Clinical and Translational Gastroenterology最新文献

Introduction: Dairy consumption has been linked to the development of autoimmune diseases. We aimed to examine the association between dairy intake and risk of incident inflammatory bowel disease (IBD).

Methods: We conducted a prospective cohort study of 197,763 participants without a baseline diagnosis of IBD in 1986 in Nurses' Health Study (NHS), 1991 in Nurses' Health Study II (NHSII), and 1986 in Health Professionals Follow-up Study (HPFS). Data on dairy intake were collected every 2-4 years using a validated semi-quantitative food frequency questionnaire and modeled according to quintiles for total intake and quartiles for components of dairy. We used Cox proportional hazard modeling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).

Results: Through the end of follow up in 2016 in NHS and HFPS, and 2017 in NHSII, we documented 347 Crohn's disease (CD) cases and 428 cases of ulcerative colitis (UC). In our primary analysis, we observed an inverse association between baseline dairy intake (Ptrend=0.04) and risk of UC (aHR of 0.72 (95%CI 0.52-1.00 comparing extremes of quintiles). Among dairy components, baseline yogurt consumption (HR=0.70; 95%CI 0.5-0.99; Ptrend=0.05) was most strongly associated with decreased risk of UC. There was no consistent association between dairy intake and risk of CD.

Conclusion: In three large prospective cohort studies, we observed a suggestive inverse association between baseline dairy intake, particularly from yogurt, and risk of UC. Future studies are needed to confirm these results.

Introduction: Disruptions to colorectal cancer (CRC) screenings occurred during the COVID-19 pandemic, but lingering effects and equity of this impact remain unclear. We evaluated local patterns and trends in CRC screening and cancer staging across four time periods and examined disparities by neighborhood social deprivation index (SDI).

Methods: Colonoscopies, fecal immunochemical test (FIT), fecal occult blood test (FOBT), and sigmoidoscopies, were identified at our institution through the electronic medical record from March 2018 to February 2023 (n=27,946). Screenings were linked to zip code-level SDI and aggregated by month across 4 periods: pre-pandemic (March 2018-February 2020), pandemic (March 2020-February 2021), post-pandemic year 1 (March 2021-February 2022), and post-pandemic year 2 (March 2022-February 2023). ANOVAs compared monthly screening volumes and proportions from high-SDI areas across periods; chi-square tests assessed differences in cancer staging.

Results: CRC screenings dropped during March-May 2020 but rebounded, resulting in no significant difference in monthly averages across periods (p =0.52). However, colonoscopies declined, whereas FIT use increased over time. The proportion of patients from high-SDI neighborhoods declined from 32.2% pre-pandemic to 28.9% by post-pandemic year 2 (p=0.002), largely driven by reduced FIT screenings among individuals from these areas (30.9% to 23.7%, p<0.0001). Later-stage diagnoses increased during the pandemic and post-pandemic year 1 but returned to baseline by year 2.

Conclusion: Despite volume recovery, shifts in modality use and declining representation from high-SDI neighborhoods suggest growing disparities in CRC screening. Targeted outreach is needed to understand and address unmet screening needs, to support equitable prevention efforts moving forward.

Background: Gastric cancer (GC) is one of the most prevalent and lethal gastrointestinal malignancies. MutS homolog 2 (MSH2), a DNA mismatch repair protein, has emerged as a promising prognostic biomarker. However, traditional histopathological evaluation is limited by restricted fields compared with whole-slide imaging. This study aimed to investigate whether machine learning-derived digital pathomics features could predict MSH2 expression and clinical outcomes in GC.

Methods: Hematoxylin and eosin-stained whole-slide images from 234 patients were analyzed to extract quantitative pathological features. A pathomics score (PS) was developed to estimate MSH2 expression. The association between PS and overall survival (OS) was assessed using univariate and multivariate Cox regression. Survival differences between high- and low-PS groups were evaluated using Kaplan-Meier analysis. Functional enrichment and immune infiltration analyses were performed to explore potential biological mechanisms.

Results: Digital image analysis identified pathomics features associated with MSH2 expression. The PS served as a surrogate marker for MSH2 and effectively stratified patients into prognostic subgroups with significant different OS. High PS was associated with features suggestive of a stronger anti-tumor immune response, whereas low PS was linked to an immunosuppressive microenvironment.

Conclusion: The machine learning-derived pathomics signature shows potential in predicting MSH2 expression. It can serve as a complementary research tool and provide clinically meaningful prognostic information for GC.

Objectives: US guidelines recommend surveillance colonoscopy following polyp removal, but stool testing may offer a more efficient, acceptable strategy for patients with non-advanced lesions. We conducted exploratory analyses to evaluate the diagnostic accuracy of quantitative FIT results to diagnose advanced colorectal neoplasia (ACN) in patients undergoing surveillance colonoscopy.

