Introduction

Recently, some guidelines recommend conducting colorectal cancer (CRC) screening at ages younger than 50 years. However, there are few data on the preventive effect of colonoscopy at ages 40-49 years at the population level.

Aims & Methods

In this study, the risk of CRC according to the presence or absence of CSP in their 40s was evaluated in a retrospective cohort design using a nationwide database. Using the Korean National Health Insurance System data between 2004 and 2006, we constructed 1:5 colonoscopy cohort (CsC) and non-colonoscopy cohort (NCsC) at ages 40-49 years and followed through 2014. A total of 2,940,792 subjects were enrolled and CRC risk was evaluated after propensity score matching between CsC and NCsC based on age, sex, smoking, metabolic syndrome (MetS) and potentially relevant variables related CRC risk.

Results

Among 490,132 CsC subjects and 2,450,660 NCsC subjects at baseline periods in 40-49 ages, 689 (0.14%) and 9,440 (0.39%) cases of CRC were found during 10 years follow up period, respectively. According to age group, cumulative CRC incidences in early 40’s (40-44) were 0.10% in CsC and 0.25% in NCsC respectively. For late 40’s (45-49), those were 0.17% in CsC group and 0.49% in NCsC group, respectively. Compared with NCsC, the adjusted hazard ratios (aHRs) for CRC development in CsC group were 0.42 (men, 95% CI: 0.35-0.50) and 0.37 (women, 95% CI: 0.30-0.47) in early 40’s and 0.33 (men, 95% CI: 0.29-0.37) and 0.39 (women, 95% CI: 0.33-0.45) in late 40’s.

Conclusion

Overall, colonoscopy in their 40s significantly lowered the risk of colorectal cancer development by 58-67%. This cancer prevention effect of colonoscopy was different according to age and gender, and it was most effective in men in their late 40s, suggesting the rationales for optimization of age and gender to start colonoscopy.

Disclosure

Korea Health Technology R&D Project through the Korea Health Industry Development Institute, National Research Foundation of Korea grant and the National R&D Program for Cancer Control through the National Cancer Center funded by the Korea Ministry of Health & Welfare, Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education.

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

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.