Introduction

Control of intraoperative bleeding is vital in endoscopic submucosal dissection (ESD) for gastric neoplasms. We developed an ESD method specialized for hemostasis (Spray-ESD) focusing on the Spray coagulation mode (VIO3; ERBE) with high voltage, easy spark control, and improved incision performance.

Aims & Methods

This study aimed to determine the efficacy of Spray-ESD for gastric neoplasms compared to conventional ESD (C-ESD).
An open-label, randomized, controlled trial was conducted from June 2021 to February 2022 at five centers in Japan, and patients with gastric neoplasms meeting the absolute indication for ESD were included in the study. (The clinical registration number is UMIN000034353) Patients were randomized 1:1 to Spray-ESD or C-ESD, and the outcomes of both groups were compared. ESD was performed with an electrosurgical knife: ProKnife. Hemostatic forceps: Hemostat-Y was used for soft coagulation when bleeding was difficult to control. The primary endpoint was the completion rate of ESD using the knife alone without hemostatic forceps. Secondary endpoints were the number and duration of hemostatic forceps use, ESD procedure time, radical cure, and safety.

Results

We analyzed 130 registered cases (Spray-ESD: 65 cases, C-ESD: 65 cases). The completion rate of ESD using the knife alone was significantly higher in Spray-ESD (83.1% vs. 13.8%, P<0.001). The number and duration of hemostatic forceps use were significantly lower in Spray-ESD (median: 1 vs. 3.5 times, P<0.001; 2.0 min vs. 5.5 min, P<0.001). ESD procedure time was not significantly different between the two groups (48.0 min vs. 56.0 min, P=0.11). Both groups had equally high resection rates (complete en bloc resection rate: 100% vs. 95.4%, P=0.24; curative resection rate: 90.8% vs. 87.7%, P=0.78), with a low adverse events rate. (3.1% [posterior bleeding in 2 cases] vs. 6.2% [intraoperative perforation in 1 case, posterior bleeding in 3 cases], P=0.68).

Conclusion

Spray-ESD has been shown to significantly reduce major bleeding requiring hemostats while maintaining a high en bloc resection rate; mastery of the Spray coagulation mode allows for safe ESD with reduced bleeding risk.

Introduction

Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is the most prevalent hepatic disorder worldwide. While histology remains the gold standard, a shift is evident in emerging studies favoring Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) over biopsy as a reliable alternative for steatosis assessment. Similarly, Controlled Attenuation Parameter (CAP) enables the noninvasive assessment of liver steatosis.

Aims & Methods

To assess the accuracy of CAP for MASLD diagnosis as defined by MRI-PDFF. We performed a cross-sectional, diagnostic accuracy study with prospectively collected data. We included consecutive adult participants with type 2 diabetes (T2D) and increased body mass index (BMI ≥25 kg/m²). We used receiver operating characteristic (ROC) curve analyses to assess the accuracy of CAP for diagnosing MASLD (MRI-PDFF ≥5%), and hepatic fat content (HFC) ≥10%. For each ROC analysis, we calculated the area under the ROC (AUROC) alongside 95% Confidence Intervals (CIs), and cutoffs for ruling out (sensitivity >90%) and ruling in (specificity >90%) the target condition. For each cutoff, we calculated the negative (NPV) and positive predictive values (PPV), as well as negative (LRn) and positive (LRp) likelihood ratios with their 95% CIs.

Results

We included 113 participants (58.4% males, mean age 59.6 years). Most participants (95.6%) had a BMI ≥30 kg/m². CAP measurements were performed with the M probe in 36.3% of the participants, and the remaining (63.7%) were scanned with the XL probe. MRI-PDFF values ranged from 1.9% to 37.8% covering the whole spectrum of steatosis. The prevalence of MASLD was 72.6%. The AUROC of CAP for MASLD diagnosis was 0.82 (0.74 to 0.89). The threshold for ruling out MASLD was 249 dB/m yielding a sensitivity (Sens) of 90.2% (81.7 to 95.7), specificity (Sp) 35.5% (19.2 to 54.6), LRp 1.40 (1.07 to 1.83), LRn 0.27 (0.12 to 0.62), PPV 78.7% (73.8 to 82.9) and NPV 57.9% (37.9 to 75.6). Similarly, the threshold for ruling in MASLD was 328 dB/m yielding a Sens, Sp, LRp, LRn, PPV and NPV of 47.6% (36.4 to 58.9), 90.3% (74.2 to 98.0), 4.91 (1.64 to 14.75) and 0.58 (0.46 to 0.74), 92.9% (81.2 to 97.5) and 39.4% (34.0 to 45.2), respectively. The AUROC of CAP for detecting HFC ≥10% was 0.81 (0.73 to 0.88). CAP thresholds for ruling out/in HFC ≥10% were 271 dB/m and 345 dB/m respectively. CAP measurements with IQR < 30 dB/ did not improve the accuracy of CAP for MASLD diagnosis

Conclusion

CAP has acceptable diagnostic accuracy in identifying patients with MRI-PDFF defined MASLD. Thresholds below 249 and 271 dB/m can be used to exclude MALSD and HFC ≥10% with adequate sensitivity. Similarly, CAP values over 328 and 345 dB/m can rule in MASLD and HFC ≥10% respectively.

