BACKGROUND:Oncological principles favour en bloc R0 excision for curative endoscopic resection. In Barrett's neoplasia, endoscopically curable cancers include T1a and selected early T1b disease. Although endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are established treatments, optimal lesion selection remains debated. OBJECTIVE:To evaluate the oncological impact of two selective resection strategies: (1) prioritising ESD for suspected Barrett's cancers >15 mm and (2) a historical approach reserving ESD mainly for advanced cancers. DESIGN:Multicentre retrospective observational study comparing an ESD-first strategy (period 2, 2017-2024) with a historical selective ESD approach (period 1, 2004-2016). Lesion allocation was based on endoscopic assessment of invasion in both periods. Outcomes included basal R0 resection, curative resection, recurrence and adverse events. RESULTS:A total of 581 resections were performed in 542 patients (median lesion size 20 mm). Cancer was present in 271 cases (178 T1a and 93 T1b). Period 2 had a higher cancer burden (52.3% vs 34.9%) and greater ESD use (77.1% vs 21.2%). Basal R0 resection improved from 69.7% to 91.2% (p<0.001), with the greatest benefit in T1b lesions (33.3% to 81.9%, p<0.001). In T1b cancers, curative resection increased (9.5% to 30.5%, p=0.043) and recurrence decreased (55.6% to 23.6%, p=0.043). ESD achieved higher 2-year cancer-free survival than EMR (87.4% vs 50%, p=0.021). Adverse events were infrequent (2.2%) and similar between techniques. CONCLUSION:Prioritising ESD for Barrett's cancers >15 mm improves basal R0 resection, reduces recurrence and improves short-term survival for T1b disease, supporting routine ESD for all larger Barrett's cancers.

BACKGROUND:Esophageal adenocarcinoma (EAC) represents one of the most increasing malignancies in Western countries. The disease is multifactorial, involving modifiable risk factors and genetic susceptibility variants. These variants can be aggregated to a polygenic risk score (PRS) that reflects individual genetic risk. Investigation of the effects of lifestyle factors, PRS, and co-medication on EAC age at onset (AAO) is critical for shaping prevention strategies. METHODS:A detailed questionnaire was used to assess pre-diagnostic exposure to lifestyle factors and clinical information from a large German EAC cohort. Linear regression analysis was performed to identify factors associated with EAC AAO in 1742 EAC patients. PRS was available for 1190 patients. Subgroup analyses were conducted to estimate the effects of the analyzed factors on AAO according to age group (early vs. late onset), sex, and prior diagnosis of Barrett's esophagus (BE). RESULTS:Earlier AAO was significantly associated with gastroesophageal reflux (GER), smoking and a higher PRS, whereas later AAO was associated with physical activity and higher consumption of fish and fruits. Among co-medication, combined use of proton pump inhibitors (PPIs) and acetylsalicylic acid (ASA) showed the most significant effect on AAO, whereas the use of PPIs and ASA alone showed weaker effects. DISCUSSION:This study represents the largest questionnaire-based analysis to date investigating factors influencing EAC development. Our findings show that the combined use of PPIs and ASA, both cost-effective medications, is associated with delayed EAC onset. In addition, lifestyle and genetics contribute to EAC AAO.

