Introduction

We determined the impact of an increased two-stool FIT cutoff on colonoscopy positivity and relative sensitivity and specificity in the randomised controlled screening trial SCREESCO conducted in Sweden.

Aims & Methods

We performed a cross-sectional analysis of participants in the FIT arm that performed FIT between March 2014 and March 2020 within the study registered with ClinicalTrials.gov, NCT02078804, who had a fecal hemoglobin concentration of at least 10 μg/g in at least one of two stool samples and who underwent a colonoscopy (n=3841). For each increase in cutoff, we computed the positive predictive value (PPV), numbers needed to scope (NNS), sensitivity and specificity for finding colorectal cancer (CRC) and advanced neoplasia (AN; advanced adenoma or CRC) relative to cutoff 10 μg/g.

Results

Number of colonoscopies, number with finding of advanced neoplasia (AN), positive predictive value (PPV), numbers needed to scope (NNS), relative sensitivity and relative specificity by FIT-cutoff (maximum of two stool samples).
Cutoff	N colonoscopies (%)	N with advanced neoplasia	PPV	NNS	relative sensitivity	95% CI	relative specificity	95% CI
(μg/g)
10	3841 (100)	882	23	4.4	100		0
20	2319 (60)	667	29	3.5	76	74-77	44	44-46
40	1428 (37)	473	33	3.0	54	52-55	68	67-69
60	1059 (28)	384	36	2.8	44	42-45	77	76-78
80	861 (22)	331	38	2.6	38	36-39	82	81-83
120	653 (17)	272	42	2.4	31	29-32	87	87-88
160	541 (14)	240	44	2.3	27	26-29	90	89-90

The PPV for advanced neoplasia (colorectal cancer, or adenoma with high grade dysplasia or size >10mm or villous component) increased from 23.0% (95% CI: 22.3-23.6%) at cutoff 10 μg/g to 28.8% (95% CI: 27.8-29.7%) and 33.1% (95% CI: 31.9-34.4%) at cutoffs 20 and 40 μg/g respectively while the NNS to find a CRC (not shown in the table) correspondingly decreased from 41 to 27 and 19. The PPV for advanced neoplasia was higher in men than women at each cutoff, e.g. 31.5% (95% CI: 30.1-32.8%) in men and 25.6% (95% CI: 24.3-27.0%) in women at 20 μg/g. The relative sensitivity and relative specificity were similar in men and women at each cutoff.

The table shows the results for for advanced neoplasia with the number of colonoscopies and number of findings with AN for each cutoff. Furthermore for each cutoff the positive predictive value (PPV) and numbers needed to sccope to find one AN is given. The relative sensitivity and specificity (each with 95% CI given) are calculated relative to the cutoff 10 μg/g.

Conclusion

The risk of advanced adenoma and colorectal cancer increased with increasing fecal hemoglobin concentration in both men and women, and a low cutoff around 20 to 40 μg/g for two-stool FIT allows detection and removal of many advanced adenomas and colorectal cancers. The findings suggest that a higher cutoff in women than in men could lead to comparable colonoscopy positivity for advanced adenomas and cancer.

References

Brenner H, Werner S. Selecting a Cut-off for Colorectal Cancer Screening With a Fecal Immunochemical Test. Clin Transl Gastroenterol 2017; 8: e111.
Brenner H, Haug U, Hundt S. Sex differences in performance of fecal occult blood testing. Official journal of the American College of Gastroenterology| ACG 2010; 105: 2457-64.
Meulen MPV, Kapidzic A, Leerdam MEV, et al. Do Men and Women Need to Be Screened Differently with Fecal Immunochemical Testing? A Cost-Effectiveness Analysis. Cancer Epidemiol Biomarkers Prev 2017; 26: 1328-36.
Blom J, Löwbeer C, Elfström KM, Sventelius M, Öhman D, Saraste D, Törnberg S. Gender-specific cut-offs in colorectal cancer screening with FIT: Increased compliance and equal positivity rate. Journal of medical screening 2019; 26: 92-7.
Forsberg A, Westerberg M, Metcalfe C, et al. Once-only colonoscopy or two rounds of faecal immunochemical testing 2 years apart for colorectal cancer screening (SCREESCO): preliminary report of a randomised controlled trial. Lancet Gastroenterol Hepatol 2022; 7: 513-21.
Stromberg U, Bonander C, Westerberg M, et al. Colorectal cancer screening with fecal immunochemical testing or primary colonoscopy: An analysis of health equity based on a randomised trial. EClinicalMedicine 2022; 47: 101398.

