Introduction

Conventional endoscopic mucosal resection (CEMR) and underwater endoscopic mucosal resection (UEMR) are techniques for the removal of colorectal lesions.

Aims & Methods

The our study aim is to compare the efficacy and safety of UEMR versus CEMR in patients with lesions under 30mm in diameter.
The study included 124 patients with colorectal lesions with a diameter < 20mm, 20-30mm, type 0-Ip (hot-snare polypectomy), 0-Is, 0-IIa or 0-IIa+Is according to the Paris Classification. Cases were divided into two groups: Group I 64/124(51,61%) CEMR cases (0-Is, 0-IIa, 0-IIa+Is - < 20mm 43,75%, 20-30mm 20,31%; type 0-Ip - 35,93%) and Group II 60/124(48,38%) UEMR patients (0-Is, 0-IIa, 0-IIa+Is - < 20mm 45%, 20-30mm 23,33%; type 0-Ip - 31,66%). Cases with deep submucosal invasion were not included. Optical evaluation with chromoscopy and NBI was performed by expert endoscopist, followed by endoscopic resection. The outcomes were the lesion recurrence rate, en-bloc resection, R0 resection rates, adverse events. Data were analysed using Chi-sq, descriptive statistic by SPSS version 26.0.

Results

The recurrence rate was lower for II Group (UEMR) (1/14; 7,14%) in cases of 20-30mm lesions size (I Group (CEMR) - 2/13; 15,38%), and in 0-Ip (hot-snare polypectomy) cases (II Group (UEMR) - 1/19; 5,26%; I Group (CEMR) - 3/23; 13,04%); en-bloc resection rates was higher in II Group (UEMR) (13/14; 92,85%) in cases of 20-30mm lesions size. The R0 resection and adverse events showed the same tendency, only for polyps between 20 and 30 mm. There were no differences in the overall recurrence rate between groups. Underwater endoscopic mucosal resection was faster and easier to perform than CEMR.

Conclusion

Underwater endoscopic mucosal resection is safety method and could be considered for treatment of colorectal lesions with low adverse events rates.

References

Karl Kwok, Tri Tran, Daniel Lew. Polypectomy for large polyps with endoscopic mucosal resection. Gastrointest Endoscopy Clin N Am 32 (2022) 259–276.
https://doi.org/10.1016/j.giec.2021.12.004

Joaquín Rodríguez Sánchez, Marco A. Alvarez-Gonzalez, María Pellisé, et al. Underwater versus conventional EMR of large nonpedunculated colorectal lesions: a multicenter randomized controlled trial. Gastrointest Endosc 2023; Volume 97, No. 5: 941-51.e2.

Chandan S, Khan SR, Kumar A, et al. Efficacy and histologic accuracy of underwater versus conventional endoscopic mucosal resection for large (>20 mm) colorectal polyps: a comparative review and meta- analysis. Gastrointest Endosc 2021;94:471-82.e9.

Introduction

Endoscopic or percutaneous bile duct brushing is often performed as first step to differentiate between benign and malignant biliary strictures. Although brush cytology has a high specificity (95-100%), the sensitivity for detection of malignancy has been reported to be poor (41-67%).(1-4) This results in repeated diagnostic procedures with potential treatment delay, adverse events, and additional costs.

Aims & Methods

Aim of this study was to evaluate a change in protocol for brush cytology with optimization of handling and rating, Next Generation Sequencing (NGS), and the use of two brushes plus intraductal biopsies in patients with suspected perihilar or intrahepatic cholangiocarcinoma (pCCA/iCCA). Patients with suspicion of pCCA or iCCA were prospectively included between June 2021 and December 2023. Preferably two brushes and 2-4 intraductal fluoroscopy guided biopsies were taken during the initial procedure. Cells were dislodged in a Cytolyt container within 30 seconds of which two ''thin prep'' slides were prepared. Double reading was routinely performed by at least two expert cytopathologists. NGS was performed in samples with an uncertain diagnosis of atypia. A historical cohort (January 2017-June 2021) was used as control. In this cohort a single brush was performed without intraductal biopsies. The obtained cells were preserved in a Roswell Park Memorial Institute (RPMI) 1640 medium of which four cytospins were done. Double reading and NGS were not routinely performed. In both cohorts morphological diagnosis was assessed according to the Papanicolau society of cytopathology system for reporting pancreatobiliary cytology. Both the diagnostic category ‘suspicious for malignancy’ and ‘malignant’ were classified as results compatible with malignant disease. Final diagnosis was confirmed by either histological proof of malignancy or in case unavailable, follow-up compatible with malignant disease. Primary endpoint was the sensitivity before and after implementation of the protocol; secondary endpoints were the sensitivity of the individual steps of the modified protocol in the prospective cohort e.g. the sensitivity of only the first brush and additional value of NGS, the second brush, and intraductal biopsies.

