Clinical and Translational Gastroenterology最新文献

Abstract: Gastric varices present a unique therapeutic challenge for endoscopists. Although 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 is the standard for diagnosis and staging. Although early access to endoscopic ultrasound (EUS) may enable timely systemic therapy and improve resectability, uncertainty remains regarding how delays to EUS affect 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 or older 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 2 outcomes: (i) pancreatic surgical resection and (ii) 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 (adjusted odds ratio 1.65, 95%CI 1.09-2.51), whereas those with more comorbidities were less likely (adjusted odds ratio 0.95, 95%CI 0.90-0.99). Delayed EUS was associated with a lower likelihood of surgery (hazard ratio [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).

Discussion: 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.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease, yet extrametabolic contributors such as oral health remain underexplored. While periodontitis has been linked to nonalcoholic fatty liver disease, untreated caries and unmet dental care needs have been less examined under new MASLD criteria. We evaluated associations between examiner-assessed oral health indicators and MASLD in a nationally representative sample of US adults.

Methods: We analyzed 2,528 adults aged 18 years or older from the 2017-2020 National Health and Nutrition Examination Survey with valid liver transient elastography. MASLD was defined as steatosis (controlled attenuation parameter ≥285 dB/m) plus ≥1 metabolic risk factor. Examined oral health indicators included examiner-assessed need for dental care, decayed teeth, gum disease, and a composite of decayed teeth or gum disease. Survey-weighted logistic regression estimated odds ratios (ORs) adjusted for sociodemographic and behavioral factors.

Results: MASLD prevalence was 38.9%. In fully adjusted models, needing dental care (OR = 1.42, 95% CI: 1.02-1.95) and having decayed teeth (OR = 1.52, 95% CI: 1.05-2.20) were associated with higher MASLD odds. After false discovery rate correction, only dental care need remained significant (q = 0.043). Sex-stratified analyses revealed pronounced associations in women, who had 91% higher MASLD odds if dental care was needed (OR = 1.91, 95% CI: 1.18-3.10) and 156% higher odds with decayed teeth (OR = 2.56, 95% CI: 1.35-4.84). Significant associations were also observed in adults aged 45-59 and 60 years or older.

Discussion: Unmet dental needs and caries are associated with MASLD, with particularly strong associations observed in women. These findings highlight oral health as a potential marker for MASLD risk and underscore the value of integrated oral-systemic assessments in preventive care.

Introduction: Calculating detection rates using data from colonoscopies for all indications, rather than screening examinations, is simpler and can mitigate gaming by endoscopists. We hypothesized that calculating sessile serrated lesion detection rates (SSLDR-A) using all examinations may also be a quality metric for predicting postcolonoscopy colorectal cancer (PCCRC) risk.

Methods: The cohort included New Hampshire Colonoscopy Registry 115,762 patients with an index colonoscopy. The primary outcome was PCCRC, defined as colorectal cancer (CRC) diagnosed ≥6 months after the index colonoscopy. The exposure variables were endoscopist-specific SSLDR-A (using all examinations) and SSLDR-S (using screening examinations), stratified into quintiles. Cox regression was used to model the hazard of PCCRC on SSLDR, adjusting for relevant covariates, such as patient age and sex.

Results: There were 177 PCCRCs diagnosed in 115,762 patients with index colonoscopies. Higher SSLDR-A and SSLDR-S rates were associated with lower PCCRC risks. After adjusting for covariates, we observed that higher SSLDR-A rates were associated with lower hazard ratios (HRs) as compared with the reference group (SSLDR-A: <1.5%; HR = 1.0 vs SSLDR-A: 1.5% to <3.0%; HR = 0.53, 95% CI 0.35-0.79; SSLDR-A: 3.0% to <5.0%; HR = 0.59, 95% CI 0.38-0.92; SSLDR: 5.0% to <8.0%; HR = 0.44, 95% CI 0.28-0.70; and SSLDR: 8.0+%; HR = 0.20, 95% CI 0.08-0.46). The highest quintile of SSLDR-A (8.0%+) (HR = 0.20, 95% CI 0.08-0.46) and SSLDR-S (8.0%+) (HR = 0.20, 95% CI 0.09-0.44) provided similar protection from PCCRC.

Discussion: These findings demonstrate that colonoscopies performed by endoscopists with higher SSLDR-A are associated with a lower risk of PCCRC, validating SSLDR-A as a quality metric. Furthermore, our data suggest that endoscopists should aim for an SSLDR-A of 6% and have an aspirational SSLDR-A of 8.0% or higher.

Introduction: Limited data exist regarding the portal hypertension progression in cirrhotic patients with variceal bleeding as the initial decompensation event. This study evaluated the impact of sequential endoscopic therapy on long-term clinical outcomes.

