Introduction

Alcohol related liver disease, and particularly alcohol related hepatitis, is characterised by specific hepatic and systemic histo- and physiopathological changes (inflammation, ballooning, fibrosis, cholestasis, etc) [1]. On the other hand, increased HVPG was demonstrated to predict a worse outcome in AH [2]. In this study, we aimed to detect which specific AH changes are associated with an increased HVPG. Secondly, we analyzed the interrelation between canalicular cholestasis, systemic inflammation markers, and sepsis.

Aims & Methods

In this study, we aimed to detect which specific AH changes are associated with an increased HVPG. Secondly, we analyzed the interrelation between canalicular cholestasis, systemic inflammation markers, and sepsis.
We retrospectively re-evaluated the transjugular liver biopsy (TJLB) specimens of 90 patients with alcohol-related liver disease between 2016 and 2020 and rescored them using the SALVE scoring/grading system.
Serum from the biobank was used for ELISA tests for cytokeratin18 (CK18), heat shock protein 90 (Hsp90), toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNFα), and lipopolysaccharide (LPS).
We analyzed the correlation between HVPG, systemic inflammation, infection, and the SALVE grading/staging criteria.

Results

Of the 90 enrolled patients, 81 went through TJLB and HVPG measurement. The gender ratio was 24 (29.6%) female to 57 (70.4%) male. The age range was 28-73 (median of 45). Median MELD score and MaddreyDF scores were 22 (6.61 SD, 95% CI) and 82.5 (37.57 SD, 95% CI), respectively. Median HVPG was 20 mmHg (4.9 SD, 95%CI). The biopsy length had a median of 20 mm (range 8-80 mm).
In the univariate analysis, ductular cholestasis was correlated with the prognostic scores (MELD, Maddrey DF, Child-Pugh), which was confirmed at the multivariate analysis (p<0.05). The canalicular type of cholestasis was correlated in both univariate and multivariate analysis with the scores, but also with the number of leucocytes, neutrophils, platelets, the C-reactive protein (CRP), bilirubin level, and HVPG ( p<0.05).
HVPG was correlated with canalicular cholestasis, but not with the ductular type. There was a significant difference in the mean HVPG value between patients without canalicular cholestasis (M=19.14; SD=4.79) and those with canalicular cholestasis (M=21.61; SD=4.84); t(80)=2.31, p=0.023.
One-way ANOVA revealed a statistically significant difference in the HVPG value between the non-cirrhotic and the 3 cirrhotic stages, i.e., SALVE fibrosis stage (SFS) 4A, 4B, and 4C (F(3, 78)=3.99; p=0.01). HVPG did not show a correlation with other histological criteria, such as steatosis, ballooning, and neutrophils.
The systemic inflammation markers CK18, Hsp90, TLR4, TNFα, and LPS did not correlate with cholestasis in the univariate analysis.
Patients who had canalicular cholestasis on histology also had a higher probability of being infected (Pearson Chi square p=0.041) than those with the ductular type of cholestasis (p=0.611).
Overall survival was not influenced by the presence of cholestasis or the canalicular/ductular type (Chi square test p=0.476).

Conclusion

From the histological SALVE criteria, HVPG is correlated with cholestasis, particularly the canalicular type, and the SFS 4A-C.
Cholestasis was found to be an independent predictor of infection in these patients, although, in this vicious circle, infections and sepsis are usually the cause of cholestasis.

References

[1] Lackner C, Stauber RE, Davies S, Denk H, Dienes HP, Gnemmi V, Guido M, Miquel R, Paradis V, Schirmacher P, Terracciano L, Berghold A, Pregartner G, Binder L, Douschan P, Rainer F, Sygulla S, Jager M, Rautou PE, Bumbu A, Horhat A, Rusu I, Stefanescu H, Detlefsen S, Krag A, Thiele M, Cortez-Pinto H, Moreno C, Gouw ASH, Tiniakos DG. Development and prognostic relevance of a histologic grading and staging system for alcohol-related liver disease. J Hepatol. 2021 Oct;75(4):810-819. doi:10.1016/j.jhep.2021.05.029.
[2] Rincon D, Lo Iacono O, Ripoll C, Gomez-Camarero J, Salcedo M, Catalina MV, Hernando A, Clemente G, Matilla A, Nuñez O, Bañares R. Prognostic value of hepatic venous pressure gradient for in-hospital mortality of patients with severe acute alcoholic hepatitis. Aliment Pharmacol Ther. 2007 Apr 1;25(7):841-8. doi: 10.1111/j.1365-2036.2007.03258.x.

Disclosure

The authors have nothing to declare.

Introduction

The VAC-Stent is a fully covered stent encased in a polyurethane sponge cylinder, offering a promising approach for treating upper gastrointestinal (UGI) tract leaks and defects¹; however, available evidence remains limited and preliminary.

Aims & Methods

This prospective study enrolled all consecutive patients with UGI leaks treated with VACStent placement from May 2023 to September 2024 at San Raffaele Hospital, Milan, Italy. The primary outcome was clinical success (CS). Secondary outcomes included technical success (TS) and adverse events (AEs). CS was defined as defect healing confirmed by endoscopic and radiologic evaluation, while TS was defined as successful stent placement and removal.

Results

Fourteen patients [64.3% male, median age 65 years (IQR 59–75); 11 with anastomotic leaks after Ivor-Lewis esophagectomy and 3 with perforations after circumferential esophageal ESD] were enrolled. VACStent was the first-line treatment in 92.9% of cases, with a median leak size of 6 mm (IQR 5-11), and 28.6% of patients had previously undergone re-surgery. The median time from surgery/endoscopy to initial VACStent placement was 7 days (IQR 3-9). The median treatment duration was 9.5 days (IQR 7-14), with a median hospital stay of 29.5 days (IQR 21-63) and a median of 2 VACStents per patient (IQR 1-2).
CS rate was 69.2% (9/13 patients); among the 4 remaining cases, three required rescue surgery, and one patient died of sepsis. All patients treated for perforations following esophageal ESD achieved complete healing without developing strictures. TS was 96.7% (30/31); one case of technical failure occurred in a patient with an anastomotic leak who had previously received radiotherapy for mediastinal lymphoma. No VACStent-related AEs were observed (Table 1)

Table 1: VACStent outcomes

Conclusion

This prospective series suggests that the VACStent is an effective and safe treatment option for upper GI leaks, including perforations after esophageal ESD. Larger controlled studies are warranted to better define its role and optimize outcomes in this complex setting.

References

1. Dell'Anna G, Fanti L, Fanizza J, et al. VAC-Stent in the Treatment of Post-Esophagectomy Anastomotic Leaks: A New "Kid on the Block" Who Marries the Best of Old Techniques-A Review. J Clin Med. 2024;13(13):3805. Published 2024 Jun 28. doi:10.3390/jcm13133805

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

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.