United European Gastroenterology Journal最新文献

Background and aims: We assessed the cost-effectiveness and cost-utility of therapeutic drug monitoring (TDM)-guided mercaptopurine treatment compared with placebo in ulcerative colitis (UC) patients failing 5-aminosalicylates.

Methods: Data were gathered alongside the randomized controlled OPTIC trial (EudraCT: 2015-005260-41). The evaluation was performed from a health care and societal perspective as cost-effectiveness and cost-utility analyses with a time horizon of one year. Volumes and costs of in-hospital care, out-of-hospital care, out-of-pocket expenses and productivity loss were assessed. The main outcomes were the extra costs per additional patient who achieved clinical remission and endoscopic improvement at 52 weeks (responders) and extra costs per quality-adjusted life-year (QALY) gained.

Results: In total, 59 patients were randomized to the intervention (n = 29) and control (n = 30) group. Non-significant differences in costs were €63 (-€1267 to €1434; P = 0.93) in favour of placebo from a health care perspective and -€742 (-€3683 to €2016; P = 0.64) in favour of mercaptopurine from a societal perspective. The higher proportion of responders and a non-significant QALY difference of 0.0475 (-0.024-0.117) (P = 0.184) favouring patients on mercaptopurine treatment resulted in €165 extra costs per additional responder and €1326 extra costs per QALY gained from a health care perspective. From a societal perspective, dominance over placebo was observed with cost savings of €1937 per additional responder and €15,621 per QALY gained. The probability of optimised mercaptopurine treatment being cost-effective was 0.80 at a willingness to pay per additional QALY of €20,000.

Conclusions: TDM-based mercaptopurine treatment in UC patients failing 5-aminosalicylates is a cost-effective strategy from a societal perspective.

Background: Mucosal healing (MH) is an established treatment goal in inflammatory bowel disease (IBD). However, various definitions of MH exist. We aimed to identify how MH is defined in randomized controlled trials (RCTs) in ulcerative colitis (UC) and Crohn's disease (CD).

Methods: We searched MEDLINE, EMBASE, and the Cochrane library from inception to December 2023 for phase 2 and 3 RCTs of advanced therapies in IBD.

Results: One hundred forty-four studies were included, 72 in UC and 72 in CD, published between 1997 and 2023. In UC, 64% (46/72) RCTs reported MH as an endpoint. 12 definitions of MH were found, from endoscopic assessment alone (35/46; 76%) to the more recent combination of histology and endoscopy (10/46; 22%). 96% (44/46) of studies used the Mayo Endoscopic Subscore. In CD, reporting of MH lagged behind UC, with only 12% (9/72) of trials specifically defining MH as an endpoint, 7 as "absence of ulceration," 2 as Simplified Endoscopic Score for CD score ≤2 or 0. Histological assessment was performed in 3 RCTs of CD. Centralized reading of endoscopy was used in 48% (35/72) of RCTs of UC and 22% (16/72) of CD. Only 1 RCT included transmural healing as an endpoint.

Conclusions: A standard definition of MH in IBD is lacking. Definitions have evolved particularly in UC, which now includes the addition of histological evaluation. Transmural healing holds promise as a future target in CD. We support a greater standardization of definitions as we expect endpoints to become increasingly stringent and multimodal with computers automating the assessment.

Objective: To evaluate the diagnostic yield of pancreatic cancer screening in individuals at risk (IAR) from familial pancreatic cancer (FPC) families with respect to the presence or absence of pathogenic germline variants predisposing to pancreatic adenocarcinoma (PDAC).

Design: In a 20 years period, IAR from FPC families were enrolled in a prospective screening program of the national case collection for FPC of Germany, including magnet resonance imaging (MRI) and endoscopic ultrasound (EUS). The diagnostic yield was analyzed regarding significant pancreatic lesions such as PDAC, high-grade pancreatic-intraepithelial-neoplasia (PanIN3) and intraductal-papillary-mucinous-neoplasia (IPMN) with high-grade dysplasia. Screening results were compared between carriers of pathogenic variants and variant-negative IAR.

