Clinical and Translational Gastroenterology最新文献

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.

Introduction: The liver clock of hepatocytes is actively involved in regulating their proliferation, metabolism, oxidative stress response, and chronic liver disease (CLD) progression. However, the relationship between circadian rhythms and CLD remains poorly understood. This study aimed to examine the associations of circadian rhythms with metabolic dysfunction-associated steatotic liver disease, cirrhosis, and hepatocellular carcinoma.

Methods: This study included 94,006 participants from the UK Biobank. Circadian rhythms were assessed by a 7-day accelerometer by relative amplitude (RA), which indicates the difference between the most and least active periods. Cox regression and restricted cubic splines were used to evaluate the associations between circadian rhythms and CLD. Liver fat content and hepatic inflammation were additionally assessed using magnetic resonance imaging-measured proton density fat fraction and corrected T1 scores.

Results: During the follow-up of 9.8 years, individuals in the lowest quartile of RA had higher hazard ratios of 1.54 (95% CI: 1.32-1.78) for metabolic dysfunction-associated steatotic liver disease, 1.79 (95% CI: 1.38-2.32) for cirrhosis, and 1.65 (95% CI: 1.02-2.76) for hepatocellular carcinoma than those in the highest third quartile did. A dose‒response relationship between RA and CLD was observed ( P < 0.001). Furthermore, there was a joint and independent relationship between polygenic risk scores, RA, and the CLD. RA was negatively correlated with proton density fat fraction and corrected T1 scores, demonstrating a dose‒response pattern ( P < 0.001).

Discussion: Abnormal circadian rhythm is significantly associated with the risk of CLD, potentially due to increased liver fat content and hepatic inflammation. Therefore, disrupted circadian rhythms may be a risk factor for liver disease and represent a potential target for intervention.

Introduction: Heavy metals can increase perfluoroalkyl and polyfluoroalkyl substances (PFAS) adsorption. However, no research has examined the relationship of coexposure to PFAS and heavy metals in metabolic dysfunction-associated steatotic liver disease (MAFLD).

Methods: Data were obtained from the National Health and Nutrition Examination Survey database (2017-2018 cycle). The influence of PFAS and heavy metals on MAFLD or controlled attenuation parameter (CAP) was analyzed using logistic or linear regression, weighted quantile sum regression, and Bayesian kernel machine regression. A network of gene-gene interactions for the overlapping genes related to PFAS, heavy metals, and MAFLD was generated by GeneMANIA. The biological function of the overlapping genes was explored by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.

Results: The study analyzed 1,270 participants, with 36.378% of participants suffering from MAFLD. Perfluoromethylheptane sulfonic acid isomers (Sm-PFOS), Cd, and Se were identified as MAFLD risk factors (all P < 0.05). Positive associations were observed between perfluorononanoic acid, n-perfluorooctane sulfonic acid, Sm-PFOS, selenium, manganese, and CAP (all P < 0.05). Se, Pb, Sm-PFOS, and Mn played a significant role in the combined effect on both MAFLD and CAP. Bayesian kernel machine regression revealed a positive relationship of coexposure to PFAS and heavy metals on MAFLD or CAP. The top gene interaction type of 51 overlapping genes was coexpression (59.55%). Kyoto Encyclopedia of Genes and Genome results involved environmental information processing, human diseases, metabolism, and organismal systems.

Discussion: Perfluorononanoic acid, Sm-PFOS, Pb, Se, Mn, and Cd were associated with MAFLD or CAP. Reducing exposure to PFAS and heavy metals may help prevent MAFLD development or CAP increase.

Introduction: Elexacaftor-tezacaftor-ivacaftor (ETI) is a highly effective therapy for over 70% of people with cystic fibrosis (pwCF), improving lung disease, quality of life, and survival. The aim of this prospective study was to explore ETI's effects on the gastrointestinal manifestations of cystic fibrosis.

Methods: In this prospective cross-sectional study, performed in a single tertiary referral center for cystic fibrosis, clinical and laboratory data, intestinal ultrasound (IUS) findings, and pancreatic stiffness (2D-SWE) were assessed at baseline (T0) and during ETI treatment at 6 and 12 months (T6, T12). Abdominal pain, alterations in stool frequency, form, and consistency (diarrhea, constipation) were monitored.

Results: The participants were 86 pwCF (57% male, mean age 21.6 years) and 22 healthy controls enrolled for pancreatic stiffness comparison. IUS abnormalities (e.g., bowel wall thickening, inspissated intestinal contents, lymph node hypertrophy), and abdominal pain (63% at T0 to 2% at T12) significantly decreased ( P < 0.05). Constipation dropped from 7% at T0 to 0% at T12 and recurrent diarrhea from 77% to 9% ( P < 0.0001). Pancreatic stiffness normalized after 1-year treatment (T0: 4.21 vs T12: 5.7 kPa, P < 0.05). Body mass index increased (T0: 21.0 vs T12: 22.4 kg/m 2 , P < 0.001), and glycemic control improved, with reduced fasting glucose (T0: 97.8 vs T12: 86 mg/dL, P < 0.001) and hemoglobin A1c (38 vs 36 mmol/mol, P < 0.001). High-density lipoproteins cholesterol increased, whereas low density lipoprotein and triglycerides remained stable.

