Introduction

Gastric Gastrointestinal Stromal Tumors (GISTs) are among the most common mesenchymal tumors arising in the gastrointestinal tract. Despite many international guidelines, the treatment of GISTs with tumor diameters less than 50 mm remains controversial. Although surgical resection is indicated for histologically diagnosed GISTs, endoscopic resection has recently been reported. However, endoscopic resection, mainly Endoscopic submucosal dissection (ESD), often requires a full-layer resection of the gastric wall, which requires extensive suturing. Therefore, we have developed an ESD technique for endoscopic resection of the gastric wall that uses a threaded clip and a detachable snare to strangulate the muscle layer prior to resection and allows safe and easy complete resection without perforation (EISMR: Endoscopic inversion and strangulation of the muscle layer and resection). We now report seven cases of EISMR for gastric GISTs.

Aims & Methods

We evaluated the safety and efficacy of EISMR for GISTs. Seven gastric GISTs (4 males and 3 females) with tumor diameters of 50 mm or less for which we performed EISMR were included in this study, and the en bloc resection rate, R0 resection rate, procedure time, and complications were investigated. All patients underwent EUS and abdominal CT scan before treatment to confirm that the pathological diagnosis was GIST, that the tumor diameter was less than 50 mm, and that the tumor was intraluminal growth type.
In the EISMR procedure, sodium hyaluronate solution was first injected into the submucosal layer of the lesion to dissect the submucosa as in ESD. After a yellowish GIST continuity with the muscularis propria is observed, the submucosa and muscle layer are dissected to expose as much of the submucosa as possible without damaging the tumor. Next, a threaded clip is attached to the tumor and pulled in order to invert the muscle layer. The muscle layer is then retracted into the gastric lumen to form a polyp-like shape, and the base of the muscle layer is strangulated using an detachable snare (PolyLoop Ligating Device, Olympus). The upper margin of the strangulated area is then incised to complete the resection. After confirming that there is no perforation, the strangulated area is additionally sutured with a clip.

Results

All seven cases could be resected en bloc, with a median time of 90.5 minutes (58-120). Of the seven EISMR cases, five cases were performed by experts and two by non-experts. All patients were discharged on postoperative day 5 or 6 without adverse events. Pathology results showed complete resection in the low-risk GIST group. Upper endoscopy 3-6 months after EISMR showed no tumor recurrence and only scarring.

Conclusion

EISMR for gastric GISTs is potentially safe, easy and useful without excessive invasion.

Introduction

Endoscopic Submucosal Dissection (ESD) is the best endoscopic technique that enables en bloc resection of superficial colorectal neoplasms.Despite its effectiveness, ESD is not very widespread in Western countries due to technical complexity, long procedure times, and a steep learning curve. These barriers have created a significant gap in adoption and outcomes between Eastern and Western centers. Underwater ESD (U-ESD) has been introduced to simplify the procedure. This study aimed to evaluate the effectiveness of U-ESD versus conventional gas-based ESD (G-ESD) in a Western center, focusing on procedural efficiency and safety.

Aims & Methods

This is a single-center, prospective randomized controlled trial conducted at Fondazione Campus Bio-Medico in Rome between December 2024 and April 2025.Forty patients with non-pedunculated colorectal lesions were randomly assigned in a 1:1 ratio to undergo either Underwater ESD (U-ESD) or conventional ESD with insufflation of Carbon Dioxide (CO2) (G-ESD).The primary outcome was total procedure time. Secondary outcomes included dissection speed, en bloc and R0 resection rates, use of hemostatic forceps, and the incidence of adverse events such as delayed bleeding, perforation, and post-ESD coagulation syndrome (PECS).

