United European Gastroenterology Journal最新文献

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.

Background and aims: Beta-blockers are successfully used to treat hemangioma and may decrease the proliferation of cancer cells. We hypothesized that individuals with colorectal polyps may also benefit from beta-blocker initiation.

Methods: Individuals diagnosed with their first colorectal polyp 2006-2016 in the nationwide Swedish ESPRESSO histopathology cohort aged 45-79 years without CRC were eligible. We excluded individuals with previous indications for beta-blocker (cerebrovascular disease, heart failure, aortic aneurysms, myocardial infarction) and individuals with contraindications for preventive beta-blocker initiation (COPD, dementia, liver cirrhosis, Charlson score > 5 or metastatic cancer). Using duplication and inverse probability weighting, we emulated a target trial of beta-blocker initiation within 2 years of the first polyp diagnosis. Main outcomes were incident CRC, CRC mortality, and all-cause mortality until 2019.

Results: In total, 30,399 individuals met our inclusion criteria and were followed for a median of 8 years. Beta-blockers were initiated in 2083 (6.9%) eligible individuals. The 10-year cumulative incidence in initiators versus non-initiators was 5.8% versus 8.6% for CRC incidence, 0.9% versus 1.1% for CRC mortality. The corresponding fully adjusted hazard ratios (HRs) were 0.87 (95% confidence interval, 95% CI: 0.85-0.89) and 0.96 (0.83-1.09). CRC mortality was significantly reduced in women HR 0.78 (0.68-0.99) but not in men HR = 1.14 (0.80-4.46). Cumulative CRC mortality was 0.6% in initiating women versus. 1.1% in non-initiating women.

Conclusion: Beta-blocker initiation within 2 years of polyp diagnosis was linked to a lower CRC incidence for all subgroups, and a lower CRC mortality in women, indicating that beta-blocker initiation may improve long-term outcomes in this high-risk population.

Background: Perinuclear-antineutrophil cytoplasmic antibodies (pANCA) have been identified in familial ulcerative colitis (UC), but the mechanism underlying their expression remains elusive. We assessed the role of genetic predisposition, environmental factors and systemic subclinical inflammation in the development of pANCA in a twin cohort with UC.

Methods: A total of 48 twin pairs (Leuven, Belgium n = 4, Maastricht, The Netherlands n = 6 and Örebro, Sweden n = 38) with UC were included. Among these, 18 were monozygotic (3 concordant and 15 discordant for UC) and 30 were dizygotic (1 concordant and 29 discordant for UC). P-ANCA was detected through standardised ELISA, an indirect immunofluorescence assay and DNase treatment. In addition to high sensitivity C-reactive protein (hs-CRP), 92 inflammatory protein markers were measured in serum by proximity extension assay.

Result: Perinuclear-ANCA was present in 15/52 (29%) of UC twins vs. 4/44 (9%) healthy twin siblings (p = 0.02). No agreement in the presence of pANCA or their levels was observed between twin siblings in monozygotic pairs discordant for UC [intraclass correlation coefficient (ICC) = 0.09] or dizygotic pairs (ICC = -0.20). Female sex was associated with an increased likelihood of pANCA (odds ratio, OR 5.25; 95% confidence interval, CI 1.36-20.30) and higher ANCA levels (ratio of geometric means 1.86; 95% CI 1.18-2.93). Active smoking was associated with lower concentrations of ANCA (ratio of geometric means 0.31; 95% CI 0.14-0.68) and potentially reduced the likelihood of pANCA (OR 0.20; 95% CI 0.03-1.34) in twins with UC but not in their healthy siblings. In healthy twin siblings, significant correlations between ANCA levels and hs-CRP, CDCP1, IL17 A, CXCL9 and IL5 (correlation coefficients 0.36-0.41, p-values < 0.05) were observed.

Conclusion: Female sex and tobacco smoking outweighed genetics regarding the generation and levels of pANCA and ANCA antibodies. The correlations between ANCA levels and inflammatory markers in healthy twin siblings suggest that pANCA may result from subclinical inflammation.

Background and aims: The European Reference Network on Hepatological Diseases (ERN RARE-LIVER) is a Europe-wide network for centers of excellence in the management of rare liver diseases. We aimed to evaluate the current diagnostic and therapeutic trends of primary biliary cholangitis (PBC).

Methods: Prospective data of PBC cases diagnosed from 2017 to March 2024 were extracted from the R-LIVER registry of ERN-RARE LIVER. Cases without two follow-ups within 24 months were excluded from the treatment analysis. Biochemical response according to Toronto criteria and normalization of alkaline phosphatase (ALP) values after 12 months of Ursodeoxycholic Acid (UDCA) were evaluated.

