Introduction

Pathological esophageal acid exposure may persist in patients with Barrett’s esophagus (BE) despite standard proton pump inhibitor (PPI) therapy and symptom control, although current guidelines recommend at least standard-dose PPI for all patients with BE.¹

Aims & Methods

Aim was to evaluate the role of esophageal function testing in assessing acid exposure in BE patients on PPI therapy and in predicting neoplastic progression. We conducted a multicenter retrospective study including asymptomatic BE patients (defined by GerdQ total score <8 and a score of 0 on the first GerdQ item) who underwent high-resolution manometry and 24-hour pH impedance monitoring while on various PPI regimens. Maximal PPI therapy included esomeprazole 40 mg, pantoprazole 40 mg, rabeprazole 20 mg, or lansoprazole 30 mg, all administered twice daily. All other regimens were considered standard dosing. Index upper endoscopy with biopsies was performed under the same therapeutic regimen. Histologically, presence and degree of neoplasia (all confirmed by a second pathologist) was recorded. Acid exposure time (AET) <4% was defined as adequate acid control; AET >6% as pathological reflux. Predictors of pathological reflux and neoplasia were assessed using logistic regression analysis.

Results

A total of 135 patients (2016-2025) were included (mean age 58 ± 15 years; 73% male). Median BE length was C1 (range 0–3 cm) and M2 (range 1–5 cm), with 41% (n=56) classified as having long-segment BE. Sixty-seven patients (50%) were on standard-dose PPI. Pathological reflux was identified in 37 patients (27%), of whom 25 (67%) were on standard-dose therapy. Fourteen patients (10%) had borderline AET values (4–6%). Among the 84 patients (62%) with adequate acid control, 33 (39%) were taking standard-dose PPI. On multivariable analysis, standard-dose PPI (OR 3.04; 95% CI 1.34–6.89; p=0.008) and type III esophagogastric junction morphology (OR 2.52; 95% CI 1.01–5.01; p=0.047), consistent with manometric hiatal hernia, were independently associated with pathological reflux. Non-dysplastic BE was found in 112 patients, while 13 (10%) had neoplasia at index endoscopy (8 low-grade dysplasia, 3 high-grade dysplasia, 2 intramucosal adenocarcinoma). Pathological reflux was the only independent predictor of neoplasia (OR 10.41; 95% CI 2.65–41.26; p<0.001).

Table 1. Logistic regression analysis for factors associated with neoplasia on index endoscopy.

Conclusion

Nearly one-third of asymptomatic BE patients exhibit pathological reflux on pH-monitoring despite PPI treatment, predominantly among those on standard-dose and with manometric hiatal hernia. Nonetheless, adequate acid control is achieved in over one-third of patients on standard PPI therapy. Pathological reflux is associated with a 10-fold increased risk of neoplasia.

References

1. Shaheen NJ, Falk GW, Iyer PG, et al. Diagnosis and Management of Barrett's Esophagus: An Updated ACG Guideline. Am J Gastroenterol. 2022;117(4):559-587.

Introduction

Corpus atrophic gastritis (CAG) requires endoscopic-histological surveillance due to the risk of developing gastric neoplastic lesions (GNL). This study aimed to identify variables associated with GNL development at long-term follow-up using a feature ranking method based on a novel One-Class Support Vector Machine (SVM) model.

Aims & Methods

A dataset containing clinical, endoscopic, and histological variables from consecutive CAG patients (2001-2023) adhering to a surveillance program was considered. GNL presence at the longest available follow-up was recorded. Gastric biopsies and histological evaluations were conducted according to the updated Sydney system. CAG patients with any missing data or a GNL diagnosis at the baseline gastroscopy were excluded from the final analysis. A Fisher score-based feature ranking method and One-Class SVM were used to select the optimal subset of baseline variables associated with GNL development, aiming to achieve average sensitivity (Se) and specificity (Sp) above 80%.

Results

Overall, 355 CAG patients were initially considered. Of these, 36 were excluded due to the presence of GNL at baseline gastroscopy, and 216 for missing data. Thus, a total of 103 patients were considered and grouped into: CAG patients with [22 patients (F 68.1%), median age 68 (35-83) years] and without GNL at follow-up [81 patients (F 72.8%), median age 59(26-84) years]. After a median follow-up of 60 (12-192) months, 13 epithelial GNL (gastric adenocarcinoma or high/low-grade dysplasia) and nine type-1 gastric-neuroendocrine-tumors (T1gNET) were recorded. Parietal-cell-antibodies and pepsinogen-I < 30 μg/l were associated with both epithelial GNL and T1gNET. Antral inflammation and age > 60 were linked to epithelial GNL, while anti-thyroperoxidase-antibodies, smoking, and dyspeptic symptoms at CAG diagnosis were linked to T1gNET. Low-dose aspirin and H. pylori eradication therapy showed inverse associations with epithelial GNL and T1gNET, respectively.

