Translational gastroenterology and hepatology最新文献

Background and objective: Gastrointestinal (GI) cancers represent a substantial global health burden due to their high morbidity and mortality rates. These cancers are often diagnosed at advanced stages, leading to poor prognosis and limited treatment options. Early detection and personalized treatment strategies are critical to improving outcomes, yet traditional diagnostic methods, such as tissue biopsies and imaging, often fall short in sensitivity, specificity and the ability to capture tumor heterogeneity. Circulating tumor DNA (ctDNA), which comprises small fragments of tumor-derived DNA shed into the bloodstream, has emerged as a transformative tool in the diagnosis and management of GI cancers. This review aims to summarize the clinical and utility of ctDNA in GI cancers and highlight areas for future research.

Methods: This narrative review integrates findings from recent studies evaluating ctDNA in GI malignancies. In doing so, we searched PubMed/MEDLINE, Google Scholar, ClinicalTrials.gov, and the Cochrane Library between October 1, 2024 and August 5, 2025. Eligible studies were restricted to English-language articles without geographic limitations to the USA.

Key content and findings: ctDNA enables non-invasive, real-time monitoring of tumor burden, treatment response, and resistance mechanisms, making it a valuable tool for precision oncology. Evidence supports its use across colorectal, pancreatic, hepatobiliary, and esophageal cancers, with the most established role in colorectal cancer. While ctDNA offers potential to improve patient outcomes, challenges remain, including technical limitations, variability in detection methods, and issues related to cost and standardization.

Conclusions: ctDNA is a promising biomarker in GI oncology, with potential to advance early detection, treatment monitoring, and prognostication. A clearer understanding of existing limitations will be critical to unlocking its full potential and establishing ctDNA as a reliable tool in the management of GI cancers.

Background: Hepatocellular carcinoma (HCC) with right atrial tumor thrombus (RATT) carries a poor prognosis with limited therapeutic options. This case report demonstrates that multimodal therapy combining hepatic arterial infusion chemotherapy (HAIC), targeted immunotherapy, and anticoagulation can achieve durable clinical responses in this challenging condition.

Case description: We describe two male patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) and RATT. The first case, a 67-year-old man, presented with extensive tumor thrombus extending to the right atrium. He was treated with a combination of HAIC (FOLFOX), lenvatinib, pembrolizumab, and nadroparin anticoagulation. Follow-up imaging after two months showed complete radiographic resolution of the RATT and marked regression of the intrahepatic lesion. The second case, a 63-year-old man with a history of hepatitis B, developed RATT after progressing on initial systemic therapies. He was subsequently treated with seven cycles of HAIC (FOLFOX) combined with sintilimab, bevacizumab, and peri-procedural anticoagulation. This resulted in a substantial reduction of the intracardiac thrombus. This patient maintained stable disease for 4 years since his initial HCC diagnosis, with the RATT remaining stable for 3 years.

Conclusions: Multimodal therapy integrating HAIC with targeted immunotherapy and anticoagulation achieved exceptional tumor control in these HCC-RATT cases. This approach warrants further investigation to optimize protocols and improve outcomes in this difficult-to-treat population.

Background: Drug-induced liver injury (DILI) is a known significant adverse effect of pirfenidone and nintedanib, essential antifibrotic agents for idiopathic pulmonary fibrosis (IPF). However, real-world evidence on the risk profiles is limited. We aimed to describe the clinical profiles and identify risk factors for antifibrotic DILI in real-world practice to inform risk mitigation strategies.

Methods: A retrospective case-control study was conducted among patients receiving pirfenidone at our tertiary hospital between October 2011 and December 2022 (approval No. ES-2024-K064-01). Hepatic safety signals were also evaluated through disproportionality analysis of the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) using reporting odds ratios (RORs).

