Therapeutic Advances in Gastroenterology最新文献

Background: Therapeutic drug monitoring of adalimumab (ADA) is still controversial.

Objectives: To study the association between ADA trough levels in the early stages of treatment with biological remission (BR) and drug survival in Crohn's disease (CD).

Design: Retrospective cohort study.

Methods: Patients treated with ADA with available trough levels at weeks 2 and 6 (after the first induction and maintenance dose, respectively) were included. Fecal calprotectin (Fcal) and C-reactive protein (CRP) were registered at baseline, week 24, and week 52. BR was defined as Fcal <200 µg/g and CRP <5 mg/dl. Treatment survival and the need for dose escalation were assessed at week 52. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic accuracy of ADA cutoff levels for BR. Quartile-specific comparisons were performed to evaluate differences in the proportion of patients achieving BR at weeks 24 and 52, drug survival, and dose escalation.

Results: In all, 112 patients were included. ADA trough levels at week 6 were higher in patients achieving BR at week 24 (12.32 μg/ml vs 10.3 μg/ml, p = 0.0008), week 52 (12.3 μg/ml vs 10.8 μg/ml, p = 0.035), and in patients with 1-year treatment persistence (12.17 μg/ml vs 9.7 μg/ml, p = 0.03), but lower in patients requiring maintenance intensification (9.7 μg/ml vs 12.2 µg/ml, p < 0.0001). ADA week 6 trough levels >12.27 μg/ml predicted BR at week 24 with 79.7% specificity and 79.5% positive predictive value. Patients in the third quartile (Q3) and fourth quartile (Q4) of ADA levels at week 6 exhibited higher rates of BR at week 24, BR at week 52, 1-year drug survival, and less need for dose escalation (all p-values <0.05). In logistic regression, Q3 and Q4 of week 6 levels were significantly associated with BR at week 24 (p = 0.02 and p = 0.001); and week 6 Q4 with BR at week 52 (p = 0.02), treatment persistence (p = 0.03), and lower dose escalation (p = 0.004). ADA trough levels at week 2 did not show similar associations.

Conclusion: ADA trough levels at week 6 are associated with BR at weeks 24 and 52, drug survival, and need for dose escalation in CD. However, ADA concentrations at week 2 failed to yield similar results.

Background: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) that have a negative impact on patient quality of life (QOL).

Objective: To evaluate QOL, work productivity, use of healthcare resources, and medical costs in patients with IBD from the RISE-MX trial.

Design: RISE-MX was a non-interventional, multicentric, cross-sectional, retrospective study conducted in a Mexican population with IBD.

Methods: The 36-item Short Form Health Survey (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ) were used to assess QOL. The burden of disease was analyzed using the Work Productivity and Activity Impairment Questionnaire (WPAI), healthcare resources use, and medical costs.

Results: Of 326 subjects, 95 (29.1%) had CD, and 231 (70.8%) had UC. In patients with CD, 43 patients (45.3%) showed moderate-to-severe activity, and 42 (18.1%) had moderate-to-severe disease activity in patients with UC. In all SF-36 dimensions, a significant difference between moderate-to-severe and mild activity/in remission groups was observed in patients with UC, while in patients with CD, the difference between activity groups was significant only for physical functioning and social functioning dimensions. In patients with CD, a higher but non-significant IBDQ score difference between activity groups was observed while a statistical difference between activity groups was observed for all dimensions in UC patients. In WPAI, the total percentage for work impairment (absenteeism plus presenteeism) and the percentage of regular daily activity impairment were statistically significant between activity groups only for UC. The annual total costs (direct and indirect) per patient in CD were USD 19,757 (moderate-to-severe activity group) and USD 12,587 (mild activity/in remission group), while in patients with UC were USD 11,702 and USD 9144, respectively.

Conclusion: Moderate-to-severe activity of disease was associated with a substantial impact on QOL, work productivity, and medical costs in Mexican patients with IBD. Total costs were higher for patients with CD than for patients with UC.

Background: The Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) are established classification systems used to evaluate atrophic gastritis and intestinal metaplasia, respectively.

Objectives: We evaluated the association of OLGA and OLGIM scores and the risk of gastric cancer (GC) in only prospective cohort studies.

