United European Gastroenterology Journal最新文献

Introduction: Since the publication of the first European Society for the Study of Coeliac Disease (ESsCD) guidelines in 2019, significant advancements have emerged in the diagnosis of coeliac disease (CeD) in adults. These 2025 guidelines incorporate new evidence to refine diagnostic strategies, aiming for improved accuracy of testing, and enhance overall quality of clinical care.

Methods: A multidisciplinary panel of experts revised the ESsCD guidelines using the AGREE II instrument (Appraisal of Guidelines for Research and Evaluation II) and the GRADE methodology (The Grading of Recommendations Assessment, Development, and Evaluation). Clinical questions were structured using the PICO format, and statements and recommendations were finalised through a Delphi consensus process. Literature quality was assessed using AMSTAR-2 and QUADAS-2 tools.

Results: The updated guidelines are presented in two parts. Part 1 focuses on adult CeD diagnosis, introducing major changes such as a conditional no-biopsy approach for selected adults with high-titre IgA anti-TG2 serology (≥ 10 × ULN). Regarding serology, the use of validated high-performance ELISAs displaying a high diagnostic accuracy is emphasised, while routine use of IgA anti-Endomysium serology is no longer recommended for confirmation. Revised duodenal biopsy protocols now mandate at least four samples from the second part of the duodenum, with bulb biopsies conditionally included. The guidelines provide structured approaches for diagnosing potential CeD, seronegative villous atrophy, and CeD in individuals already on a gluten-free diet. HLA-DQ2/DQ8 typing is recommended for diagnostic clarification in select cases.

Conclusions: The updated 2025 ESsCD guidelines provide a comprehensive framework for the diagnosis of CeD in adults. By integrating evolving diagnostic strategies, minimising over-testing, and patient-centred care approaches, they aim to optimise patient outcomes, quality of life and use of diagnostic resources at the same time.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers, with chemotherapy as the mainstay but highly variable efficacy and toxicity. Current regimens, such as FOLFIRINOX and gemcitabine-based combinations, are selected empirically without validated biomarkers to guide choice. Several strategies have been explored to personalize therapy. Patient-derived organoids and molecular classifiers such as PurIST have improved biological understanding but have limited clinical applicability. More recently, predictive transcriptomic signatures have emerged as practical tools. GemPred identifies patients likely to benefit from adjuvant gemcitabine; GemCore, validated in both resected and metastatic tumors, is compatible with small biopsies; and Pancreas-View integrates multiple drug-specific predictors, including for all FOLFIRINOX components and gemcitabine, enhanced by AI. These approaches, retrospectively validated in large cohorts and clinical trials, consistently link predicted sensitivity with improved survival. Beyond regimen selection, signatures enable treatment de-escalation, optimize first-line choices, and identify multidrug-resistant tumors. Ongoing prospective trials will establish their feasibility, supporting transcriptomic profiling as a step toward precision chemotherapy in PDAC.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is very common and associated with significant morbidity and mortality due to its potential progression to cirrhosis and liver cancer. Whereas hepatic fat accumulation is the key to MASLD progression, little is known regarding changes in liver fat content over time in the general population. We aimed to investigate changes in liver fat in a longitudinal study of the general population.

Methods: We conducted a longitudinal study involving 195 randomly selected individuals from the general population, evaluated at two time points, 5 years apart. Participants with hepatic steatosis at baseline did not receive any specific treatment. The primary objective was to assess changes in liver fat content, as estimated by controlled attenuation parameter (CAP) using transient elastography. We also examined the frequency of steatosis resolution and development. CAP variability was assessed in two measurements 7 days apart in a cross-sectional study of 101 volunteers, with a mean variability of 9.9%. Steatosis resolution was defined as reduction of CAP > 10% from baseline with a final value < 275 dB/m, while steatosis development was defined as increase in CAP > 10% with a final value ≥ 275 dB/m.

Results: Remarkable variations in liver fat content were observed. Among the 88 participants with steatosis at baseline, 34% had resolution of steatosis (CAP decreased from 300 to 237 dB/m; p < 0.001). Resolution was associated with weight loss and reductions in transaminases and gamma-glutamyl transferase levels. In contrast, 29% of the 107 participants without steatosis at baseline developed it during follow-up. Increase in liver stiffness measurement (≥ 8 kPa) was associated only with persistent hepatic steatosis but not with steatosis resolution.