Results: For pirfenidone, among 3,199 treated patients, 63 (3.18%) developed DILI, typically within two weeks of therapy initiation. Significant risk factors included body mass index (BMI) ≤23.9 kg/m² [odds ratio (OR) =7.32, P<0.001], ≥4 comorbidities (OR =7.18, P<0.001), pre-existing liver disease (OR =3.31, P=0.004), and alcohol consumption (OR =4.52, P=0.002). FAERS analysis recorded 904 hepatic adverse event (AE) reports, with 338 positive signals, most involving men aged 65-74 years and occurring within 30 days of initiation (6.89%). For nintedanib, 3.2% of exposed patients experienced DILI. FAERS analysis documented 2,114 hepatic AE reports, with 1,634 positive signals, predominantly in men aged 65-74 years, with 30.29% occurring within 30 days of initiation.

Conclusions: Both pirfenidone and nintedanib carry notable hepatotoxicity risks. Close liver function monitoring is advised during early treatment, especially in patients with low BMI, multiple comorbidities, pre-existing liver disease, or alcohol consumption.

Background: Acute pancreatitis (AP) is characterized by dysregulated pancreatic enzyme activation and pancreatic tissue injury. Orosomucoid (ORM), an acute-phase protein with immunomodulatory functions, exhibits organ-specific expression patterns, but its role in AP remains unclear. This study investigated the isoform-specific effects of ORM2 in AP pathogenesis and repair.

Methods: We established cerulein-induced mouse model of AP using both wild-type and pancreas-specific ORM2 knockout mice to investigate ORM2's protective role. Primary acinar cells were used for in vitro validation. Proteomics and functional assays elucidated mechanisms.

Results: In AP models, we observed opposing expression patterns of ORM, with increased levels in the liver but decreased levels in the pancreas. Genetic deletion of pancreatic ORM2 significantly worsened AP severity, while exogenous ORM2 administration provided protection against pancreatic injury. Specifically, ORM2 upregulated SPINK1 while downregulating PRSS2, leading to reduced trypsin activation.

Conclusions: ORM2 protects against AP by modulating the SPINK1-PRSS2 axis to prevent premature trypsin activation and alleviate acinar cell injury. Its tissue-specific regulation suggests therapeutic potential for AP.

Background: Hepatolithiasis, prevalent in East and Southeast Asia, often leads to complications such as cholangitis, strictures, and cholangiocarcinoma. Conventional interventions frequently leave residual stones, requiring repeat treatments. We evaluated a modified laparoscopic left-sided hepatectomy guided by dilated bile ducts (DBDs) as anatomical landmarks [modified laparoscopic left-sided hepatectoMy guided by dilated bile ducTs as aNatomical lAnmarks (MITNA) approach]-with reference to the middle hepatic vein (MHV) when necessary-to optimize stone clearance and preserve healthy liver.

Methods: In this prospective study, 32 consecutive patients undergoing laparoscopic left-sided hepatectomy for hepatolithiasis at 108 Military Central Hospital (January 2023-January 2025) were enrolled. Preoperative imaging identified the extent of DBDs. Patients with disease confined to the left lateral lobe underwent left lateral hepatectomy (LLH) with the transection line placed to the right of the falciform ligament. Those with disease extending to segment 4 or near the hilum underwent left hemihepatectomy (LHH), using a transection plane between DBDs and the MHV. Perioperative data (operative time, blood loss, complications, stone clearance) and follow-up outcomes were collected.

Results: All 32 patients completed laparoscopic hepatectomy without conversion, 22 underwent LLH and 10 had LHH. The mean operative time was 140.7±46.8 min with the mean blood loss 111.5±70.8 mL. Postoperative complications occurred in 12.5% of patients (Clavien-Dindo grade I-IIIa). The mean hospital stay was 7.7±2.5 days. At a mean follow-up of 9.50±4.08 months, only one patient (3.1%) had residual stones, which were successfully cleared through endoscopic intervention, resulting in a final stone clearance rate of 100%.

Conclusions: The MITNA approach is a feasible and promising approach for left-sided hepatolithiasis. This approach ensures complete resection of affected bile ducts and stones while sparing normal liver parenchyma, resulting in high stone clearance rates and low morbidity.