Methods: 196 hospitalized cases were included and divided into esophageal varices (EV), type 1 gastroesophageal varices (GOV1), type 2 GOV (GOV2), and type 3 GOV (GOV3) groups. The Fine-Gray test was used to analyze the cumulative incidence of outcome events. Survival was calculated using the Kaplan-Meier method, and the Cox proportional risk regression model was used for multivariate analysis of factors affecting outcomes.

Results: During a median follow-up period of 104.9 months, distinct cumulative outcomes were observed across esophageal and gastric variceal subtypes. The 1-, 3-, and 5-year cumulative rebleeding rates progressively increased across subtypes: EV (16.2%, 29.7%, 41.9%), GOV1 (18.8%, 39.6%, 45.8%), GOV2 (19.1%, 34.0%, 46.8%), and GOV3 (44.4%, 63.0%, 66.7%) (Gray test, P = 0.009). Corresponding survival rates demonstrated an inverse pattern, declining with longer follow-up: EV (91.9%, 82.4%, 58.1%), GOV1 (91.7%, 79.2%, 60.4%), GOV2 (91.5%, 76.6%, 55.3%), and GOV3 (74.1%, 55.6%, 48.1%) (log-rank test, P = 0.016). Rebleeding was an independent risk factor associated with survival (hazard ratio: 3.518, P < 0.001). Multivariate analysis showed that variceal shape, variceal type, and the treatment courses to variceal eradication (whether > 3) were significant risk factors for rebleeding ( P < 0.05).

Discussion: In this study, rebleeding dominated the clinical course of different subtypes and was an independent predictor of death. More aggressive treatments, such as salvage transjugular intrahepatic portosystemic shunt, should be considered in patients who were at higher risk of rebleeding.

Introduction: Early detection of pancreatic ductal adenocarcinoma (PDAC) improves survival. However, screening recommendations are limited to individuals with hereditary risk, accounting for only 10% of PDAC. We explore the feasibility of developing and validating an electronic health record-based model to identify high-risk individuals for PDAC screening within the asymptomatic general population.

Methods: Using multivariable Cox regression, we developed a diagnostic model to predict time to PDAC within 3 years in the Veterans Health Administration. We evaluated the final model using internal and temporally separate data sets using Akaike Information Criterion, Harrell c statistic, calibration curves, and sensitivity/specificity corresponding to a 3-year risk screening threshold of 1%.

Results: Among 9,351,261 individuals, 26,119 (0.3%) developed PDAC (107.6 cases per 100,000 person-years) within 3 years. The final model included age, pancreatic cyst, pancreatitis, smoking status, history of a localized solid tumor, race/ethnicity, and body mass index. Glucose and albumin values were highly important, in addition to other metabolic, inflammatory, and liver-related laboratory values. The c statistic (95% CI) was 0.75 (0.75-0.76) in development, 0.75 (0.75-0.76) in internal validation, and 0.74 (0.73-0.75) in temporal validation. At a 3-year risk threshold of 1.0%, 11% of the population would undergo screening, capturing 30% of the PDAC cases.

Discussion: We demonstrate good model discrimination in independent data. Compared with current screening practices targeting only genetically predisposed individuals, its implementation could identify 3 times as many PDAC cases. However, predictors beyond the electronic health record (EHR) may be needed to further improve the feasibility of generalized screening.

Introduction: Over one-third of people are not up-to-date with colorectal cancer (CRC) screening, and blood-based tests offer a promising alternative to existing options. We used conjoint analysis to quantify the proportion of people who would prefer a hypothetical blood test over current methods (e.g., fecal immunochemical test, multitarget stool DNA test, colonoscopy).

Methods: We conducted a conjoint analysis survey in a US nationally representative sample of average risk individuals aged 40-75 years who were not up-to-date with CRC screening. We performed latent class analysis to identify groups with similar decision-making profiles and estimated the proportion who would prefer a blood test every 3 years over existing methods.

Results: Overall, 1,009 participants completed the survey. Using latent class analysis, we identified 2 distinct groups: (i) prioritized how the test is performed-39.4%, and (ii) prioritized the accuracy of detecting CRC and advanced adenomas-60.6%. Through simulations using the conjoint data, most individuals in the first group preferred a blood test every 3 years (65.1%), whereas 53.0% of the second group also favored the blood test. In additional simulations that incorporated test accuracy for CRC and advanced adenoma detection, these performance characteristics emerged as important drivers of screening preferences across the different testing options.

Discussion: Among individuals not up-to-date with CRC screening, our findings suggest that many would generally prefer a blood-based screening test over other options, but preference may depend on test accuracy. Offering a blood test option may improve CRC screening uptake, particularly among individuals who are unscreened or overdue for screening.

Introduction: The Donor Risk Index (DRI) is a widely used liver transplant allograft risk model but does not account for the increasing adoption of machine perfusion (MP).