BACKGROUND:Artificial intelligence (AI)-based computer-aided detection (CADe) systems improve adenoma detection in average-risk colorectal cancer screening. Meanwhile, evidence in Lynch syndrome surveillance is sparse and inconsistent. We assessed the effect of CADe on adenoma detection during Lynch syndrome surveillance. Computer-aided optical diagnosis (CADx) performance for optical differentiation of colorectal lesions was evaluated as a secondary aim. METHODS:CADLY2 was an international, multicentre, open-label, randomised controlled superiority trial at nine specialised hereditary cancer surveillance centres in Belgium, Germany, the Netherlands, and Spain. Adults aged 18 years or older with genetically confirmed Lynch syndrome scheduled for surveillance colonoscopy were randomly assigned (1:1) to high-definition white-light (HD-WL) colonoscopy alone or to HD-WL colonoscopy with computer-aided assistance from CAD EYE (Fujifilm, Tokyo, Japan). CAD EYE was used for CADe during withdrawal and for CADx after lesion detection. Randomisation was done centrally through a secure web-based system using Pocock's minimisation algorithm with a stochastic component and was stratified by centre, sex, previous colorectal cancer, underlying pathogenic variant, and interval since previous colonoscopy. Allocation concealment was ensured through the centralised web-based system. Patients were masked to group allocation until the start of withdrawal in procedures with mild sedation, or until completion of the procedure in procedures with propofol-based sedation. Endoscopists were not masked. The primary outcome was adenoma detection rate, defined as the proportion of patients with at least one histopathologically confirmed adenoma, analysed in the full analysis set (defined as all randomly allocated patients with available data for the primary outcome). The diagnostic performance of the CADx system was evaluated as a secondary outcome. The safety analysis set comprised all randomly allocated patients who underwent a study colonoscopy. This study is registered with the German Clinical Trials Register, DRKS00030695, and is completed. FINDINGS:Between May 9, 2023, and Oct 30, 2025, 757 patients were randomly allocated to HD-WL colonoscopy (377 patients) or to AI-assisted colonoscopy (380 patients); 733 patients were included in the full analysis set (369 HD-WL and 364 AI-assisted). The median age was 49 years (IQR 38-59) in the HD-WL group and 50 years (38-59) in the AI-assisted group; 213 (58%) were female and 156 (42%) male in the HD-WL group, and 207 (57%) were female and 157 (43%) male in the AI-assisted group. The adenoma detection rate was 30·9% (114 of 369 patients) with HD-WL versus 33·8% (123 of 364 patients) with CADe assistance (odds ratio 1·14 [95% CI 0·83-1·57], p=0·41). For CADx differentiation of neoplastic versus non-neoplastic lesions in the paired lesion-level analysis, with histopathology as the reference standard and sessile serrated lesions and traditional serrated adenomas classified as non-neoplastic, CADx sensitivity was 85·9% (95% CI 82·0-89·1) and specificity was 91·4% (89·4-93·0). Three adverse events occurred in the AI-assisted group: two mild post-polypectomy bleedings and one serious pulmonary embolism or deep venous thrombosis unrelated to the procedure. No adverse events occurred in the HD-WL group. INTERPRETATION:CADe-assisted colonoscopy did not show the absolute improvement in adenoma detection rate that was assumed in the prespecified sample-size calculation. CADx did not clearly improve lesion differentiation beyond expert optical diagnosis in expert Lynch syndrome surveillance settings. FUNDING:Third-party research funding of the National Center for Hereditary Tumor Syndromes, University Hospital Bonn.

Abstract:Gastroenterology offers a broad, evidence-based range of preventive measures that goes beyond colorectal cancer screening. As a specialty of systemic relevance, it plays a key role in preventing, detecting, and controlling severe diseases - from colorectal and liver cancer to pancreatic, esophageal, and gastric cancers. Preventive strategies include lifestyle interventions, structured screening programs, vaccination approaches, and targeted early detection in high-risk groups. The success of statutory programs such as colorectal cancer and hepatitis screening highlights the potential of early interventions. However, gaps remain between the evidence-based recommendations of the DGVS guidelines and clinical practice. There is also a substantial need for further research, particularly in developing risk-adapted prevention strategies, innovative diagnostic tools, and in harnessing health data and artificial intelligence. A coordinated, cross-sector prevention strategy is essential to structurally anchor and further advance gastroenterological prevention. The declaration of a "National Decade for Prevention" would represent a logical continuation of the National Decade Against Cancer - fully leveraging the preventive potential of gastroenterology for the benefit of patients and the healthcare system.