Disclosure

This study was supported by the Hellenic Association for the Study and Education of Diabetes Mellitus

Introduction

Various endoscopic closure procedures including over-the-scope systems and endoscopic hand suturing have been tested in preventing delayed bleeding after endoscopic resection1). Conventional procedures are technically difficult with long procedure time1), which partially explains its limited application in clinical practice. The novel through-the-scope (TTS) helix and tack suture system has been reported with high success rates and acceptable procedure time using in vivo porcine models along with clinical experience2,3). However, past reports have not identified the proficiency rate of the TTS suture system.

Aims & Methods

The objective of this study is to determine the number of cases needed in achieving closure time of literature-based mean closure time. One beginner with less than 400 experiences of upper gastrointestinal endoscopy and one expert with clinical experience of over 500 endoscopic submucosal dissections participated in this study. Both endoscopists were familiarized with the functionality and troubleshooting of the novel TTS suture system via educational videos. Four in vivo porcine models were used to create 24 mucosal defects with diameter of 2-4 cm in the stomach. Each endoscopist were randomly allocated 12 mucosal defects to close with one set of TTS suture system per procedure. The TTS suture system engages four 5 mm helical tacks tethered to a suture thread into the defect margin and approximates the mucosal defect by applying suture tension with a cinch. The primary outcome was the number of procedures required to achieve closure procedure time below the literature-based mean closure time (7.7 minutes) by inverse curve fitting with nonlinear regression. The secondary outcomes were the success rate of complete closure and the incidence of adverse events. Complete closure was defined as over 90% closure of defect in endoscopy image assessed by two certified endoscopy technicians.

Results

Mean (±SD) size of the mucosal defects was 2.9 (±0.2) cm. Both endoscopists required six cases to achieve a closure time of less than 7.7 minutes. The median closure time was 8.2 (IQR: 5.6-10.1) minutes for the expert and 8.0 (IQR: 6.3-9.4) minutes for the beginner (P = 0.8624). The success rates of complete closure were 75.0% (9/12) for the expert and 83.3% (10/12) for the beginner. Neither endoscopist experienced any adverse events.

Conclusion

The novel TTS suture system requires a small number of cases for both expert and beginner to achieve proficiency in endoscopic closure.

References

1) Kobara H, et al. Dig Endosc. 2023;35(2):216-31.
2) Hernandez A, et al. Endosc Int Open. 2021;09:E572-7.
3) Farha J, et al. Endoscopy. Published online: 12 Jan 2023; doi:10.1055/a-1970-5528.

Introduction

Steatotic liver disease (SLD) encompasses a spectrum of conditions, including metabolic dysfunction-associated SLD (MASLD), alcohol-related liver disease (ALD), and the overlapping category of MetALD. SLD affects more than a third of adults globally, but the majority remain undiagnosed, partially due to its lack of symptoms and limited awareness among patients and physicians. Adults undergoing screening colonoscopy, typically aged ≥50 years, represent a key population for targeted SLD detection, as they have a higher prevalence of cardiometabolic risk factors and is already engaged with preventive healthcare.

Aims & Methods

We examined 610 consecutive individuals aged ≥50 years with no known history of chronic liver disease who were referred for a colonoscopy for colorectal cancer screening. The protocol included sonographic assessment of liver steatosis and point shear wave elastography (pSWE) for liver fibrosis quantification, anthropometric measurements, biochemistry, medical history and alcohol intake evaluation. From the collected data, non-invasive fibrosis scores were calculated and used for aetiological and risk stratification.

