Introduction

The advent of new therapeutic agents might change the management of acute severe ulcerative colitis (ASUC) by reducing the risk of colectomy and thereby changing the natural history of the disease. Thus, the effectiveness and safety of sequential treatment should be elucidated in patients admitted for ASUC. The main aim was to evaluate colectomy-free survival in patients with ASUC refractory to intravenous corticosteroids who failed to infliximab (IFX) or ciclosporin (CyA) and received a second-line (2L) therapy. The secondary aims were to evaluate the short- and long-term effectiveness and to assess the safety of this strategy.

Aims & Methods

Multicentre study of patients admitted with ASUC refractory to corticosteroids who received a 2L therapy after failing either CyA or IFX during the same hospitalisation. Clinical activity was classified based on partial Mayo score and Lichtiger activity index. Patients who stopped the 2L therapy due to disease activity or adverse events were considered failures. Patients were followed-up until colectomy or one year after 2L initiation. Predictors of short-term colectomy-free survival were assessed by logistic regression analysis, while long-term was evaluated by Kaplan-Meier curves and Cox regression models.

Results

A total of 78 patients from 24 European centres were included. As first-line therapy (after failing corticosteroids), IFX was administered to 32 patients, and CyA to 46. The median age at hospital admission was 35 years (IQR 26-47), and 42 (54%) were men. The prescribed therapy after IFX failure was: CyA in 17, tofacitinib in 13, and ustekinumab (UST) in two patients. After CyA failure, IFX was prescribed in 45 patients, and UST in one. At last study visit, 26 patients (33%) were still under the 2L therapy (IFX in 15, CyA in two, tofacitinib in two, and UST in one).

A total of 29 patients (37%) underwent colectomy during the follow-up; the majority of them (93%) within the first eight weeks. Median time to colectomy after starting the 2L therapy was 14 days (IQR 3-23). The main indication of colectomy was primary non-response in 23 patient (79%). In multivariate analysis, older age at hospital admission (OR 1.1, 95%CI 1.0-1.1), the use of CyA as rescue therapy (OR 8.0, 95%CI 1.3-48), and severe disease (vs. moderate) before the rescue therapy initiation (OR 8.7, 95%CI: 2.0-38) were associated with the likelihood of colectomy.
A total of 31 patients (44%) at week 12 and 18 (30%) at week 52 achieved clinical remission under the 2L therapy; 39 patients (55%) at week 12 and 20 patients (33%) at week 52 reached clinical response (including remission). Corticosteroid-free clinical remission was maintained in 26% and 19% of patients at week 12 and at week 52, respectively. Clinical relapse was observed in 43 patients (55%); of them, six patients (14%) intensified the therapy and five (83%) regained response.
25 patients (32%) had adverse events (AE); 14 had serious AE. Resolution with no sequelae was observed in 20 patients (80%). Infections were the most frequent AE, reported in 12 patients (15%), followed by infusion reactions in five (6%). No differences in AEs between the 2L therapies prescribed were observed. There were two deaths: one due to cerebral thrombophlebitis and another due to bacteriemia after colectomy, both when CyA was the therapy prescribed.

Conclusion

A 2L salvage therapy avoids colectomy in a considerable percentage of patients admitted by ASUC and therefore it can be considered after IFX or CyA failure. The individual therapeutic approach must be discussed with patients due to the risk of serious AE

