Introduction

Accurate and timely endoscopic evaluation is critical for the management of postoperative Crohn’s disease (CD). Although numerous established and novel indices exist, their relative operating properties and the optimal instrument for routine use in clinical and research settings are unknown.

Aims & Methods

We characterised the reliability and responsiveness of both historical and novel endoscopic indices using centrally assessed ileocolonoscopy videos from a randomised controlled trial comparing infliximab versus placebo for preventing postoperative CD (PREVENT; NCT01190839). Three blinded central readers independently assessed 70 videos from the PREVENT trial using the Rutgeerts and modified Rutgeerts scores, POCER index, REMIND score, Simple Endoscopic Score for CD (SES-CD), and the CD Endoscopic Index of Severity (CDEIS). Indices were scored separately for the neoterminal ileum, the anastomosis (including the blind loop of a side-to-side anastomosis), and the distal colonic segment. Intra- and inter-rater reliability was quantified using the intraclass correlation coefficient (ICC) and was interpreted using the Landis and Koch benchmarks.¹ Responsiveness was quantified using the win probability (WinP), defined as the probability of a patient receiving infliximab having a better endoscopic score than a patient receiving placebo, and interpreted using Cohen’s benchmarks.²

Results

Inter-rater reliability was substantial for the Rutgeerts (ICC 0.74 [95% CI: 0.62-0.83]) and modified Rutgeerts scores (0.79 [0.68-0.86]), ileal REMIND score (0.79 [0.67-0.87]), SES‑CD (0.79 [0.70-0.86]), and CDEIS (0.80 [0.72-0.86]). Inter-rater reliability was moderate for the POCER index (ICC 0.49 [0.26-0.64]) and fair for the anastomotic REMIND score (0.30 [0.14-0.47]). Intra-rater reliability was almost perfect for all indices (ICC≥0.81) (Table 1). The Rutgeerts (WinP 0.77 [95% CI: 0.65-0.86]) and modified Rutgeerts scores (WinP 0.81 [0.69-0.89]), ileal REMIND score (WinP 0.83 [0.72-0.91]), SES-CD (WinP 0.80 [0.66-0.89]), and CDEIS (WinP 0.75 [0.61-0.86]) demonstrated a large degree of responsiveness when treatment assignment was the criterion for change. The POCER index (WinP 0.54 [0.43-0.65]) and the anastomotic REMIND score (WinP 0.53 [0.42-0.64]) had a small degree of responsiveness. The reliability and responsiveness of all indices were consistently lower when assessed at the anastomosis or distal colon compared to the neoterminal ileum.

Table 1. Reliability and responsiveness of endoscopic scores

Conclusion

Existing endoscopic indices are reliable and responsive for assessing postoperative CD activity in the neoterminal ileum but are suboptimal for assessing the anastomosis or distal colon.

References

1. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977; 33 (1):159-174.
2. Zou G, Zou L, Qiu SF. Parametric and nonparametric methods for confidence intervals and sample size planning for win probability in parallel-group randomized trials with Likert item and Likert scale data. Pharm Stat 2023; 22 (3):418-439.