Conclusions: There is marked variation in liver fat content among participants from the general population over a period of 5 years, indicating its dynamic nature. These variations should be considered in epidemiological studies of MASLD.

Background: Most T1 gastric cancer (GC) harbor lymph node metastasis (LNM) at a rate of < 20%; however, owing to the difficulty in accurately diagnosing LNM preoperatively, many patients with T1 GC undergo unnecessary invasive radical gastrectomy with lymphadenectomy. In the present study, we established an epigenetic liquid biopsy assay for the preoperative diagnosis of LNM in T1 GC.

Methods: A comprehensive biomarker discovery was performed by analyzing genome-wide DNA methylation profiling. We obtained 277 clinical specimens, including 177 surgical tissues and 100 pre-operative plasmas. DNA methylation biomarkers were trained and validated using quantitative methylation-specific polymerase chain reaction (qMSP) assays.

Results: We identified six novel differentially methylated regions, including at least two differentially methylated CpG probes (|Delta-beta| > 0.12 and p < 0.05) within 100 bp, through genome-wide biomarker discovery. A DNA methylation panel was generated using qMSP assays in clinical tissue specimens, with an area under the curve (AUC) of 0.80. This panel was validated in an independent clinical cohort, and a combined model, which integrated the DNA methylation model with preoperative computed tomography -based findings, was established through multivariate logistic regression analyses (AUC: 0.84). Finally, we translated this model into a liquid biopsy, and this cell-free DNA (cfDNA) methylation model exhibited robust performance for LNM identification in T1 GC (AUC: 0.86) and allowed 44% of patients to avoid unnecessary invasive operations, without missing any LNM-positive patients.

Conclusions: We have successfully developed a cfDNA methylation signature-based liquid biopsy diagnostic assay that allows for robust and less-invasive LNM detection in patients with T1 GC.

Purpose: The global incidence and mortality of early-age onset colorectal cancer (EOCRC, or CRC diagnosed under 50 years) has increased in recent decades. High-risk surveillance and personalised oncological treatment may improve patients' outcomes. This study aims to characterise real-world somatic and germline molecular profiles in European EOCRC patients.

Patients and methods: Consecutive patients across the UK, Spain, Germany and Italy from the GEOCODE and SECOC consortia were identified using electronic patient records. Clinicopathological, somatic and germline testing data were collected on EOCRC patients. Tests included mismatch repair (MMR), somatic next generation sequencing (NGS) and germline multi-gene panels.

Results: Eight hundred ninety-three EOCRC patients were identified from 23 European centres (45.7% female, median age 42, range 14-49), predominantly in the distal colorectum: 205/893 (22.9%) patients with right-sided tumours, 302/893 (33.8%) left-sided tumours, 288/893 (32.2%) rectal tumours and 97/893 (10.8%) unknown. On somatic analysis, 735/893 (82.3%) of patients had pMMR tumours and 148/893 (16.5%) dMMR. Although 534/893 (59.7%) did not receive NGS somatic testing, somatic variants were detected in 233/359 (64.9%) of those tested. Germline variants were detected in 133/210 (63.3%) patients tested. Lynch syndrome was diagnosed in 93/210 (44.2%), of whom 17/93 (18.2%) presented with pMMR tumours. Systematic recording of family history in these real-world data was variable. In all patients with family history recorded, 153/484 (31.4%) patients reported a relative with CRC.

Conclusions: Our results support universal and paired somatic and germline multi-gene panels for all EOCRC patients, regardless of MMR status or family history. Systematic molecular testing approaches are necessary to address disparities in people with EOCRC. Larger unselected cohort studies would support validation of testing prediction models and estimates of clinically relevant variant actionability.

Background: Post-endoscopy gastric cancer (PEGC) is a gastric cancer (GC) diagnosed within 3 years after an esophago-gastro-duodenoscopy (EGD) negative for cancer. Post-endoscopy gastric cancer has a prevalence of 9%-11% in the western population and is potentially reducible through adequate surveillance and high-quality endoscopy. However, Post-Endoscopy Gastric Cancer features are not well defined.

