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

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

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

Computer-aided detection (CADe) systems improve adenoma detection rate (ADR). However, there is some concern that the long-term use of CADe systems might lead to a decline in endoscopists’ independent detection skills, particularly their ability to detect lesions without assistance—a phenomenon referred to as "deskilling".

Aims & Methods

This study aims to evaluate the impact of CADe on the learning curve of endoscopists for ADR. This was a propensity score–matched (PSM), prospective, single-center, observational study conducted at a tertiary care hospital from January 2021 to December 2023. CADe systems were installed in half of the endoscopy units, and patients were equally distributed between the rooms. Patients in CADe-equipped rooms were examined using EndoBRAIN-EYE (Olympus Corp, Tokyo, Japan). Patients aged ≥ 20 years scheduled for colonoscopy were included, excluding those with polyposis, inflammatory bowel disease, known polyps, incomplete colonoscopy, emergency cases, previous colorectal surgery, and examination by novices. Endoscopists were classified as high-detectors (ADR ≥ 25%) or low-detectors (ADR < 25%) based on the ADR recorded before CADe implementation. The primary outcome was to evaluate the learning effect of CADe using cumulative summation (CUSUM) analysis based on ADR during both CADe and non-CADe procedures to assess skill acquisition and transfer. The CUSUM scores were calculated from the acceptable probability of failure and unacceptable probability of failure. Acceptable and unacceptable ADR were defined as 40% and 30% for high detectors, and 35% and 25% for low detectors, respectively. Performance was judged based on the boundary lines (h0 and h1): acceptable if the CUSUM plot fell below h0, unacceptable if it went above h1, and inconclusive requiring further observation if it stayed between these boundaries. The secondary outcomes included ADR, advanced adenoma detection rate (AADR), and sessile serrated lesion detection rate (SSLDR). The study received ethics approval (no.19H072) and complied with the Declaration of Helsinki.

Results

Out of 5,717 patients initially enrolled, 4,712 patients (2,356 in CADe group and 2,356 in non-CADe group) were analyzed after PSM for known factors (age, sex, indication, and bowel preparation). During CADe-assisted procedures, both high-detectors and low-detectors showed patterns below the acceptable performance line (h0), indicating improved adenoma detection performance with AI support. However, during non-CADe procedures, the patterns diverged significantly. For high-detectors, their CUSUM plots consistently fell below the acceptable performance line (h0) over time during non-CADe colonoscopies, indicating that they successfully acquired and maintained improved adenoma detection skills even without AI assistance. In contrast, the CUSUM plots of the low-detectors remained between the acceptable (h0) and unacceptable (h1) limits throughout the study period, showing no significant change in learning trajectory during non-CADe procedures. The CADe group had a significantly higher ADR (40.5% [95% CI: 38.5-42.5%]) compared to non-CADe group (32.4% [95% CI: 30.5-34.4%]; p < 0.001). SSLDR was also significantly higher in the CADe group (6.9% [95% CI: 5.9-8.0%] vs. 4.5% [95% CI: 3.7-5.4%]; p = 0.001), while AADR showed no significant difference (4.1% [95% CI: 3.4-5.0%] vs. 4.7% [95% CI: 3.9-5.6%]; p = 0.39).

Conclusion

The implementation of the CADe system did not result in deskilling regarding adenoma detection.

Disclosure

The conflict of interests were following: Shin-ei Kudo and Masashi Misawa received speaking honoraria from Olympus Corporation and have an ownership interest of the products of Cybernet Systems. Kensaku Mori received research grants from Cybernet Systems, Morita Mfg, Atom Medical Inc, and Asahi Intecc. Additionally, Kensaku Mori serves as a Technical Advisor for Sanyu Industry. Tetsuo Nemoto received a research grant from Olympus Corporation for other studies. Other authors have nothing to declare.

Introduction

Faecal calprotectin (FC) is of value in differentiating Inflammatory Bowel Disease (IBD) from other causes of lower gastrointestinal (GI) symptoms and is recommended in national guidance. This study aims to examine its role and factors associated with faecal calprotectin requesting in primary care.

Aims & Methods

Retrospective open cohort study using Clinical Practice Research Datalink (CPRD Aurum) of adults aged over 18 years with lower GI symptoms between 2015 and 2019. FC requested 30 days before to 3 months after a lower GI symptom record in primary care were included. Logistic regression analysis explored patient level factors associated with FC testing. Referral pathways and outcomes (IBD diagnoses) of patients with and without FC testing were also examined.

Results

Of 741,190 symptomatic patients, only 18,320 (2.5%) had FC requested in primary care: median age 38.3 (IQR 28.9-50.7); 51.4% female. The rate of FC requesting in symptomatic patients increased from 0.02% in 2010 to 4.4% in 2019 (p=0.001).
FC value of <50 ug/g and 50-200 ug/g were predominantly seen in patients with abdominal pain (42.1% and 37.9% respectively), while FC > 200 ug/g was predominantly seen in patients with diarrhoea (45.3%). Factors associated with FC requesting included: increasing age (>70 years adjusted Odds Ratio 0.16 (95% CI 0.15-0.18)); female (0.89 (0.86-0.92); Black (0.61(0.56-0.66) or Asian (0.75 (0.70-0.80) ethnicity; obesity (0.89(0.85-0.93); lower socioeconomic status (0.91(0.86-0.98); comorbidity score >2 (0.73(0.68-0.79); current smoking (0.89(0.85-0.92)); change in bowel habit (7.31(6.90-7.75), rectal bleeding (2.04(1.95-2.13) or diarrhoea (2.88(2.78-2.99) compared to abdominal pain; and ex-smokers (1.06(1.03-1.11).
IBD was diagnosed in 21.5% of patients referred with a FC >200 ug/g, but only 2.9% of referred patients with a FC 50-200 ug/g. The only patients with a significant risk of IBD with FC 50-200ug/g were patients with rectal bleeding (8%), with the risk in all other patients only 1.7%. 27.8% patients with a normal FC test result were still referred to secondary care, of which only 0.4% had IBD.

Conclusion

Despite an increase in FC requests in recent years, only 4.4% of patients with relevant lower GI symptoms had an FC requested in primary care as recommended. Despite a negative FC test, a third of patients were still referred to secondary care, with very few diagnosed with IBD . Patients with an FC between 50 ug/g and 200 ug/g without rectal bleeding have a low risk of IBD and can be safety netted in primary care.