Disclosure

JH reports consulting fees from Abbvie,Alimentiv Inc,Eli Lilly,Janssen,and Takeda.
SKV,GZ,LMS report consulting fees from Alimentiv Inc.
BB reports advisory/speaker fees from: Ferring,Janssen,Abbvie,Takeda,Pfizer,BMS,Merck,Sandoz,Organon,Lifelabs,Celltrion,Alimentiv,Gilead,Iterative Health,Celgene,Merck,Amgen,Pendopharm,Eli Lilly,Fresenius Kabi,Mylan,Viatris,Bausch Health,BioJamp Pharma,Eupraxia; research support: Janssen,Abbvie,GSK,BMS,Amgen,Genentech,Merck.
MAS reports advisory fees from: Janssen,Takeda,Sandoz,Samsung Bioepis,Galapagos,AbbVie,Bristol-Myers Squibb,Tillotts,Pfizer,STADA,Sanofi,MSD; and lecture fees from: Bristol-Myers Squibb,Janssen,Takeda,MSD,Falk,AbbVie,Galapagos,Lilly.
MH is a former employee of Alimentiv Inc.
JR is an employee of Alimentiv Inc.
PDC reports advisory/speaker/consulting fees from AbbVie,Baxter,Ferring,Janssen,Celltrion,Emerge Health,Shire,and Takeda. PDC is sup­ported by an NHMRC Emerging Leader 2 Fellowship and reports research support from AbbVie,Ferring,Shire,Janssen,Pfizer,and Takeda.
MR reports advisory/consulting fees from Abbvie,Janssen,UCB,Takeda,Pfizer,BMS,Organon,Amgen,Genentech,Gilead,Salix,Prometheus,Lilly,Celgene,Boehringer Ingelheim Pharmaceuticals Inc. (BIPI),Celltrion,Roche,Merck,Sanofi,Biocon,Abavax.
SS reports research grants from Pfizer
RWS reports advisory/consulting fees from AbbVie,Bristol Myers Squibb,CorEvitas,Eli Lilly,Exact Sciences,Gilead,Johnson and Johnson,Merck,Okura Theraeutics,Pfizer,and Takeda; received investigator initiated research funding from Abbvie,Bristol Myers Squibb,Johnson and Johnson,and Merck; holds intellectual property and equity on medical imaging and endoscopic analysis technologies licensed by the University of Michigan to PreNovo,LLC,AMI,LLC and PathwaysGI,Inc.
MD reports speaking fees from Bristol Meyers Squibb,Takeda,Galapagos,Janssen,Dr. Falk; advisory board fees from Abbvie,Bristol Meyers Squibb,Celltrion,Galapagos/Alfasigma,Janssen,Takeda; grant/research support: Pfizer,Bristol Meyers Squibb,Galapagos/Alfasigma,Janssen.
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Introduction

Endoscopic diagnosis of gastric dysplasia (GD) and early gastric cancer (EGC) remains challenging. Raman spectral analysis is a biomolecular specific vibrational analytical technique which measures inelastic light scattering process within samples. This technique detects disease via biomolecular "fingerprinting", which may be applied to objectively diagnose gastric lesions.

Aims & Methods

We aim to develop a machine learning model based on Raman spectra to diagnose intestinal metaplasia (IM), GD and EGC with biomarker correlations. Raman spectra were prospectively collected prior to endoscopic resection and correlated with histopathology. GD and EGC were classified as high-risk (HR) lesions; while IM and gastritis as low-risk (LR). Two methods were employed to identify significant Raman wavenumber for group differentiation: Partial Least Squares-Discriminant Analysis with Variance Importance in Projection analysis, and a theory-based statistical approach. Next, these features were tested using XGBoost model for best accuracy. A similar approach was applied to differentiate IM versus LGD, and the model was tested with leave-one-out cross-validation (LOOCV) method for the Support Vector Machine (SVM).

Results

20 participants were recruited from April 2022 to July 2023. A total of 1961 Raman spectra were collected from 33 lesions for HR versus LR differentiation. The results are as shown in Table 1. The diagnostic accuracy and F1 score for PLS-DA VIP and theory-based ranking were similar at 75.5% and 0.8318, respectively. XGBoost testing revealed that the model attained peak performance with the top 400 wavenumbers from PLS-DA VIP sorting, and the top 200 wavenumbers from the theory-based ranking. An overlap of 192 wavenumbers emerged, and the model achieved a peak F1 Score of 0.84 and 76.9% accuracy. These 192 wavenumbers were then mapped to the Raman spectrum and can be correlated with 8 Raman peaks of biochemicals related to gastric cancer including lipids, proteins, phospholipids and leucine. For LGD versus IM, we utilized 487 Raman signals from 25 lesions. was an overlap of 100 wavenumbers with accuracy of 74.1%.
The diagnostic accuracy and F1 score for PLS-DA VIP and theory-based ranking were similar at 74.4% and 0.79 respectively. LOOCV with SVM testing revealed that the model attained peak performance with the top 200 wavenumbers from PLS-DA VIP sorting, and the top 100 wavenumbers from the theory-based ranking. An overlap of 100 wavenumbers emerged, and the model achieved a peak F1 Score of 0.80 and 74.7% accuracy.

Table 1 Current AI model (XGBoost for differentiaton high risk and low risk lesions; LOOC method with SVM performance: intestinal metaplasia ) performance with selected wavenumbers for differentiation between gastric lesions.

Conclusion

A Raman spectroscopy-based AI algorithm may be useful for real time diagnosis of GIM, GD and EGC.

