Introduction

The progression of Barrett’s Esophagus (BE) to malignancy is accompanied by increasing copy number alterations (CNAs). However, the timing of CNAs events during evolution remains unclear. This study leverages multi-regional, longitudinal sequencing of BE to map CAN temporal dynamics, identify key drivers of BE progression, and improve risk stratification.

Aims & Methods

Two BE cohorts were analyzed. The discovery cohort included shallow whole-genome sequencing (sWGS, 0.4X) from 777 BE samples across 88 patients, while the validation cohort included 256 BE samples from 95 patients. We refined the bioinformatics tool RASCAL¹ to improve absolute CNA analysis by automatically selecting high-quality samples. Phylogenetic trees were generated by MEDICC2² to classify CNAs along an evolutionary timeline (Figure 1). Risk scores were computed based on the probability of CNA occurrence in non-progressing vs. dysplastic BE samples. A random forest model was trained to predict dysplasia based on risk score and validated in an independent cohort.

Results

In the discovery cohort, 52.3% (260/497) of NDBE and 75.2% (124/165) of dysplastic samples were high-quality, with 16.9% (21/124) of dysplastic samples exhibiting whole genome doubling (WGD). In the validation cohort, 79.4% (181/228) of NDBE and 86.2% (25/29) of dysplasia/cancer samples were high-quality, with WGD in 24.0% (6/25) of dysplastic cases. Early-stage CNAs in non-progressing BE showed specific chromosomal gains and losses, whereas later-stage CNAs in dysplasia were more widespread and less commonly shared. Risk scoring of known drivers revealed that SMAD4 losses and CCND3/GATA4 gains were linked to dysplasia. Our model with divergent evolutionary patterns predicted dysplasia with an AUC of 0.89 (Sensitivity: 80.6%, Specificity: 95.7%) in the discovery set and AUC of 0.84 in the validation set (Sensitivity: 73.1%, Specificity: 93.9%).

Conclusion

This study maps CNA evolutionary trajectories in BE, demonstrating selective constraints in early evolution and stochastic processes in dysplastic progression. CNA-based risk scores offer a promising tool for lesion risk stratification.

References

1. Sauer C M, Eldridge M D, Vias M, et al. Absolute copy number fitting from shallow whole genome sequencing data. Biorxiv, 2021: 2021.07. 19.452658.
2. Kaufmann T L, Petkovic M, Watkins T B K, et al. MEDICC2: whole-genome doubling aware copy-number phylogenies for cancer evolution. Genome biology, 2022, 23(1): 241.

Introduction

Delayed bleeding remains a significant complication after endoscopic resection procedures in the gastrointestinal tract. Effective strategies to prevent post-procedural bleeding and promote optimal healing are critical for improving patient’s outcomes. Self-assembling peptide (SAP) is a new hemostatic agent that forms protective nanofibers scaffold after contact with body fluids. Its application may reduce delayed bleeding and support tissue healing after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). Early clinical data has shown promising results, but evidence is still limited.

Aims & Methods

This study evaluates the impact of SAP use on delayed bleeding rates and healing process after advanced endoscopic therapies. The findings may support the integration of SAP into standard post-endoscopic care protocols.
A retrospective analysis was conducted on patients after EMR or ESD at a single tertiary endoscopy center. Two primary outcomes were assessed: delayed bleeding and post-resection defect healing. Delayed bleeding was defined as clinically evident bleeding occurring within 30 days following the index endoscopy. Healing was evaluated endoscopically using the Sakita-Fukutomi classification at 4, 8, and 24 weeks. The size of the resection defect was measured during the procedure using endoscopic forceps or a polypectomy snare for reference. Data were collected from medical reports.​​​​​​​​

Results

A total of 141 patients (55 women, 86 men) were included in the analysis. The majority underwent ESD (n=96; 68 %), followed by piece-meal EMR (n=36; 26 %), hybrid procedure EMR+ESD (n=7; 5 %), and en-bloc EMR (n=2; 1 %). 35 lesions (25 %) were located in upper GI tract, 106 lesions (75 %) in colon and rectum with an average lesion size of 48 mm. R0 resection was achieved in 71 (78 %) of all 91 en-bloc resections. Delayed bleeding occurred in 6 patients (4.3%), with an average onset of 4 days after the procedure. All these patients had subsequent endoscopy with various hemostatic approaches, including SAP alone (n=3), SAP with coagulation (n=1), coagulation with hemoclips (n=1), and coagulation with hemospray (n=1). In all cases hemostasis was achieved. 2 patients required transfusion. The post-resection defect averaged 51 mm after index endoscopy. At 4, 8, and 24 weeks post-procedure, its size decreased to 20 mm, 14.5 mm, and 10 mm, marking reductions of 61%, 72%, and 80%, respectively.

Conclusion

SAP is effective in preventing delayed bleeding and healing post-resection defects. Its use can increase overall safety of advanced endoscopic procedures. Further studies are needed to establish optimal indications and integration into standard post-procedure protocol.
Supported by program projects of the Ministry of Health of the Czech Republic with reg. no. NU22-08-00424, MO1012 and Cooperatio.