Design: Systematic review and meta-analysis.

Data sources and methods: We systematically searched four databases for prospective cohorts that evaluated the use of OLGA and OLGIM staging systems in predicting the risk of GC. We primarily compared OLGA/OLGIM III-IV versus OLGA/OLGIM 0-II categories and GC events. Pooled risk ratios (RR) and absolute risk differences with their 95% confidence intervals (CIs) were calculated.

Results: Eight studies were included (n = 12,526). The mean age of the patients ranged from 48.2 to 64.9 years. OLGA III-IV and OLGIM III-IV were associated with the development of GC in comparison to their 0-II categories (RR 32.31, 95% CI 9.14-114.21 and RR 12.38, 95% CI 5.75-26.65, respectively). OLGA III-IV and OLGIM III-IV were associated with an increase in the absolute risk of GC of 4% and 5%, respectively. The risk remained significant if we only included countries with high incidence of GC, and was greater if we excluded one study that included mostly patients with autoimmune gastritis. OLGA II and OLGIM II were associated with higher risk of high-grade dysplasia (HGD) and GC in comparison with OLGA 0-I and OLGIM 0-I, respectively.

Conclusion: Higher stages in OLGA and OLGIM systems are associated with a significantly increased risk of developing HGD and GC, validating these scoring systems for the assessment of GC risk and the design of endoscopic surveillance programs.

Trial prospero registration: CRD42024565771.

Background: Bleeding is a serious and frequent adverse event that occurs during and after endoscopic papillectomy (EP). Previous studies have highlighted the effectiveness of preventive clipping closure of the resection site in preventing post-EP bleeding. However, the optimal length of closure remained unclear.

Objectives: We aimed to clarify the optimal clipping length at the post-EP resection site to prevent delayed bleeding.

Design: This study was a multicenter retrospective cohort study.

Methods: We retrospectively analyzed patients who were consecutively admitted to nine high-volume centers for EP between November 2003 and October 2023. The primary outcome was the frequency of delayed bleeding based on the closure length. The optimal closure length rate of the resected site to prevent delayed bleeding was determined using a receiver operating characteristic curve. Secondary outcomes were the incidence, treatment outcomes, and risk factors for post-EP delayed bleeding.

Results: A total of 130 patients who underwent EP were analyzed. Delayed bleeding was observed in 22 (17%) patients, occurring more frequently in cases without clipping closure than in those with clipping closure (28% (13/47) vs 11% (9/83); p = 0.014). Among 83 patients who underwent clipping closure, delayed bleeding occurred more frequently with a closure length rate <65% than in those with a closure rate ⩾65% (25% (5/20) vs 6% (4/63); p = 0.019). Multivariate analysis showed that a closure rate <65% was the risk factor for delayed bleeding (odds ratio, 6.3; 95% confidence interval, 1.2-33; p = 0.030) in cases with clipping.

Conclusion: Clipping closure was effective in preventing delayed bleeding, and closure length rate ⩾65% of the resected site significantly reduced post-EP delayed bleeding.

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, with its progression intricately linked to gut microbiota dysbiosis. Disruptions in microbial homeostasis contribute to tumor initiation, immune suppression, and inflammation, establishing the microbiota as a key therapeutic target. Fecal microbiota transplantation (FMT) has emerged as a transformative approach to restore microbial balance, enhance immune responses, and reshape the tumor microenvironment. This review explores the mechanisms underlying FMT's therapeutic potential, evaluates its advantages over other microbiota-based interventions, and addresses challenges such as donor selection, safety concerns, and treatment standardization. Looking forward, the integration of FMT into personalized CRC therapies requires robust clinical trials and the identification of predictive biomarkers to optimize its efficacy and safety.