Introduction

In addition to gluten and a genetic predisposition, other external factors dictate the onset of coeliac disease (CeD). These, including the microbiota, have not yet been well characterised, but could explain why the disease occurs later in life in a large proportion of patients. Microbiota-associated barrier defects may contribute to this process.

Aims & Methods

Our aim was to investigate the potential of microorganisms to alter small intestinal epithelial polarity as well as epithelial barrier function - in particular with regard to epithelial gluten peptide uptake.
The study was designed in two phases. In the screening phase, the cell lines Caco2-Bbe and Caco2-PIP2 were exposed to different microorganisms. Caco2-PIP2 was stably transfected with a GFP-labelled PIP2 binding unit, which allowed for analysis of cell polarity. Read-outs in the screening phase included transepithelial resistance (TER), tight junction (TJ) integrity and epithelial polarity (IF and confocal imaging) and paracellular permeability by sandwich assay. In experimental phase II, the microorganisms (including a invasio-defective ALS3-mutant) were selected for a detailed analysis using human duodenal organoid 2D monolayers (isolated from healthy individuals and CeD patients). Read-outs included: TER, TJ integrity, epithelial polarity, 33mer-gliadin translocation and differential transcriptome analysis of bulk-RNA isolated from microbiota-exposed duodenal organoids.

Results

​Pseudomonas aeruginosa and Candida albicans were selected in phase I. They caused a decrease in TER by 90% and 95% of the original TER, respectively. Escherichia coli K12 and Saccharomyces cerevisiae were used as controls for P. aeruginosa and C. albicans, respectively. In phase II, both candidates revealed a reduced TER, an abolition of epithelial polarity and disrupted TJs as well as an increased epithelial 33mer uptake in CeD and control 2D organoids. Candida invaded – in an ALS3-dependent manner – the 2D organoid duodenal epithelia and thereby interacted with epithelial dynamin. On the other hand, differential gene expression of P. aeruginosa-exposed epithelia revealed altered apoptosis, barrier function and ion transport.

Conclusion

Our results suggest that distinct microorganisms can cause an epithelial barrier defect and increase 33mer transport in epithelial monolayers, thereby contributing to CeD immune pathology.

Introduction

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. A remarkable increase in early onset colorectal cancer (EOCRC), defined as diagnosis before the age of 50 years, has been observed globally over the past decades. Recent data indicate that EOCRC presents distinct clinicopathological features, such as advanced stage at diagnosis and unique molecular signatures. Interestingly, EOCRC has been reported to be more likely to occur in the left sided colon, commonly called early onset left sided colorectal cancer (EOLCC). However, the underlying molecular mechanisms of EOLCC carcinogenesis and progression have still not been fully explored.
Concurrently, the prevalence of metabolic syndrome (MetS), including central obesity, insulin resistance, hypertension, and dyslipidemia, has increased in younger populations. As reported, MetS promotes carcinogenesis through chronic inflammation, hyperinsulinemia, and oxidative stress. Importantly, MetS is more common in patients with EOLCC. Although a hypothesis has been proposed regarding the possible link between MetS and EOLCC, the genetic and molecular mechanisms involved remain largely unexplored. Moreover, possible targeted treatment strategies for patients with both conditions remain limited.

Aims & Methods

This study aimed to investigate and elucidate key biomarkers associated with MetS-related EOLCC progression and treatment response.
The in-hospital cohort was employed to evaluate the clinical implications of the original tumor location in early-onset colorectal cancer (EOCRC). By utilizing differentially expressed genes (DEGs) and weighted gene coexpression network analysis (WGCNA), we identified potential genes associated with MetS-related EOLCC. The potential mechanisms of MetS-related EOLCC were analyzed using functional pathway enrichment. Random forest (RF) and support vector machine recursive feature elimination (SVM-RFE) algorithms were used to screen candidate biomarkers. The analyses of survival implications, expression patterns, and diagnostic performance were conducted to identify the key biomarkers. The responses to treatment were evaluated. Potential candidate compounds were screened, and molecular docking was performed. The expression and functional signatures were validated in single-cell RNA sequencing (scRNA-seq) datasets and experiments in vitro.