Disclosure

M.J. García has received financial support for travelling and educational activities from Janssen, Pfizer, AbbVie, Takeda, Kern Pharma, Faes Farma and Ferring.
S.Riestra has served as speaker, consultant, and advisory member for or has received research funding from MSD, AbbVie, Takeda, Janssen, Pfizer, Mylan, Biogen, Kern Pharma, Ferring and Faes Farma.
A. Amiot has received consulting fees from Abbvie, Tillotts pharma, Janssen, Hospira, Takeda, Fresenius Kabi, Pfizer and Gilead as well as lecture fees and travel accommodations from Abbvie, Janssen, Biocodex, Hospira, Ferring, Biogen, Tillotts pharma, Fresenius Kabi, Takeda and MSD.
M. Julsgaard has received research grants for other investigator-driven studies from Takeda, has received consultation fee from Ferring and Takeda, and has received speaker's fees from MSD, Ferring, and Takeda.
M. Calafat has served as a speaker or has received educational or advisory fees from Takeda, Janssen, Faes Farma, Ferring, Galapagos, Gilead and MSD.
M.J. Casanova has received education funding from Pfizer, Takeda, Janssen, MSD, Ferring and Abbvie.
E.Savarino has served as speaker for AbbVie, AGPharma, Alfasigma, EG Stada Group, Fresenius Kabi, Grifols, Janssen, Innovamedica, Malesci, Medtronic, Novartis, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda and Unifarco; has served as consultant for Alfasigma, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Falk, Fresenius Kabi, Janssen, Merck & Co., Reckitt Benckiser, Regeneron, Sanofi, Shire, SILA, Sofar, Synformulas GmbH, Takeda and Unifarco; and has received research support from Reckitt Benckiser, SILA, Sofar and Unifarco. "Grants or contracts from any entity AbbVie, Janssen, Kern, Takeda, Galapagos, Pfizer Consulting fees: Janssen. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, AbbVie, Janssen, Takeda, Pfizer. Support for attending meetings and/or travelFerring, Janssen. Educational activities research projects scientific meetings or advisory boards sponsored by MSD, Ferring, Abbvie.
T. Raine has received research/educational grants and/or speaker/consultation fees from Abbvie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda and UCB and has received speaker's fees from Tillots.
J. P. Gisbert has served as a speaker, a consultant and advisory member for or has received research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene, Gilead, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, and Vifor Pharma.
M. Chaparro has served as a speaker, as consultant or has received research or education funding from MSD, AbbVie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Biogen, Gilead and Lilly.

Introduction

Esophageal squamous cell carcinoma (ESCC) often develops the synchronous or metachronous multiple ESCC. Although the Japanese guideline recommended endoscopic examination as surveillance at least once a year after endoscopic resection (ER) of ESCC, the optimal surveillance modality was not specified. In clinical practice, image-enhanced endoscopy (IEE) followed by Lugol chromoendoscopy (LCE) is commonly performed. While LCE reduces the proportion of missed lesion, it has low specificity and causes severe discomfort to the patients, so attempts have been made to omit Lugol's staining. It is unknown what lesions may be missed at this time point by omitting LCE in surveillance after esophageal ER.

Aims & Methods

Thus, this study aimed to clarify clinicopathological characteristics of synchronous or metachronous multiple ESCCs missed by IEE but detected by LCE in surveillance endoscopy after esophageal ER. We retrospectively analyzed the consecutive lesions that fulfilled all of the following inclusion criteria: (1) treated with endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) at our institution between April 2021 and March 2022; (2) newly detected during surveillance endoscopy after ER or during preoperative endoscopy for other ESCC; (3) underwent narrow-band imaging (NBI) or blue laser imaging (BLI) observation followed by LCE observation in the esophagus using a high-definition endoscope at the endoscopic examination of lesion detection; and (4) biopsy-proven or strongly suspected squamous cell carcinoma. Patients with a history of chemotherapy, radiotherapy, or surgery for esophageal cancer were excluded. Lesions were classified into the IEE group (detected by NBI/BLI) and the LCE group (detected only after Lugol staining). The lesion in the IEE group were defined when the lesion was clearly visualized and in focus on the endoscopic images with NBI or BLI, or the endoscopic report described that it was detected with NBI/BLI. We evaluated the features of the lesions in the LCE group by comparing the clinicopathological characteristics between the lesions in the IEE group and LCE group. The endpoints were proportion of　LCE detected lesion and the proportion of target ESCC, defined as ESCC with pathological invasion depth of the muscularis mucosae (pT1a-MM) or deeper and/or positive lymphovascular invasion (LVI) on histological evaluation after ER.