Discussion: ETI normalized IUS parameters and significantly improved pancreatic stiffness, gastrointestinal symptoms, glycemic control, and cholesterol metabolism in pwCF.

Introduction: Few studies have examined outcomes of laparoscopic cholecystectomy for acute cholecystitis in patients with heart failure (HF). This study was to assess the impact of HF on cholecystectomy outcomes.

Methods: Data from the United States Nationwide Inpatient Sample (NIS) from 2016 to 2020 were examined. Adults 20 years and older diagnosed with acute cholecystitis who underwent laparoscopic cholecystectomy were included. Patients were categorized into groups with and without pre-existing HF.

Results: Outcomes assessed included inhospital mortality, nonroutine discharge, length of hospital stay, total hospital cost, and complications. Propensity score matching at a 1:1 ratio was conducted to balance between-group characteristics. Associations between HF and the outcomes were determined using univariate and multivariable regression analyses. After propensity score matching, 11,646 patients were included in the analysis: 5,823 with HF and 5,823 without. Patients with HF had significantly elevated risks of inhospital mortality (adjusted odds ratio [aOR] = 2.14, 95% confidence interval [CI]: 1.44-3.17), nonroutine discharge (aOR = 1.80, 95% CI: 1.61-2.01), and complications (aOR = 1.51, 95% CI: 1.40-1.63). Patients with HF also had longer length of hospital stay (1.52 days, 95% CI: 1.45-1.60) and higher total hospital costs (16.64 thousand USD, 95% CI: 15.58-17.70). The outcomes of patients with HF were seen in those with HF reduced ejection fraction and HF with preserved ejection fraction.

Discussion: Patients with HF, either HF reduced ejection fraction or HF with preserved ejection fraction, have increased risk of adverse inpatient outcomes after laparoscopic cholecystectomy for acute cholecystitis. This emphasizes the importance of tailored perioperative care to optimize patient outcomes.

Introduction: The magnitude and modifiers of the association between acute pancreatitis (AP) and pancreatic cancer (PC) are unclear. This systematic review and meta-analysis aimed to quantify the occurrence of PC in AP, the association of PC after AP, and the impact of specific risk factors on PC diagnosis.

Methods: The systematic search was conducted in PubMed, EMBASE, and Central Register of Controlled Trial from inception until July 14, 2025 (PROSPERO: CRD42023470350). Eligible studies included adult populations reporting on the association between AP and PC. Primary outcomes included prevalence, incidence, and diagnosis of PC in individuals with AP, including subset analyses of specific clinical and demographic factors. Meta-analyses were performed using random-effects models to calculate pooled outcome measures and corresponding 95% confidence intervals (CI).

Results: A total of 61 studies were included. The prevalence of PC among AP patients was 2% (CI: 2%-4%). The time-dependent analysis revealed an increased hazard of PC in AP vs no AP: <24 months (HR: 31.94, CI: 9.35-109.09), 24-60 months (HR: 2.68, CI: 1.65-4.37), and >60 months (HR: 1.71, CI: 1.22-2.40). AP patients with subsequently diagnosed chronic pancreatitis (OR: 3.71, CI: 2.00-6.90), new-onset diabetes mellitus (OR: 2.22, CI: 1.02-4.84), idiopathic AP (OR: 2.97, CI: 1.44-6.13), and older than 50 years (OR: 4.04, CI: 2.73-5.97) showed significantly increased odds of having PC. We found no evidence for increased odds for PC with AP severity, smoking, and alcoholic and gallstone etiologies.

Discussion: Patients with AP have a higher likelihood of PC diagnosis, especially within the first 2 years. Although the association decreases with time, it remains significant long term. Newly diagnosed chronic pancreatitis, new-onset diabetes mellitus, idiopathic AP may further elevate the likelihood of PC diagnosis. PC diagnosed after AP tends to occur at a younger age, more often at an earlier stage, typically in the pancreatic head.

Introduction: Endoscopic removal of a bony foreign body is accompanied by risks, such as perforation. The use of a transparent cap attached to the tip of the endoscope has become an increasingly recommended technique for removing esophageal foreign bodies. However, its effectiveness specifically for bony foreign bodies remains uncertain, as does the optimal timing for cap application. This study aimed to investigate the effectiveness and the optimal timing of a transparent cap.

Methods: From January 1, 2010-May 30, 2025, patients with reported bony esophageal foreign body for endoscopic removal were retrospectively analyzed. The primary outcome was the technical failure rate of endoscopic removal of a bony foreign body.