Introduction

The TOGAS consortium (TOwards GAstric cancer Screening) was established to explore effective gastric cancer screening strategies within Europe. One key method involves the detection and eradication of Helicobacter pylori (H. pylori), the leading causative agent of gastric cancer. In Western Europe, infection rates are higher among males, smokers, and individuals of lower socioeconomic status—groups that tend to engage less with preventive health services.

Aims & Methods

This pilot study aimed to determine whether targeted screening in high-risk occupational settings improves participation and outcomes compared to population-based screening via general practice.
Key outcome measures included;

1. Response rate
2. Prevalence of the infection
3. Treatment effectiveness

This prospective pilot study recruited individuals aged 30–34 years from January 2024 to March 2025. Participants were invited either through general practices (general population group, GP) or through two occupational screening programs (targeted group, TG) representing higher-risk, male-dominated workforces: the Irish Defence Forces and Construction Workers Health Trust. Exclusion criteria included prior H. pylori treatment or gastrectomy. All participants underwent serologic screening (BIOHIT H. pylori IgG antibody). The TG was offered initial on-site screening at their workplace; the GP group attended a local hospital. All seropositive individuals were offered confirmatory 13-C urea breath testing (Richen IR Force 200) in a local hospital. Confirmed cases were offered a 10-day regimen of PYLERA (Metronidazole/Tetracycline/Bismuth subcitrate) with Esomeprazole 40 mg BD. Eradication was assessed ≥6 weeks post-treatment. Response rates, demographics, infection prevalence, and treatment outcomes were analyzed using Mann-Whitney U and Chi² tests (significance p < 0.05).

Results

3030 individuals were invited for screening: 2824 in the GP group(GPG), 206 in the TG. Key demographics and risk factors of each group are shown in Table 1. The invitation response and participation rates were significantly higher in the TG versus the GPG (31% v’s 14%; p < 0.001, 30% v’s 14% p <0.00, respectively). H. pylori seroprevalence rates were similar between groups: 18% (11/60) in the TG, 19% (64/333) in the GPG (p<0.70). Confirmatory 13-C UBT was completed in 91% (10/11) of those who tested positive in the TG and 98% (63/64) of the GPG. Overall, ‘true’ prevalence rates based on serology & confirmatory 13-C UBT results were 10%(6/59) in the TG v’s 14% (44/325) in the GPG(p = 0.47). Treatment adherence exceeded 90% in both groups, with 100% adherence in the TG and 90% in the GPG. Among those who completed post-treatment testing (n=37), eradication was achieved in 100% of the TG (2/2) and 89% of the GPG (31/35).

Table 1 Basic Demographics by Group

	Targeted group	General population
Gender, male	97%	33%
Median age, years	31	32
Smoking status Current/previous Non-smoker	41% (24) 59% (34)	34% (137) 66% (266)
Socioeconomic status(self-rated) Higher Middle Lower Prefer not to answer	69% (40/58) 22% (13/58) 0 9% (5/58)	85% (337/397) 11% (42/397) 0% (2/397) 4% (16/397)
Family history of H.pylori infection	3% (2)	9% (36)

Conclusion

Targeted occupational screening in high-risk populations demonstrated superior response and engagement rates compared to general practice-based screening. These early results suggest this approach may be a more effective and resource-conscious strategy in low-to-intermediate risk countries and merit further evaluation in broader implementation efforts.