Results

A total of 40 patients referred to our endoscopic unit for ESD between December 2024 and April 2025. The mean size of the colorectal lesions was 57.4 mm and 40.7 mm in the U-ESD and G-ESD groups. The location of the lesions was in the rectum in 15% and 55% of the U-ESD and C-ESD groups, respectively; in the right side of the colon in 35% and 20% of the U-ESD and G-ESD groups, respectively. The morphology of LST was classified as LST-nongranular in 20 % and 25% of the U-ESD and G-ESD groups, respectively; as LST granular in 60% and 35% of the U-ESD and G-ESD groups, respectively. Fibrosis (grade 1 and 2) was present in 45% and 30% of the U-ESD and G-ESD groups, respectively. The mean total procedure time was shorter in the U-ESD group compared with the G-ESD group (53.3 ±33 minutes vs 78.7 ± 25.6 minutes; mean difference,–25.4 minutes; P=0.009).Mean dissection speed was faster in the U-ESD group compared with the G-ESD group (42 ± 26.3 mm2/min vs 13.3 ± 8 mm2/min; mean difference, 28.7 mm2/min; P= 0.001). En bloc and R0 resection rates in both groups were 100%. The use of a hemostatic forceps was significantly lower in U-ESD compared G-ESD (40% vs 90%, P= 0.001). Delayed bleeding occurred in only one patient in G-ESD group and was managed successfully by endoscopic clipping. No perforations occurred in either group. PECS was noted in only one patient in the G-ESD group.

Conclusion

UESD has shown a significantly shorter procedure time and faster dissection speed compared with GESD. These both empower the possibility of considering U-ESD as the preferred colorectal ESD method for colorectal lesions.

Introduction

Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC), with demonstrated efficacy in patients (pts) with baseline modified Mayo Score (MMS) 4–9.¹ No prior clinical trials of advanced therapies in UC have studied efficacy only in pts with baseline MMS ≤6.

Aims & Methods

GLADIATOR (NCT04607837) was a proof-of-concept, global, randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of etrasimod in adults with mildly to moderately active UC (MMS 4–6; endoscopic subscore ≥2; rectal bleeding subscore ≥1) and inadequate response, loss of response or intolerance to ≥1 UC therapy. Pts were randomised 2:1 to etrasimod 2 mg or placebo once daily, stratified by previous biologic/Janus kinase inhibitor exposure and baseline corticosteroid use. GLADIATOR used a treat-through design (12-week [wk] induction period followed by a 40‑wk maintenance period). From Wk 12, pts whose disease had worsened or not improved vs baseline may have been eligible to enrol in an open-label extension trial (NCT03950232). The primary efficacy endpoint was the proportion of pts achieving clinical remission at Wk 52; additional endpoints are shown in the Table. Safety was monitored throughout the study.

Results

In the primary analysis set for efficacy, 127 and 60 pts received etrasimod and placebo, respectively. At Wk 52, 26.0% and 18.3% of pts receiving etrasimod and placebo, respectively, were in clinical remission (p=0.2524; Table). At Wk 12, a greater proportion of pts receiving etrasimod achieved clinical remission, endoscopic improvement (EI) and endoscopic improvement-histologic remission (EIHR) vs placebo (p<0.05; Table). Pts receiving etrasimod were more likely to achieve sustained clinical remission vs placebo (p=0.0104; Table). Etrasimod was generally well tolerated and findings were consistent with the known safety profile.

Conclusion

In pts with mildly to moderately active UC, etrasimod demonstrated higher rates of clinical remission, EI and EIHR at Wk 12, as well as sustained clinical remission at Wk 52, vs placebo. However, the primary endpoint of clinical remission at Wk 52 was not met. Etrasimod demonstrated efficacy in pts with UC with an MMS 4–9, including those with an MMS 4–6, in the ELEVATE UC clinical programme.¹ The proof-of-concept GLADIATOR trial further supports etrasimod’s efficacy in active UC and provides important insights on studying pts with mildly to moderately active UC.