Results: 337 IAR, including 74 (22%) variant-carriers and 263 IAR of variant-negative FPC families (mean age 49; standard deviation [SD] + 8.9) were followed 64 (SD + 55) months. IAR underwent 5.1 (SD + 3.9) screening visits with 1733 MRI (5.1,SD + 3.9 per IAR) and 728 EUS (2.2,SD + 1.7 per IAR). In 12 (4%) cases, significant pancreatic lesions were detected, including 4 PDAC, 3 PanIN3 and 5 high-grade IPMN. Three of 4 IAR with PDAC died after a mean of 27 months postoperatively, and one IAR is alive without evidence of disease after 31 months. The diagnostic yield for significant lesions was 13.5% (10/74) for variant carriers compared to 0.8% (2/263) for IAR of variant-negative FPC families (p < 0.001). Logistic regression analysis revealed that a negative variant status was almost always accompanied by the absence of a significant lesion over time with a negative predictive value of 99.2% (95% CI 97.3%-99.9%).

Conclusion: The diagnostic yield seems to justify PDAC screening in IAR of FPC-families with pathogenic germline variants in PDAC predisposing genes, not in IAR of variant-negative families.

Introduction: Gastric cancer (GC) is one of the most lethal malignancies worldwide. Helicobacter pylori is the primary cause of GC; therefore, its eradication reduces the risk of developing this neoplasia. There is extensive evidence regarding quadruple therapy with relevance to the European population. However, in Latin America, data are scarce. Furthermore, there is limited information about the eradication rates achieved by antibiotic schemes in European and Latin American populations.

Objective: To compare the effectiveness of standard triple therapy (STT), quadruple concomitant therapy (QCT), and bismuth quadruple therapy (QBT) in six centers in Europe and Latin America.

Methods: A retrospective study was carried out based on the LEGACy registry from 2017 to 2022. Data from adult patients recruited in Portugal, Spain, Chile, Mexico, and Paraguay with confirmed H. pylori infection who received eradication therapy and confirmatory tests at least 1 month apart were included. Treatment success by each scheme was compared using a mixed multilevel Poisson regression, adjusting for patient sex and age, together with country-specific variables, including prevalence of H. pylori antibiotic resistance (clarithromycin, metronidazole, and amoxicillin), and CYP2C19 polymorphisms.

Results: 772 patients were incorporated (64.64% females; mean age of 52.93 years). The total H. pylori eradication rates were 75.20% (255/339) with STT, 88.70% (159/178) with QCT, and 91.30% (191/209) with QBT. Both quadruple therapies (QCT-QBT) showed significantly higher eradication rates compared with STT, with an adjusted incidence risk ratio (IRR) of 1.25 (p: <0.05); and 1.24 (p: <0.05), respectively. The antibiotic-resistance prevalence by country, but not the prevalence of CYP2C19 polymorphism, showed a statistically significant impact on eradication success.

Conclusions: Both QCT and QBT are superior to STT for H. pylori eradication when adjusted for country-specific antibiotic resistance and CYP2C19 polymorphism in a sample of individuals residing in five countries within two continents.

Background: The potential of molecular markers in the removed polys as reliable predictors of metachronous lesions is still uncertain.

Aim: Our aim was to evaluate the role of somatic mutations in KRAS in polyps of patients with high-risk adenomas to predict the risk of advanced polyps or colorectal cancer (CRC) within 3 years.

Methods: A total of 518 patients were prospectively enrolled. The included patients had adenomas ≥10 mm, high-grade dysplasia, villous component or ≥3 more adenomas at baseline and were scheduled to undergo surveillance colonoscopy at 3 years ± 6 months. Somatic KRAS mutation was performed on 1189 polyps collected from these patients. At surveillance, advanced lesions were defined as adenomas with a size of ≥10 mm. High-grade dysplasia or villous component, serrated polyps ≥10 mm or with dysplasia or CRC.

Results: At baseline, 81 patients (15.6%) had KRAS mutations in at least one polyp. Patients with KRAS mutated polyps had more frequent villous histological lesions and size ≥20 mm. In the multivariate analysis, adjusted for age and sex, only age (odds ratios [OR], 1.06; 95% confidence interval [CI], 1.02-1.09; p < 0.001), ≥5 adenomas (OR, 3.92; 95% CI, 1.96-7.82), and KRAS mutation (OR, 2.54; 95% CI, 1.48-4.34; p < 0.01) were independently associated with the development of advanced lesions at surveillance.

