Introduction

Eosinophilic Esophagitis (EoE) is a chronic, inflammatory, immune-mediated disease, characterised by eosinophilic infiltration. EoE requires a lifelong pharmacological treatment, aimed at achieving clinical (ie. symptoms of esophageal dysfunction), endoscopic and histological remission, and slowing down the possible process of esophageal fibrosis. Recently, a novel formulation of budesonide orodispersible tablet (BOT) has become available, showing a high efficacy in randomised placebo-controlled trials. Nowadays, only few real-life data are available in literature.

Aims & Methods

This is a multicentre, prospective, observational study, aimed to evaluate in real-life setting the long-term safety profile and the clinical, endoscopic and histological effectiveness of BOT in EoE patients. Patients diagnosed with EoE, aged ≥ 18 years, treated with BOT 1 mg bid, as induction treatment for 12 weeks (T1), and with 1 mg qd as maintenance for 52 weeks (T2), were enrolled. Clinical, demographic and medication data were collected at baseline. BOT treatment outcomes were evaluated after T1 and after T2, considering EoE Endoscopic Reference Score (EREFS) for endoscopic appearance, and 3-segments eosinophilic peak infiltration for histological assessment. Moreover, the Dysphagia Symptom Questionnaire (DSQ) and Health-Related Quality of Life (HRQoL) were also collected in order to evaluate clinical response.

Results

Two-hundreds ninety-two patients (232 males, 79%; mean age 37±14) treated with BOT were enrolled, in 8 Italian Centres and 1 Israelian Centre. The most frequent symptoms at diagnosis were dysphagia (82%) and food bolus impaction (68%). At least 1 allergic comorbidity was present in 67% of patients. 259 patients were evaluated at T1: endoscopic remission was achieved in 53% of patients, with a reduction of the mean EREFS score from 3±2 to 2±1 (p<0.0001). Histological remission was obtained in 93% of patients, with 19/259 treatment non-responders. The DSQ showed a significant reduction from 30±23 vs 6±12 (p<0.001). HRQoL questionnaire score passed from 112±37 to 153±30 (p<0.0001). 136 patients completed 1 year of treatment, and 76% of them resulted in endoscopic remission. In particular, the presence of stenosis passed from 31/292 at baseline (T0) to 1/136 at T2 (p<0.0001). Histological remission was maintained in 92%, while 11/136 lost histological response after BOT tapering. As well as for T1, both DSQ (4±10) and HRQoL score (153±28) resulted improved (p<0.0001). Side effects occurred in 36 out of 292 patients (12%), and the main one was candidiasis (25/36, 70%). Only 15 of patients needed to stop the treatment. All data are resumed in Table 1.

Conclusion

This study confirms the effectiveness of the treatment with BOT in both inducting and maintaining remission of EoE in a real-life setting, either considering clinical, endoscopic and histologic outcomes. Our data also showed a good safety profile, with a few patients requiring drug interruption.

References

Geow R, Arena G, Siah C, Picardo S. A retrospective real-world study on the safety and efficacy of budesonide orodispersible tablets for the induction therapy of eosinophilic oesophagitis. Therap Adv Gastroenterol. 2024 Oct 16;17:17562848241290346. doi: 10.1177/17562848241290346. PMID: 39421000; PMCID: PMC11483688.
Lucendo AJ, Miehlke S, Schlag C, Vieth M, von Arnim U, Molina-Infante J, Hartmann D, Bredenoord AJ, Ciriza de Los Rios C, Schubert S, Brückner S, Madisch A, Hayat J, Tack J, Attwood S, Mueller R, Greinwald R, Schoepfer A, Straumann A; International EOS-1 Study Group. Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial. Gastroenterology. 2019 Jul;157(1):74-86.e15. doi: 10.1053/j.gastro.2019.03.025. Epub 2019 Mar 26. PMID: 30922997.
Straumann A, Lucendo AJ, Miehlke S, Vieth M, Schlag C, Biedermann L, Vaquero CS, Ciriza de Los Rios C, Schmoecker C, Madisch A, Hruz P, Hayat J, von Arnim U, Bredenoord AJ, Schubert S, Mueller R, Greinwald R, Schoepfer A, Attwood S; International EOS-2 Study Group. Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis. Gastroenterology. 2020 Nov;159(5):1672-1685.e5. doi: 10.1053/j.gastro.2020.07.039. Epub 2020 Jul 25. PMID: 32721437.

Introduction

The European Union has signalled gastric cancer screening and prevention as a major health priority. The TOGAS consortium (TOwards GAstric cancer Screening in the European Union; togas.lu.lv), funded in response to this call, investigates different strategies for primary and secondary prevention of gastric cancer in Europe. One pilot study aims at determining the yield of having an oesophagogastroduodenoscopy (OGD) on the same day of a colonoscopy for colorectal cancer screening or polyp surveillance.

Aims & Methods

This is the first interim data on n=602 individuals recruited in 8 centres across Europe (France, Germany, Ireland, Latvia, Lithuania, the Netherlands, Portugal, and Spain). Individuals of the age of 50-74 years, attending for screening or surveillance colonoscopy, were invited to participate if they did not have a past diagnosis of gastric preneoplastic conditions requiring surveillance. Standardization of endoscopic procedures was assured by a rigorous protocol including all quality parameters defined by ESGE. This included standards for image documentation and biopsy sampling. Demographics, comorbidities, medication and the previous surgical and family history were recorded. Patients with marked preneoplastic changes (i.e. glandular atrophy or intestinal metaplasia [IM] at OLGA/OLGIM stage 3 or 4, and/or EGGIM score >5) were registered as requiring further endoscopic surveillance. Mann-Whitney U-test was applied for comparison of age between groups and Chi2 test for comparison of categorical variables (significance for p<0.05).