Methods: Using Bayesian updating, we incorporated MP into the DRI framework (DRI-MP). A Bayesian proportional hazards model with informative priors derived from the original DRI was applied to Organ Procurement and Transplantation Network data from January 2022 to June 2024. Model performance was assessed using Harrell Concordance-statistic, calibration plots, and Brier scores.

Results: DRI-MP, defined as DRI × 0.7 for MP cases, improved 90-day graft survival discrimination (Harrell Concordance-statistic: = 0.546 vs 0.535, P = 0.040), while maintaining robust calibration.

Discussion: The Bayesian-updated DRI-MP modestly improves donor risk discrimination, reflecting contemporary transplant practice and providing an implementable tool with continuity from the original DRI.

Introduction: The aim of treat-to-target (T2T) algorithms in inflammatory bowel disease was to maximize the benefit of medical therapies by establishing a framework for disease activity assessment to guide therapeutic decisions. There are limited data on adoption rates of T2T monitoring in real-world practice. We aimed to describe rates of T2T monitoring, predictors of completion, and associations with clinical outcomes.

Methods: A retrospective cohort study was conducted from 2015 to 2021 of individuals with inflammatory bowel disease starting new biologic or small molecule therapy within a multistate healthcare system. The completion of biochemical monitoring including fecal calprotectin or C-reactive protein and structural monitoring including endoscopy or enterography, or both, was assessed between 3 and 6 months and 6 and 12 months, respectively. Healthcare utilization (HCU), defined as emergency department visits, hospitalizations, prednisone prescriptions, or abdominal surgery within 2 years, was also assessed.

Results: A total of 823 patients were included in the cohort, and 127 (15.4%) completed some form of T2T monitoring. Twenty-two patients (2.7%) completed both biochemical and structural monitoring. The completion of T2T was not associated with lower HCU. The completion of only biochemical T2T, but not structural or both biochemical and structural T2T, was associated with decreased 12-month medication persistence (hazard ratio 0.36, 95% confidence interval 0.17-0.75). The completion of just structural T2T (hazard ratio 1.59, 95% confidence interval 1.05-2.39) was associated with higher HCU.

Discussion: In this retrospective cohort of individuals initiating new therapy, the rates of T2T monitoring were low. The completion of all T2T was not associated with lower HCU. The completion of only biochemical T2T monitoring was associated with lower 12-month medication persistence and only structural T2T with higher HCU.

Introduction: Sound speed correction endoscopic ultrasound (SSC-EUS) is a novel imaging technique with limited previous validation. The aim of this study was to evaluate the diagnostic efficacy of SSC-EUS for solid pancreatic lesions (SPL) and compare it with B-mode endoscopic ultrasound (B-EUS), elastography endoscopic ultrasound (EG-EUS), and contrast-enhanced endoscopic ultrasound (CE-EUS).

Methods: A prospective, single-blind, randomized trial included 240 patients with computed tomography/magnetic resonance imaging-confirmed SPL (solid portion >80% of lesion volume). Participants were equally divided into 4 groups (B-EUS, EG-EUS, CE-EUS, and SSC-EUS). Diagnostic thresholds were determined through receiver operating characteristic curves. Subgroup analyses assessed the impact of lesion location (head/body/tail), tumor size (≤3 vs >3 cm), and cancer stage (I/II vs III/IV). Statistical analysis used SPSS 23.0 and GraphPad Prism 8.

Results: Among 240 patients, 138 (57.5%) had malignant lesions. SSC-EUS achieved optimal diagnostic performance at a cutoff sound speed of 1,563 m/s (area under the receiver operating characteristic curve = 0.822, sensitivity = 82.8%, specificity = 78.9%, accuracy = 81.7%). CE-EUS demonstrated the highest overall efficacy (sensitivity = 90.3%, specificity = 82.8%, accuracy = 86.7%), followed by SSC-EUS and EG-EUS, both outperforming B-EUS (accuracy = 70.0%). Subgroup analysis revealed superior sensitivity for pancreatic body lesions (SSC-EUS: 87.5%; CE-EUS: 90.0%), tumors >3 cm (SSC-EUS: 84.2%; CE-EUS: 90.0%), and stage III/IV cancers (SSC-EUS: 81.8%; CE-EUS: 90.9%). EG-EUS strain ratio (cutoff = 4.44) showed limited accuracy (61.7%), whereas elastic strain value A (cutoff = 0.065%) exhibited moderate utility (accuracy = 75.0%).

Discussion: CE-EUS remains the most effective imaging modality for SPL diagnosis. SSC-EUS demonstrates comparable accuracy with EG-EUS and is particularly advantageous for larger tumors (>3 cm) and advanced-stage malignancies. EG-EUS strain ratio lacks clinical robustness, whereas elastic strain value A warrants further validation. Tailoring imaging method selection to lesion characteristics (location, size, and stage) may optimize diagnostic outcomes.