Integrating artificial intelligence (AI) into histologic disease assessment is transforming the management of inflammatory bowel disease (IBD). AI-aided histology enables precise, objective evaluations of disease activity by analysing whole-slide images, facilitating accurate predictions of histologic remission (HR) in ulcerative colitis and Crohn's disease. Additionally, AI shows promise in predicting adverse outcomes and therapeutic responses, making it a promising tool for clinical practice and clinical trials. By leveraging advanced algorithms, AI enhances diagnostic accuracy, reduces assessment variability and streamlines histological workflows in clinical settings. In clinical trials, AI aids in assessing histological endpoints, enabling real-time analysis, standardising evaluations and supporting adaptive trial designs. Recent advancements are further refining AI-aided digital pathology in IBD. New developments in multimodal AI models integrating clinical, endoscopic, histologic and molecular data pave the way for a comprehensive approach to precision medicine in IBD. Automated assessment of intestinal barrier healing - a deeper level of healing beyond endoscopic and HR - shows promise for improved outcome prediction and patient management. Preliminary evidence also suggests that AI applied to colitis-associated neoplasia can aid in the detection, characterisation and molecular profiling of lesions, holding potential for enhanced dysplasia management and organ-sparing approaches. Although challenges remain in standardisation, validation through randomised controlled trials and ethical considerations. AI is poised to revolutionise IBD management by advancing towards a more personalised and efficient care model, while the path to full clinical implementation may be lengthy. However, the transformative impact of AI on IBD care is already shining through.

Background: Dietary therapy is commonly used as a treatment for Crohn's disease (CD). High dietary adherence is associated with achieving clinical remission. Crohn's disease exclusion diet (CDED) is a relatively new therapy in the management of CD.

Objective: This publication aims to assess the first real-life patient experience with and adherence to Crohn's disease exclusion diet plus partial enteral nutrition (CDED + PEN) in Dutch children and adults with mild-to-moderate CD.

Design: Interviews were performed with patients and/or caregivers prospectively after phases I, II, and III, and once after finishing therapy in a retrospective cohort.

Methods: We obtained data on patient experiences with CDED and the accompanying Modulife patient support platform and assessed effectiveness from patients' and physicians' perspectives based on medical and clinical data obtained from the patient file. The interview contained open questions, 5-point Likert scales, and Net Promotor Scores (NPS).

Results: Sixty-nine patients were included (52 pediatric and 17 adults). Approximately half of the patients in the prospective cohort and the majority (83%) of patients in the retrospective cohort would recommend CDED to others. Two-thirds of the patients would reconsider starting CDED again. A positive NPS (31) was given for recommending the support platform to others with the recipes feature as the most used and esteemed part. Median fecal calprotectin and C-reactive protein gradually decreased from baseline to 18 weeks of therapy in both children and adults. Two-thirds of the physicians assessed the diet as showing good effectiveness and would continue the dietary therapy at each phase of the diet.

Conclusion: Many mild-to-moderate active CD patients may experience positive outcomes and have good experiences with the CDED + PEN dietary therapy and the associated Modulife patient support platform. This study might add valuable patient perspectives to the growing clinical use of CDED in managing CD.

Background: It is not clear that antiviral therapy for hepatitis C virus (HCV) after recovery from curative treatment for hepatocellular carcinoma (HCC) has an effect on suppressing recurrence or improving survival rates.

Objectives: We analyzed the impact of eradication by interferon (IFN)-free direct-acting antiviral (DAA) therapy on clinical outcomes of patients with HCV-associated HCC who underwent curative treatment.

Design: This was a retrospective study.

Methods: We retrospectively reviewed 109 consecutive patients with sustained virologic response with DAA therapy after HCC treatment and analyzed HCC recurrence and overall survival (OS). Among these patients are those with a history of HCC recurrence and curative HCC treatments administered as definitive HCC treatments prior to initiation of DAA therapy.

Results: Among 109 patients, 64 received DAA therapy after curative treatment for HCC; the remaining 45 received ⩾2 subsequent treatments for HCC. Cumulative HCC recurrence rates at 1, 3, and 5 years were 23%, 47%, and 56%, respectively. Multivariate analysis identified predictive factors for suppression of HCC recurrence as tumor number (hazard ratio (HR) 2.293 for multiple; p = 0.006) and number of HCC treatments before DAA therapy (HR 2.928 for ⩾2; p = 0.001). Among 64 patients who received curative treatment for HCC, cumulative first HCC recurrence rates at 1, 3, and 5 years were 12%, 34%, and 44%, respectively, second recurrence rates were 11%, 28%, and 39%, and third recurrence rates were 0%, 22%, and 53%, respectively; recurrence tended to be suppressed until 3 years. Cumulative OS rates at 3 and 5 years were 87% and 75%, respectively. On multivariate analysis, tumor number (HR 2.452 for single; p = 0.026) was the only independent predictor of OS.