References

1. Teo CH, Ng CJ, Booth A, White A. Barriers and facilitators to health screening in men: A systematic review. Soc Sci Med. 2016 Sep;165:168-176. doi: 10.1016/j.socscimed.2016.07.023. Epub 2016 Aug 1. PMID: 27511617. 5.
2. Lou L, Wang L, Zhang Y, et al. Sex difference in incidence of gastric cancer: an international comparative study based on the Global Burden of Disease Study 2017.BMJ Open 2020;10:e033323. doi: 10.1136/bmjopen-2019-033323
3. Salmani H, Ahmadi M, Shahrokhi N. The Impact of Mobile Health on Cancer Screening: A Systematic Review. Cancer Informatics. 2020;19. doi:10.1177/1176935120954191
4. CSO. (2023, May 30). Employment, Occupation, Industry and Commuting - CSO -Central Statistics Office. https://www.cso.ie/en/releasesandpublications/ep/pcpsr/censusofpopulation2022- summaryresults/employmentoccupationindustryandcommuting/

Disclosure

Dr. Deane reports receipt of research funding support from EU4 Health grant GA number: 101101252. Receipt of ​13-C Urea Breath Test bags for this study was provided for by Richen - Dr Deane was the winner of the Richen Global ​Research Competition 2023

Introduction

Eosinophilic esophagitis (EoE) is a chronic, progressive, esophageal disease driven by type 2 inflammation.

Aims & Methods

The aim of this analysis was to determine the histopathologic effect of dupilumab on esophageal inflammation in patients aged 1–11 years with eosinophilic esophagitis (EoE) from the phase 3 EoE KIDS trial. In Part A, patients were randomized to receive weight-tiered dupilumab or placebo for 16 weeks. In Part B, all patients received weight-tiered dupilumab for 36 weeks. Biopsies from proximal, mid, and distal esophageal regions were analyzed. Peak eosinophil count (PEC) and EoE Histologic Scoring System (HSS) grade/stage scores were assessed at baseline, Week 16, and Week 52.

Results

At Week 16, dupilumab vs placebo treatment resulted in significantly greater improvements in PEC (least squares mean percent change -86.09% vs 20.98%, respectively; P<0.0001) and improvements from baseline were observed in EoE-HSS grade and stage total scores, and inflammatory and architectural sub-scores (Table). Improvements were maintained at Week 52 with continued dupilumab. For those who switched from placebo at Week 16, improvements were observed at Week 52. Improvements in individual component scores were also observed.

Table. Mean percent change from Part A baseline in EoE-HSS scores at Weeks 16 and 52.

	Week 16a			Week 52
	Placebo (N=34)	Dupilumab (N=37)	LS mean difference	Placebo (N=18)	Dupilumab (N=37)
EoE-HSS grade
Total score	5.0%	-64.4%	-69.4****	-63.6%	-68.5%
Inflammatory sub-score	5.7%	-77.4%	-83.1****	-79.4%	-83.7%
Architectural sub-score	1.0%	-50.5%	-51.5****	-45.3%	-55.5%
EoE-HSS stage
Total score	5.8%	-62.3%	-68.1****	-58.2%	-63.5%
Inflammatory sub-score	7.9%	-96.3%	-104.3****	-89.6%	-96.6%
Architectural sub-score	9.0%	-41.0%	-50.0****	-32.4%	-51.0%

****P<0.0001. ^aLS mean percent change.
EoE-HSS, Eosinophilic Esophagitis Histologic Scoring System; LS, least squares.

Conclusion

Dupilumab treatment improved a range of histopathologic aspects of EoE through 52 weeks versus placebo in children aged 1–11 years with EoE.

Disclosure

Collins MH: Arena, Pfizer, AstraZeneca, Calypso Biotech, EsoCap Biotech, GSK, Receptos, Celgene, Bristol Myers Squibb, Regeneron Pharmaceuticals Inc., Robarts Clinical Trials Inc. Alimentiv, Inc., Sanofi, Shire, a Takeda company – advisory board/consultancy fees.
Lerner D: Regeneron Pharmaceuticals Inc. – educational board fees.
Pesek RD: Regeneron Pharmaceuticals Inc. – advisory board/consultancy fees.
Zevit N: AstraZeneca, Rafa Inc., Regeneron Pharmaceuticals Inc., Sanofi, Takeda – advisory board/consultancy fees. Adare Pharmaceuticals, Dr. Falk Pharma – advisory board/consultancy fees. Dr. Falk Pharma, Rafa Inc., Regeneron Pharmaceuticals Inc., Sanofi – speaker fees. Rome Foundation – honoraria.
Xia C, Raphael BP, Radwan A: Regeneron Pharmaceuticals Inc. – employees and shareholders.
Zaghloul S, Angello JT: Sanofi – employees, may hold stock and/or stock options in the company.

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

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.