Introduction

Inflammation is one of the key hallmarks of gastric cancer (GC) development, and the arachidonic acid (AA) pathway with more than 90 members has been shown to play a significant role in this process. Recent advances in omics technology have shed light on the molecular changes in cancer, providing a foundation for the identification of candidate biomarkers for use in diagnosis, prognosis, and screening. Thus, the purpose of this study was to revisit the AA pathway in GC using a transcriptomics approach, in order to identify which genes are particularly dysregulated and thus potentially representing targetable biomarkers.

Aims & Methods

RNA-Seq gene expression data (Level 3) and clinical data of the stomach adenocarcinoma TCGA cohort (STAD), containing 414 tumor samples, was obtained using cBioportal (http://cbioportal.org) and UCSC Xena (http://xena.ucsc.edu/). Shapiro–Wilk normality test was used to determine variable normality, and statistically significant differences of gene expression levels between tumor tissue and adjacent normal tissue were evaluated using the nonparametric Wilcoxon test. Hazard ratios for prognosis assessment were calculated using a univariate Cox regression model. Differential gene expression (DGE) analysis was performed using limma and edgeR R-packages. All statistical analyses were performed using R software (version 4.2.1), and p-values < 0.05 were considered statistically significant.

Results

A total of 53 genes were found to be differentially expressed in GC tumors compared with normal adjacent tissues. Overall, 29 genes were down regulated and 24 were up regulated, with the majority being involved in prostaglandin regulation and synthesis. The top down regulated genes include CYP4B1, AKR1C2, HPGD and AKR1C. Such genes encode proteins involved in AA metabolism and prostaglandin regulation and degradation, except for PTGS1, which encodes COX-1, an enzyme associated with prostaglandin synthesis. SOX9, GPX2, PON1, andFAAH2 accounted for the top up regulated genes. In the univariate analysis, four of the top DEGs correlated with worse overall survival: CYP11A1, SOX9, PON1 and FAAH2.

Conclusion

Overall, using a transcriptomic approach, the AA pathway was shown to be dysregulated in GC, with over half of the genes exhibiting altered expression, and going beyond inflammatory biomarkers, highlighting the pivotal role this pathway has in tumor development and progression and the potential for targetable actions.

Introduction

Obesity is a global health challenge associated with significant morbidity, mortality, and economic burden. Endoscopic Sleeve Gastroplasty (ESG) has emerged as a safe, incisionless, and minimally invasive alternative to bariatric surgery for patients with obesity who are either unwilling or unsuitable for surgical options. While ESG has demonstrated promising short-term results in terms of weight loss and metabolic improvement, there remains a paucity of data on long-term outcomes, particularly beyond one year. This study aims to evaluate the long-term efficacy of ESG in a large Asian cohort, focusing on total body weight loss (TBWL) as the primary outcome, with body mass index (BMI) change and absolute weight loss as secondary outcomes.

Aims & Methods

We conducted a retrospective review of 236 patients who underwent ESG at Singapore General Hospital between November 2020 and December 2025. All procedures were performed by a single experienced endoscopist using a U-shaped suturing pattern. The primary outcome was the percentage of total body weight loss (%TBWL) at 6, 12, and 24 months post-procedure.

Results

The cohort consisted predominantly of female patients (69%), with the majority being of Chinese ethnicity (42.8%). The mean age at baseline was 41.4 years (SD ± 10.6), and the mean baseline BMI was 35.0 kg/m² (SD ± 6.1). All ESG procedures were technically successful, with an average of five sutures placed per patient and a mean procedure time of 75 minutes (SD ± 17). No major complications were reported, and the average hospital stay was one day.
Follow-up data were available for 114 patients at 6 months, 86 at 12 months, and 41 at 24 months. The mean percentage total body weight loss was 15.9% (SD ± 10.5) at 6 months, 12.7% (SD ± 7.8) at 12 months, and 9.9% (SD ± 7.8) at 24 months, reflecting a sustained reduction in weight over time. As secondary outcomes, BMI decreased significantly from baseline by a mean of 6.0 kg/m² (SD ± 5.3) at 6 months, 4.2 kg/m² (SD ± 5.7) at 12 months, and 3.5 kg/m² (SD ± 5.7) at 24 months (all p < 0.001). These were accompanied by corresponding mean weight losses of 16.8 kg (SD ± 17.1), 12.1 kg (SD ± 8.6), and 9.6 kg (SD ± 9.0) at the respective timepoints, all statistically significant (p < 0.001).

