Introduction

Gastric cancer screening is not formally recommended in Portugal, despite having an incidence rate of 26/100,000 inhabitants, which contrasts with recommendations from other countries with moderate incidence.

Aims & Methods

Aims: To assess the frequency of screening indications and correspondent diagnoses in patients referred for upper endoscopy from primary healthcare.
Methods: A multicenter cross-sectional study including patients who underwent upper endoscopy at 13 national endoscopy units from January to March 2024.

Results

6320 patients were included (57% male, mean age 58). Cancer screening was the indication for upper endoscopy in 1775 patients (28% of total; 52% male, mean age 60). Biopsies of the antrum and corpus were performed in 91% of those exams, and virtual chromoendoscopy was used in 19% of screening endoscopies (vs 34% for atrophic gastritis surveillance, p<0.05). Endoscopic staging for intestinal metaplasia was performed in 13%. By regions, screening indication was more common in Minho (35%) and less in the Lisbon region (15%, p<0.05 vs other regions). Only 21% of exams were considered normal, with the main findings being: erythematous gastritis (31%); atrophic gastritis (16%, 1% autoimmune gastritis), reflux esophagitis (15%), papular gastritis (10%), erosive gastritis (8%), gastric polyps (5%), erosive duodenitis (3%), peptic ulcers (3%), subepithelial lesions (1.5%) and Barrett's esophagus (0.5%). Histologically, 30% of patients had intestinal metaplasia, 5% in both the antrum and corpus. Fourteen neoplastic lesions (0.8%) were identified: 5 gastric neoplasms (0.3%), 4 superficial gastric lesions (0.2%), 2 esophagus/junction neoplasms (0.1%), 2 superficial junction lesions (0.2%), and 1 ampulloma (0.1%). Ten percent of patients would require future endoscopic surveillance.

Conclusion

A significant proportion of upper endoscopies in Portugal are already performed for cancer screening, which seems justifiable given the high proportion of clinically relevant alterations identified. The low proportion of exams with chromoendoscopy suggests that measures are needed to increase the use of this technique in clinical practice.

Introduction

The first international guideline for managing preneoplastic conditions of the stomach (MAPS I) was published in 2012, followed by an update (MAPS II) in 2019. As adherence to these guidelines remains uncertain, we evaluated adherence by comparing the management of preneoplastic gastric conditions before and after the introduction of MAPS I and II in selected European centers.

Aims & Methods

Patient data were retrieved from nine endoscopy units in seven European countries during three periods: pre-MAPS I (2010/2011), post-MAPS I (2017/2018), and post-MAPS II (2022/2023). Screening and dyspepsia-related endoscopies were included. Data on endoscopy, histopathology, Helicobacter pylori (H. pylori) treatment, and surveillance were collected using a standardized form. Adherence to nine MAPS recommendations was assessed, with improvement defined as a ≥10% increase in guideline-concordant management.

Results

A total of 2,426 patients were included. Most centers (57%) improved in at least seven of the nine recommendations over time. Virtal Chromoendoscopy use improved in six centers, with four reporting its use in >50% of cases. All centers improved in performing biopsies from the antrum and corpus, five conducted random biopsies in nearly all patients, and four performed these plus an incisura biopsy in >90% of cases. Endoscopic scores for patient stratification were rarely used, while five centers improved in histological scoring or intestinal metaplasia subtyping. H. pylori treatment recommendation remained high (71%-100%), and endoscopic surveillance adherence improved in four of seven centers

Conclusion

Adherence to MAPS guidelines improved in most centers. However, gaps in virtual chromoendoscopy, targeted biopsies, and endoscopic/histopathological scoring remain, potentially affecting surveillance recommendations. This underscores the need for a more tailored approach to enhance implementation.

References

1. Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 74(3), 229–263. https://doi.org/10.3322/caac.21834
2. Anderson, L. A., Tavilla, A., Brenner, H., Luttmann, S., Navarro, C., Gavin, A. T., Holleczek, B., Johnston, B. T., Cook, M. B., Bannon, F., Sant, M., & EUROCARE-5 Working Group: (2015). Survival for oesophageal, stomach and small intestine cancers in Europe 1999-2007: Results from EUROCARE-5. European journal of cancer (Oxford, England : 1990), 51(15), 2144–2157. https://doi.org/10.1016/j.ejca.2015.07.026
3. Pimentel-Nunes, P., & Dinis-Ribeiro, M. (2015). Endoscopic Submucosal Dissection in the Treatment of Gastrointestinal Superficial Lesions: Follow the Guidelines!. GE Portuguese journal of gastroenterology, 22(5), 184–186. https://doi.org/10.1016/j.jpge.2015.08.002
4. Pimentel-Nunes P, Dinis-Ribeiro M, Ponchon T, et al. Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2015;47(9):829-854. doi:10.1055/s-0034-1392882
5. Latorre G, Vargas JI, Shah SC, et al. Implementation of the updated Sydney system biopsy protocol improves the diagnostic yield of gastric preneoplastic conditions: Results from a real-world study. Gastroenterol Hepatol. 2024;47(8):793-803. doi:10.1016/j.gastrohep.2023.08.005