Results: This study included 327 incident cases from six centers. Median age was 56 years, 89.3% were female. At the time of diagnosis, median values of ALP were 1.37 x ULN, and median bilirubin was 0.49 x ULN. Transient elastography (TE) was performed in 230 patients (70.3%) at baseline; median liver stiffness was 6.2 kPa. Out of 316 subjects, treatment with UDCA was started in 312 patients (98.7%); 246 (85.1%) achieved ALP values < 1.67 x ULN at 12 months. Normalization of ALP values occurred in 143 subjects (49.5%) at 12 months. Among 43 patients with inadequate response, 18 (41.9%) were treated with second-line therapies, and had worse liver biochemistry at baseline.

Conclusion: In the current era, patients with PBC are diagnosed at an early stage using non-invasive methods and are almost all treated with UDCA. The biochemical response rate is 85.1%, but the use of second-line therapies for inadequate responders remains suboptimal.

Background and aims: Acute necrotising pancreatitis carries high mortality, especially if infected necrosis occurs. While percutaneous drainage may be required when internal drainage is not feasible, reliable guidelines for managing percutaneous drains are lacking. This study aimed to assess the common practice of percutaneous drainage therapy for infected pancreatic necrosis.

Methods: This retrospective study among 29 tertiary care centres included all patients hospitalised for necrotising acute pancreatitis from 01/2016 until 12/2022 with at least one percutaneous drain. The length of hospital stay was the primary endpoint, with mortality as the secondary endpoint. Between-group comparisons were conducted using the ratio of restricted mean survival time (RMST) after adjusting for confounders.

Results: 585 patients (67% male) from 29 tertiary care centres in 15 countries in Europe, Canada and Bolivia were included in the analysis. Length of hospitalisation or mortality did not differ between the flushed (n = 398) and non-flushed groups (RMST ratio 1.04, p-value = 0.42 and RMST ratio 1.05, p-value = 0.1 respectively). Mortality was significantly lower in those patients who received a combination of percutaneous and internal drains (dual-modality drainage, n = 243) as compared to those who received percutaneous drains only (RMST ratio 1.05, p-value = 0.01). Flushing with antibiotics as compared to saline was not associated with shorter length of hospital stay or lower mortality (RMST ratio 0.98, p-value = 0.78 and 0.97, p-value = 0.48 respectively).

Conclusions: This study reveals notable differences in therapeutic concepts and flushing management for percutaneous drains. While flushing itself was not associated with a shorter length of hospitalisation or lower in-hospital mortality, a lower mortality was observed when internal and percutaneous drainage were used in combination.

Clinical trial registration: The study was prospectively registered in the German Clinical Trials Register (Deutsches Register Klinischer Studien, DRKS) under the registration number DRKS00032231.

Background: Few data are available on the impact of primary sclerosing cholangitis (PSC) on inflammatory bowel disease (IBD).

Objective: We conducted a retrospective study using TriNetX to compare the outcomes of patients with IBD and those with concomitant IBD and PSC.

Methods: All patients with a confirmed diagnosis of Crohn's disease (CD), ulcerative colitis (UC), or indeterminate colitis with or without PSC were eligible. One-to-one propensity score matching was employed to balance demographic parameters, comorbid conditions, and IBD medications between cohort 1 (IBD) and cohort 2 (IBD and concomitant PSC). The primary endpoint was a composite endpoint including the risk of mortality, hospitalization, and surgery. Risks were expressed as Hazard Ratio (HR) with a 95% confidence interval (CI).

Results: A total of 398,980 IBD patients were analyzed (cohort 1: 395,874 and cohort 2: 3106). After propensity-score-matching, 3007 patients from each group were included (mean age 48.1 ± 19.4 years, female 40%, UC 75% CD 24.8%). Approximately 1%-2% of patients were treated with advanced therapies. Cohort 2 patients had a higher risk of experiencing the composite endpoint compared to cohort 1 group (HR:1.32, 95%CI:1.23-1.42). Similarly, a higher risk of hospitalization and mortality was identified in subjects with IBD and concomitant PSC (HR:1.32, 95% CI: 1.22-1.43 and HR: 1.69, 95%CI: 1.46-1.96). Both CD and UC patients with concomitant PSC had a higher risk of achieving the composite endpoint (HR: 1.18, 95%CI: 1.02-1.37 and HR: 1.29, 95%CI: 1.18-1.40). An increased risk of mortality and hospitalization was found both in patients with CD (HR: 2.16, 95%CI:1.58-2.95, and 1.20, 95%CI:1.03-1.41) and UC (HR: 1.87, 95%CI: 1.57-2.22 and HR: 1.27, 95%CI:1.16-1.40) and concomitant PSC.

Conclusion: In this administrative study of patients with IBD and PSC, concomitant PSC was associated with an increased risk of mortality and hospitalization.