Results

The in-hospital cohort revealed the EOCRC patients had the greater proportion of EOLCC. Through the use of the edgdR package and WGCNA, we identified co-expressed genes common to both EOLCC and MetS, which are notably enriched in pathways related to stromal remodeling and metabolic regulation. By utilizing machine learning, 3 candidate biomarkers were highlighted. Moreover, only CD151 was associated to the prognosis of EOLCC and advanced stage. CD151 were found closely linked to stromal reconstruction and chemoresistance. Meanwhile, the potential compounds targeted to MetS-related EOLCC were identified by molecular docking. Subsequent scRNA-seq analysis confirmed the expression and function patterns of CD151, with especially prominent expression in tumor cells. Ultimately, the bioinformatics findings were validated by quantitative real-time PCR (qRT-PCR) and Immunohistochemical (IHC) staining of clinical samples.

Conclusion

This study investigated CD151 as the key biomarker in MetS-related EOLCC, leading to insights into prognosis, tumor biological status, and personalized treatment strategies. This key biomarker serves as a valuable reference for further exploring the development of clinical applications.

References

1. Wolf AMD, Fontham ETH, Church TR, et al. (2018) Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin 68: 250–281.
2. Frostberg E, Rahr HB (2020) Clinical characteristics and a rising incidence of early-onset colorectal cancer in a nationwide cohort of 521 patients aged 18-40 years. Cancer Epidemiol 66: 101704.
3. Soto J, Gutiérrez Alonso N, Bringas Beranek M, et al. (2022) Analysis of survival trends, clinical, and molecular characteristics of patients with early-onset colorectal cancer (EOCRC). J Clin Oncol 40: 59–59.
4. Dharwadkar P, Greenan G, Singal AG, et al. (2021) Is Colorectal Cancer in Patients Younger Than 50 Years of Age the Same Disease as in Older Patients? Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc 19: 192-194.e3.
5. Ushula TW, Mamun A, Darssan D, et al. (2022) Dietary patterns and the risks of metabolic syndrome and insulin resistance among young adults: Evidence from a longitudinal study. Clin Nutr Edinb Scotl 41: 1523–1531.
6. Bitzur R, Brenner R, Maor E, et al. (2016) Metabolic syndrome, obesity, and the risk of cancer development. Eur J Intern Med 34: 89–93.

Introduction

Gastric cancer is a major cause of cancer-related mortality, and early detection improves outcomes. However, organized gastric cancer screening programs are largely absent in Europe, and vulnerable groups often have low awareness of preventive services. Roma communities face pronounced health disparities and barriers to healthcare, including social exclusion and low literacy, which may limit their use of preventive services [1].

Aims & Methods

We aimed to explore the knowledge, attitudes, and preferences regarding gastric cancer screening among Roma adults with low health literacy in Cluj-Napoca, Romania, to inform culturally tailored outreach strategies, as part of the TOGAS project. Approximately 40 Roma adults (18–72 years) were recruited via community centers for three focus groups (two urban, one rural) in Cluj-Napoca. All participants first attended a brief educational session on digestive health and gastric cancer to ensure baseline understanding. Guided by trained moderators, groups discussed their awareness of gastric cancer and perceptions of screening methods (endoscopy, blood tests, stool tests). All discussions were audio-recorded, transcribed, and thematically analyzed.

Results

Baseline awareness of gastric cancer screening was minimal. Most participants had never heard of any screening test or program for gastric cancer, indicating a major knowledge gap. Nevertheless, after receiving information, many expressed interest in screening for early detection. A prominent theme was communication preferences: nearly all participants preferred to receive health information via mobile phone or social media (e.g., messaging) and also through traditional channels like primary care providers. Overall, participants were open to screening if it was offered conveniently and respectfully.

Conclusion

Outreach is needed to improve engagement in cancer prevention among underserved populations. The lack of awareness in this Roma community echoes reports of poor knowledge of cancer prevention in other Roma groups and signals the need for targeted health promotion to reduce inequalities. As European health authorities consider implementing gastric cancer screening, input from vulnerable communities will be vital for equitable uptake.

References

1. Leja M. Where are we with gastric cancer screening in Europe in 2024? Gut. 2024 Nov 11;73(12):2074-2082.

Introduction

Optical diagnosis (OD) with a “resect and discard” strategy involves diagnosing diminutive polyps with high confidence, photodocumenting and resecting these without sending to histology. This greener, more efficient and cost-effective process underwent a comprehensive evaluation in the DISCARD3 study which showed, in a single screening centre, this meets the threshold for implementation and is feasible and safe with a quality assurance (QA) process in place. The NHS Bowel Cancer Screening Programme (NHSBCSP) in England approved implementation in 2023. Early learning from translating this research into a population based programme is presented.