Methods: We classified patients by prior colonoscopy findings as having low, intermediate, or high risk polyps. We compared the diagnostic performance for detecting ACN at an optimal cutoff identified by the Youden index versus the standard cutoff of 100 ng/mL. We also estimated cumulative sensitivity and specificity for serial FIT testing in patients with non-advanced findings.

Results: Among the 449 participants (mean ± SD age 65.4 ±7.1, 53.2% female, and 92.7% white), the median interval between colonoscopies was 5.0 years (IQR 3.5, 5.6); adequate or better bowel prep was achieved in 89.3% and cecal intubation in 98.4%. We detected 55 advanced-precancerous lesions (APL), but no cancers. For patients with prior non-advanced lesions (n = 378), the optimal cutoff was 26 ng/mL. Compared with the standard cutoff, the optimal cutoff increased sensitivity (14.3% to 35.7%, p <0.01) but reduced specificity (95.5% to 79.2%, p <0.01). Estimated cumulative sensitivity across 3 rounds of FIT testing was 73.4% at the optimal cutoff versus 37.1% with the standard cutoff.

Conclusions: Lowering the FIT hemoglobin cutoff markedly improved sensitivity for detecting APL in patients without prior advanced polyps. Serial testing could further enhance detection. FIT-based surveillance should be further evaluated as a potential strategy to prioritize, delay, or replace colonoscopy.

Introduction: Crohn´s disease is associated with varying degrees of mesenteric adipose tissue (MAT) hypertrophy. The study aimed to evaluate whether MAT hypertrophy, measured by MAT volume, is associated with worse response to anti-TNF-α therapy in biologic-naïve CD patients.

Methods: A cohort of consecutive CD patients who underwent computed tomography (CT) or magnetic resonance imaging (MRI) before the start of the anti-TNF-α therapy was included. Total MAT volume, excluding large vessels, was estimated. Primary outcomes - dose intensification, surgery, and withdrawal of anti-TNF-α therapy - were evaluated at 3 and 12 months after the initiation of treatment. We performed a multivariate logistic regression model to identify MAT volume as an independent risk factor for poor response to anti-TNF-α.

Results: 50 biologic-naïve, consecutive CD patients were included. The median MAT volume was 559.5 cm3 (IQR: 410.3-891.9). MAT volume was positively correlated with weight (ρ = 0.66, p < 0.001) and age (ρ = 0.5, p < 0.001). Multivariate regression model showed that higher MAT volume independently predicted a poor response to anti-TNF-α treatment, as indicated by a greater need for dose intensification of anti-TNF-α agents within 12 months (adjusted odds ratio (ORa): 1.36; 95% CI: 1.08-1.81; p = 0.016) and an increased risk of CD surgery within 3 months (ORa: 1.65; 95% CI: 1.08-3.05; p = 0.048).

Conclusions: MAT volume predicted an increased need for anti-TNF-α dose intensification and surgery in biological-naïve Crohn's disease. MAT volume could be a valuable measure for identifying patients at risk of a poor anti-TNF-α response.

Background: The value of esophageal baseline impedance (BI) in assessing proximal reflux and laryngopharyngeal symptoms (LPS) is unclear.

Methods: 208 patients with LPS underwent 24-hour combined hypopharyngeal-esophageal impedance-pH monitoring. Proximal/distal BI were obtained and a slope-and-intercept model of proximal BI contour was constructed.

Results: Proximal BI correlated with proximal/pharyngeal reflux (r=-0.21, p<0.01) and reflux symptom index (r=-0.14, p=0.08). Proximal BI contour model incorporating both BI change (slope) and BI just below upper esophageal sphincter (intercept) outperformed models using individual BI measures in predicting proximal (AIC: 110 vs 251-253) or pharyngeal (AIC: 32 vs 141-148) reflux.

Conclusion: Proximal esophageal impedance contour predicts proximal reflux n patients with LPS.

Introduction: Anti-integrin αvβ6 (anti-αvβ6) autoantibodies serve as a diagnostic biomarker and are associated with poor prognosis in ulcerative colitis (UC). We aimed to investigate whether anti-αvβ6 autoantibody levels predict treatment outcomes of advanced therapies in patients with moderately to severely active UC.

Methods: Anti-αvβ6 autoantibody levels were measured using prospectively collected serum samples at the initiation of advanced therapies. The primary outcome was treatment persistence up to one year; secondary outcomes included clinical remission rates at weeks 2, 6, 14, 24, and 48, comparing low- and high-level groups stratified by an optimal cutoff from receiver operating characteristic analysis.