Results

In this study, a total of 167 patients were evaluated (51 prospectively and 116 historical controls). The final diagnosis was malignant disease in 153 patients (91.6%). After implementation of the protocol, the sensitivity rose to 86% (95%CI, 72.6-93.7%) versus 48.5% (95%CI, 38.7-58.5%) prior to implementation (difference 37.5%; 95%CI, 22.3-52.6%). Specificity was 100% in both groups (1/1 vs 13/13). Sensitivity of the first brush in the prospective cohort was 76% (95%CI, 61.5-86.5%). NGS was of additional diagnostic value in 3 patients with uncertain brush cytology results, increasing the sensitivity to 82% (95%CI, 68.1-91%). A second brush was performed in 37 patients; in one of these patients, the second brush had additional diagnostic value over the first brush. Intraductal biopsies were performed in 26 patients (4 benign, 9 suspicious of malignancy, 13 malignant), leading to a malignant diagnosis in 2 out of 12 patients with false-negative brush cytology.

Conclusion

A modification in the handling of cytopathology, led to a significant improvement in the sensitivity of bile duct brushes to 76% for patients with suspected pCCA or iCCA. Furthermore, adding NGS, use of two brushes, and intraductal biopsies in the initial procedure could further increase sensitivity to 86%.

References

1. Mehmood S, Loya A, Yusuf MA. Biliary Brush Cytology Revisited. Acta Cytol. 2016;60(2):167-72.
2. Kobayashi M, Ryozawa S, Araki R, Nagata K, Tanisaka Y, Fujita A, et al. Investigation of Factors Affecting the Sensitivity of Bile Duct Brush Cytology. Internal Medicine. 2019;58(3):329-35.
3. Volmar KE, Vollmer RT, Routbort MJ, Creager AJ. Pancreatic and bile duct brushing cytology in 1000 cases: review of findings and comparison of preparation methods. Cancer. 2006;108(4):231-8.
4. Weber A, von Weyhern C, Fend F, Schneider J, Neu B, Meining A, et al. Endoscopic transpapillary brush cytology and forceps biopsy in patients with hilar cholangiocarcinoma. World J Gastroenterol. 2008;14(7):1097-101.

Disclosure

Jeska A. Fritzsche, Esmée Smit, Otto M. van Delden, Frederike Dijk, Arantza Farina Sarasqueta, Sybren L. Meijer, Anne M. Uyterlinde, Mattheus C.B. Wielenga, IJsbrand A.J. Zijlstra, and Joanne Verheij have no conflicts of interest or financial ties to disclose.
Paul Fockens performed as a consultant for Olympus and Cook Endoscopy.
Geert Kazemier reports research support and travel fees from SAS Analytics and research grants from KWF, ZonMw, Cancer Center Amsterdam Foundation, and Bennink Foundation outside the submitted research.
Heinz-Josef Klümpen performed in advisory board for Janssen, Astra-Zeneca and IPSEN, and received Speaker’s fees from CCO and MedTalks.
Cyriel Y. Ponsioen reports research grants from Gilead and Perspectum, performed as a consultant for Pliant, Takeda and Shire, and received speaker’s fees from Tillotts.
Roy L.J. van Wanrooij performed as a consultant for Boston Scientific.
Rogier P. Voermans reports research grants from Boston Scientific and Prion Medical, performed as a consultant for Boston Scientific, and received speaker’s fee from Mylan and Zambon.
All outside the submitted work.

Introduction

Stent placement by endoscopic retrograde cholangiopancreatography (ERCP) is one of the preferred methods for biliary drainage in unresectable malignant biliary obstruction. Nevertheless, clinical success of palliative drainage is not easy to predict, especially at the time of ERCP.

Aims & Methods

We conducted a multicentre retrospective cohort study in 3 centres in Portugal, involving patients with unresectable malignant biliary obstruction (UMBO) submitted to palliative ERCP-guided biliary stenting between 2015 and 2022. This study aimed to evaluate clinical success of biliary drainage in our population, as well as to evaluate the performance of two recently developed and internally validated risk scores for predicting successful biliary drainage after ERCP-guided endobiliary stenting in UMBO, created by the group of Pausawasdi N. et al. This group developed a first score for predicting early clinical success of biliary drainage (decrease ≥50% in total bilirubin (TB) levels within 2 weeks after stenting), using as variables the presence/absence of extrahepatic biliary obstruction, peritoneal carcinomatosis, the type of biliary stent (plastic or metallic) and pre-endoscopic alkaline phosphatase level. The second score was developed to predict complete clinical success of biliary drainage (normalization of TB levels within 6 weeks after stenting) including pre-endoscopic TB levels, presence/absence of extrahepatic biliary obstruction and type of stent as variables. We included 217 patients for this study. However, due to the limitations of a retrospective analysis, we could not evaluate the performance of these scores for all the patients of our cohort. Statistical analysis was performed using SPSS v.29.