Conclusion

This is the first study in which an AI model simultaneously considers clinical, endoscopic, and histological characteristics from a dataset of CAG patients, showing good sensitivity and specificity in identifying those variables associated with developing GNL. Nonetheless, we acknowledge the need for improved variable standardization and data balancing between groups to enhance model performance further.

Introduction

Genome-wide association studies (GWAS) have identified more than 250 risk variants linked to inflammatory bowel disease (IBD). Most genetic variants increase the risk of disease onset, and their impact on clinical presentation is limited.^1,2,3 Variants in NOD2 and IL23R not only modulate the risk of disease onset, but also influence disease behaviour and localisation. Their role in predicting treatment response remains unclear.^3,4
A variant in an intron of TNRC18 (rs7486781, allele frequency 3.6%) was recently identified as having a strong risk-increasing effect (OR 3.2, p=2.4x10-61) for IBD in the FinnGen biobank study. The same allele was also associated with a risk for ankylosing spondylitis (AS), uveitis and psoriasis.⁵ The functional effect of rs7486781 is not yet fully established.⁶

Aims & Methods

The FinnGen biobank study includes the genotype data of 520 000 individuals and their longitudinal register data from national health registers, including 11 298 individuals with verified diagnosis for IBD. The data also include drug purchases, procedure codes and laboratory measurements of the individuals.
Our aim was to study the impact of the TNRC18-variant on IBD phenotype, particularly disease behavior. We assessed established aspects of disease severity⁷: use of immunosuppressants and advanced therapies, necessity to switch medications, frequent use of corticosteroids and risk of procedures. We also evaluated the presence of extraintestinal manifestations (EIM) and other disease complications.

Results

Regarding disease severity, the use of therapies beyond 5-ASA was more common among variant carriers; the use of thiopurines and other immunosuppressants (OR 1.21-1.27, p-values 1.35x10^-5 - 0.00849), ustekinumab and other IL-inhibitors (OR 1.46-1.48, p-values 0.00324 - 0.00286) and TNF-α-inhibitors (OR 1.26, p=0.00753) was more frequent.
In addition, perianal and anal canal operations were more prevalent with TNRC18 variant carriers (OR 2.44, p=1.41x10^-4), indicating perianal disease.
Assessing EIM, we observed that diagnoses for AS and uveitis (OR 1.62-1.67, p=1.3x10^-5 - 1.55x10^-4) were more frequent within IBD in patients with rs7486781.
Interestingly, a reduced risk of primary sclerosing cholangitis (PSC) was implicated by lower number of cholangitis (K83.0) diagnoses (OR 0.617, p=0.00221) and fewer purchases of ursodeoxycholic acid (OR 0.55, p=2.83x10^-5), in addition to lower levels of ALP (mean 75 vs 82, p=0.00296), IgG4 (mean 0.45 g/l vs 0.81 g/l, p=4.81x10^-5) and IgM (0.12 vs 0.15, p=0.00115) among variant carriers. All events survived the false discovery rate–adjusted p threshold of 0.05.
Our results also suggest that the cumulative risk for IBD related procedures⁸ (patients with procedures n=2209) from diagnosis and birth were elevated in TNRC18 variant carriers (HR=1.12 and HR=1.14, p=0.050 and p=0.023, assuming additive effect) using a Cox regression model.
Finally, our results in ulcerative colitis indicate that TNRC18 variant carriers are at higher risk of transitioning from 5-ASA/immunomodulators to biologics/JAK-inhibitors (HR=1.38, p=0.016). Variant carriers receiving immunomodulators or advanced therapies were not, however, in increased risk of colectomy (HR~0.97-1.34, p~0.86-0.37).

Conclusion

TNRC18 variant was associated with greater risk of operative treatment, the need of more advanced medication and perianal disease. AS and uveitis were more common EIMs, but PSC appeared less infrequent. Our preliminary results indicate that TNRC18 variant carriers might benefit from early intervention with immunomodulators or advanced therapies.

References

1. Chang, J. T. Pathophysiology of Inflammatory Bowel Diseases. N Engl J Med 383, 2652–2664 (2020).

2. Cleynen, I. et al. Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: a genetic association study. Lancet 387, 156–167 (2016).