Conclusion

ESG is a safe and effective endoscopic intervention for weight loss, with sustained and clinically meaningful reductions in total body weight, BMI, and absolute weight observed up to two years post-procedure. These real-world data from a large tertiary Asian centre support the long-term utility of ESG as a viable non-surgical option for obesity management.

Disclosure

​Nil

Introduction

The management of obesity is often complicated by associated comorbidities such as type 2 diabetes, hypertension and hyperlipidaemia—all of which contribute to significant polypharmacy. High pill burden is linked to reduced adherence, increased healthcare costs, and lower quality of life. While Endoscopic Sleeve Gastroplasty (ESG) has been established as a minimally invasive intervention for weight loss, its impact on medication use remains underexplored. This study aims to evaluate changes in medication burden following ESG in a real-world cohort, with a focus on the potential for pharmacological de-escalation alongside weight loss.

Aims & Methods

We conducted a retrospective review of 236 patients who underwent ESG at Singapore General Hospital between November 2020 and December 2025. All procedures were performed by a single experienced endoscopist using a U-shaped suturing pattern. The primary outcome was change in medication burden, defined as the total number of prescribed medications at baseline, 6 months, and 12 months following ESG. Data on medication count were collected from electronic medical records, including all chronic medications prescribed for obesity-related comorbidities.

Results

At baseline, 17.8% of patients were on one or more oral anti-diabetic medications, 2.6% were on insulin, 30.9% were taking antihypertensives, and 22% were on lipid-lowering therapy. At 6 months post-ESG, the proportion of patients on anti-diabetic medications decreased to 15.2%, and insulin use dropped slightly to 2.1%. Anti-hypertensive use declined to 20.8%, and lipid-lowering therapy was reduced to 17.1%. By 12 months, further reductions were observed: 12.7% of patients remained on anti-diabetic medications, only 1.4% were on insulin, and use of anti-hypertensives and lipid-lowering agents fell to 20.8% and 18.8%, respectively.
The total number of medications per patient decreased significantly over time. At baseline, patients were on an average of 1.36 medications targeting diabetes, hypertension, and hyperlipidemia. This declined to 0.61 medications at 6 months and 0.59 at 12 months, corresponding to mean reductions of 0.75 (95% CI: 0.42–1.07, p < 0.001) and 0.77 (95% CI: 0.46–1.08, p < 0.001), respectively. These reductions were consistent across all major cardiometabolic drug classes.

Conclusion

In addition to driving meaningful weight loss, ESG contributes to a measurable reduction in medication burden for obesity-related comorbidities. These findings support the broader role of ESG in promoting pharmacologic de-escalation, potentially improving long-term adherence and quality of life in patients with obesity.

Disclosure

NIL

Introduction

MAESTRO-NASH is an ongoing 54-month, randomized, double-blind, placebo-controlled Phase 3 trial evaluating the efficacy of resmetirom in patients with biopsy-confirmed MASH and fibrosis. 966 patients with biopsy-confirmed NASH were randomized 1:1:1 to resmetirom 80 mg, resmetirom 100 mg, or placebo once daily. Dual primary endpoints at Week 52 were achieved with both resmetirom 80 mg and 100 mg: NASH resolution with no worsening of fibrosis (NR) or ≥1-stage improvement in fibrosis with no worsening of NAS (FI). Both Week 52 liver biopsy endpoints, NR and FI, were achieved. Resmetirom was recently approved for the treatment of adult patients with noncirrhotic NASH and liver fibrosis consistent with F2 to F3 stages. Expert guidance recommends treatment with resmetirom based on staging fibrosis using Vibration-Controlled Transient Elastography (VCTE). EASL recommends stratifying patients using Fibrosis-4 Index (FIB-4). Most guidelines recommend using VCTE cutoffs lower than 10 to <15 kPa for treatment.