Results

In our cohort, a decrease in total bilirubin (TB) levels ≥50% within 2 weeks after biliary stenting was reached in 81.9%(N=113) of the patients of a subpopulation of 138 patients in which these TB levels were available. TB normalization in 6 weeks after stenting occurred in 55%(N=72) of the cases from a subpopulation of 131 patients in which this TB level was measured. In our population, the predictive scores for early and complete clinical success had an AUROC of 0.597 (95% CI, 0.471-0.723; p = 0.13) and of 0.737 (95% CI, 0.650-0.825; p <0.001), respectively.

Conclusion

In our cohort, the predictive score for complete clinical success of biliary stenting in UMBO (at 6 weeks) had a good accuracy (AUROC 0.74), similar to the AUROC reported by this study group (AUROC 0.76 in the validation cohort). The main advantage of this score relies on the fact that it can be applied before ERCP, since its variables can all be determined pre-endoscopically or, at the most, by the time of ERCP (type of stent), possibly allowing the definition of a better strategy for the management and follow-up of these patients.

References

Pausawasdi, N., Termsinsuk, P., Charatcharoenwitthaya, P., Limsrivilai, J., & Kaosombatwattana, U. (2022). Development and validation of a risk score for predicting clinical success after endobiliary stenting for malignant biliary obstruction. PloS one, 17(8), e0272918. https://doi.org/10.1371/journal.pone.0272918

Introduction

Non-variceal gastrointestinal bleeding is a common condition associated with significant morbidity and mortality. Several approaches are available for primary endoscopic treatment. The standard endoscopic approach uses contact thermal methods or hemoclips with or without pre-injection of diluted epinephrine. A newer alternative is the use of an over-the-scope clip (OTSC).

Aims & Methods

The aim of our study was to evaluate the efficacy of these two modalities in the treatment of non-variceal gastrointestinal bleeding.
Methods: PubMed, EMBASSE and the Cochrane Library databases were searched for multicentre randomised controlled trials comparing the efficacy of OTSC with standard endoscopic procedures for the primary treatment of non-variceal gastrointestinal bleeding published up to January 2024. The primary outcome measure was the 7-day re-bleeding rate. We also assessed the presence of persistent bleeding, 30-day rebleeding rate, length of hospital stay and mortality. A systematic review and network meta-analysis was performed for both treatments.

Results

Four trials met the inclusion criteria and were included. Regarding the 7-day rebleeding rate, OTSC showed superior efficacy compared to standard endoscopic therapy in the treatment of non-variceal gastrointestinal bleeding (RR 0.29, 95%CI 0.14-0.62). OTSC was also superior to standard endoscopic therapy in terms of re-bleeding within 30 days (RR 0.43, 95%CI 0.24-0.78). In terms of failure to achieve primary haemostasis, results were similar between the two methods, with a trend in favour of OTSC (RR 0.37, 95%CI 0.37-1.02). Finally, no differences were found in mortality (RR 0.61, 95%CI 0.25-1.51) and length of hospital stay (SMD -0.01, 95%CI -0.20-0.17).

Conclusion

OTSC significantly reduced the 7-day and 30-day re-bleeding rate compared to standard endoscopic therapy. There were no differences in mortality and length of hospital stay.

Disclosure

Julio Iglesias-Garcia: Advisor Fuji

Introduction

Etrasimod is an investigational, once-daily (QD), oral, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator in development to treat immune-mediated inflammatory disorders. CULTIVATE (NCT04173273) is a seamless phase 2/3 trial comprising 5 substudies designed to evaluate the efficacy, safety and tolerability of etrasimod in patients with moderately to severely active Crohn’s disease (CD).