Results

A total of 122 lesions in 96 patients were included. The IEE group comprised 99 lesions (81.1%) in 75 patients, while the LCE group comprised 23 lesions (18.9%) in 21 patients, thus proportion of LCE detected lesion was 18.9%. Most patients (92.7%, 89/96) had grade C of Lugol voiding staining. The median lesion size was 15 mm (range: 4-60 in the IEE group, which was higher than that in the LCE group at 10 mm (5-30). The lesions located on the anterior (23.5%) and left wall (31.3%) tended to be more frequently detected by LCE than those on the right (10.8%) and posterior wall (13.9%). Finally, 26 lesions were treated with EMR and 96 with ESD. The pathological diagnosis was pT1a-MM in 5 lesions and pT1b-SM1 in 2, resulting in the proportion of target ESCC of 5.7% (7/122). By group, the proportions of target ESCC were 7.1% (7/99) in the IEE group and 0% in the LCE group.

Conclusion

The characteristics of missed lesions in IEE observation tended to be small and located on the left or anterior wall of esophagus at surveillance endoscopy. Furthermore, all of these lesions were curatively resected with ER, resulting pT1a-EP/LPM without LVI in the pathological diagnosis.

Introduction

Standardized classification of the gastroesophageal valve, achievable using the Hill classification, is a common step during gastroscopy. Given the visual nature of endoscopic examinations, artificial intelligence (AI) can support this task. We conducted a single-center prospective study to compare the performance of a self-developed AI model in determining the Hill classification with that of examiners.

Aims & Methods

From October 2023 to January 2024 consecutive patients with unaltered anatomy of the gastroesophageal junction were enrolled in the study. The AI model ran in the background during routine gastroscopy, providing real-time predictions, while physicians assessed the Hill grade without knowledge of the model's output. The Gold standard was established through a majority vote of a three-member expert committee in the cases where a clear image of the hiatus was available. The primary outcome was accuracy in Hill grade assessment, with secondary outcomes including precision and sensitivity for each grade.

Results

Out of 150 patients that participated, 131 were eligible for analysis. Our AI model exhibited an accuracy of 84.7%, surpassing the physicians' accuracy with 61.8% (p<0.01). Regarding rating the different Hill grades the AI's lowest accuracy, precision and sensitivity were 88%, 53% and 60% respectively, while physicians achieved lowest scores of 66%, 20%, and 30%. Post hoc analysis of the videos using the systems capability for real-time explainability via heatmaps highlighting image regions influencing the classification, revealed that the model used the correct anatomical region for classification.

Conclusion

Our AI system demonstrates superior accuracy compared to physicians in Hill grade assessment. Future research should explore the impact of physician-AI interactions during examinations through a randomized controlled trial. (ClinicalTrials.gov, Trial register number: NCT06040723)

Introduction

Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) are frequently associated with acute (AP) or recurrent pancreatitis (RP), likely due to the mucin-induced obstruction of the main pancreatic duct (MPD). According to the 2024 Kyoto Guidelines, pancreatitis represents an indication for surgical evaluation in IPMN patients. However, pancreatic sphincterotomy (PS) may represent a less invasive alternative for patients who are unfit for surgery or as a bridge to surgery, aiming to reduce the risk of further pancreatitis episodes.

Aims & Methods

This single-center retrospective study aimed to assess the efficacy and safety of PS in patients with BD-IPMN and RP. We included 33 patients who underwent PS between 2016 and 2023, with at least 12 months of follow-up. Patients with other causes of RP or prior pancreatic surgery were excluded. The frequency of pancreatitis episodes before and after PS was compared. Clinical success was defined as complete resolution or ≥50% reduction in pancreatitis episodes. Adverse events, presence of worrisome features (WF), and progression to high-risk stigmata (HRS) were evaluated. Statistical analysis was performed using paired t-test and Fisher’s exact test, with p < 0.05 considered significant.