Aims & Methods

All 506 screening colonoscopists in England have been invited to undertake accreditation in OD. Part 1 of the process involves attendance at a training day including a pre- and post-training test where 120 polyps are optically diagnosed. Pass criteria is ≥85% accuracy for high confidence optical diagnoses and overall ≥50% high confidence calls. Part 2 involves supervised OD at each endoscopists’ base hospital of 20 consecutive high confidence, optical polyp diagnoses with assessment of photodocumentation quality and diagnostic accuracy. To pass part 2 photodocumentation quality is required to be adequate in ≥90% of cases using the “3C photo quality score” and diagnosis accuracy ≥85%. Once achieved, individuals are fully accredited to perform OD with a resect and discard strategy for screening cases and must undertake re-accreditation with online assessment of a further 120 polyp images every 2 years to demonstrate competency. Those accredited are supported by “Optical Diagnosis Champions” at each screening centre who monitor performance and support QA. Once in place “Optical Diagnosis Champions” will support those becoming accredited in OD.

Results

65 screening colonoscopists attended part 1 of the accreditation in March 2024. 85% (55/65) passed the post-test on the first attempt with a further 7 individuals passing on repeat attempts. Overall 62/65 (95%) have completed part 1. Of these, 55/62 (89%) have successfully completed part 2 and are fully accredited.
As of 31 March 2025, 9618 polyps have been resected and discarded with a cost saving equivalent to £355866 (assuming a cost of £37 per polyp). An estimated 3206 hours of histopathology time has been saved (assuming 20 minutes per polyp).
Further training days have been held in September 2024, February 2025 and March 2025 increasing the total number of screening participants to over half of all screeners in England (310/506). The results from these will be reported in due course.

Conclusion

The NHSBSCP is the first population based screening programme in the world to implement OD with a resect and discard strategy. Quality assurance and monitoring is ongoing. In this early stage there have already been cost and time savings for the NHS which are expected to increase substantially once roll out completes in 2027.

References

Ahmad A et al. Implementation of optical diagnosis with a “resect and discard” strategy in clinical practice: DISCARD3 study. Gastrointestinal Endoscopy 2022; 96(6): 1021-1032.e2.

Disclosure

BPS has done consultancy and speaker work for Olympus. There are no other relevant current conflicts of interest to declare.

Introduction

Endoscopic sleeve gastroplasty (ESG) is a minimally invasive and effective treatment for obesity. However, concerns remain regarding gastric mucosal folding and the resulting reduced visibility of the gastric lining. To address these limitations, we developed a novel peroral endoscopic myo-neurotomy (POEM-N) technique (1), adapted from peroral endoscopic myotomy (POEM), as a weight-loss procedure. Although promising, the original POEM-N was time-consuming. This study aims to evaluate the safety and efficacy of a revised POEM-N (R-POEM-N) technique using a submucosal approach as a less invasive bariatric option in a porcine model.

Aims & Methods

Twelve pigs were assigned to either the R-POEM-N group (n = 8) or a sham endoscopic control group (n = 4). Myo-neurotomy was performed at four gastric sites in the R-POEM-N group: two on the greater curvature of the gastric body and two in the antrum. All pigs were fed a hypercaloric diet (twice the standard weight-based intake) and monitored for eight weeks post-procedure. The primary outcome was the proportional change in body weight at 8 weeks, calculated as the ratio of weight change to baseline weight. Secondary outcomes included food intake, changes in serum glucolipid levels, and assessments of safety and procedural duration.

Results

R-POEM-N was successfully completed in all pigs without major adverse events. The mean procedure time was 171.3 ± 3.0 minutes. At 8 weeks, the proportional change in body weight was significantly lower in the R-POEM-N group compared to controls (P = 0.017). Food intake was also significantly reduced in the R-POEM-N group (P < 0.05). No significant differences were observed in serum glucolipid levels between groups.

Conclusion

R-POEM-N effectively limited weight gain in a porcine model and demonstrated a favorable safety profile. These findings suggest that R-POEM-N may serve as a promising, minimally invasive bariatric intervention.

References

(1) Hamada K, Yamasaki Y, Takaki A, et al. Gastric peroral endoscopic myo-neurotomy as less-invasive bariatric surgery in porcine models: an experimental study. iGIE. 2024; 3: 358–65 doi: 10.1016/j.igie.2024.06.002.