Aims & Methods

We assessed results from baseline noninvasive tests (FIB-4, VCTE) against biopsy results in MAESTRO-NASH to measure how well they diagnosed noncirrhotic patients with NASH (consistent
with F2-F3 stages at baseline). We assessed the utility of a lower VCTE cutoff (8.5 to <10 kPa) in capture of F2 and F3 patients who otherwise would be missed. Also evaluated was the addition of
MRE/MRI-PDFF or ELF to VCTE to assess diagnostic utility.

Results

FIB-4 poorly predicted patients in the non-cirrhotic fibrosis stages: F2 (60% patients fell into low-risk) and F3 (40% fell into low-risk). Including a lower cutoff of VCTE (8.5 to <10 kPa) captured
F1B (34% 8.5 to <10 kPa) and many F2 (25% 8.5 to <10 kPa) and F3 patients (19% 8.5 to <10 kPa). The addition of MRE/MRI-PDFF to VCTE increased diagnostic accuracy for F2/F3 to 68% and
F4 to 81%. The addition of the ELF to the VCTE suggested that a low ELF result paired with high VCTE may warrant a VCTE repeat.

Conclusion

Identification of patients with NASH F2 to F3 was achieved with VCTE. F1B are F2 equivalent (F1B is moderate fibrosis on biopsy). Patients with fibrosis stage F4 were effectively ruled out. In addition to VCTE, practitioners may consider expanded noninvasive criteria (ELF, MRE) to help refine fibrosis staging.

Disclosure

This study was supported by Madrigal Pharmaceuticals, Inc.

Introduction

ESD has become the standard treatment for early gastric cancer. Recently, the number of patients taking antithrombotic agents (ATAs) has increased, and the prevention of post-ESD bleeding is a main concern. EHS after gastric ESD has been developed to solve these problems, but the effectiveness and procedural success rate of EHS is not known. Here we investigate the successful introduction of EHS and evaluate the safety and effectiveness of the EHS.

Aims & Methods

11 patients who underwent EHS after gastric ESD from December 2022 to April 2024 were included in this study. Patient and lesion background, endoscopic findings, and treatment outcomes were reviewed retrospectively. A V-loc 180 available barbed suture (VLOCL0604; Covidien, Mansfield, Mass, USA) and through-the scope flexible needle holder (SutuArt, Olympus, Tokyo, Japan) were used for EHS. The same endoscopist and the assistant performed Ex vivo training model prior to clinical introduction.

Results

Mean age was 74.8±7.3 years, 9 males and 2 females, and 4 with and 7 without ATAs. The lesion locations were as follows: upper/middle/lower = 4/0/7. Mean tumor size was 15.4±5.3 mm, mean defect size was 30.3±5.4 mm, and mean resection time was 46.6±26.4 minutes. The mean time needed for suturing was 30.6±9.6 minutes, and a mean of 4.7±0.4 stitches were placed. Suturing speed （resection area/suturing time) was 20.9±7.5 mm²/min. Complete suture was achieved in all patients, and they began clear fluid on POD1. There were no adverse events during EHS such as bleeding or perforation.

Conclusion

In EHS, complete suture was achieved in all cases, with no post-ESD bleeding or delayed perforation. Further data is needed to confirm its effectiveness.

References

1) O. Goto et al. Endoscopic hand-suturing is feasible, safe, and may reduce bleeding risk after gastric endoscopic submucosal dissection: a multicenter pilot study (with video). Gastrointest Endosc 2020 ; 91(5): 1195-1202.