Results

Among the 33 patients analyzed (39.4% female, 60.6% male, mean age 59 ± 13.9 years) clinical success was achieved in 81.8% of the cases. Specifically, 72.7% of the patients experienced no further AP episodes after PS and 9.1% experienced a reduction in episode frequency, while 18.2% of patients did not respond to treatment. Adverse events occurred in 15% of patients, including: 12% with post-ERCP pancreatitis (all mild) and 3% with intra-procedural bleeding; no perforations were reported. During follow-up WF emerged in 5 patients (15%), while no cases of HRS were identified. Among the 6 non-responders, 3 underwent a second PS, with 2 achieving clinical improvement, and 3 underwent duodenocephalopancreasectomy (DCP), including 1 for a concomitant pancreatic ductal adenocarcinoma (PDAC) unrelated to IPMN progression. Notably, no cases of IPMN degeneration were observed in the series

Conclusion

Pancreatic sphincterotomy appears to be a safe and effective approach for managing recurrent pancreatitis in patients with BD-IPMN, potentially reducing the need for surgery in selected cases.

Introduction

Short-septum Zenker’s diverticulum (ZD) is considered difficult-to-treat because the limited anatomical space which restricts the operating area. Recently, peroral endoscopic septotomy (POES) emerged as a novel third-space technique for addressing this condition.

Aims & Methods

This study aims to compare the effectiveness and safety of POES with traditional flexible endoscopic septotomy (FES) for the treatment of symptomatic patients with short-septum ZD (<25 mm). In this single-center, prospective study we included all consecutive patients referred to Humanitas Research Hospital with symptomatic short-septum ZD who were scheduled to undergo either FES or POES. The primary outcome was the rate of technical success and adverse events (AEs). The secondary outcome was the rate of clinical success at 12 months and recurrence requiring a retreatment. A sensitivity analysis was conducted using propensity score matching. Hazard Ratio (HR) and its associated 95%CI were used for a time-dependent analysis of recurrence.

Results

A total of 94 patients (63.8% male; mean age 72.7 + 10.7 years) underwent endoscopic treatment for a short-septum ZD (mean size 17.0 + 4.3 mm) were included. Among them, 41.5% (n=39) were treated with FES and 58.5% (n=55) with POES (p=n.s.). Overall, the mean procedural duration was 25.3 + 15.7 min, while the mean hospital stay was 0.3 days. Septotomies were performed under deep sedation in 91.5% of patients (n=86), while in 8.5% of them (n=8) the procedure was performed under general anesthesia. Technical success was achieved in 98.9% of patients (n=93), while AEs occurring in 5.3% of cases (n=5), with no statistical difference between groups (p=n.s.). Clinical success was observed in 91.5% of patients (n=86), while recurrence necessitating retreatment in 14.9% of cases (n=14) with no statistical difference between groups (p=n.s.).

Conclusion

Our findings suggest that POES is an effective and safe technique for the treatment of short-septum ZD, showing comparable outcomes to traditional FES.

References

Repici A, Spadaccini M, Belletrutti PJ, et al. Peroral endoscopic septotomy for short-septum Zenker's diverticulum. Endoscopy. 2020 Jul;52(7):563-568.

Introduction

The Swiss Eosinophilic Esophagitis Cohort Study (SEECS) is a national prospective cohort for adults with eosinophilic esophagitis (EoE) that was established in 2015 with the aim of improving quality of care considering EoE’s increased incidence. The SEECS allows for documentation of EoE’s natural history, patients’ quality of life (QoL) and monitoring of treatment efficacy and safety. It also aims to promote clinical and translational research projects with the availability of standard operating procedures (SOPs) for the submission of scientific protocols. The first cohort update was published in 2017. Between 2020 and 2022, paper questionnaires were gradually replaced by fully electronic data capture using Research Electronic Data Capture (REDCap) software. We aim to provide a second update of the cohort, eight years after its launch.