Background: Video capsule endoscopy (VCE) is a noninvasive modality in the assessment among patients with very early onset inflammatory bowel disease (VEOIBD). Little is known about the application of VCE in this rare disorder. The aim of this study is to evaluate the features of patients with VEOIBD undergoing VCE.

Methods: We retrospectively reviewed 37 VEOIBD patients who underwent VCE from five tertiary centers. Clinical data, including endoscopic findings and treatment were retrieved from medical records. Next generation sequencing was performed to confirm the monogenic defects.

Results: During a decade, a total of 37 VEOIBD patients were retrospectively included from 5 specialist centers. The total number of VCE procedures performed was 58. The VCE was performed at an average age of 7.8±3.2 years. Twelve patients had undergone follow-up VCE. Next-generation sequencing confirmed the known monogenic inflammatory bowel disease (IBD) in 18 patients. Multiple ulcers, erosions and pseudo-polyps have been identified among patients with TNFAIP3, XIAP and PIK3CD mutations. No adverse effect including capsule retention or endoscopic delivery procedures related adverse effects were reported. Eighteen patients (48.6%) achieved clinical remission.

Conclusions: This multicenter study showed the features of small bowel lesions among VEOIBD by VCE. Safety of VCE in VEOIBD patients have also been demonstrated.

Acute gastroenteritis (AGE) causes impairment of the gastrointestinal mucus and epithelium. Adjuvant treatment to oral rehydration is recommended to shorten the duration of diarrhea. The objective of this review was to review and discuss the available evidence of gelatin tannate in the management of AGE in pediatrics. Data from MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, LILACS and grey literature were analyzed. Several trials performed in Turkey, Italy and Romania in overall 782 children showed that gelatin tannate decreased the duration of the diarrhea with a beneficial efficacy on stool consistency demonstrated already 12 hours after the start of its administration. Differences in favor of gelatin tannate were already apparent after 12 hours of administration. All trials showed beneficial outcomes, except the Polish study (72 children) which showed no difference between gelatin tannate and placebo in duration of diarrhea. In another trial testing a different tannate, diarrhea lasted for 2.0±0.27 days in the intervention group versus 3.75±0.30 days in the placebo group (P<0.001). The administration of gelatin tannate in combination with oral rehydration solution (ORS) was shown to be effective and of rapid onset in children presenting infectious AGE, showing a shortening of the diarrhea within ±24 hours. It would be of particular interest to test gelatin tannate in developing countries, since most data come from Eastern Europe.

Background: Obesity, meaning an overweight problem, can be considered an epidemic disease that is strongly related to non-alcoholic fatty liver disease (NAFLD). Clinical studies indicate that the consumption of probiotics and prebiotics modulates the intestinal microbiota, promoting weight loss, decreasing adipose tissue and proinflammatory factors. The aim of the study was to analyze the response of the liver (transcriptomic and histology) to a dietary supplementation with probiotics and prebiotics of a murine model.

Methods: We evaluated the liver transcriptome using an obese murine model (C57BLACK6) by inducing obesity with a high-fat diet for 8 weeks followed by synbiotic supplements in a normocaloric diet for another 8 weeks. Pool screening analysis (5 samples) was completed using a synthesis of cDNA. The transcriptome was analyzed by DNA microarrays hybridizing on 22,000 mouse genes. Differentially expressed genes (DEGs) were analyzed under 3 hybridization processes with the aid of GenArise software using the z-score value. As a result of transcriptome analysis, fatty acid-binding genes (Cyp7a1 and Acox2) were selected to analyze the liver response, molecular and histologically.

Results: The transcriptome analysis results indicate 1.26% overexpression and a 2.2% average repression in relation to the hybridized genome; DEGs allow us to identify genes associated with fatty acid metabolism. The synbiotic treatment increases the expression of Cyp7a1 and Acox2 significantly (P<0.05) in correlation with a decrease in the histological level of accumulated fat in the tissue.

Conclusions: The synbiotic could be an adjuvant treatment to obesity and NAFLD as it can increase the production of bile acids coming from the classical pathway which promotes the absorption of ectopically accumulated lipids thus reducing the development of NAFLD at histological and molecular level.