Introduction

Colorectal cancer surveillance recommendations for individuals with Lynch Syndrome (LS) differ between professional associations and the data on interval colorectal cancer (I-CRC) and interval advanced polyps (I-AP) are limited. We aimed to measure the rate of I-CRC and I-AP within a surveillance program.

Aims & Methods

Retrospective study involved individuals with LS who participated in CRC surveillance program at Clalit Health hospitals, Israel. The main outcomes were the rates of I-CRC and I-AP ≤36 months, categorized by 12-month intervals. Included only colonoscopies with adequate preparation. I-CRC and I-AP (≥10 mm or containing high-grade dysplasia or villous histology) were defined as interval advanced neoplasia (I-AN).

Results

The cohort included 342 individuals, 52.3% females, with a median age at data analysis of 49.0 (IQR 37.7-64). At interval ≤ 12 months, there were 7 cases of I-CRC [6/142 (4.2%) of MSH2; 1/46 (2.2%) of MLH1] and 13 cases of I-AP (10/142 (7.0%) of MSH2, 2/46 (4.3%) of MLH1, 1/136 (0.7%) of MSH6]. At 12-24 months, there were 3 cases of I-CRC [2/142 (1.4%) of MSH2, 1/136 (0.7%) of MSH6] and 10 cases of I-AP [8 /142 (5.6%) of MSH2, 1/46 (2.2%) of MLH1, 1/136 (0.7%) of MSH6]. At 24-36 months, there were 3 cases of I-CRC [2/142 (1.4%) of MSH2, 1/18 (5.6%) of PMS2] and 4 cases of I-AP [1 /142 (0.7%) of MSH2, 3/136 (2.2%) of MSH6]. Of all I-CRC, four were diagnosed at stage 3 [4/342 (1.2%)], all at interval ≤24months [3-MSH2, 1-MSH6]. Increasing age and path_MSH2 were significantly associated with I-AN.

Conclusion

Extending surveillance colonoscopy intervals could result in significant rates of I-CRC and I-AP. Diagnosis of I-CRC at advance stage can occur at interval less than 24 months.

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.

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

High-resolution colonic manometry (HRCM) is the gold standard for measuring colonic contractility and guiding decisions for subtotal colectomy in refractory slow-transit constipation (STC). However, it is only available in a handful of centers worldwide. Body surface colonic mapping (BSCM) is a recently validated technology that allows for easy-to-apply and non-invasive transcutaneous evaluation of pre- and post-prandial colonic motility, and has shown strong correlation with HRCM.

Aims & Methods

We sought to evaluate pre- and post-prandial colonic activity using BSCM in patients with refractory STC and correlate with real-time symptoms.
We applied BSCM to refractory chronic constipation patients while undergoing standard diagnostic HRCM. After bowel prep and an overnight fast a HRCM catheter (36 sensors, 3 cm spacing) was advanced and clipped to the caecum. Two BSCM electrode arrays (each 8x8 sensors, 2 cm spacing, Alimetry) were placed on the abdomen after skin prep. Simultaneous HRCM and BSCM recordings were obtained during a 1-hour fasting period, 1 hour after a standardized low-fat meal, and 1 hour after luminally applied 10 mg of bisacodyl. BSCM electrical recordings were band-pass filtered to isolate colonic cyclic motor patterns (CMPs) of 4-10 cycles per minute. The BSCM motility index (MI) was computed from the global continuous wavelet transform spectrum and compared to a real-time symptom score (1-10 scale). Meal response was quantified based on the fasted-fed ratio (FFR) and response time (RT), a marked rise in MI relative to mealtime. Symptoms were recorded for 15 min. during 3,5h.

Results

A total of 9 patients with refractory STC (mean age 45, range 27-60, 22% male) were enrolled. BSCM MI correlated with bloating in 6 subjects, whereof strongly in 2 subjects (R= 0.53 and 0.74). Abdominal discomfort was even correlated to the BSCM MI in 8 subjects, whereof strongly in 2 (R0.74 and 0.79). Flatulence was only reported by 6 subjects and correlated to the BCSM MI in 4 of them, of which 2 strongly (Rs=0.67). While the desire to defecate was correlated with BSCM MI in 6 subjects, the urge to defecate was in 5. However, in both symptoms, there was a strong correlation in 3 subjects (R between 0.69-0.85). These symptoms were mainly provoked by the administration of bisacodyl, followed by strong colonic contractions. Lastly, BSCM MI correlated well with stomach ache symptoms in 6 subjects, of which 2 strongly (R=0.74 and 0.84). Overall symptom burden was strongly correlated with BSCM MI in 3 subjects (R between 0.61-0.8). One subject had clear increases in symptoms, while the colonic activity was low, whereas another subject had an almost perfect correlation between the two. The other subjects had an overall average correlation between symptoms and colonic motility.

Conclusion

BSCM is an easy-to-apply, painless, non-invasive tool that has the potential to elucidate underlying mechanisms driving symptoms in patients with refractory STC. Relating colonic motility to symptoms could aid in developing a more personalized approach to manage these patients' clinical treatment pathway

Introduction

Vedolizumab (VDZ) is a monoclonal antibody therapy approved in China in 2020 for the treatment of patients with inflammatory bowel disease (IBD; Crohn's disease [CD] and ulcerative colitis [UC])² who were intolerant to conventional therapies.¹ VDZ has a unique, gut-selective, anti-lymphocyte trafficking (GSALT) mechanism of action.³ However, data on the efficacy and safety of VDZ in Chinese patients with IBD in the real-world setting are limited.⁴ This study evaluated the safety of VDZ in adult patients with IBD.