Results

A total of 543 patients were included in the final analysis, after excluding patients with an invalid pSWE measurement (5.3%, n=29) and then excluding patients with incomplete results (n=38). The median age was 64 years (IQR 57-70) and 54.0% were male. The median BMI was 28.7 kg/m² (IQR 25.8–31.4) in males and 28.3 kg/m² (IQR 24.2-31.5) in females. SLD was identified in 63.4 % (n=344) of participants. Elevated liver stiffness (pSWE ≥ 1.30 m/s) was found in 26.9 % (n=146), and 4.8% (n=26) had values ≥1.70 m/s, suggestive of compensated advanced chronic liver disease. Among patients with pSWE ≥ 1.30 m/s, MASLD was the predominant aetiology (69.9%, n=102), followed by MetALD (15.8%, n=23), ALD (1.4%, n=2), cryptogenic (11.6%, n=17) and other etiologies (1.4%, n=2). Preselection using EASL-EASD-EASO criteria (i.e. presence of type 2 diabetes or central obesity plus ≥1 cardiometabolic risk factor and elevated liver enzymes) would have detected 365 at-risk individuals (67.2% of the cohort) of whom 55.9% (n=204) had a FIB-4 index ≥1.30. This approach would have identified only 30.4% (n=38) of all the patients with MASLD/MetALD with elevated liver stiffness (n=125).

Conclusion

Opportunistic screening for SLD in patients undergoing screening colonoscopy could be a useful strategy for detecting asymptomatic and potentially progressive liver disease. This approach identified a high prevalence of SLD (63.4%) and elevated liver stiffness (26.9%) in this population, primarily due to MASLD and MetALD. The integration of ultrasound and elastography added minimal burden to the existing workflow while enabling early risk stratification without the need for additional patient visits or referrals.

References

1 Tacke F, Horn P, Wong VWS, Ratziu V, Bugianesi E, Francque S, et al. EASL–EASD–EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). Journal of Hepatology [Internet]. 2024 Jun 7;81(3):492–542.
2 Lazarus JV, Miralles-Sanchez JE, Agirre-Garrido L, Brachowicz N, Nicolàs A, Armenta A, et al. A call to action to address the steatotic liver disease public health threat in Barcelona. The Lancet Regional Health - Europe [Internet]. 2025 Mar 22;52:101272.
3 Barr RG, Wilson SR, Rubens D, Garcia-Tsao G, Ferraioli G. Update to the Society of Radiologists in Ultrasound Liver Elastography Consensus Statement. Radiology [Internet]. 2020 Jun 9;296(2):263–74.

Introduction

Delayed bleeding (DB) is a possible adverse event following gastric endoscopic submucosal dissection (ESD). The Bleeding after ESD Trend from Japan (BEST-J) score was created as a risk prediction model for DB following gastric ESD, but is yet to be validated in non-Asiatic populations.

Aims & Methods

We aimed to apply and validate the BEST-J score on a European sample.
We have conducted a longitudinal study of all consecutive patients undergoing gastric ESD on a European Endoscopic Unit. DB was defined as a hemorrhage with clinical symptoms and confirmed by emergency endoscopy from the time of completion of ESD to 28 days after ESD.
BEST-J score (use of vitamin K antagonists +4, direct oral anticoagulants +4, aspirin or P2Y12R antagonists +2; withdrawing antithrombotic drugs -1; chronic kidney disease +3; multiple lesions +1; lesion ≥30mm +1; lesion in lower-third of the stomach +1) was calculated in each patient and confronted with the outcome (DB).

Results

Final sample included 161 patients, 102 (63.4%) male, with a mean age of 68±8 years. From these, 10 (6.2%) presented DB following ESD, with a median time to bleeding of 7 days (IQR 6.8).
According to BEST-J score, bleeding risk was low (0-1 points) in 111 (68.9%), intermediate (2 points) in 29 (18.0%), high (3-4 points) in 16 (9.9%) and very high (≥5 points) in 5 (3.1%) patients.
BEST-J score presented an excellent accuracy predicting DB in our sample, with an AUC=0.907 (95%CI=0.801-1.000; p<0.001). The optimal cut-off value to predict DB was a BEST-J score ≥3, which matches the cut-off value for high-risk of bleeding in the original investigation. This value had a sensitivity of 90% and specificity of 92%.

Conclusion

The BEST-J score still presents excellent accuracy in risk stratification for post-ESD bleeding in European individuals. Thus, this score may help to guide which patients benefit the most from prophylactic therapies following gastric ESD in this setting.

Introduction

ESSENCE (NCT04822181) is an ongoing 247-week Phase 3, randomised, placebo-controlled trial evaluating the effect of the glucagon-like peptide-1 analogue, semaglutide 2.4 mg subcutaneous once weekly (OW) in participants with non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH). We report the baseline characteristics of the randomised participants.

