Introduction

Hereditary diffuse gastric cancer (HDGC) associated with CDH1 germline pathogenic variants (PV), carries a high lifetime risk of signet ring cell carcinoma (SRCC). Clinical and molecular events driving progression from early SRCC to advanced cancer are elusive, therefore there is uncertainty to whom and when to recommend risk reducing total gastrectomy (RRTG). We hypothesise a high number of early SRCC lesions (SRCC burden) could be a risk factor for progression to clinical gastric cancer. This study aimed to identify predictors of SRCC burden and provide evidence to modify surveillance intervals.

Aims & Methods

We analyzed data from 53 CDH1 PV carriers who underwent RRTG prospectively recruited between Jan 2006 and Dec 2024 (RRTG dataset) and a separate cohort of 95 CDH1 carriers with ≥2 surveillance endoscopies and 0-2 positive biopsies at baseline (endoscopy dataset). Targeted biopsies (TB) and systematic random biopsies (RB) were obtained using the Cambridge protocol. Multivariable negative binomial regression was used to assess the association of clinical (age, sex, family history, ethnicity, CDH1 variant type) and endoscopic factors (mean number of positive TB and RB per endoscopy) with SRCC burden in RRTG specimens. A logistic regression model with significant predictors was trained to classify patients into low (≤20 foci) and high (>30 foci) cancer burden, validated over 1,000 iterations. Temporal trends in biopsy findings were analyzed using linear mixed-effects models in endoscopy dataset. Surveillance effectiveness at 6- and 12-month intervals was compared in a subset of 38 patients with at least one positive endoscopy followed by subsequent surveillance.

Results

Among 53 RRTG patients (median: 3 surveillance endoscopies over 19 months), 47 (90%) had pT1aN0M0 cancer, and 6 (11%) had pT0N0M0. The mean number of SRCC foci on RRTG specimens was 13, with a median of 33 (IQR: 2-37) and a range of 0 to 273. Among clinical factors, whereas the average number of positive TB (p = 0.001) and RB (p < 0.001) per endoscopy were independent predictors. The model based on endoscopy factors achieved an AUC of 0.88 (0.87, 0.89) for predicting cancer burden under RRTG. No significant trend in biopsy positivity over time was observed (Estimate = 0.0046, p = 0.176). Extending surveillance intervals from 6 to 12 months in patients with low-level positivity did not significantly reduce detection of increased positive biopsies (22% vs. 19%, p = 0.78). Furthermore, using ≥3 positive biopsies as a trigger for recommending RRTG, only 6 patients (16%) met this threshold. The median time after the first positive endoscopy to meeting this criterion was 9 months (95% CI: 0-29) under the 6-month surveillance strategy and 12 (95% CI: 3-33) months under the 12-month surveillance strategies.

Conclusion

Endoscopic surveillance using targeted and random biopsies by experienced endoscopists provides a reliable estimate of SRCC burden in HDGC. Our findings suggest that extending surveillance intervals and delaying surgery in patients with low early SRCC burden is clinically safe.

Introduction

Several Randomized Controlled Trials (RCTs) have evaluated the role of artificial intelligence (AI) Computer-Aided Detection (CADe) systems to enhance polyp detection. However, these studies have focused exclusively on locally deployed hardware-based AI systems, whereas cloud-based systems may improve the accessibility and upgrading of CADe technology. ‘CADDIE’ (Odin Vision, an Olympus company) is a cloud-based CADe system that receives the live endoscopy image stream via the hospital’s internet network, where the AI algorithm processes the images, and overlays real-time bounding boxes on the endoscopy screen to highlight suspected polyps.

Aims & Methods

This prospective RCT aimed to evaluate the efficacy and safety of the novel cloud-based CADe-system in improving polyp detection.

