United European Gastroenterology Journal最新文献

Background: Complications related to portal hypertension (PH) in patients with alcohol-related liver disease (ALD) can be controlled by transjugular intrahepatic portosystemic shunt (TIPS) placement; however, the impact of ongoing alcohol use (AU) after TIPS remains scarcely investigated.

Methods: ALD patients undergoing TIPS implantation between 2000 and 2022 were included. Laboratory/demographic parameters and clinical events/outcomes were compared per post-TIPS AU status and to a group of n = 55 decompensated ALD patients with ongoing AU who did not receive TIPS.

Results: Overall, 248 TIPS patients (78.2% male; median age: 55.5 years; ascites: 69.8%; median MELD: 12), including 90 (36.3%) with ongoing AU after TIPS were included. AU post-TIPS was independently associated with ACLF (asHR 2.27; 95% CI 1.40-3.66; p < 0.001) and liver-related death (asHR 1.68; 95% CI 1.05-2.67; p = 0.030) among patients undergoing TIPS in adjusted multivariable competing risks analysis. When comparing matched decompensated AU patients treated versus non-treated by TIPS, multivariable competing risks regression revealed MELD (asHR 1.07; 95% CI 1.01-1.13; p = 0.033) but not TIPS use (asHR 0.70; 95% CI 0.45-1.10; p = 0.120) as independent risk factors for ACLF, despite TIPS patients having higher levels of systemic inflammation (CRP).

Conclusion: Post-TIPS AU was frequent and an independent risk factor for ACLF and liver-related death, underlining the importance of interdisciplinary measures supporting alcohol abstinence. TIPS should still not be withheld from ALD patients developing PH complications, since it does not predispose them to ACLF and may prevent liver-related death.

Background: Colorectal cancer (CRC) is a major health concern. In Sweden, a CRC screening program was implemented nationwide between 2019 and 2022. This study evaluated participation, colonoscopy adherence, and diagnostic outcomes for the program's first five years.

Methods: The target group of screening was all residents 60-74 years old. Data were retrieved from SveReKKS, the Swedish national quality register for CRC screening and colonoscopies. A positive FIT test was defined as ≥ 40 μg Hb/g for females, ≥ 80 μg Hb/g in feces for males. Participation, FIT positivity, colonoscopy adherence, quality indicators, and neoplasia detection rates were assessed.

Results: Among 884,866 invitees, the overall participation rate was 64.3%. Participation was higher in older age groups, among females, but lower in regions with low population density. FIT positivity was 2.7%, with no major variation by age or sex. Colonoscopy adherence among FIT-positive individuals was 82%, with lower adherence among men and regional variation. The detection rate for CRC was 6.6%, 29.9% for advanced adenomas and adenocarcinoma, and an overall adenoma detection rate of 49.7%. Quality metrics were high: 98% had adequate bowel preparation, caecal intubation rate was 96%, and the complication rates (bleeding and perforation) were low (0.5% early, 0.7% late).

Conclusion: The first 5 years of the implementation of CRC screening in Sweden demonstrated high participation and excellent diagnostic performance, although colonoscopy adherence fell slightly below the guideline targets. These findings support the effectiveness of FIT-based screening and highlight areas for further improvement, including enhancing colonoscopy uptake among men and in low-density regions.

Background: Bowel urgency (BU) is reported by over 80% of patients with ulcerative colitis (UC) and 60% of those with Crohn's disease (CD). However, the impact of advanced therapies on BU has not been consistently evaluated.

Objectives: To assess the effect of advanced therapies on BU improvement in patients with UC and CD.

Methods: This retrospective cohort study included all consecutive patients with confirmed UC or CD who started an advanced therapy with available data regarding BU before and after induction therapy between 2023 and 2024 at two tertiary centers. BU was assessed using the numeric-rating-scale urgency score (NRS-us), with BU defined as NRS-us ≥ 3. The primary endpoint was BU improvement (NRS-us ≤ 3 or reduction of at least two points) after the induction phase. Multivariate logistic regression analysis identified factors associated with BU improvement.

Results: A total of 159 patients were included (56% male; 65% UC; median age: 36 years (Interquartile range [IQR] 27-25)). TNFα inhibitors were the most frequently used agents (49.6%). At baseline, the median NRS-us was 7. After induction, 50.9% of patients achieved BU improvement, with a mean reduction of 2.3 ± 2.9 points. BU improvement was significantly associated with clinical remission (false-discovery-rate [FDR] = 0.009 in CD and FDR = 0.010 in UC), normalization of fecal calprotectin (FDR = 0.001), CRP (FDR = 0.008), and bowel wall thickness on intestinal ultrasound (FDR = 0.001). No significant differences were observed between therapeutic classes.

Conclusion: BU improved in approximately half of IBD patients following induction with advanced therapies. Its improvement correlated with clinical, biochemical, and ultrasound remission, supporting the incorporation of BU assessment into routine clinical monitoring.