3. Atreya, R. & Neurath, M. F. Biomarkers for Personalizing IBD Therapy: The Quest Continues. Clin Gastroenterol Hepatol 22, 1353–1364 (2024).

4. Kayali, S. et al. NOD2 and Crohn’s Disease Clinical Practice: From Epidemiology to Diagnosis and Therapy, Rewired. Inflamm Bowel Dis 31, 552–562 (2025).

5. Kurki, M. I. et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature 613, 508–518 (2023).

6. Rahimov, F. et al. A genome-wide CRISPR screen supported by human genetics identifies the TNRC18 gene locus as a novel regulator of inflammatory signaling. bioRxiv 2023.10.04.560902 (2023) doi:10.1101/2023.10.04.560902.

7. Swaminathan, A. et al. The Disease Severity Index for Inflammatory Bowel Disease Is a Valid Instrument that Predicts Complicated Disease. Inflamm Bowel Dis 30, 2064–2075 (2024).

Disclosure

Anna Aarni: Speaker fee from Abbvie, Clinic visit: travelling expenses from Tillots Pharma

Pauliina Molander: Speaker, consultancy and advisory board member fees from Abbvie, Johnson & Johnson, Lilly, Pfizer and Takeda. Clinic visit: traveling expenses from Tillots Pharma

Jukka Koskela: Pfizer-FinnGen genetic advisory board, traveling, clinic and congress visits: FinnGen partners, Tillots Pharma, Takeda, consulting: Pfizer

Introduction

Endoscopic submucosal dissection (ESD) is an effective treatment for superficial esophageal cancer, but postoperative stenosis remains a significant concern. Particularly, probability of the stenosis is less investigated in cases with a 50%-75% circumferential mucosal defect.

Aims & Methods

This study aimed to identify influential factors for postoperative stenosis after the moderate circumferential resection in esophageal ESD. This multi-center retrospective observational study analyzed data from 513 patients across 19 institutions who underwent esophageal ESD from April 2018 to March 2022 and showed 50% to 75% of the circumferential mucosal defect. We firstly overviewed the current status on the postoperative stenosis, the steroid use, and postoperative adverse events in these patients. Subsequently, we identified influential factors for postoperative stenosis. Patients were categorized into stenosis and no stenosis groups, and univariate and multivariate analyses were performed for each parameter. We further investigated influential factors of stenosis in two cohorts: steroid and no steroid groups. Finally, the parameters were compared between the steroid and no steroid groups to assess the tendency of the steroid use in general practice.

Results

Postoperative stenosis was observed in 28 cases (5%). Univariate analysis comparing the stenosis group (n = 28) and no stenosis group (n = 485) revealed significant differences in the prior endoscopic treatment near the lesion (p = 0.02), cervical esophageal location (p = 0.04), defect circumference (p =0.01), and procedure duration (p = 0.02). There was no significant difference in the steroid use between two groups. Multivariate analyses identified history of prior endoscopic treatment close to the lesion (p = 0.01, odds ratio [OR], 5.10), cervical esophageal lesions (p = 0.03, OR, 3.97), large circumferential defect (p <0.01, OR, 3.78), and longer procedure duration (p <0.01, OR, 3.83) as independent risk factors for stenosis formation. Among the steroid group, significant associations of the postoperative stenosis were revealed with the prior endoscopic treatment near the lesion (p = 0.02), cervical esophageal location (p = 0.04), and >5/8 of defect circumference (p = 0.02). In the no steroid group, only the procedure duration (p = 0.01) showed a significant difference between the stenosis and non-stenosis groups. Comparison between the steroid (n = 223) and no steroid groups (n = 290) revealed significant differences in the prior endoscopic treatment near the lesion (p <0.01), cervical esophageal lesions (p <0.01), and resected specimen dimensions (p <0.01). The stenosis rates were 7% in the steroid group and 4% in the no steroid group, without a significant difference. No significant difference in adverse events was observed between the two groups.

Conclusion

In esophageal ESD with a 50%-75% circumferential mucosal defect, the steroid was used in over 40% of patients, and postoperative stenosis still occurred in 5%. Because wider circumference, location of the cervical esophagus, prior endoscopic treatment close to the lesion, and prolonged operative time were identified as independent risk factors on the stenosis, steroid therapy should be preferred in these cases. Particularly, lesions with a history of endoscopic treatment, on cervical esophagus, and with >5/8 of defect circumference should require more aggressive countermeasures than currently applied.