This international, multi-centre, parallel-group RCT was conducted across eight centres in four European countries. Participating endoscopists had a baseline of >1000 colonoscopy procedures and an adenoma detection rate (ADR) of ≥25%. Patients aged ≥40 years and at average risk for colorectal cancer undergoing screening or surveillance indications for colonoscopy were recruited. Patients were randomised in a 1:1 ratio to standard colonoscopy (SoC) or CADDIE-assisted (CADe-arm) colonoscopy. The co-primary endpoints were superiority in adenomas per colonoscopy (APC) as the efficacy endpoint, and non-inferiority for the Positive Percent Agreement (PPA), defined as the percentage of resections that are histologically confirmed adenomas, SSLs and large (>10mm) hyperplastic polyps of the proximal colon, as the safety endpoint.

Results

Overall, 22 endoscopists and 841 participants were included in the analysis. The CADe-arm significantly increased APC by 33% (0.62 vs 0.82, Ratio 1.33 [95%CI 1.06-1.67], p=0.01) and ADR (35.9% vs 43.2%, difference of 7.3% [95%CI 0.7%-13.9%], p=0.03) compared to the SoC-arm. The mean detection of sessile serrated lesions (SSLs) (0.03 vs 0.08, Ratio 3.30 [95%CI 1.41-7.57], p<0.01), large adenomas (0.04 vs 0.09; Ratio 1.93 [95%CI 1.03-3.62], p=0.04), and large polyps (0.05 vs 0.12; Ratio 2.36 [95%CI 1.33-4.17], p<0.01) also significantly improved. A higher proportion of large polyps (27.3% vs. 37.0%) and large adenomas (15.8% vs 24.2%) were non-polypoid ‘flat’ morphology in the CADe-arm compared to the SoC-arm. Other detection metrics, including neoplastic polyps per colonoscopy (0.66 vs 0.91; Ratio 1.39 [95%CI 1.12-1.73], p<0.01) and polyps per colonoscopy (1.06 vs 1.41 (Ratio 1.35 [95%CI 1.13-1.61], p<0.01), also significantly increased.

Non-inferiority in PPA was achieved (53.4% vs 53.9%; 0.5% (-5.0%,∞)), with no increase in unnecessary resections.

Outcome	Study Arm	Patients (N)	Results	Difference (95% CI)	P-value
APC	SoC	424	0.62 ± 1.19	1	0.01
	CADe	417	0.82 ± 1.40	1.33 (1.06, 1.67)
ADR	SoC	424	35.9%	0	0.03
	CADe	417	43.2%	7.3% (0.7%, 13.9%)
SSL-PC	SoC	424	0.03 ± 0.16	1	<0.01
	CADe	417	0.08 ± 0.45	3.30 (1.41, 7.57)
PPC	SoC	424	1.06 ± 1.53	1	<0.01
	CADe	417	1.41 ± 1.85	1.35 (1.13, 1.61)

Table 1: Study results. ADR = Adenoma detection rate, APC = mean Adenomas Per Colonoscopy, PPC = Polyps Per Colonoscopy, SSL-PC = Sessile Serrated Lesions Per Colonoscopy.

Conclusion

This trial demonstrates the safety and efficacy of a cloud-based CADe-system to increase endoscopists' polyp detection across multiple metrics, notably for large adenomas, large polyps, and SSLs.

Disclosure

AR, CS, LBL, RK have received medical consultancy fees from Odin Medical Ltd

Introduction

Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder characterized by atrophy of the gastric corpus mucosa and preservation of the antrum. This condition is marked by the replacement of specialized oxyntic glands with pseudopyloric metaplasia (PPM) and/or intestinal metaplasia (IM) (1,2). Two main subtypes of gastric IM have been described: complete (cIM) which resembles the epithelium of the small intestine, containing Paneth cells (PanC), absorptive cells with a brush border (BB), and goblet cells (gobC), and incomplete (icIM) which exhibits histological features similar to the colonic epithelium, typically lacking PanC and/or absorptive cells (3,4). Gastric IM may progress to dysplasia (GD) and ultimately to cancer (GC), with the icIM subtype being more strongly associated with an elevated risk of neoplastic transformation (2,5).Surveillance of atrophic gastritis is particularly recommended in icIM (6,7). AAG has been reported to be associated to cIM rather than icIM(8) and also for this reason GC risk in AAG has been reported to be negligible (9).