Aims & Methods

Following a 14-week screening phase, 800 participants (part 1) of 1200 planned (part 2) with MASH and fibrosis stages 2/3 (F2/F3) were randomised 2:1 to receive semaglutide 2.4 mg subcutaneous OW or placebo OW added to standard of care. In part 1, the two primary endpoints at 72 weeks are resolution of steatohepatitis and no worsening of liver fibrosis, and improvement in liver fibrosis and no worsening of steatohepatitis. Based on a central pathologist evaluation, inclusion criteria were histological presence of steatohepatitis stages F2/F3 per the Nonalcoholic Steatohepatitis Clinical Research Network classification, and a non-alcoholic fatty liver disease activity score (NAS) of ≥ 4, with a score of ≥ 1 in steatosis, lobular inflammation and hepatocyte ballooning.

Results

800 participants (250 F2; 550 F3) were randomised. Mean (SD) age was 56 (11.6) years; 57.1% were female; ≥ 99% had ≥ 1 cardiometabolic risk factor(s) in accordance with the metabolic dysfunction-associated steatotic liver disease (MASLD) definition. Mean (SD) NAS was 5.05 (0.95), and higher in F3 versus F2 (5.11 [0.95] vs 4.92 [0.93], respectively). Notably, participants with a higher NAS had more cardiometabolic risk factors for MASLD (52.9% with NAS ≥ 5 vs 45.3% with NAS 4). Similarly, a greater proportion of participants with F3 had all five cardiometabolic risk factors versus F2 (52.9% vs 44.8%, respectively). Although cardiometabolic comorbidities were highly prevalent, 44.5% of participants did not have type 2 diabetes (T2D), and 27.3% did not have obesity. Normal liver transaminases were observed in 26.3% of participants (28% F2; 26% F3). Mean (SD) FibroScan liver stiffness was 12.8 (6.9) kPa, and values of < 8 kPa were observed in 15.3% of participants. Mean (SD) controlled attenuation parameter value was 329 (46) dB/m; mean (SD) enhanced liver fibrosis (ELF) score was 10.0 (1.0), and 43.5% of participants had an ELF score of < 9.8. Overall, 8.8% and 9.0% of participants with/without T2D did not meet any of the following non-invasive criteria: Fibrosis-4 index ≥ 1.3, vibration-controlled transient elastography ≥ 8.1, or ELF ≥ 9.8, and more participants with F2 (14.7–16.4%) did not meet these criteria versus F3 (4.5–6.7%).

Conclusion

The ESSENCE baseline population includes participants with significant fibrosis (F2 and F3) and approximately 91% of the trial population had ≥ 1 positive diagnostic non-invasive test. Cardiometabolic risk factors were found in ≥ 99% of participants, and in increased numbers in those with higher NAS and fibrosis stages.
This is an encore of an abstract that will be presented for the first time at the European Association for the Study of the Liver (EASL) Congress, 5–8 June 2024, Milan, Italy.

Disclosure

The ESSENCE trial is funded by Novo Nordisk A/S.
PNN: reports grants from Novo Nordisk, and has received consulting fees from Novo Nordisk, Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, Bristol Myers Squibb (BMS), Pfizer, Sun Pharma, Madrigal and GSK. PNN also reports honoraria as a speaker for Novo Nordisk and AiCME; support for attending meetings for Novo Nordisk; and participation on an advisory board for Novo Nordisk, Boehringer Ingelheim, Gilead, Intercept, Poxel Pharmaceuticals, BMS, Pfizer, Sun Pharma, Madrigal and GSK.
EB: served as a consultant or advisory board member for Boehringer Ingelheim, Gilead, Intercept, Merck, Novo Nordisk, Pfizer, ProSciento, and as a speaker for Gilead, Intercept, Merck, Novo Nordisk and Pfizer. EB has also received a research grant from Gilead for fatty liver research.
VR: received consulting fees from Novo Nordisk, Sagimet, Madrigal, Enyo, Poxel, Northsea, Intercept and ProSciento, and research grants (to institution) from Gilead and Intercept.
MER: consults for Boehringer Ingelheim, CytoDyn, GSK, Novo Nordisk, HistoIndex, Intercept, Madrigal, NGM Bio and Sonic Incytes.
MR: reports grants from Boehringer Ingelheim and Novo Nordisk, and has received fees for consulting or participation in advisory boards for Boehringer Ingelheim, Echosens, Eli Lilly and Novo Nordisk. MR also reports honoraria as a speaker for AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Madrigal.
AJS: consults for and advises Avant Santé and AstraZeneca. AJS also consults for and has received grants from Akero, BMS, Intercept, Eli Lilly, Madrigal and Novo Nordisk. AJS consults for and owns stock in Rivus, and also consults for AGED Diagnostics, Albireo, Alnylam, Altimmune, Boehringer Ingelheim, 89Bio, Echosens, Genentech, Gilead, GSK, HistoIndex, Mallinckrodt, Merck, NGM Bio, Novartis, PathAI, Pfizer, Poxel, Regeneron, Salix, Siemens, Surrozen, Takeda, Terns and Zydus. AJS owns stock in Durect, Exalenz, Genfit, Indalo, Inversago and Tiziana, and has received royalties from Elsevier and Wolters Kluwer.
KAE, IK, LHØ, DV and JZ: employees and stockholders of Novo Nordisk A/S.