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) has been linked to colorectal cancer (CRC), adenoma, and advanced adenoma,^{(1, 2)} although lesion definitions have varied across studies. The 2020 US Multi-Society Task Force (US MSTF) on CRC identified specific adenoma features associated with high risk of metachronous lesions and recommended follow-up colonoscopy within three years⁽³⁾. To date, no study has assessed the association between MASLD and adenomas with these features.
Lean MASLD, defined by a BMI <25 kg/m² (<23 kg/m² in Asian populations)⁽⁴⁾, has been associated with higher risk of CRC than non-lean MASLD in some studies⁽⁵⁾, but its relationship with colorectal adenoma remains unclear.

Aims & Methods

This cross-sectional study aimed to assess the prevalence of colorectal adenomas and adenomas with high-risk features requiring follow-up colonoscopy within three years in patients with MASLD and lean MASLD. High-risk features were defined, per the 2020 US MSTF recommendations, as one or more of the following: ≥5 adenomas, any adenoma ≥10 mm, villous histology, high-grade dysplasia, or traditional serrated adenoma.⁽³⁾
We included adults undergoing health check-ups at Fu Jen Catholic University Hospital (Taiwan) between April 2018 and December 2023. Data collected included BMI, waist circumference, blood tests, colonoscopy, liver ultrasonography and a structured questionnaire. Patients with regular alcohol intake were excluded. MASLD was defined as hepatic steatosis plus ≥1 cardiometabolic risk factor.⁽⁶⁾ Lean MASLD was defined as MASLD with BMI <23 kg/m². Patients with steatosis but no metabolic risk factors were categorised as “other steatotic liver disease (SLD)”; those without steatosis as “normal liver”. Logistic regression was used to assess associations between patient groups and colorectal adenomas, including those with high-risk features, adjusting for age ≥45 years, sex, smoking, and physical activity.

Results

Of 5,616 patients, 2,528 (45.0%) with MASLD, 136 (2.4%) other SLD, and 2,952 (52.6%) normal liver. Lean MASLD accounted for 11.6% of MASLD cases.
MASLD patients were older (median age: 50 vs. 46 vs. 45 years) and more frequently male (64.0% vs. 42.5% vs. 38.2%) compared to the normal liver and other SLD groups.
Within the MASLD group, lean patients were older (53.0 vs. 50.0 years), less frequently male (40.1% vs. 67.1%), and had lower rates of abnormal triglycerides (34.7% vs. 42.3%) and hypertension (16.7% vs. 24.1%) than their non-lean counterparts.
Colorectal adenomas were more prevalent in MASLD patients than in those with normal liver (23.9% vs. 15.7%, p < 0.001) or other SLD (23.9% vs. 16.2%, p = 0.04). Adenomas with high-risk features were also more frequent in MASLD than normal liver (5.1% vs. 3.0%, p < 0.001).
Logistic regressions confirmed that MASLD as independently associated with colorectal adenomas (adjusted odds ratio [aOR] 1.324, 95% confidence interval [CI]: 1.148–1.528, p < 0.001) and adenomas with high-risk features (aOR 1.463, 95% CI: 1.099–1.946, p = 0.009). Among MASLD patients, lean MASLD was not associated with either outcome; however, higher BMI was independently associated with colorectal adenomas (aOR 1.040, 95% CI: 1.014–1.067, p = 0.002).

Conclusion

MASLD is associated with an increased prevalence of colorectal adenomas, including those with high risk of metachronous lesions. Among MASLD patients, lean individuals did not show higher rates of adenoma, while higher BMI may remain an independent risk factor. Further research is warranted to guide individualised CRC screening in MASLD populations.

References

1. Zeng Y, Cao R, Tao Z, Gao Y. Association between the severity of metabolic dysfunction-associated fatty liver disease and the risk of colorectal neoplasm: a systematic review and meta-analysis. Lipids Health Dis. 2022;21(1):52.
2. Mantovani A, Petracca G, Beatrice G, Csermely A, Tilg H, Byrne CD, et al. Non-alcoholic fatty liver disease and increased risk of incident extrahepatic cancers: a meta-analysis of observational cohort studies. Gut. 2022;71(4):778-88.
3. Gupta S, Lieberman D, Anderson JC, Burke CA, Dominitz JA, Kaltenbach T, et al. Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2020;158(4):1131-53.e5.
4. Long MT, Noureddin M, Lim JK. AGA Clinical Practice Update: Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Lean Individuals: Expert Review. Gastroenterology. 2022;163(3):764-74.e1.
5. Souza M, Diaz I, Barchetta I, Mantovani A. Gastrointestinal cancers in lean individuals with non-alcoholic fatty liver disease: A systematic review and meta-analysis. Liver Int. 2024;44(1):6-14.
6. Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023;79(6):1542-56.