References

1. Sandborn WJ et al. Lancet 2023; 401: 1159–1171.

Disclosure

SD: Lecture fees: AbbVie, Amgen, Ferring Pharmaceuticals Inc, Gilead, Janssen, Mylan, Pfizer Inc, Takeda; Consultancy fees: AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Gilead Sciences, Hospira, Janssen, Johnson&Johnson, MSD, Mundipharma, Pfizer Inc, Roche, Sandoz, Takeda, TiGenix, UCB, Vifor; Directorship: Gastroenterology and Endoscopy.
MG, KL: Employees of Pfizer AG; shareholders of Pfizer Inc.
LPB: Consultancy fees: AbbVie, Abivax, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GlaxoSmithKline, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer Inc, Prometheus, Protagonist, Roche, Roivant, Samsung, Sandoz, Sanofi, Takeda, Theravance, Thermo Fisher, Tigenix, Tillotts, Viatris, Vifor, Vectivbio, Ventyx, Ysopia; Grants: Takeda, Fresenius Kabi, Celltrion; Lectures: AbbVie, Amgen, Arena, Biogen, Celltrion, Ferring, Galapagos, Genetech, Gilead, Janssen, Lilly, Medac, MSD, Pfizer Inc, Sandoz, Takeda, Tillotts, Viatris, Vifor.
AJY: Consultancy fees: AbbVie, Arena, BMS, Celltrion, Pfizer Inc, Takeda; Lectures: AbbVie, BMS.
MCD: Consultancy fees: AbbVie, Abivax, Arena Pharmaceuticals, AstraZeneca, BMS, Eli Lilly, Galapagos, Genentech, Gilead Sciences, Janssen Pharmaceuticals, Johnson&Johnson, Merck, Pfizer Inc, Prometheus Laboratories, Prometheus Biosciences, Sanofi, Sphyre, Takeda, UCB; Shareholder: Trellus Health; Directorship: Trellus Health.
DTR: Consultancy fees: AbbVie, Abivax SA, Altrubio, Avalo Therapeutics, Bausch Health, Bristol Myers Squibb, Buhlmann Diagnostics Corp, Celltrion, ClostraBio, Connect BioPharma, Douglas Pharmaceuticals, Eli Lilly & Co., Foresee, Genentech, Image Analysis Group, InDex Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Odyssey Therapeutics, Pfizer Inc, Sanofi, Takeda Pharmaceuticals, Throne, Vedanta; Grants: Takeda.
BGF: Senior Scientific Director of Alimentiv Inc, which provides central reading services. He is not a company employee and has no equity stake in the organisation, which is owned by a medical trust; Speaker fees: AbbVie, Janssen, Takeda; Consultancy fees: AbbVie, AbolerIS, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport Inc, Arena Pharma, Avoro Capital Advisors, Atomwise, BioJamp, Biora Therapeutics, Boehringer Ingelheim, Boxer, Celsius Therapeutics,Celgene/BMS, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, First Word Group, Galapagos, Galen Atlantica, Genentech, Gilead, Gossamer Pharma, GSK, Hinge Bio, Hot Spot Therapeutics, Index Pharma, Imhotex, Immunic Therapeutics, JAKAcademy, Janssen, Japan Tobacco Inc, Kaleido Biosciences, Landos Biopharma, Leadiant, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer Inc, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen Inc, Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx Biosciences, VHSquared Ltd, Viatris, Ysios, Ysopia, Zealand Pharma; Shareholder: Gossamer Pharma.
GRDH: Advisory fees: AbbVie, AstraZeneca, Alimentiv, BMS, Boehringer Ingelheim, Celltrion, Cosmo, Eli Lilly, Galapagos, GSK, Johnson&Johnson, Takeda, Pfizer Inc, Polpharma, Prometheus Biosciences, Tillotts, Ventyx; Speaker fees: AbbVie, Boehringer Ingelheim, Celltrion, Eli Lilly, Johnson&Johnson, Takeda, Pfizer Inc, Tillotts.
FB: Research/grants: AbbVie, Amgen, Eurogenerics, Janssen, Takeda; Lectures: AbbVie, Arena Pharmaceuticals, Celltrion, Ferring, Galapagos, Janssen, Merck Sharp & Dohme, Pfizer Inc, Takeda; Consultancy fees: AbbVie, Abivax, Amgen, Arena Pharmaceuticals, Celgene, Celltrion, Ferring, Fresenius Kabi, Janssen, Merck Sharp & Dohme, Pfizer Inc, Sandoz.
GG, JY, NL, CZ, WW, SM, EHL, IM, SS, WN: Employees/shareholders of Pfizer Inc.
SV: Lectures: AbbVie, Dr. Falk Pharma, Ferring, Galapagos, Hospira, Janssen, MSD, Takeda, Tillotts; Consultancy fees: AbbVie, AbolerIS Pharma, Alimentiv, Arena, AstraZeneca, Avaxia, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Dr Falk Pharma, Eli Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Hospira, Imidomics, Janssen, Johnson&Johnson, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer Inc, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance Biopharma, Tillotts Pharma AG, Zealand Pharma; Grants: AbbVie, MSD, Pfizer Inc, Galapagos, Janssen, Takeda.