Aims & Methods

To characterize the IM subtype in AAG patients who developed GC or GD in order to clarify the relationship between cIM or icIM and gastric neoplastic lesions in AAG.
We conducted a case-control study by performing histopathological assessment of gastric IM on formalin-fixed paraffin-embedded gastric corpus mucosa biopsies obtained from two groups:
1) cases (AAG GC+ or GD+): AAG pts (n=15, F 86%, median age 69) who developed GC (n=8) or GD (n=8) at AAG diagnosis or during long-term follow-up (FU) (median 7, range 0-13 yrs).
2) controls (AAG GC-GD-): AAG pts (n=38, F 60%, age 56 yrs) monitored for at least once 3 yrs after diagnosis who did not develop GC or GD over long-term FU (median 6 yrs, 3-17).
AAG was histologically diagnosed (1,2) and pts (cases or controls) with H.pylori (Hp) positivity at histology and/or serology and/or previous history of Hp were excluded.
Histopathological subtyping of gastric IM was performed on haematohylin-eosin-stained slides. cIM was defined by the presence intestinal metaplastic epithelium containing Paneth cells (PanC), goblet cells (gobC) and absorptive enterocytes with a brush border (BB)(9).

Results

AAG GC+GD+ (cases, n=15) and AAG GC-GD- (controls, n=37) were similar for sex, age, 1^st degree family history of GC, parietal cell autoantibodies positivity, presence of PPM and long-term FU.
The presence of PanC (13/15, 87% vs 31/37, 84%, p=0.80), gobC (15/15, 100% vs 37/37, 100%, p=1.00), and BB (14/15, 93% vs 35/37, 95%, p=0.86) was similar in AAG GC+GD+ and AAG GC-GD- pts. The presence of all 3 markers of cIM (PanC, gobC, BB) was found in 12/15 (80%) AAG GC+GD+ and 31/37 (81%) AAG GC-GD- pts (p=0.75). Also, the various combinations of these markers (PanC+gobC, PanC+BB, gobC+BB) were similar between groups: 87% vs 81%, 67% vs 81%, and 93% vs 95%, respectively (p>0.05). All pts had at least 2 of 3 markers.

Conclusion

Eighthy percent of AAG pts with GC or GD exhibited all defining histological features of cIM, including the presence of PanC, gobC, and absorptive cells with a BB, compared to 81% of AAG pts without neoplastic lesions.
In AAG with and without GC or GD, cIM is more common than icIM and gastric neoplastic lesions may occur in the absence of icIM. Therefore, icIM is not reliable as predictor for neoplastic risk and further studies are needed to identify new markers of neoplastic progression in AAG pts.

References

1) Lenti MV et al. Autoimmune gastritis. Nat Rev Dis Primers 2020
2) Rugge M et al. RE.GA.IN: the Real-world Gastritis Initiative-updating the updates. Gut 2024
3) El Zimaity HMT et al. Gastric intestinal metaplasia: subtypes and natural history. J Clin Pathol 2001
4) Sugano K et al. Gastric Intestinal Metaplasia: Real Culprit or Innocent Bystander as a Precancerous Condition for Gastric Cancer? Gastroenterology 2023
5) Du S et al. Gastric Cancer Risk of Intestinal Metaplasia Subtypes: A Systematic Review and Meta-Analysis of Cohort Studies. Clinical and Translational Gastroenterology 2021
6) Shah SC et al. AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review. Gastroenterology. 2021
7) Dinis-Ribeiro M et al. Management of epithelial precancerous conditions and early neoplasia of the stomach (MAPS III): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG) and European Society of Pathology (ESP) Guideline update 2025. Endoscopy 2025
8) Genta R et al. Incomplete Intestinal Metaplasia Is Rare in Autoimmune Gastritis. Dig Dis 2023
9) Rugge M et al. Autoimmune gastritis: long-term natural history in naïve Helicobacter pylori-negative patients. Gut 2023