Background: Intraductal papillary mucinous neoplasms with low-grade dysplasia (IPMNs w/LGD) and benign cysts, including serous cystadenomas (SCAs), are common pancreatic cystic lesions (PCLs) that are better managed conservatively. The burden of patients who undergo surgical resection for these cysts is unknown. Our study aims to estimate the global prevalence of surgical resections for IPMNs w/LGD and benign cysts, as well as the pre-operative misclassification rate among all resected PCLs.

Methods: We searched the literature through September 2023 to identify full-text articles that reported the surgical histopathology of resected PCLs. A proportional meta-analysis was performed using a random-effects model, with prevalence estimates reported as pooled proportions. Subgroup analysis and meta-regression were performed based on use of endoscopic ultrasound (EUS), years of enrollment, and geographic location.

Results: Sixteen studies (n = 5830) were identified. Among all surgically resected PCLs, 24% were IPMNs w/LGD (95% CI: 18%-32%), 16% were SCAs (95% CI 13%-19%), 4% were other benign cysts (95% CI: 3%-6%), and 24% were pre-operatively misclassified (95% CI: 16%-34%). Of the resected IPMNs, 62% had LGD (95% CI: 51%-71%). An increasing use of pre-operative EUS is associated with a lower prevalence of resected SCAs (p < 0.05) but has not impacted the rate of resections for IPMNs w/LGD. The pre-operative misclassification of PCLs has significantly decreased over time (p < 0.01), although not significantly influenced by increasing EUS utilization or geographic location.

Conclusion: One quarter of PCLs are pre-operatively misclassified and ∼44% are surgically resected for benign cysts or IPMNs w/LGD. Implementation of advanced diagnostic tools might improve pre-operative classification and reduce overtreatment of PCLs.

Background: The ACCURE trial demonstrated that appendicectomy reduces relapse rates within 1 year in patients with ulcerative colitis (UC) in remission. We aimed to explore appendiceal histopathology in quiescent UC and assess its association with postoperative relapse.

Methods: Appendix specimens from Dutch participants in the ACCURE trial were reassessed by a blinded gastrointestinal pathologist using the Robarts Histopathology Index (RHI; range 0-33). Active appendiceal inflammation was defined as RHI > 3. Clinical data, preoperative endoscopic findings including peri-appendiceal red patch (PARP), and outcomes were correlated with histopathological findings. Inter-observer agreement between local and central scoring was assessed, along with relapse-free survival in relation to RHI severity.

Results: Of 65 patients, 49 (75.4%) maintained remission and 16 (24.6%) relapsed within one year. Active inflammation was present in 55.4% (36/65). Inter-observer agreement was moderate (κ = 0.47, 95% CI 0.29-0.64, p < 0.001). Inflammation was more frequent in patients diagnosed at a younger age (median 28 vs. 34 years, p = 0.09), and greater in those with PARP (RHI 15.5 vs. 5.0, p = 0.005). Extensive epithelial neutrophil involvement (> 5% of crypts) was associated with higher relapse rates (44.4% vs. 18.0%, p = 0.05). Relapsing patients also had larger appendiceal diameters (median 9 vs. 7 mm, p = 0.03).

Conclusion: Active appendiceal inflammation is prevalent in quiescent UC and showed a trend toward association with relapse risk. Although the benefit of appendicectomy in this group cannot be confirmed on these data alone, the finding might be clinically relevant as relapse rates are significantly reduced in the appendicectomy group.

Background & aims: Metabolic dysfunction-associated steatohepatitis (MASH) increasingly drives hepatocellular carcinoma (HCC) development. We characterized inflammatory infiltrates in liver biopsies from MASH patients who developed HCC versus controls to identify predictive immune signatures.

Method: Formalin-fixed paraffin-embedded (FFPE) liver biopsies from MASH patients were categorized as pre-HCC MASH (n = 10) or control MASH (n = 13) by the ESCALON consortium. Standardized histological analysis and multiplexed immunohistochemistry were performed targeting CD4, CD8, PD1, PDL1, FoxP3, CXCR6, CD3, CD68, and CD20 using a PhenoImager Fusion scanner. Single-cell RNA-seq datasets characterized hepatic CD4 T cell heterogeneity. Clinical parameters measured included ALT, AST, GGT, alkaline phosphatase, platelets, and INR.

Results: Pre-HCC MASH showed inflammation extending from portal to periportal areas versus portal-only distribution in controls. Analysis of 291,908 cells revealed significantly higher CD4+ density (p = 0.0243) and CD4+PD1+ cells (p = 0.017) in pre-HCC patients, while CD8+ and regulatory T cell densities remained unchanged. Single-cell RNA-seq identified potential phenotypic shifts from Th1 cytotoxicity toward tissue-repair and Th17 CD4+ T cells in MASH livers. Combined immunological and clinical variables (sex, age, CD4+ T cell numbers, ALT, alkaline phosphatase and platelets) achieved excellent predictive performance (ROC-AUC = 0.944) for HCC development.

Conclusions: Increase in liver CD4+ T cell infiltration characterizes MASH-to-HCC progression. These immune signatures combined with clinical parameters demonstrate remarkable predictive value for identifying high-risk MASH patients.