Introduction

The European Union has signalled gastric cancer screening and prevention as a major health priority. The TOGAS consortium (TOwards GAstric cancer Screening in the European Union; togas.lu.lv), funded in response to this call, investigates different strategies for primary and secondary prevention of gastric cancer in Europe. One pilot study aims at determining the yield of having an oesophagogastroduodenoscopy (OGD) on the same day of a colonoscopy for colorectal cancer screening or polyp surveillance.

Aims & Methods

This is the first interim data on n=602 individuals recruited in 8 centres across Europe (France, Germany, Ireland, Latvia, Lithuania, the Netherlands, Portugal, and Spain). Individuals of the age of 50-74 years, attending for screening or surveillance colonoscopy, were invited to participate if they did not have a past diagnosis of gastric preneoplastic conditions requiring surveillance. Standardization of endoscopic procedures was assured by a rigorous protocol including all quality parameters defined by ESGE. This included standards for image documentation and biopsy sampling. Demographics, comorbidities, medication and the previous surgical and family history were recorded. Patients with marked preneoplastic changes (i.e. glandular atrophy or intestinal metaplasia [IM] at OLGA/OLGIM stage 3 or 4, and/or EGGIM score >5) were registered as requiring further endoscopic surveillance. Mann-Whitney U-test was applied for comparison of age between groups and Chi2 test for comparison of categorical variables (significance for p<0.05).

Results

The mean age of participants was 62 years (SD +/- 8.0), with 55.8% being male. Of 245 individuals who underwent an OGD prior to inclusion, 93.1% of these procedures were done >3years before and 60.4% were done at a tertiary centre. We identified 6 (1.0%) malignant/neoplastic lesions, 4 gastric cancers/dysplastic lesions and 2 oesophageal carcinomas. A positive H. pylori status was diagnosed in 34.2%. Endoscopically, a diagnosis of preneoplastic conditions was made in 217 participants (36.0%). Of these, 84 (14.0%) showed gastric atrophy, 45 (7.5%) gastric IM and 75 (12.5%) both conditions combined. Of those with gastric atrophy, this was classified as multifocal in 44 (27.6%) individuals, of those with IM in 45 (37.5%). OLGA stages 3 and 4 were confirmed for 1.9% and 0.8%, OLGIM stages 3 and 4 for 2.3% and 0.4%. Benign ulcers were diagnosed in 28 (4.7%) participants. The majority being gastric ulcers in 19 (3.2%) individuals, duodenal ulcers in 9 (1.5%), and oesophageal ulcers in 2 (0.3%). An additional 13 (2%) participants were diagnosed with Barrett’s oesophagus. It is of note that also 12 (2.0%) colorectal cancers were identified in the cohort. A positive H. pylori status was associated with the need for gastric surveillance (p=0.031).

Conclusion

This interim analysis of the first European pilot study on a combined screening for upper and lower GI tumours shows that this approach is feasible. Regarding the detection of upper GI malignancy and preneoplastic conditions, our findings are in line with previous systematic reviews, but we also demonstrate a reasonable rate of non-malignant findings that are also of relevance when defining the best screening strategy in Europe.

Disclosure

JB: Advisory fee from Flynn Pharma Ltd, Juvise Pharmaceuticals.
MCWS: Research Support from Sysmex, Norgine, Sentinel
OK: Speakers fee, advisory fee from Abbvie, Pfizer, Takeda, Janssen, Shire.