Aims & Methods

Here, we report the induction data from the first substudy (Substudy A). Substudy A was a phase 2, randomised, double-blind study using a 14‑week induction period followed by a 52-week extension period. Adults (18–80 years) with moderately to severely active CD and an inadequate response, loss of response or intolerance to ≥1 conventional or advanced treatments for CD were randomised 1:1 to etrasimod 2 or 3 mg QD. Patients were stratified by baseline biologic failure status and oral corticosteroid use. The primary efficacy endpoint was achievement of endoscopic response (defined as endoscopic remission [SES-CD ≤4 and ≥2-point reduction from baseline with no subscore >1] or ≥50% decrease in SES-CD score) at Week 14. Secondary/exploratory endpoints included achievement of endoscopic remission, clinical remission (CDAI <150) and IBDQ remission (IBDQ ≥170), at Week 14. Outcomes were analysed in the full analysis set (all randomised patients treated with ≥1 dose of etrasimod) using non-responder imputation or observed data.

Results

Of 83 patients randomised to either etrasimod 2 or 3 mg QD, 32/42 (76.2%) and 36/41 (87.8%) completed Week 14, respectively. Overall, 21.4% and 9.8% of patients receiving etrasimod 2 and 3 mg QD, respectively, achieved the primary endpoint of endoscopic response, 14.3% and 7.3% achieved endoscopic remission, 31.0% and 43.9% achieved clinical remission, and 33.3% and 40.0% achieved IBDQ remission at Week 14. Most TEAEs were mild or moderate. The incidence of serious TEAEs (4.8% and 2.4%) and TEAEs leading to discontinuation (4.8% and 7.3%) was low with etrasimod 2 and 3 mg QD, respectively (Table). Two patients randomized to etrasimod 3 mg QD experienced second-degree atrioventricular block type I TEAEs (one patient during 2-mg titration).

Conclusion

Data from this substudy of patients with moderately to severely active CD suggest endoscopic and clinical improvement with both etrasimod 2 and 3 mg QD. However, the small sample size and lack of a placebo arm limit the ability to draw conclusions about efficacy, including comparison between the etrasimod 2 and 3 mg groups. Both doses were well tolerated, and safety was consistent with other etrasimod clinical programmes. Data from the extension phase of Substudy A and the placebo-controlled, dose-ranging phase 2b Substudy 1 are forthcoming.

Disclosure

GD’H: advisor: AbbVie, AstraZeneca, Alimentiv, Bristol-Myers Squibb, Boehringer Ingelheim, Celltrion, Cosmo, Eli Lilly, Galapagos, GSK, Johnson & Johnson, Takeda, Pfizer, Polpharma, Prometheus, Tillotts, Ventyx; speaker: AbbVie, Boehringer Ingelheim, Celltrion, Johnson & Johnson, Takeda, Pfizer, Tillotts.
MCD: grant/research: Janssen; consultancy: AbbVie, Arena, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, Janssen, Pfizer, Prometheus, Takeda, Trellus Health, UCB; shares/royalties: Trellus; directorship/ownership interests: Trellus.
LPB: grant/research: Takeda, Fresenius Kabi, Celltrion; consultancy: AbbVie, Alimentiv, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Bristol-Myers Squibb, Celltrion, CONNECT Biopharm, Cytoki, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer, GSK, HAC, IAG Image Analysis, Index, Inotrem, Janssen, Eli Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM, ONO, OSE, Pandion, Par'Immune, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, TiGenix, Tillotts, Viatris, Vifor, Ysopia, Abivax; speaker: Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillotts, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Eli Lilly, Gilead, Viatris, Medac, Sanofi; stock: CTMA.
SD: consultancy/advisory: AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Gilead, Hospira, Janssen, Johnson & Johnson, MSD, Mundipharma, Pfizer, Roche, Sandoz, Takeda, TiGenix, UCB, Vifor; speaker: AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, Takeda; directorship/ownership interests: Gastroenterology and Endoscopy.
BES: grant/research: Arena, Janssen. Lecture fees/Speakers Bureau: BMS, Janssen, Lilly, Pfizer, Takeda; consultancy/advisory: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer-Ingelheim, BMS, Celltrion, Fresenius Kabi, Genentech, GSK, Janssen, Lilly, Merck, Pfizer, Prometheus Biosciences, Sun Pharma Global, Takeda Pharmaceuticals International, Teva Branded Pharmaceutical Products R&D; stock: Ventyx Biosciences; non-financial support: Janssen, Lilly, Pfizer, Takeda.
DCW: grant/research: AbbVie, Arena, Bristol Myers Squibb, Janssen, Pfizer, Takeda, Ventyx; speaker: AbbVie, Bristol Myers, Squibb, Janssen, Pfizer, Takeda; consultancy: AbbVie, Arena, Bristol Myers Squibb, Janssen, Pfizer, Takeda.
AJY: consultancy: Pfizer, Arena, Takeda, Bristol-Myers Squibb; speaker: Bristol-Myers Squibb.
MVC: grant support: Pfizer, Janssen, Novartis, Bristol-Myers Squibb; consultancy fees: AbbVie, Arena, Bristol-Myers Squibb, Medtronic, Pfizer, Prometheus, Eli Lilly, Janssen, Takeda; speaker fees: AbbVie, Janssen, Medtronic, Pfizer, Bristol-Myers Squibb, Takeda.
DD: employee of Pfizer Inc at the time of the abstract.
IM, HT, GG, CS: employees & shareholders of Pfizer Inc.
CL, FC: employees of Pfizer Inc at the time of this analysis.
JZ: employee & shareholder of Arena Pharmaceuticals.
AMcD: employee & shareholder of Pfizer Ltd.
SS: speaker: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk, Fresenius, Janssen, MSD, Pfizer, Takeda; consultancy/advisory: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk, Fresenius, Gilead, IMAB, Janssen, MSD, Mylan, Pfizer, Protagonist, Provention, Takeda, Theravance.
BGF: consultant/advisory board: AbbVie, AbolerIS, AgomAB, AllianThera, Amgen, AnaptysBio, Applied Molecular Transport, Arena, Avoro Capital, Atomwise, BIOJAMP, Biora, Boehringer Ingelheim, Boxer, Celsius, Celgene/Bristol-Myers Squibb, Connect, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, FirstWord, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer, GSK, Hinge, HotSpot, InDex, Imhotex, Immunic, JAK, Janssen, Japan Tobacco, Kaleido, Landos, Leadiant, L.E.K., Lenczner Slaght, LifeSci, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic, Mylan, OM, Origo, Orphagen, Pandion, Pendopharm, Pfizer, Prometheus, Diagnostics, Play to Know AG, Progenity, Protagonist, PTM, Q32, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres, Silverback, Surrozen, Takeda, Teva, Thelium, TiGenix, Tillotts, Ventyx, VHSquared, Viatris, Ysios, YSOPIA, Zealand; speaker: AbbVie, Janssen, Takeda; Alimentiv Senior Scientific Director, provides central reading services; not a company employee, no equity stake; shareholder: Gossamer.
SV: grant/research: AbbVie, MSD, Pfizer, Galapagos, Takeda; consultancy/advisory: AbbVie, AbolerIS, Alimentiv, Arena, AstraZeneca, Avaxia, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Dr. Falk, Eli Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Hospira, Imidomics, Janssen, Johnson & Johnson, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillotts, Zealand; speaker: AbbVie, Dr. Falk, Ferring, Hospira, MSD, Takeda, Tillotts.