Results: A total of 595 patients with bony esophageal foreign bodies underwent endoscopic removal during the study period: 216 underwent the transparent cap-assisted method and 379 underwent the conventional method. Among these foreign bodies, fish bones accounted for the majority (91.4%). The endoscopic failure rate of bony foreign body removal was lower in the cap-assisted group than in the conventional group (3.2% vs 7.9%, P = 0.022). Subgroup analysis demonstrated the incidence of esophageal erosions and ulcerations was higher in patients who underwent endoscopy withdrawal for capping than in those who received capping before the examination (58.5% vs 32.8%, P < 0.001).

Discussion: The use of a transparent cap is an effective method to reduce the technical failure rate for endoscopic removal of an esophageal bony foreign body. Applying the transparent cap before the start of the endoscopic examination reduced the complication rates.

Introduction: Biliary strictures present diagnostic challenges, necessitating early differentiation between benign and malignant cases. This study evaluates the diagnostic value of biliary and serum carcinoembryonic antigen (SCEA, BCEA) and carbohydrate antigen 19-9 (BCA19-9, SCA19-9) to enhance diagnostic accuracy.

Methods: A single-center retrospective cohort study enrolled 268 endoscopic retrograde cholangiopancreatography-treated patients, divided into training (n = 160) and validation (n = 108) sets. Levels of SCEA/SCA19-9 and BCEA/BCA19-9 were measured, and a combined diagnostic model was developed using receiver operating characteristic analysis and logistic regression. A meta-analysis of 7 studies assessed pooled odds ratios and heterogeneity in marker detection.

Results: BCEA and BCA19-9 levels significantly exceeded serum levels, with the combined model achieving an area under the curve of 0.921 (training) and 0.911 (validation), sensitivity 85.0%-83.3%, and specificity 83.7%-87.0%. Meta-analysis demonstrated a pooled odds ratio of 25.65, sensitivity of 95.0%, and specificity of 83.7%. CA19-9 cutoff variations had an insignificant impact, and the model improved pre-endoscopic retrograde cholangiopancreatography diagnostic accuracy by 20.7%.

Discussion: BCEA and BCA19-9 exhibit superior expression levels and diagnostic efficacy in distinguishing benign and malignant biliary strictures. The multimarker model enhances diagnostic performance, suggesting the relevance of integrating serum and biliary markers for accurate differentiation. Future studies should focus on optimizing cutoff values for enhanced diagnostic precision.

Introduction: Indomethacin is often used experimentally to induce intestinal hyperpermeability, enabling evaluation of interventions targeting barrier function.

Methods: We conducted a randomized, double-blind, placebo-controlled study (NCT05538247) in healthy volunteers to assess whether a supplement could mitigate indomethacin-induced hyperpermeability. Participants received 150 mg/d of indomethacin for 6 days, either before or during placebo/supplement administration. Permeability was measured using 13 C-mannitol and lactulose urinary excretion.

Results: Contrary to expectations, indomethacin failed to increase 13 C-mannitol excretion in either group. No meaningful elevations in serum (zonulin, claudins) or fecal (calprotectin) biomarkers were observed.

Discussion: Our findings suggest that the expected increase in intestinal permeability after indomethacin administration may not be consistently observed in healthy volunteers. These results highlight the need to carefully consider the reproducibility and sensitivity of this model in future clinical studies aiming to investigate gut barrier function.

Introduction: Celiac disease (CD) may affect quality of life (QoL), health care use, and societal costs in various ways both before and after diagnosis. However, detailed evidence remains limited about how costs and QoL change after diagnosis and which patient characteristics (e.g., symptom duration) influence those changes. The aim of this study was to evaluate CD patients' QoL and societal costs before and after diagnosis.

Methods: In this cross-sectional study, 2,691 patient-members of the Dutch Celiac Society completed a questionnaire about their life before and after diagnosis. Data collection included sociodemographic and clinical characteristics, health care use, non-health care costs, and QoL (measured using the EuroQol 5-Dimension 5-Level). Mean QoL and annual health care and societal costs were compared prediagnosis and postdiagnosis. Multivariate regression models were used to identify factors associated with QoL and costs in both periods (and difference between periods).

Results: On average, respondents recalled experiencing 4-5 symptoms before diagnosis. QoL improved significantly postdiagnosis, with greater improvements among childhood diagnoses. Annual health care and societal costs decreased by 23% and 36%, respectively, postdiagnosis, except for societal costs in those diagnosed during childhood. Age at diagnosis and the number of prediagnosis symptoms were associated with lower and higher recalled prediagnosis QoL, respectively. Number of symptoms, comorbidities, and nonadherence to a gluten-free diet were associated with lower postdiagnosis QoL.

Discussion: After CD diagnosis, QoL significantly improved and health care and societal costs decreased, except for societal costs among childhood diagnoses. These findings enhance the understanding of CD's burden and economic impact, supporting health care and policy efforts for timely CD identification.