Results

The mean age of participants was 62 years (SD +/- 8.0), with 55.8% being male. Of 245 individuals who underwent an OGD prior to inclusion, 93.1% of these procedures were done >3years before and 60.4% were done at a tertiary centre. We identified 6 (1.0%) malignant/neoplastic lesions, 4 gastric cancers/dysplastic lesions and 2 oesophageal carcinomas. A positive H. pylori status was diagnosed in 34.2%. Endoscopically, a diagnosis of preneoplastic conditions was made in 217 participants (36.0%). Of these, 84 (14.0%) showed gastric atrophy, 45 (7.5%) gastric IM and 75 (12.5%) both conditions combined. Of those with gastric atrophy, this was classified as multifocal in 44 (27.6%) individuals, of those with IM in 45 (37.5%). OLGA stages 3 and 4 were confirmed for 1.9% and 0.8%, OLGIM stages 3 and 4 for 2.3% and 0.4%. Benign ulcers were diagnosed in 28 (4.7%) participants. The majority being gastric ulcers in 19 (3.2%) individuals, duodenal ulcers in 9 (1.5%), and oesophageal ulcers in 2 (0.3%). An additional 13 (2%) participants were diagnosed with Barrett’s oesophagus. It is of note that also 12 (2.0%) colorectal cancers were identified in the cohort. A positive H. pylori status was associated with the need for gastric surveillance (p=0.031).

Conclusion

This interim analysis of the first European pilot study on a combined screening for upper and lower GI tumours shows that this approach is feasible. Regarding the detection of upper GI malignancy and preneoplastic conditions, our findings are in line with previous systematic reviews, but we also demonstrate a reasonable rate of non-malignant findings that are also of relevance when defining the best screening strategy in Europe.

Disclosure

JB: Advisory fee from Flynn Pharma Ltd, Juvise Pharmaceuticals.
MCWS: Research Support from Sysmex, Norgine, Sentinel
OK: Speakers fee, advisory fee from Abbvie, Pfizer, Takeda, Janssen, Shire.

Introduction

Local excision (LE) is increasingly used to treat early rectal cancer (cT1-2N0M0), but its role in pT2 cancer remains controversial due to a reported 20–30% risk of lymph node metastasis (LNM). Since this risk is largely linked to adverse histological features, patients without these risk factors may safely avoid completion total mesorectal excision (cTME). We aimed to refine LNM risk in pT2 rectal cancer following LE to better guide decisions on rectal-preserving treatment strategies.

Aims & Methods

Patients with pT2 rectal cancer who underwent en bloc LE for cT1-2N0M0 lesions were retrospectivelly enrolled from seven international centres (2015-2025). Eligible patients received either cTME or active surveillance with MRI follow-up for at least two years. Exclusion criteria were positive resection margins (<0.1mm), synchronous or recurrent colorectal cancer and (neo)adjuvant therapy. LNM were confirmed through TME histology or considered absent when no suspicious lymph nodes appeared on follow-up MRI. A detailed histological review of LE specimens was conducted by specialised pathologists at each participating centre using a standardised protocol. Assessed risk factors included high-grade differentiation and/or mucinous subtype, lymphovascular invasion (small and/or large vessels), tumour budding grade 2-3 and/or poorly differentiated clusters grade 2-3, and perineural invasion. Primary endpoint was LNM rate in patients without histological risk factors. Secondary endpoints included the association between individual risk factors and LNM, as well as locoregional recurrences during active surveillance.

Results

A total of 103 patients (mean age 66 (SD 10), 56% male) with a median lesion size of 25mm (IQR 15) were included. Endoscopic LE was performed in 31 patients (30%) and surgical LE in 72 (70%). After LE, 76 patients (74%) underwent cTME while 27 (26%) opted for active surveillance. The overall LNM rate was 17.5% (18/103). Among the 36 patients (35%) without histological risk factors, the LNM rate was 5.6% (2/36; OR 0.19, 95% CI 0.04-0.87, p=0.032). Both LNM cases were detected in the cTME group. LNM rates per individual risk factor are presented in Table 1.
In the active surveillance group, no locoregional recurrences occurred in the ten patients without risk factors during a median follow-up of 53 months (IQR 26). Among patients with risk factors, two of 14 patients with one risk factor developed a locoregional recurrence and one of two patients with two risk factors. All recurrences occurred intramurally following prior surgical LE. The only patient with three risk factors had no locoregional recurrence but died from unrelated cause at 24 months.

Table 1. Univariate analyses of histological risk factors for lymph node metastasis

Conclusion

In this group of pT2 rectal cancer patients treated with LE, detailed histological analysis suggests a low LNM risk (5.6%) in patients without histological risk factors. No locoregional recurrences occurred in this low-risk group during active surveillance. As 35% of pT2 rectal cancers lacked histological risk factors, a risk-stratified approach could potentially allow a substantial proportion of patients to avoid cTME. Prospective validation in larger cohorts is needed before clinical implementation.