Introduction

Endoscopic Retrograde Cholangiopancreatography (ERCP) is the most commonly used therapeutic procedure for pancreaticobiliary disorders. However, how to best achieve safe and effective bile duct cannulation is still debated. Endoscopists doing ERCP routinely recognize the differences in the macroscopic appearance of the major papilla. This has led to a conception that certain appearances of the papilla are more difficult to cannulate and, therefore, more prone to adverse events.

Aims & Methods

We aimed to quantify the influence of papilla morphology on ERCP outcomes.
PROSPERO registration number: CRD42022360894. We systematically searched three medical databases from inception in September 2022. Studies detailing the cannulation or the rate of adverse events in the context of papilla morphology were included. For the primary classification of the major papilla, the Haraldsson system was used, differentiating four morphological types. Data on studies using other classification systems were also collected. A pooled event rate with a 95% confidence interval (CI) was used for the effect size measure. For the test of subgroup differences, a "Cochrane Q" test was used. The risk of bias assessment was performed using the Joanna Briggs Institute Critical Appraisal tool for studies reporting prevalence.

Results

A total of 17 studies were eligible, and 14 were included in the quantitative synthesis. In studies using the Haraldsson classification, the rate of difficult cannulation was the lowest in type I („regular”) papilla (26%; CI: 18–37), followed by type III („protruding or bulging”) (35%; CI: 25–48) and type II („small”) papilla (39%; CI: 28–52). The highest rate was observed in the case of type IV („creased or ridged”) papilla (41%; CI: 28–55). For post-ERCP pancreatitis, the event rate was the highest in type II („small”) papilla (11%; CI: 8–15) and the lowest in type I („regular”) (6%; CI: 5–8) and III („protruding or bulging”) papilla (6%; CI: 4–8). There was no statistically significant difference in the cannulation failure and post-ERCP bleeding event rates between the different papilla types. Similar trends were observed in the analyses including other classification systems comparable to the Haraldsson's. Most studies carried a low risk of bias.

Conclusion

In conclusion, other types are associated with a higher rate of difficult cannulation compared to the regular papilla type. The small papilla is associated with a higher rate of post-ERCP pancreatitis.