BACKGROUND AND STUDY AIMS:Motorized spiral enteroscopy (MSE) was introduced as a major advancement in small-bowel enteroscopy, enabling higher complete enteroscopy rates with shorter procedure times. However, after a fatal adverse event (AE) involving severe esophageal injury, the device was withdrawn from the market in July 2023. This raised questions about whether earlier safety signals were missed. METHODS:We conducted a systematic review and meta-analysis comparing MSE with balloon-based enteroscopy (double-balloon [DBE] and single-balloon enteroscopy [SBE], analyzed together). Outcomes included overall AEs, serious AEs (SAEs), and data collection quality. Results from the German PowerSpiral Registry were included, comprising 647 MSE procedures in 523 patients (January 2020-July 2023) before registry closure following device withdrawal. RESULTS:Thirteen MSE studies (including the registry) and 55 DBE/SBE studies were analyzed, totaling 12,559 enteroscopies (2024 MSE; 10,535 DBE/SBE). MSE showed significantly higher rates of AEs (10.8% vs. 1.6%) and SAEs (1.5% vs. 0.4%). Procedure-related SAEs were also more frequent with MSE (1.1% vs. 0.3%). Esophageal injury (0.10% vs. 0.009%) and intestinal perforation (0.5% vs. 0.1%) occurred more often with MSE, whereas acute pancreatitis (0.05% vs. 0.27%) and esophageal perforation (0% vs. 0.02%) were more common with DBE/SBE. AE reporting for MSE was detailed, but structured follow-up and reliable case tracking were inconsistent. CONCLUSIONS:MSE was associated with higher AE and SAE rates than balloon enteroscopy. These findings highlight the need for cautious adoption, rigorous safety monitoring, and more robust AE reporting when introducing innovative endoscopic technologies. STUDY REGISTRATION:The prospective and retrospective cohort studies were registered in the German Registry of Clinical Studies (DRKS), namely DRKS00026990 and DRKS00028571.

Abstract Tofacitinib, a pan–Janus kinase inhibitor, and the Janus kinase 1–preferential inhibitors Upadacitinib and Filgotinib are approved for the treatment of ulcerative colitis, yet their molecular mechanisms of action remain incompletely understood. Here, using dextran sulfate sodium–induced and T cell transfer colitis models together with analyses of individuals with ulcerative colitis, we show that all three inhibitors ameliorate colitis in mice with macrophage-specific deletion of protein tyrosine phosphatase non-receptor type 2, a model characterized by hyperactive Janus kinase–signal transducer and activator of transcription signaling. In contrast, only Upadacitinib and Filgotinib provide enhanced protection in wild-type mice – an effect that is lost upon genetic disruption of inflammasome signaling. Longitudinal single-cell transcriptomic analyses and immunostaining of intestinal biopsies further show that Upadacitinib reduces interleukin-1β expression in vivo, which associates with clinical response. Thus, indirect suppression of inflammasome activity contributes to the efficacy of Janus kinase 1–preferential inhibitors.

Rectal neuroendocrine tumors (rNET) are rare but increasingly more common entities, which are usually an incidental finding during routine colonoscopy. The rNETs are usually well-differentiated with low metastatic potential. Thus, staging is only required in high-risk situations (size ≥ 10 mm, invasion of the muscularis propria, grading > G1, L1, V1). Endoscopic resection is the most frequently used treatment. Based on the depth of invasion, endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD) or endoscopic full-thickness resection (EFTR) are applied. In cases of R1 resection, re-endoscopic resection can be conducted to achieve R0 status. Radical surgical resection with higher or lower anterior rectum (HAR/LAR) resection with total mesorectal excision (TME) is indicated for rNETs > 20 mm, rNETs between 10-20 mm with risk factors (R1 resection after second endoscopic resection, Ki67 > 10%, L1, V1), lymph node metastasis and also in cases of distant metastasis if those are also resectable. In cases of unresectable distant metastasis, systemic treatment is applied. The prognosis after treatment of well-differentiated rNETs is generally favorable.

