrieved from 5 patients with BE and or dysplasia, before and after ablation therapy. Biopsies were cut for DNA isolation and a new H&E stained slide was generated for pathology review. DNA was sequenced using a targeted oesophageal adenocarcinoma panel and potential somatic variants were identified. Neosquamous biopsy samples were examined for presence of variants found at similar oesophageal locations in BE and dysplasia samples prior to ablation. Results: Fourteen samples have been assessed from 2 patients. In both cases, the neosquamous epithelia harbor a subset of variants found in one or more BE/dysplasia biopsies prior to ablation. The remaining samples are currently being analysed and validation of variants in neosquamous epithelium is being performed. Conclusions: Mutations present in BE/dysplasia samples may persist in neosquamous epithelium following ablative therapy. If validated, this may have implications for future cancer risk in this patient population. Disclosure: No significant relationships.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".