Introduction

Aims & Methods

Results

Baseline IBD characteristics	Frequency	Percentage
Ulcerative Colitis	6	28.57
Crohn's Disease	15	71.43
E2	4	19.05
E3	2	9.52
L1	4	19.05
L2	1	4.76
L3	7	33.33
L1+L4	3	14.29

Conclusion

Introduction

Endoscopic submucosal dissection (ESD) was developed in Japan decades ago and is now widely used as a minimally invasive treatment in Western countries. On-the-job training is the major method for acquiring ESD skills; thus, learning ESD is difficult for foreign endoscopists, who have less opportunity to perform it in their country. ENDONIX (Olympus, Tokyo, Japan) is a laptop-based next-generation 3D printed endoscopy simulator that allows basic and advanced endoscopy training. This study aims to evaluate the effectiveness of ENDONIX training for improving novice foreign endoscopists’ ESD skills.

Aims & Methods

This prospective, single-center, exploratory study was conducted at National Cancer Center Hospital (NCCH) between January 2024 and January 2025. Foreign endoscopists who had performed fewer than three ESD cases and participated in an international training program at NCCH were included. Participants were assigned 1:1 to either the Group A (Day 1-14: ENDONIX training with ESD observation followed by Day 15-28: ESD observation alone) or Group B (Day 1-14: ESD observation alone followed by Day 15-28: ENDONIX training with ESD observation). During the training period, participants performed three basic and one advanced training program on ENDONIX every day. On Days 1, 15, and 29, the endoscopists performed ESD for a 2cm lesion at the lesser curvature of the middle gastric body using a non-animal ESD model (G-Master, KOTOBUKI MEDICAL, Tokyo, Japan), and their technical performance was assessed at each time point. All procedures were supervised by a single experienced endoscopist (TU). The primary endpoint was the improvement in dissection speed (mm/min²) from Day 1 to Day 15 between the groups. Paired t-test was used to compare the corresponding continuous variables.

Results

		Group A	Group B	P value
Day 1	mean (SD) [95% CI], mm2/min	12.2 (2.8) [6.8 – 17.7]	13.4 (2.2) [9.1 – 17.7]	0.75
Day 15	mean (SD) [95% CI], mm2/min	18.6 (2.8) [13.2 – 24.1]	12.6 (1.4) [9.9 – 15.4]	0.10
Day 29	mean (SD) [95% CI], mm2/min	27.4 (2.8) [22.0 – 32.8]	18.4 (1.6) [15.2 – 21.5]	< 0.05

A total of 10 foreign endoscopists were enrolled in this study. The median age was 34 in Group A and 28 years in Group B. Nationalities in Group A were Spanish (n=3), Portuguese (n=1), and Chinese (n=1); in Group B, Spanish (n=4) and Ukrainian (n=1). All Group A endoscopists specialized in gastroenterology; Group B included four gastroenterologists and one oncologist. No significant differences were found between groups in baseline endoscopic experience. All participants completed predetermined ENDONIX training during the study period. ESD was performed on all designated days using G-Master, and en-bloc resection was achieved for the target lesions on without intraoperative perforation or damaging the resected specimen. The mean dissection speed significantly increased from Day 1 to Day 15 in Group A (“ENDONIX training with ESD observation”) (12.2 vs 18.6, p < 0.05). No significant differences were observed from Day 1 to Day 15 in Group B (“ESD observation alone”) (13.4 vs. 12.6, p = 0.81), while the mean dissection speed significantly increased from Day 15 to Day 29 (12.6 vs. 18.4, p < 0.05). Although the difference on Day 15 was not statistically significant between the groups (18.6 vs. 12.6, p = 0.10), Group A demonstrated a significantly higher dissection speed than Group B on Day 29 (27.4 vs. 18.4 p < 0.05), (Table 1).