Aims & Methods

VALUE (NCT04872491) was a multicenter, single-arm, prospective, observational study to evaluate the safety of VDZ in adult Chinese patients with IBD (N=500) over a maximum observation period of 72 weeks. Incidence of adverse events (AEs), serious AEs (SAEs), treatment-related adverse drug reactions (ADRs), and AEs of special interest (AESIs) was evaluated. This was the final analysis of the VALUE study conducted in patients with IBD.

Results

A total of 500 patients (UC: n=409; CD: n=91) received VDZ 300 mg. Mean (±standard deviation) age of patients was 44.3 (±15.2) years, and 61.4% (n=307) were male. The mean duration for VDZ exposure was 414 days (UC: 416 days; CD:407 days). A total of 500 patients developed 674 AEs (Table), and the most frequent AEs were infections and infestations (I&I; UC: 115 [28.1%]; CD: 24 [26.4%]), followed by gastrointestinal disorders (GIDS; UC: 87 [21.3%]; CD: 18 [19.8%]). Incidence rates of AEs (/patient-years) were 1.2 and 1.0 in patients with UC and CD, respectively. Overall, 13 (3.2%) patients with UC and 10 (11.0%) with CD had AEs leading to study discontinuation. SAEs were observed in 78 patients with UC and 18 with CD (Table). A total of 19 AESIs were reported by patients with UC and 9 AESIs by those with CD, with the most common AESIs being I&I (UC: 13 [3.2%]; CD: 4 [4.4%]) and malignancy (UC: 3 [0.7%], CD: 2 [2.2%]). The most common I&I disorders reported by patients with UC and CD were Clostridium difficileinfection (4 [1.0%]) and pneumonia (1 [1.1%]), respectively. Overall, 17 (4.2%) patients with UC and 7 (7.7%) with CD had at least 1 AESI. A total of 91 and 15 treatment-related ADRs were observed in patients with UC and CD, respectively; I&I were the most frequently documented ADRs to VDZ treatment (Table). A total of 10 (UC: 5 [1.2%]; CD: 5 [5.5%]) patients treated under concomitant IBD advanced therapy (CIBDAT) experienced a total of 16 AEs (UC: 9; CD: 7), with the most common AEs being I&I (UC: 1 [20.0%]; CD: 2 [40.0%]) and GIDS (UC: 3 [60.0%]; CD: 1 [20.0%]) with CIBDAT. No deaths were reported during the study.

Conclusion

The VALUE study indicated that VDZ was well tolerated in Chinese patients with IBD, with no new safety concerns.

References

1. Scribano ML. World J Gastroenterol. 2018; 24: 2457-2467.
2. Yamamoto S et al., Cureus. 2024;16: e59691.
3. Soler D et al. J Pharmacol Exp Ther. 2009; 330: 864-875.
4. Baili C et al. Am J Gastroenterol. 2023; 118: S213-S214.

Disclosure

This study was funded by Takeda (China) International Trading Co. Ltd. Li Li, Haiyan Zhang, Chengxia Liu, and Xiaomei Sun have no conflicts of interest. Xiaoyu Qian and Fang Zhou are Takeda employees and hold Takeda stock options. Minhu Chen received speaker honorariums from Takeda China, AstraZeneca China, Xian Janssen, and Eisai China.
Medical writing support for the development of this abstract under the direction of the authors was provided by Vibhuti Singh, Ph.D., of Cactus Life Sciences (part of Cactus Communications), funded by Takeda (China) International Trading Co., Ltd.

Introduction

The treatment of esophageal motor disorders (EMD) has historically been focused on decreasing pressure at the gastro-esophageal junction (GEJ) by disrupting muscular fibers at this level. The classic management through dilatation, botulinum toxin injection, and Heller's myotomy (HM) underwent a revolution with the advent of third-space endoscopy, offering safe access to the submucosal space and enabling peroral endoscopic myotomy (POEM).
In this prospective national multicenter study, the results of the implementation period of this technique in Spain from 2016 to the present are analyzed, examining its short, medium, and long-term outcomes. Furthermore, outcomes based on EMD, previous treatments, and other multiple variables are also investigated.

Aims & Methods

The primary aim of this study was to ascertain the clinical efficacy of POEM.
Secondary objectives included the identification of predictors of clinical success and the measurement of the incidence of post-POEM GERD and significant complications, as well as the determination of the risk factors for complications
This is a prospective multicenter study conducted across 13 hospitals in Spain. Symptomatic patients undergoing POEM for any EMD were recruited between June 2016 and February 2023. Baseline characteristics, procedural details and outcomes related to efficacy and safety during short and long-term follow-up were analyzed.

Results

A total of 441 patients were enrolled, with type II achalasia representing the most common diagnosis (62.1%). POEM was the primary treatment in 277 patients (62.8%). Clinical success data were available for 396 patients, with a success rate of 94.4% at the last available follow-up (2 years in 117 patients, 1 year in 140, <1 year in 139). A higher baseline Eckardt score was an independent risk factor for clinical failure in the long-term follow-up (p = 0.024). Symptomatic reflux occurred in 4.7% of the patients, with a significant esophagitis rate of 10.1%. Complication incidence was 9.3% (41/441), including 14 (3.2%) severe events. Older age (p = 0.025) and total procedure duration (p=0.036) were independent risk factors for complications, while mucosal injury was found to be a predictor of severe complications (p = 0.027).

Conclusion

These findings confirm the clinical efficacy and safety during the implementation phase of POEM for all EMD in Spain.