Aims & Methods

The SEECS includes adult patients (age ≥18 years) with EoE, gastro-esophageal reflux (GERD) and healthy controls (HC) using strict eligibility criteria in line with the most recent guidelines. Upon inclusion and follow-up (typically once a year), patients and physicians complete questionnaires in REDCap which are available in German, French, and English. Patients reported outcomes (PROs) and biologic activity are assessed all on the same day using validated instruments (EEsAI PRO for symptoms; EoE-QoL-A for QoL; EREFS for endoscopic activity; modified EoE-HSS for histologic activity). The SEECS biobank includes biosamples (blood samples, esophageal biopsies) from patients with EoE, GERD, and HC.

Results

As of July 2023, the SEECS includes 778 patients [716 (92%) with EoE, 29 (3.8%) with GERD, and 33 (4.2%) HC; 559/778 (71.9%) are male]. Mean age±SD (years) according to diagnosis is as follows: EoE 41.9±12.9, GERD 53.6±16.4, HC 51.7±17.2. Mean diagnostic delay for the EoE group is 89.6±96.2 months. Concomitant GERD is found in 200 patients (27.9%) of the EoE cohort. Concomitant allergic disorders (asthma, rhinoconjunctivitis, neurodermitis) are present in 500 patients (74.4%) with EoE. At inclusion, 694 (96.9%) of EoE patients have an ongoing treatment [orodispersible budesonide tablet: 290 patients (41.8%); budesonide/fluticasone syrup: 281 patients (40.5%); PPI: 162 patients (23.3%); elimination diets: 103 patients (14.8%); esophageal dilation at last visit: 166 patients (23.9%)]. Esophageal biopsies are available from 525/778 (67.5%) patients including 468 EoE patients (65.4%).

Conclusion

Our findings are in line with the available literature on EoE’s natural history. To our knowledge, the SEECS is the only national cohort for EoE adult patients that includes both GERD and healthy controls with their biosamples. Data capture is based on validated instruments and is fully electronic using REDCap. The SEECS offers up-to-date epidemiologic data on EoE and promotes research projects.

Disclosure

Jeanine Wakim has no relevant financial, professional, or personal relationships to disclose. Ekaterina Safroneeva reports (i) consulting fees from Avir Pharma, Inc., Aptalis Pharma, Inc., Celgene Corp., Novartis, AG, and Regeneron Pharmaceuticals Inc; (ii) being an employee of Tillotts Pharma AG. Catherine Saner has no relevant financial, professional, or personal relationships to disclose. Jean-Benoit Rossel has no relevant financial, professional, or personal relationships to disclose. Sven Trelle has no relevant financial, professional, or personal relationships to disclose. Marcel Zwahlen has no relevant financial, professional, or personal relationships to disclose. Luc Biedermann received consulting fees and/or speaker fees and/or research grants from Adare/Ellodi Pharmaceuticals, Inc., AstraZeneca, AG, Switzerland, Receptos-Celgene-BMS, Dr. Falk Pharma, GmbH, Germany, Glaxo Smith Kline, AG, Nestlé S. A., Switzerland, Novartis, AG, Switzerland, and Regeneron-Sanofi Pharmaceuticals. Andrea Kreienbuehl has no relevant financial, professional, or personal relationships to disclose. Thomas Greuter received consulting fees and/or speaker fees and/or research grants from Adare/Ellodi Pharmaceuticals, Inc., AstraZeneca, AG, Switzerland, Receptos-Celgene-BMS, Dr. Falk Pharma, GmbH, Germany, Glaxo Smith Kline, AG, Nestlé S. A., Switzerland, Novartis, AG, Switzerland, and Regeneron-Sanofi Pharmaceuticals. Philipp Schreiner received consulting fees and/or speaker fees from Dr. Falk Pharma, GmbH, Takeda, Regerenon-Sanofi Pharmaceuticals, Abbvie, Janssen-Cilag, Receptos-Celgene-BMS. Peter Netzer has no relevant financial, professional, or personal relationships to disclose. Annett Franke has no relevant financial, professional, or personal relationships to disclose. Stephan Brand has no relevant financial, professional, or personal relationships to disclose. Chantal Hasler has no relevant financial, professional, or personal relationships to disclose. Patrick Aepli has no relevant financial, professional, or personal relationships to disclose. Emanuel Burri has no relevant financial, professional, or personal relationships to disclose. Achim Weber has no relevant financial, professional, or personal relationships to disclose. Christine Sempoux has no relevant financial, professional, or personal relationships to disclose. Ruggero Biral has no relevant financial, professional, or personal relationships to disclose. Wolfram Jochum has no relevant financial, professional, or personal relationships to disclose. Joachim Diebold has no relevant financial, professional, or personal relationships to disclose. Niels Willi has no relevant financial, professional, or personal relationships to disclose. Alex Straumann received consulting fees and/or speaker fees and/or research grants from Adare/Ellodi Pharmaceuticals, Inc., AstraZeneca, AG, Switzerland, Receptos-Celgene-BMS, Dr. Falk Pharma, GmbH, Germany, Glaxo Smith Kline, AG, Nestlé S. A., Switzerland, Novartis, AG, Switzerland, and Regeneron-Sanofi Pharmaceuticals. Alain Schoepfer received consulting fees and/or speaker fees and/or research grants from Adare/Ellodi Pharmaceuticals, Inc., AstraZeneca, AG, Switzerland, Receptos-Celgene-BMS, Dr. Falk Pharma, GmbH, Germany, Glaxo Smith Kline, AG, Nestlé S. A., Switzerland, Novartis, AG, Switzerland, and Regeneron-Sanofi Pharmaceuticals.