Background and aims: Remimazolam, a new ultra-short-acting benzodiazepine, is a safe and effective option for procedural sedation. Nevertheless, to date, no study has directly compared remimazolam and midazolam in diagnostic upper gastrointestinal endoscopy. This study aimed to evaluate the efficacy and safety of remimazolam compared with those of midazolam in this setting.

Methods: This multicenter, single-blind, randomized, positive-control, superiority, investigator-initiated phase III trial enrolled patients who were scheduled to undergo diagnostic upper gastrointestinal endoscopy at seven academic teaching hospitals from April 2023 to January 2024. Participants were randomly assigned to receive remimazolam or midazolam (1:1 ratio). The primary endpoint was total procedure time, defined as the duration from the first sedative administration to discharge.

Results: Of 133 randomized patients, 132 (remimazolam group, n = 66; midazolam group, n = 66) underwent upper endoscopy with sedation. The total procedure time was significantly shorter in the remimazolam group (30.3 vs. 48.5 min, p < 0.001). Sedation-related times (i.e., induction, sedation, recovery, and discharge times) were also significantly shorter in the remimazolam group (all p < 0.001). The incidence of adverse events did not significantly differ between the groups; however, the incidence rates of hypotension, bradycardia, and paradoxical reactions were lower in the remimazolam group. When compared to previous sedation experiences, patient satisfaction was higher in the remimazolam group (p < 0.001).

Conclusions: Compared with midazolam, the use of remimazolam in diagnostic upper gastrointestinal endoscopy allows for faster sedation induction and recovery, more rapid discharge, and higher patient satisfaction compared with previous sedation experiences, while maintaining a safety profile similar to that of midazolam.

Trial registration: ClinicalTrials.gov (NCT05836545).

Background: Filgotinib is a preferential Janus kinase 1 (JAK-1) inhibitor registered for the treatment of ulcerative colitis (UC). Real-world effectiveness of filgotinib, especially for difficult-to-treat (DTT, failure of ≥ 2 prior advanced therapies) patients, has been scarcely reported.

Objective: This study aimed to assess the effectiveness and safety of filgotinib for UC patients in routine care.

Methods: The Dutch ICC registry enrolled UC patients initiating filgotinib and prospectively evaluated outcomes up to 52 weeks. The primary outcome was corticosteroid-free clinical remission (CSFR, Simple Clinical Colitis Activity Index [SCCAI] ≤ 2 without steroid use) at week 52. Secondary outcomes included clinical remission (SCCAI ≤ 2), biochemical remission (C-reactive protein serum concentration < 5 mg/L and/or faecal calprotectin level < 250 μg/g), treatment persistence and safety.

Results: A total of 96 UC patients were included. At 52 weeks, 39.5% (34/76) of patients with disease activity at baseline were in CSFR. Out of the patients that met the criteria for DTT disease (n = 68; 71%), 36.4% achieved CSFR. Treatment persistence at 52 weeks was 71.4% (CI 56.5-90.3) and 53.4% (CI 42.6-67.0) for non-DTT and DTT patients, respectively. The main reasons for discontinuation of filgotinib were primary non-response (n = 21, 54%) or secondary loss of response (n = 8, 23%). No severe infections were documented. Most reported adverse events included headache (n = 5), nausea (n = 3) and hypercholesterolemia (n = 3).

Conclusion: Filgotinib is an effective and well-tolerated treatment option for UC, including DTT disease. No new safety signals were found.

Background: While tumor necrosis factor (TNF) inhibitors can induce paradoxical reactions, sarcoidosis-like disease has hardly been reported so far. This study aimed to describe the epidemiological, diagnostic and therapeutic features of TNF inhibitor-induced sarcoidosis-like lesions in patients with inflammatory bowel disease.

Methods: We conducted a case series across 59 institutions affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du Tube Digestif. Diagnosis of TNF inhibitor-induced sarcoidosis was based on typical clinical and radiological signs, histological evidence of non-necrotizing granuloma, exclusion of alternative diagnoses, and a timeline consistent with drug exposure. A pharmacovigilance expert reviewed each case to confirm drug causality.

Results: We identified 14 cases of sarcoidosis-like lesions, including 9 patients with Crohn's disease, 4 ulcerative colitis, and 1 with unclassified inflammatory bowel disease. The implicated medications were infliximab (8), adalimumab (5), and golimumab (1), predominantly in first-time biotherapy users (71%). The median time from treatment initiation to sarcoidosis diagnosis was 27.5 months (range 3-91). Common clinical manifestations included dyspnea (71%), coughing (50%) and fever (50%). Ten patients discontinued TNF inhibitor therapy and started oral steroids, leading to complete symptom resolution in seven cases and improvement in two. Median time from steroid initiation to clinical remission of sarcoidosis was 84 days (range 11-134). After a median follow-up of 40 months, while no relapses occurred in 13 patients, one showed persistent sarcoidosis activity.

Conclusions: TNF inhibitor-induced sarcoidosis should be considered in inflammatory bowel disease patients with chronic respiratory symptoms or fever after exclusion of mycobacterial infection. Management involves discontinuation of TNF inhibitors and a course of steroids.