Conclusions: Our results show that, in patients with high-risk adenomas, the presence of somatic mutations in KRAS is an independent risk factor for the development of advanced metachronous polyps.

Background: The Trans.IT database is a national gastrointestinal (GI) endoscopy database developed in 2012. It automatically collects anonymous data from GI endoscopy procedures in a centralized database. All endoscopists use a structured reporting tool for uniform data collection. In this study, we aim to provide an overview of the database and to evaluate its impact on data registration quality.

Methods: We used all ERCPs, colonoscopies and colorectal cancer (CRC)-screening colonoscopies performed between 2016 and 2020. We excluded centers joining after 2016 and patients below age 18. Data registration quality for ERCPs included completeness of data for: intention of ERCP, Schutz score, ASA classification, papillary status (virgin or previous sphincterotomy), cannulation (success or failure to cannulate the desired duct) and procedural success. For colonoscopies: indication, ASA-classification, Boston Bowel Preparation Score (BBPS), cecal intubation, polyp detection rate (PDR). For CRC-screening colonoscopies, ASA-classification, BBPS, cecal intubation, PDR and adenoma detection rate (ADR).

Results: A total of 14,156 ERCPs, 150,962 colonoscopies and 37,199 colorectal cancer screening colonoscopies were included in our analysis. For ERCPs, registration of procedural intention, Schutz score, ASA classification, papillary status, cannulation and procedural success improved from 34.9%, 32.7%, 72.6%, 36.5%, 34.6%, 27.2% in 2016, to 86.4%, 84.6%, 97.4%, 86.4%, 82.1%, 84.0%, respectively, in 2020. For non-screening colonoscopies, registration of indication, ASA classification, BBPS, cecal intubation and PDR improved from 40.4%, 60.5%, 47.6%, 69.8% and 32.3% in 2016 to 90.3%, 88.9%, 59.8%, 79.1% and 39.1%, respectively, in 2020. For CRC-cancer screening colonoscopy registration equaled outcome, PDR and ADR changed from 74.7% to 63.6% in 2016 to 66.3% and 53.8% in 2020, respectively.

Conclusions: The quality of endoscopy data registration has consistently improved over the years by using the Trans.IT database. This is most likely the result of feedback to performing endoscopists to review performance in real-time online and progressive awareness of quality of data registration.

Background: Patients with inflammatory bowel disease (IBD) in clinical and endoscopic remission may still experience disease relapse. Therefore, there is a need to identify outcome predictors. Recently, the role of neutrophils in predicting outcomes in ulcerative colitis (UC) has been highlighted. Furthermore, the impairment of intestinal barrier plays a key role in forecasting disease outcomes in IBD.

Objective: This observational study aimed to assess the predictive role of neutrophils according to tissue localization and intestinal barrier protein expression in IBD.

Methods: IBD patients in clinical remission who underwent colonoscopy between January 2020 and June 2022 at two tertiary referral centres were enrolled. Patients with Mayo Endoscopic Score ≤1 (UC) and Simple Endoscopic Score ≤6 (Crohn's disease) were included. Histological activity was assessed using validated scores. Experienced pathologists evaluated neutrophil localization in the epithelium and lamina propria and immunohistochemical expression of Claudin-2 and junctional adhesion molecule A (JAM-A).

Results: Of 60 UC and 76 CD patients, 59.7% had histological activity. 25.8% of patients developed an adverse outcome within 12 months. Neutrophils in the epithelium predicted adverse outcomes for UC (hazard ratio [HR] 5.198, p = 0.01) and CD (HR 4.377, p = 0.03) patients in endoscopic remission. Claudin-2 expression correlated with endoscopic and histological activity and predicted outcomes in UC. Similar results were found for JAM-A in CD despite this protein showing less specificity as a barrier predictor of outcome.

Conclusion: This study highlights the potential role of epithelial neutrophil localization and Claudin-2 'leaky gut' expression as tools for predicting IBD outcomes and guiding further patient-tailored therapy.