Diseases of the digestive organs are among the most frequent diseases and at the same time diseases with the most severe consequences in Germany. They are widespread diseases in the proper sense. Around 2.5 million people are hospitalized annually due to gastroenterological diseases and approximately 140,000 deaths per year are directly attributed to them. In addition, there are substantial impairments in the quality of life, high periods of inability to work and an immense economic burden on the healthcare system with annual costs of over €60 billion. It is particularly relevant that a substantial proportion of these diseases could be avoided or at least the course could be favorably influenced. The gastrointestinal tract including the liver and pancreas undertakes a key management function for the whole organism. Disorders of the digestive organs not only have a local effect but also influence the metabolism, cardiovascular system, immune system and the brain. Therefore, prevention in gastroenterology always also means prevention of systemic diseases. A healthy gut is a prerequisite for a healthy life. Prevention in gastroenterology is also a success story. The introduction of screening coloscopy, the vaccination against hepatitis B, the introduction of hepatitis B and C screening and the eradication of Helicobacter pylori demonstrably reduce the morbidity and mortality risks and impressively show the potential of a consistently implemented preventive strategy. This article compiles the aims, evidence, success and current deficits in gastroenterological preventive measures, names potential improvements and provides a perspective of future developments.

Zusammenfassung Die Gastroenterologie verfügt über ein breit gefächertes, evidenzbasiertes Präventionsrepertoire, das weit über die Darmkrebsvorsorge hinausgeht. Als systemrelevantes Fach trägt sie maßgeblich zur Vermeidung, Früherkennung und Eindämmung schwerwiegender Erkrankungen bei – von kolorektalem Karzinom über Leberkrebs bis hin zu Speiseröhren- Leber-, Pankreas- und Magenkarzinomen. Die präventiven Maßnahmen reichen von Lebensstilinterventionen über strukturierte Screeningprogramme und Impfstrategien bis zur gezielten Früherkennung bei Hochrisikogruppen. Der Erfolg gesetzlicher Programme wie des Darmkrebsscreenings oder des Hepatitisscreenings zeigt das große Potenzial frühzeitiger Interventionen. Gleichzeitig bestehen relevante Lücken zwischen den evidenzbasierten Empfehlungen der DGVS Leitlinien und der Versorgungspraxis. Zudem besteht erheblicher Forschungsbedarf, etwa zur Entwicklung risikoadaptierter Strategien, innovativer diagnostischer Verfahren und zur Nutzung von Gesundheitsdaten und KI. Es bedarf einer koordinierten, sektorenübergreifenden Präventionsstrategie, um gastroenterologische Vorsorge strukturell zu verankern und weiterzuentwickeln. Die Ausrufung einer „Nationalen Dekade für Prävention“ wäre ein entscheidender Schritt – als konsequente Fortsetzung der Dekade gegen Krebs. Nur durch gemeinsames Handeln von Politik, Forschung und Versorgung lässt sich das präventive Potenzial der Gastroenterologie voll entfalten – zum Nutzen von Patient:innen und Gesundheitssystem.

Background:In early esophageal adenocarcinoma (EAC), guidelines recommend endoscopic mucosal resection (EMR) for superficial (T1a) lesions and endoscopic submucosal dissection (ESD) for deeper (T1b) lesions based on visual assessment. We evaluated the outcomes of this targeted resection strategy. Methods:In a retrospective bicentric study (2009-2023), 311 T1 EACs (235 T1a, 76 T1b) underwent endoscopic resection: EMR for presumed T1a and ESD for suspected T1b lesions. The primary outcome was complete (R0) resection stratified by tumor stage and resection technique. Secondary outcomes were rates of curative resection, adverse events, and surgery. Results:EMR was appropriately applied in 63.0% of T1a cases, and ESD was correctly selected in 60.5% of T1b cases. R0 resection rates were higher with ESD than with EMR for both stages: T1a, 92.9% vs. 80.4%; T1b, 63.0% vs. 26.7%. Curative resection (ESD 60.9% vs. EMR 67.4%), surgery (19.5% vs. 14.0%), and adverse events (7.5% vs. 10.1%) were comparable. On multivariable analysis, ESD was the only independent predictor of complete resection. If surgery decisions had been based on R0 rather than curative outcomes, 20% of post-EMR and 50% of post-ESD esophagectomies could have been avoided. Conclusions:Endoscopic staging of early EAC is imperfect, leading to frequent mismatch between chosen and optimal resection techniques. ESD achieved higher complete resection rates for both T1a and T1b cancers without increased morbidity. ESD may therefore represent the preferred strategy for early EAC, potentially reducing unnecessary surgery.