Conclusion: DAA therapy after curative treatment for HCC suppresses HCC recurrence in the long term, but recurrence was higher in patients with a history of many HCC treatments.

Background: Managing extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) patients remains challenging due to considerable heterogeneity in diagnostic criteria and the lack of a standardised definition and validated diagnostic pathways. Delays in recognising and treating EIMs can lead to significant disease progression. Therefore, early detection and treatment are crucial.

Objectives: We aimed to assess the effectiveness of a dedicated immune-mediated inflammatory diseases (IMIDs) clinic in reducing EIM diagnostic delays and improving patients' outcomes.

Design: A single-centre observational study was conducted, including IBD patients presenting with EIMs red flags.

Methods: We compared the EIMs diagnostic delay between patients who attended a multidisciplinary IMID outpatient clinic (IMID-G) and those who attended individual referral specialists representing the standard outpatient clinic group (SOC-G). We further evaluated the impact of diagnostic timing on 18-month clinical outcomes, including therapeutic changes, steroid and immunosuppressant use and biological therapy switch/swap.

Results: We enrolled 238 IBD patients, 127 in the IMID-G and 111 in the SOC-G. The average time to EIM diagnosis was 2.48 ± 1.8 and 5.36 ± 2.3 months for the IMID and SOC-Gs (Δ = 2.88 months, p = 0.005). The majority of patients received a diagnosis of peripheral arthritis (IMID-G = 37.5%; SOC-G = 33.7%) and spondyloarthropathy (IMID-G = 32.1%; SOC-G = 33.7%). No significant difference was observed in the rates of EIMs between the two groups (88.2% in IMID-G vs 92.8% in SOC-G, p = 0.27). Regarding therapeutic changes, the IMID-G reported a mean time to the first therapeutic change driven by the specialist referral of 2.96 ± 1.8 months, compared to 6.09 ± 2.5 months in the SOC-G, showing a significant difference (p = 0.007). The IMID-G had a higher frequency of biological therapy switching/swapping and adding immunosuppressive treatment than the SOC-G (p = 0.008 and p = 0.04, respectively). Survival curves revealed a significant reduction in diagnostic delay and time to treatment in the IMID-G compared to the SOC-G (log-rank test, p < 0.001).

Conclusion: Attending a dedicated IMID clinic can enhance the diagnostic process for EIMs in IBD patients, thereby reducing diagnostic delays and allowing early interventions to avoid disease progression.

Background: The resection of large superficial esophageal neoplastic lesions (SENLs) presents significant challenges for traditional endoscopic submucosal dissection (ESD). Endoscopic submucosal tunnel dissection (ESTD) has emerged as an alternative that potentially reduces resection difficulty.

Objectives: We aimed to compare ESTD and ESD in the treatment of large SENLs.

Design: Meta-analysis of randomized controlled trials (RCTs).

Data sources and methods: We systematically searched MEDLINE, EMBASE, Cochrane Library, and Wanfang Data for RCTs comparing ESTD with ESD for large SENLs until July 1, 2024. The grading of recommendations assessment, development, and evaluation framework was used to assess the certainty of the evidence, whereas trial sequential analysis (TSA) was used to control for random errors and evaluate conclusion validity.

Results: Four RCTs involving 315 patients were included. The pooled analysis showed that ESTD was significantly faster than ESD (mean differences 5.06, 95% confidence interval: 3.31-6.80; p < 0.01; I ² = 0%; low certainty of evidence). TSA indicated a desired sample size of 162, with the cumulative Z curve crossing the trial sequential monitoring boundary. ESTD also had lower rates of major complications and post-operation esophageal stricture (low certainty of evidence). No significant differences were found in en bloc and curative resection rates.

Conclusion: With low certainty, ESTD appears superior to ESD for large SENLs, offering faster resection and fewer complications, with similar en bloc and curative resection rates.

Trial registration: This meta-analysis protocol was registered on PROSPERO (CRD42024520754).