Objectives: Define Post-Endoscopy Gastric Cancer prevalence in a gastric cancer low-risk area as Spain, describe its characteristics and associated factors. Evaluate adherence to current recommendations for surveillance of preneoplastic gastric lesions and endoscopic quality indicators.

Methods: A descriptive and analytical study included patients who met PEGC criteria and enrolled in the EpiGASTRIC registry-a national multicentric GC cohort-between April 2021 and May 2024.

Results: Of 289 gastric cancer patients analyzed, 21 (7.3%) presented with PEGC. No differences were found between PEGCs and new-onset gastric cancers (NOGC) regarding clinical-demographic characteristics (males 52.4%, 65 years, caucasians 78.9%, previous Helicobacter pylori infection 56.3%) except for use of proton pump inhibitors (PPI) (81.0% vs. 44.9%, p-value = 0.002). Distal stomach (antrum and/or incisure) was more frequently affected in PEGC compared with NOGC (71.4% vs. 46.2%; p-value = 0.022), without differences in tumoral staging (I-II 52.4%) or histology (intestinal type 47.6%). Median time from last negative-for-cancer EGD to diagnosis was 13.6 months (interquartile range 4.1-26.8), with 38.1% of precursor lesions in previous endoscopy (19% chronic atrophic gastritis with metaplasia, 19% dysplasia). Considering last negative-for-cancer EGD, adherence to current recommendations was 66.6% for the surveillance of gastric lesions, and 14.3% for quality indicators (complete procedure 100%, high-definition 38.1%, chromoendoscopy 10.0%).

Conclusions: PEGC patients present a higher rate of distal stomach involvement and use of PPIs. Although precursor gastric lesions are commonly identified, adherence to current recommendations for their surveillance and to established quality indicators in EGDs is scarce. Despite its low prevalence, there is room for improvement to enhance the early detection and prevention strategies for PEGC.

Background: Sarcopenia is common in patients with liver cirrhosis and is an independent predictor of morbidity and mortality. This prospective study assessed the performance of rectus femoris muscle (RFM) ultrasound in patients with liver cirrhosis to identify those at risk for sarcopenia as defined by the combination of low muscle mass and low muscle strength.

Methods: 84 patients with liver cirrhosis hospitalized at a tertiary center (05/22-02/24) were included with 6-month follow-up. Within 24-48 h of admission hand grip strength, chair rise test (CRT), timed up and go (TUG), short physical performance battery (SPPB), rectus femoris muscle ultrasound, and bioelectrical impedance analysis (BIA) were assessed. Statistical analyses included receiver operating characteristic (ROC) curves, Kaplan-Meier estimates, Cox regression, and competing risk analyses.

Results: Most (73.8%) patients had decompensated and mainly alcohol-related liver cirrhosis. Thickness and cross-sectional area of rectus femoris muscle (MT_RFM/CSA_RFM) were significantly (p < 0.01 each) lower in more advanced disease by Child-Pugh (CP) stage, also when normalized for height². MT_RFM/height² and CSA_RFM/height² demonstrated good predictive value for BIA-derived low muscle mass (ASMI < 7/5.7 kg/m²) or low phase angle ≤ 4.9° (AUROC 0.727-0.770). Impaired physical performance, in terms of prolonged CRT and TUG test time was associated with reduced MT_RFM or CSA_RFM (p < 0.05 each), respectively. Higher muscle echogenicity correlated with poorer performance in TUG and SPPB. Low rectus femoris muscle mass was associated with shorter survival and sarcopenic (prolonged CRT and low MT_RFM/height²) patients had a high 6-month mortality risk (HR 7.188; 95% CI 2.249-22.978).

Conclusion: Rectus femoris muscle ultrasound is a feasible bedside method for identifying patients with liver cirrhosis at risk of sarcopenia. Sarcopenia as diagnosed by prolonged CRT together with low RFM mass by ultrasound is an independent predictor for 6-month mortality, highlighting the clinical utility of RFM ultrasound in diagnosing sarcopenia.