BACKGROUND:In this trial, we previously showed per-oral endoscopic myotomy (POEM) to be non-inferior to laparoscopic Heller's myotomy (LHM) plus Dor fundoplication in managing symptoms in patients with idiopathic achalasia 2 years post-procedure. However, post-procedural gastro-oesophageal reflux was more common after POEM at 2 years. Here we report 5-year follow-up data. METHODS:This study is a multicentre, randomised, open-label, non-inferiority trial performed at eight centres in six European countries (Germany, Italy, Czech Republic, Sweden, the Netherlands, and Belgium). Patients with symptomatic primary achalasia were eligible for inclusion if they were older than 18 years and had an Eckardt symptom score higher than 3. Patients were randomly assigned (1:1; randomly permuted blocks of sizes 4, 8, or 12) to undergo either POEM or LHM plus Dor fundoplication. The primary endpoint was clinical success, defined by an Eckardt symptom score of 3 or less without the use of additional treatments, at 2 years, and was reported previously. Prespecified secondary endpoints at 5 years were clinical success; Eckardt symptom score; Gastrointestinal Quality of Life Index score; lower oesophageal sphincter function by high-resolution manometry; and parameters of post-procedural reflux (reflux oesophagitis according to the Los Angeles classification; pH-metry, and DeMeester clinical score). We hypothesised that POEM would be non-inferior (with a non-inferiority margin of -12·5 percentage points) to LHM plus Dor fundoplication with regards to clinical success. All analyses were performed on a modified intention-to-treat (mITT) population, which included all patients who underwent the assigned procedure. This study is registered with ClinicalTrials.gov (NCT01601678) and is complete. FINDINGS:Between Dec 7, 2012, and Oct 9, 2015, 241 patients were randomly assigned (120 to POEM and 121 to LHM) and 221 had the assigned treatment (112 POEM and 109 LHM; mITT). 5-year follow up data were available for 90 (80%) patients in the POEM group and 87 (80%) patients in the LHM group. Clinical success rate at 5 years was 75·0% (95% CI 66·2 to 82·1) after POEM and 70·8% (61·7 to 78·5) after LHM (difference 4·2 percentage points [95% CI -7·4 to 15·7]). The mean Eckardt symptom score decreased from baseline to 5 years in both groups and the overall difference in mean scores was -0·29 (95% CI -0·62 to 0·05). Change in Gastrointestinal Quality of Life Index scores, as well as in integrated relaxation pressure on manometry, from baseline to 5 years, did not differ significantly between the groups. At 5 years, 26 (41%) of 63 patients after POEM and 18 (31%) of 58 patients after LHM had reflux oesophagitis (difference 10·2 percentage points [95% CI -7·0 to 26·8]). Significant oesophagitis (Los Angeles classification grade B, C, or D) was observed in nine (14%) of 63 patients after POEM and in four (7%) of 58 patients after LHM. pH-metry was performed in 81 (37%) of 221 patients, with higher mean acid exposure time for POEM (10·2% [95% CI 7·6 to 14·2]) than for LHM (5·5% [3·1 to 11·8]). Significantly more patients in the POEM than in the LHM group had abnormal acid exposure time at 5 years (>4·5%; 28 [62%] of 45 vs 11 [31%] of 36; difference 31·7 percentage points [95% CI 9·8 to 50·5]). The presence of reflux symptoms at 5 years was similar in both groups, with a mean DeMeester clinical score of 1·3 (95% CI 1·0 to 1·6) after POEM and 1·1 (0·9 to 1·4) after LHM. The complications of peptic stricture, Barrett's oesophagus, and oesophageal adenocarcinoma were not reported. INTERPRETATION:Our long-term results support the role of POEM as a less invasive myotomy approach that is non-inferior to LHM in controlling symptoms of achalasia. Gastro-oesophageal reflux was common in both groups, but with a tendency towards higher rates in the POEM group. Thus, patients should be provided with the advantages and disadvantages of each approach in decision making. FUNDING:European Clinical Research Infrastructure Network, Hamburgische Stiftung für Wissenschaften, Entwicklung und Kultur Helmut und Hannelore Greve, Dr med Carl-August Skröder Stiftung, Dr Gerhard Büchtemann Stiftung, Agnes-Graefe Stiftung, Georg und Jürgen Rickertsen Stiftung, Reinhard Frank Stiftung, Johann Max Böttcher Stiftung, Richard und Annemarie Wolf Stiftung, Olympus Europa, German Society for Gastroenterology and Metabolism and Olympus Europe Foundation, United European Gastroenterology Week, Olympus EuroNOTES Research Fund Program, Harvard Catalyst, the Harvard Clinical and Translational Science Center, and Harvard University and its affiliated academic health-care centres.