Introduction

Globally, hepatitis C virus (HCV) infection is still common among chronic kidney disease (CKD) patients despite the advent of serologic screening of blood by enzyme-linked immunoassays, routine use of erythropoietin for patients with anemia and CKD, and better adherence to infection control procedures to prevent the spread of HCV within dialysis units. A large body of epidemiological evidence regarding HCV infection among patients undergoing maintenance dialysis in the developed world has accumulated. prevalence rates have been shown to range between 1.4% and 28.3%. The prevalence rates observed in developing countries remain much higher with prevalence rates between 4.7% and 41.9%. Treatment of CKD patients with pegylated interferon plus ribavirin was challenging and with low response rates.
On its approval, sofosbuvir was not used among CKD patients with creatinine clearance < 30 ml/min, but recently its usage was approved after demonstrating its safety among these patients.

Aims & Methods

Our aim was to determine the response rate of sofosbuvir based regimens in CKD stage 4/5 and end stage renal disease (ESRD) patients on maintenance hemodialysis and to determine the predictors of treatment failure, including (IFNL4) SS469415590 gene polymorphism.
The study included 55 HCV pateints CKD stage 4/5 and ESRD on MHD. The sample size was calculated using G Power 3.1.9.4, 2018. Based on an effect size of direct acting antiviral therapy of HCV among patients with ESRD of 0.4, alpha error of 0.05, power of 80%, the minimum required sample size was calculated to be 52 patients.

Results

Sustained virologic response was achieved in 52.7% of cases. Among those who failed to achieve SVR, platelets and albumin was significantly lower (p < 0.001), INR and total bilirubin was significantly higher (p < 0.001). Both APRI and FIB-4 scores were significantly higher among those who failed to achieve SVR (p < 0.001). The favorable IFNL4 genotype (TT/TT) was present in 36.4% of the 55 patients. 58.6% of the TT/TT genotype patients achieved SVR compared to 41.4% of the non-TT/TT genotype patients (p= 0.001). On multivariate logistic regression analysis, higher FIB-4 Score was significantly associated with failure to achieve SVR. ROC curve analysis revealed that at a cut-off ≥ 2.63, pretreatment FIB-4 had a sensitivity of 88.46%, and negative predictive value (NPV) of 90%.

Conclusion

In CKD patients with stage 4 or stage 5, greater FIB-4 scores are linked to a higher chance of failing to achieve SVR after receiving sofosbuvir-containing regimens for chronic HCV infection.