Conclusion

The systematic endoscopy training with the ENDONIX platform improved the novice foreign endoscopists’ ESD skills. Dissection speed increased in the period receiving systematic ENDONIX training, highlighting the importance of systematic endoscopy training.

Disclosure

None

Introduction

Prophylactic wound closure after Endoscopic Submucosal Dissection (ESD) is suggested in high-risk patients to reduce delayed AEs (e.g. bleeding). The closure of large wounds can be challenging with standard endoscopic devices (e.g. endoclips) and dedicated devices are needed. Endoscopic Hand-Suturing (EHS) can be a therapeutic option to close extensive gastrointestinal defects. The current study presents the EHS experience from two Italian centers, aiming to assess the feasibility and clinical effectiveness of the EHS technique.

Aims & Methods

Data from two high-volume endoscopic Italian centers were retrospectively collected. Patients with an ESD wound closed using the SutuArt (Olympus Medical Systems, Tokyo, Japan) device were enrolled in the study (Figure1). Demographics, technical data, success rate, suturing speed, and AEs were recorded

Results

Between June 2023 and August 2024 10 patients were enrolled in the study, demographics in Table 1. All patients were at high-risk for delayed bleeding after gastric or colorectal ESD (figure2). The mean lesion size was 34mm (range 15-45). In all cases SutuArt (Olympus Medical Systems, Tokyo, Japan) needle holder with V-LOC 180, size 3-0 threads (Medtronic) were used. All procedures were performed by two expert endoscopists. ESD-wound closure was successfully achieved in 90% of cases. The mean suturing time was 42 min (range: 25–65 min, SD=23.3 min) meanwhile the mean ESD time was 86 minutes (range: 15–185min, SD=38min). Suturing significantly increased the total procedure time (120min Vs 86min, p<0.001). In one case, the wound closure failed due to suture breakage, resulting in needle entrapment within the mesorectum, with the impossibility of retrieving it. No other AEs were reported.

Conclusion

ESD-defects closure with EHS is feasible and safe with promising outcomes. However, this technique is significantly time-consuming. Probably extended training may be required for endoscopists performing suturing, and further studies are needed to assess the real-life applicability and the cost-effectiveness of this technique.

Introduction

Hot endoscopic mucosal resection (H-EMR) is the standard of care for large non-pedunculated colorectal polyps (LNPCPs) without suspicion of submucosal invasion, achieving low recurrence rates after en bloc resection or piecemeal resection with margin ablation in expert centers.^1,2 However, electrocautery is also responsible for complications which can lead to significant morbidity and necessitate additional invasive procedures.^3,4 Cold snare polypectomy (CSP) has proven to be preferable to H-EMR for adenomas ≤10mm and non-dysplastic sessile serrated lesions, providing comparable efficacy with improved safety, shorter procedural time and lower costs.⁵ These advantages have driven interest in expanding CSP to larger polyps.

Aims & Methods

This meta-analysis of randomized controlled trials (RCTs) aimed to compare the risk of recurrence and adverse events between cold snare polypectomy (CSP) and hot-endoscopic mucosal resection (H-EMR) for large non-pedunculated colorectal polyps (LNPCPs).
A systematic search of Medline, Embase and Cochrane Library databases was performed through August 2024 for studies comparing recurrence, bleeding and perforation rates between CSP and H-EMR for LNPCPs ≥15mm (PROSPERO ID: CRD42024568272). RCTs were included in the quantitative analysis. A random-effects meta-analysis, with heterogeneity measured with I², was conducted to generate pooled risk ratios (RR) with 95% confidence intervals.