Supplementary Figure from eQTL Set–Based Association Analysis Identifies Novel Susceptibility Loci for Barrett Esophagus and Esophageal Adenocarcinoma

Background:Tissue diagnosis of biliary strictures is challenging and often requires multiple methods. Cryobiopsy, which is well established in bronchoscopy with high tissue yield, is presented here for the first time as a proof-of-principle feasibility study performed via the percutaneous route for biliary strictures. Methods:Patients undergoing percutaneous cholangioscopy for intraductal diagnosis of biliary strictures underwent six forceps biopsies and three cryobiopsies in a randomized order. The main objective was to assess feasibility, defined as the retrieval of at least one adequate sample per method per patient. Results:Among 15 patients (53% women; mean age 60.2 years), all had at least one adequate sample obtained by each method. Cryobiopsy yielded significantly larger (8.54 vs. 1.87 mm2; P < 0.001) and more representative specimens (97.6% vs. 74.7%; P = 0.001). It also scored higher on overall histologic quality on a Likert scale of 0–6 (5 vs. 4; P < 0.001) and had more artifact-free areas (93.5% vs. 85.5%; P = 0.01). No bleeding or perforations occurred; only minor adverse events were reported and these resolved with standard treatment. Conclusions:This feasibility study showed that intraductal cryobiopsy via percutaneous cholangioscopy yielded larger samples and may enable more detailed histologic assessment than forceps biopsies. Further studies will evaluate its accuracy, safety, and potential for use with peroral cholangioscopy during endoscopic retrograde cholangiopancreatography.

ABSTRACT Background In patients with non‐cardiac chest pain (NCCP) and non‐obstructive dysphagia (NOD), standard esophageal high resolution manometry (HRM) with water swallows and/or solid meals may miss intermittent dysmotility. To what extent prolonged 24 h‐measurements may increase the diagnostic sensitivity is currently unclear. Methods 75 patients (47 female, 58 ± 16 years) with NCCP and/or NOD underwent standard HRM (single water swallows plus rice meal) and ambulatory 24‐h‐HRM with impedance. Results were analyzed according to Chicago Classification v3.0 for water‐swallow‐HRM; adapted criteria were used for rice‐meal and 24‐h‐HRM. Patients were followed by chart review. Key Results Contractility parameters obtained by different HRM procedures always correlated ( R > 0.27, p < 0.05). During 24 h‐measurements, all parameters showed circadian variability ( p < 0.001). In comparison with water‐swallow‐HRM, rice‐meal‐HRM markedly increased the proportion of patients diagnosed with achalasia III, esophagogastric outlet obstruction with spastic features, distal esophageal spasm, or hypercontractility (10.7% vs. 21.3%, p = 0.039). The diagnostic gain regarding spastic and/or hypercontractile disorders was further increased by 24‐h‐HRM (61.3% of patients, p < 0.001). In 11 out of 21 patients with normal results in both water‐swallow‐ and rice‐meal‐HRM (15% of total cohort), 24‐h‐HRM detected a major motor disorder. Results of 24‐h‐HRM altered treatment recommendations in 41 patients (54%). Conclusions&Inferences 24‐h‐HRM revealed spastic and/or hypercontractile esophageal motor disorders in about 60% of patients with NCCP/NOD and markedly improved diagnostic yield compared with standard HRM, probably partly due to the observed circadian variability of esophageal motility. 24‐h‐HRM findings frequently altered treatment recommendations, but the ultimate clinical consequences of the increased diagnostic yield have to be examined further.