Introduction

Eosinophilic Esophagitis (EoE) is an immune-mediated chronic inflammatory disease characterized by eosinophilic infiltration in the esophageal epithelium. Other histopathologic features such as epithelial barrier dysfunction, immune infiltration and inflammation lead to clinical symptoms such as dysphagia, vomiting, abdominal pain and food impaction. Dupilumab, which targets IL-4Ra to inhibit IL-4 and IL-13 signaling, leads to improved esophageal symptoms, reduced intraepithelial eosinophils and normalized gene expression in EoE biopsies. However, the effect of dupilumab in reducing cell infiltration beyond eosinophils and restoring the epithelial milieu is not well characterized. We evaluated the pharmacodynamic effect of dupilumab on immune cells and markers of barrier function in EoE esophageal biopsies.

Aims & Methods

Mucosal pinch biopsies were collected from the proximal, mid and distal esophagus of adult EoE patients treated with dupilumab or placebo as part of LIBERTY EoE TREET (NCT03633617). A subset of dupilumab 300mg QW (N=19) or placebo (N=9) were analyzed, including patients who continued dupilumab through 52 weeks or switched from placebo to dupilumab after 24 weeks. Gene expression was evaluated by transcriptome sequencing. Immune cell markers were evaluated by immunostaining with digital image analyses. Esophageal regions were analyzed separately and averaged for each patient at each timepoint. Percent changes were calculated using median fold change from baseline for each treatment group.

Results

Transcriptome analyses demonstrated dupilumab treatment modulated expression of genes including those associated with fibrosis and barrier function. Expression of desmoglein 1 (DSG1), a barrier function protein downregulated in EoE, was normalized at week 24 of dupilumab treatment (32-fold increase from baseline). The transcriptomic effects were sustained through 52 weeks of dupilumab treatment. Immunostaining of biopsies from dupilumab treated EoE patients at week 24 demonstrated median reductions across all immune cell types and markers examined, including mast cells (tryptase+, 73%), T cells (CD3+, 62%), myeloid cells (CD68+, 87%), proliferating T cells (CD3+Ki67+, 83%), Th2 (CD3+GATA3+Ki67+, 90%) and non-Th2 (CD3+GATA3-Ki67+, 82%) T cell lineages, as well as Ki67 (77%), compared to non-significant changes in the patients who received placebo. Sustained suppression was observed for all markers examined in patients with EoE treated with dupilumab for 52 weeks.

Conclusion

Dupilumab restored markers of barrier function, normalized overall gene expression, and reduced immune cell infiltration in the esophageal epithelium of EoE patients through 52 weeks of treatment. While dupilumab has been shown to affect the eosinophilic infiltrate characteristic of EoE, these data further demonstrate that the effects of dupilumab in reducing inflammation and healing the esophageal epithelium in EoE extend beyond eosinophils. Further study is needed to understand the relationship between the cell changes in restoring the epithelial integrity with endoscopic and symptomatic response in EoE.

Disclosure

Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.
Annamaria B. Farrell, Julie E. Horowitz, Wei Keat Lim, Madison Stoms, Sandra Coetzee, Shane E. McCarthy, Nathalie Fiaschi, Allen Radin, Sara Hamon, Bram P. Raphael, Kerry A. Casey, Seblewongel Asrat, Jamie M. Orengo, Andrea T. Hooper, Jennifer D. Hamilton: Regeneron Pharmaceuticals Inc. – employees and shareholders
Margaret H. Collins: Arena/Pfizer, AstraZeneca, Calypso Biotech, EsoCap Biotech, GSK, Receptos/Celgene/Bristol Myers Squibb, Regeneron Pharmaceuticals Inc., Robarts Clinical Trials Inc./Alimentiv, Inc., Sanofi, Shire – advisory board/consultancy fees
Kelley A. Wolfe: Sanofi – employee, may hold stock and/or stock options in the company