Introduction

Budesonide orodispersible tablets (BOT) effectively induce and maintain clinical and histological remission in patients with eosinophilic esophagitis (EoE) (1, 2). A substantial fraction of patients recruited for the BUL-1 and BUL-2 studies had previously been treated with swallowed topical corticosteroids (STC) other than BOT. This post-hoc analysis aims to assess whether BOT was equally effective in adult EoE patients with and without prior use of STC (3).

Aims & Methods

This retrospective post-hoc analysis pooled 59 patients from the double-blind study phase of the BOT induction study (BUL-1) and 181 patients from the open-label induction phase of the BOT maintenance study (BUL-2). Patients were either STC-naïve (n=103) or had prior STC (n=118); for 19 patients previous treatment with STC was unknown. All patients received 1 mg BOT two times daily (BID) for 6 weeks. The primary efficacy end point was the rate of patients with clinico-histologic remission (≤2 points on numerical rating scales [0–10] each for dysphagia and odynophagia on each of the last 7 days prior to the end of treatment [EoT], and peak eosinophil count <16 eos/mm² hpf [corresponding to <5 eos/hpf]) at week 6/EoT.

Results

BOT showed similar efficacy in patients both with and without prior STC treatment. Clinico-pathologic remission was recorded for 67.8% (n=67) of patients with prior STC treatment and 65% (n=80) of patients with no prior STC (table 1).

Conclusion

This post-hoc analysis of the BUL-1 and BUL-2 study program demonstrates that pre-treatment with STC other than BOT does not reduce the likelihood of achieving clinico-histological remission by treatment with BOT.
One explanation for successful induction of remission despite prior STC treatment is that initial relapse on STC may be due to insufficient delivery of STC to the esophageal mucosa, and/or insufficient equivalent dose of alternative topical steroid compound, rather than patients becoming truly corticosteroid-refractory. In addition, the specialized formulation of BOT that delivers budesonide precisely to the esophageal mucosa may also improve adherence, owing to a more standardized and convenient method of administration.

References

1. Lucendo AJ, Miehlke S, Schlag C, Vieth M, von Arnim U, Molina-Infante J, et al. Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial. Gastroenterology. 2019;157(1):74-86 e15.
2. Straumann A, Lucendo AJ, Miehlke S, Vieth M, Schlag C, Biedermann L, et al. Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis. Gastroenterology. 2020;159(5):1672-85 e5.
3. Miehlke S, Hruz P, Vieth M, Bussmann C, von Arnim U, Bajbouj M, et al. A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis. Gut. 2016;65(3):390-9.

Disclosure

Philipp Schreiner reports fees for consulting/advisory board from AbbVie, BMS, Dr. Falk Pharma, Janssen, Pfizer, Takeda, Galapagos and Sanofi. Alfredo J Lucendo has received research funding from Dr Falk Pharma; Stephan Miehlke is a member of advisory boards for Celgene and EsoCap and has received speaker’s fee from Dr Falk Pharma GmbH and Falk Foundation. Ralph Mueller and Markus Kernbauer-Hölzl are employees of Dr Falk Pharma GmbH; Alain Schoepfer is a member of an advisory board for Dr Falk Pharma GmbH, Adare Pharmaceuticals, Celgene Pharmaceuticals, and Regeneron Pharmaceuticals. He has received research funding from Dr Falk Pharma GmbH, Adare Pharmaceuticals, Celgene Pharmaceuticals, and Regeneron Pharmaceuticals. He has received speaker’s fees from Dr Falk Pharma GmbH and Celgene Pharmaceuticals; Alex Straumann is a consultant of Calypso, EsoCap, Dr Falk Pharma GmbH, GSK, Receptos-Celgene, Regeneron-Sanofi, Shire and Tillotts, and has received speaker fees and research funding from Dr Falk Pharma GmbH. Luc Biedermann reports fees for consulting/advisory board from AbbVie, Amgen, BMS, MSD, Vifor, Dr. Falk Pharma, EsoCap, Janssen, Calypso, Ferring, Pfizer, Takeda, Janssen, and Sanofi.