Results

Four RCTs comprising 1516 LNPCPs (766 CSP and 750 H-EMR) in 1442 patients were included in the quantitative analysis. CSP demonstrated a higher recurrence risk at first surveillance colonoscopy than H-EMR in the pooled analysis (22.6% vs. 10.8%; RR=1.98; 95% CI: 1.22–3.21; p=0.02; moderate-certainty evidence), corresponding to a number needed to harm of 9. Regarding adverse events, CSP demonstrated a 67% reduced risk of delayed bleeding (1.2% vs. 3.9%; RR=0.33; 95% CI: 0.12-0.89; p=0.03; high-certainty evidence), corresponding to a number needed to treat of 37. Although CSP appeared to reduce the risk of intraprocedural bleeding (10.0% vs. 19.8%; RR=0.30, 95% CI: 0-52256.34, p=0.42), the wide confidence interval from the random-effects model included 1. There were no intraprocedural or delayed perforations in the CSP group.

Author	Study design	Number of patients		Age, mean (SD), years	Female, %	Number of LNPCPs		LNPCP size, mean/median (SD/IQR), mm	Right Location, %		Adenomatous histology, %
		CSP	H-EMR			CSP	H-EMR		CSP	H-EMR	CSP	H-EMR
O’ Sullivan T. et al., 2024	Single center, RCT	87	90	68.2 (10.0)	46.9	87	90	30 (25-35)	96.5	86.7	100	100
Steinbrück et al., 2024	Multicenter, RCT	184	192	65.9 (10.5)	48.2	193	203	30.1 (10.2)	88.1	86.2	60.7	68.5
Pohl H. et al., 2024	Multicenter, RCT	336	324	65.3 (10.2)	47.7	371	343	30 (25.4)	82.5	83.4	NR	NR
Nogales et al., 2023	Multicenter, RCT	115	114	67.9 (10.6)	43.3	115	114	25 (22-30)	80.0	78.1	71.9	77.2

Table 1. Patients, LNPCPs and procedure characteristics of the randomized controlled trials included in the quantitative analysis. (List of abbreviations: CSP, cold snare polypectomy; H-EMR, hot endoscopic mucosal resection; IQR, interquartile range; LNPCPs, large non-pedunculated colorectal polyps; NR, not reported; SD, standard deviation; RCT, randomized controlled trial)

Conclusion

CSP has nearly double the recurrence risk of H-EMR for LNPCPs. However, its superior safety profile may make it a preferable option for patients where procedural safety is prioritized over radicality, such as those with extensive comorbidities.

References

1. Ferlitsch M, Hassan C, Bisschops R et al. Colorectal polypectomy and endoscopic mucosal resection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2024. Endoscopy 2024; 56: 516-545. doi:10.1055/a-2304-3219
2. Kaltenbach T, Anderson JC, Burke CA et al. Endoscopic Removal of Colorectal Lesions: Recommendations by the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2020; 115: 435-464. doi:10.14309/ajg.0000000000000555
3. Sidhu M, Shahidi N, Gupta S et al. Outcomes of Thermal Ablation of the Mucosal Defect Margin After Endoscopic Mucosal Resection: A Prospective, International, Multicenter Trial of 1000 Large Nonpedunculated Colorectal Polyps. Gastroenterology 2021; 161: 163-170.e163. doi:10.1053/j.gastro.2021.03.044
4. Meulen LWT, Bogie RMM, Winkens B et al. Thermal ablation of mucosal defect margins to prevent local recurrence of large colorectal polyps: a systematic review and meta-analysis. Endosc Int Open 2022; 10: E1127-e1135. doi:10.1055/a-1869-2446
5. Rex DK, Anderson JC, Pohl H et al. Cold versus hot snare resection with or without submucosal injection of 6- to 15-mm colorectal polyps: a randomized controlled trial. Gastrointest Endosc 2022; 96: 330-338. doi:10.1016/j.gie.2022.03.006