Results: A total of 144 patients were analyzed (121 [84.0%] with extensive colitis and 87 [60.4%] with prior exposure to advanced therapies). The median observation period was 10 months, and treatment discontinuation occurred in 70 patients (48.6%). Treatment persistence was significantly higher in the low-level group (log-rank test, p = 0.002), and multivariable Cox analysis identified low antibody levels as the only independent predictor (hazard ratio, 1.90; 95% confidence interval, 1.09-3.32). Clinical remission rates were consistently higher in the low-level group throughout all time points, with the greatest difference at week 6 (47.5% vs. 20.0%; chi-square test, p = 0.003). Low antibody levels remained an independent predictor of remission at all time points.

Discussion: Anti-αvβ6 autoantibodies predicted both treatment persistence and clinical remission following advanced therapies, highlighting their potential as a predictive biomarker in patients with active UC.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a significant contributor to morbidity and mortality, linked to adverse cardiovascular outcomes. While extensive research highlights the cardiovascular burden in non-lean MASLD, lean MASLD remains comparatively understudied. To address this gap, our study evaluates cardiovascular outcomes in lean MASLD compared to non-lean MASLD.

Methods: This is a retrospective cohort study of patients with MASLD identified in the multi-institutional database, TriNetX. Lean MASLD was defined as a BMI <25 kg/m2. Leveraging 1:1 propensity score matching, we balanced baseline characteristics, including age, gender, comorbidities, laboratory values, and medication use. Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular events, cerebrovascular outcomes, new onset heart failure, and all-cause mortality over 1-, 3-, 5-, and 7-year follow-up.

Results: After matching, there were 67,519 patients in both groups. At 7-year follow-up, lean patients with MASLD demonstrated significantly higher rates of new onset heart failure compared to non-lean patients with MASLD (HR: 1.23 (95% CI: 1.16-1.31, p<0.0001), composite cardiovascular events (HR: 1.21 (95% CI: 1.13-1.30, p<0.0001)), cerebrovascular events (HR: 1.33 (95% CI: 1.24-1.43, p<0.0001)), and all-cause mortality (HR: 1.48 (95% CI: 1.38-1.59, p<0.0001)). These increased risks were noted at 1-, 3-, and 5-year follow-up.

Conclusion: Patients with lean MASLD are at significantly higher risks of cardiovascular events and all-cause mortality compared to non-lean patients with MASLD. Further research is needed to clarify the underlying pathophysiology and develop tailored interventions to improve outcomes for this growing population.

Abstract: Gastric varices present a unique therapeutic challenge for endoscopists. While the use of direct endoscopic cyanoacrylate glue injection is superior to band ligation, it carries a risk of systemic adverse events. This led to the development of endoscopic ultrasound (EUS)-guided therapy. EUS enables accurate measurement and targeting of vessels, allowing for the precise intravascular delivery of cyanoacrylate and/or coils. Doppler imaging can be used to confirm obliteration in real time. In this review, we highlight recent literature on varying embolization techniques and detail the technical considerations required for a successful EUS-guided approach.

Introduction: Pancreatic cancer is among the most aggressive malignancies, with a 5-year survival rate of 10%. Most patients present with advanced disease, limiting curative treatment options. Endoscopic ultrasound with fine-needle biopsy (EUS-FNB) is the standard for diagnosis and staging. While early access to EUS may enable timely systemic therapy and improve resectability; uncertainty remains regarding how delays to EUS impact surgical resection rates and overall survival, particularly in older adults. We aimed to identify factors associated with delayed EUS and to evaluate its impact on surgical resection and overall survival.

Methods: Using national Medicare claims (2011-2020), we conducted a retrospective cohort study of beneficiaries aged ≥66 years with newly diagnosed pancreatic cancer The index date was the most recent claim for a pancreatic lesion or abnormal liver enzymes, serving as the indicator for EUS referral. Delay to EUS was defined as >30 days between the index date and the EUS procedure. Multivariable logistic regression identified sociodemographic and clinical factors associated with delayed EUS. Cox proportional hazards models estimated the associations between delayed EUS and two outcomes: (1) pancreatic surgical resection and (2) all-cause mortality.

Results: Among 2,843 patients, 586 (20.6%) experienced a delay in EUS, 774 (27.2%) underwent surgery, and 1,591 (56.0%) died. Black patients were more likely to experience delay (aOR 1.65, 95%CI 1.09-2.51), while those with more comorbidities were less likely (aOR 0.95, 95%CI 0.90-0.99). Delayed EUS was associated with a lower likelihood of surgery (HR 0.73, 95%CI 0.61-0.88) but lower mortality (HR 0.58, 95%CI 0.50-0.66). Mortality increased with older age (HR 1.43, 95%CI 1.27-1.61) and comorbidity (HR 1.04, 95%CI 1.02-1.07).

Conclusions: Timely EUS was associated with higher surgical resection rates, suggesting earlier access to curative treatment. Lower mortality among patients with delayed EUS possibly reflects disease severity confounding rather than benefit.