World Journal of Gastroenterology最新文献

Liver diseases caused by diverse inflammation or cancer have serious damaged people's physical and mental health and become a heavy social burden. Stem cells possess unique properties of self-renewal and multi-directional differentiation, which are widely used for disease remodeling and regenerative medicine. Of them, human induced pluripotent stem cell-based liver organoids with self-organization of sinusoidal vessels have been reported for diverse liver cancer remodeling and drug sensitivity test, which provide unique platforms to dissect functional consequences of diverse levels of heteroplasmy of target gene mutation in liver cancers. Meanwhile, mesenchymal stem/stromal cells have been adopted for clinical treatment research on various liver diseases, including acute liver injury, decompensated liver cirrhosis, hepatic fibrosis and acute-on-chronic liver failure. In this review article, we mainly focus on the state-of-the-art literatures upon stem cell-based disease modeling and cell therapy for multifarious liver diseases from the view of basic research and clinical progress, which will provide references for the development of stem cell-based regenerative medicine in the precise diagnosis and treatment of liver diseases.

Background: Sub-Saharan Africa (SSA) and Southeast Asia account for 80% of hepatocellular carcinoma (HCC) cases globally. Public healthcare systems in low- and middle-income countries often face significant economic constraints, resulting in limited treatment options. The objectives of this study were to identify factors associated with poor outcomes in patients with Barcelona Clinic Liver Cancer (BCLC) stage C and D undergoing transarterial chemoembolization (TACE) and to compare their outcomes to patients treated tyrosine kinase inhibitors (TKIs) or best supportive care (BSC) only.

Aim: To assess clinical outcomes and identify predictive factors that may facilitate the broader implementation of TACE in patients with advanced HCC within resource-constrained settings such as SSA.

Methods: A single-center, retrospective cohort study was conducted to investigate the risk factors associated with the outcome of TACE in patients with BCLC stage C and D using univariate and multivariate regression analysis. Frequency matching was used to ensure comparable distributions of confounding factors across patients treated with TACE, TKIs, or BSC. Survival analysis was performed to compare outcomes among the matched groups.

Results: Patients with BCLC stage C and D presenting with elevated gamma-glutamyl transferase levels or elevated aspartate aminotransferase levels or portal vein infiltration were identified as high-risk and demonstrated poor response to TACE treatment. In contrast, patients with BCLC stage C disease who lacked these high-risk features showed significantly longer overall survival when treated with TACE compared to those who received BSC or TKIs.

Conclusion: Gamma-glutamyl transferase levels, aspartate aminotransferase levels, and portal vein infiltration are critical risk factors to consider when determining treatment strategies for HCC patients in SSA. Patients without these factors can derive significant benefits from TACE as an alternative to BSC or TKIs.

The vonoprazan (VPZ) triple therapy regimen for Helicobacter pylori (H. pylori) eradication developed by Han et al employs a scientifically rigorous clinical trial design. This multicenter randomized controlled trial establishes a standardized treatment framework aimed at improving H. pylori eradication rates, focusing on simplifying treatment regimens, shortening therapy duration, and optimizing therapeutic outcomes. The core of clinical translation lies in improving drug accessibility, establishing multidimensional safety evaluation systems, and optimizing cost-effectiveness. Conducting regional adaptability studies and comprehensive safety assessments is crucial for enhancing VPZ regimen effectiveness in China's diverse healthcare environments. This study provides important evidence-based support for optimizing H. pylori treatment strategies in China, though further validation of universal applicability for nationwide implementation remains necessary.

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer, with high mortality at advanced stages. Loco-regional treatment including: Radiofrequency (RF) or transarterial chemoembolization (TACE) is decided according to the size, and the site of the tumor, according to practice guidelines. Alpha fetoprotein (AFP), the most used biomarker in the guidelines, although specific, lacks sensitivity. New biomarkers are needed to understand the underlying pathophysiology, and to be used in clinical practice.

Aim: To study the effect of loco-regional treatment on telomere length, as a diagnostic and short-term (3 months) prognostic marker.

Methods: This is a prospective cohort study, and includes 60 patients visiting Ain Shams University Hospitals. The patients were divided into 2 groups: 30 patients with liver cirrhosis (group 1) and 30 HCC patients undergoing RF or TACE (group 2). Laboratory investigations for all patients included: Telomere length in peripheral leukocytes by polymerase chain reaction, AFP, and liver function. In the HCC group, the aforementioned laboratory investigations with abdominal triphasic computed tomography with contrast were performed at baseline, and after 3 months.

Results: With regard to age, Child-Pugh and Model for End-Stage Liver Disease scores, there was no statistically significant correlation with telomere length. However, there was a correlation between telomere length and age, and both scores before and after 3 months of treatment among HCC patients. On dividing the HCC group according to tumor size with a cutoff of 5 cm, and performing the Mann-Whitney test we found that at baseline telomere length was significantly lower among cases with tumor size ≥ 5 cm than in those with tumor size < 5 cm (30 patients; P = 0.03). In addition, we found a positive Spearman's rank correlation between telomere length and tumor size in the ≥ 5 cm only group (28 samples from the before and after intervention data; P = 0.025).

Conclusion: Telomere length in leukocytes is a potential marker in HCC tumor prognosis. Further research using telomerase activity and telomerase reverse transcriptase promoter gene mutation in a larger cohort is recommended.

Endoscopic ultrasound-guided shear wave elastography (EUS-SWE) represents a significant advancement in non-invasive tissue characterization, enabling objective assessment of quantitative tissue stiffness in real-time with potential clinical relevance across a variety of gastrointestinal disorders. Recent developments in EUS-SWE have expanded its application beyond hepatic fibrosis to include pancreatic diseases and the evaluation of solid tumors. EUS-SWE has demonstrated diagnostic accuracy comparable to vibration-controlled transient elastography in assessing fibrosis stages, positioning it as a potential alternative to liver biopsy. Moreover, EUS-SWE has shown promise in evaluating pancreatic tissue stiffness, aiding in the diagnosis and monitoring of chronic pancreatitis and pancreatic cancer. This technique offers a distinct advantage by allowing tissue stiffness measurements during the same procedure, thereby reducing the need for additional imaging studies and biopsies. Despite its clinical potential, challenges remain, including the need for standardized protocols, optimal cutoff values, and validation across diverse patient populations. This minireview provides a comprehensive analysis of the current literature on EUS-SWE, examining its diagnostic performance, reproducibility, and limitations. Furthermore, we discuss the future directions of EUS-SWE, including its integration into routine clinical practice and its evolving role in precision medicine, emphasizing the necessity of large-scale studies to solidify its clinical utility and establish standardized guidelines for its use.

Background: The diagnosis of inflammatory bowel disease (IBD) involves clinical, endoscopic, and radiologic evaluation. Endoscopic procedures, particularly in pediatrics, require general anesthesia and carry potential risks.

Aim: To investigate whether serum biomarkers can differentiate between pediatric patients with and without IBD. Secondary objectives included identifying biomarkers that distinguish Crohn's disease (CD) from ulcerative colitis (UC) and assessing their predictive value for progression to biologic therapy.

Methods: Pediatric patients undergoing diagnostic colonoscopy at British Columbia Children's Hospital between December 2017 and June 2022 were enrolled. Blood samples were collected at colonoscopy, and demographic clinical data, laboratory, and histopathologic evaluation were obtained. An exploratory screen of 50 biomarkers was undertaken in a subset of patients (54 IBD, 41 controls) using Legendplex^TM flow cytometry kits to identify candidates. A refined panel of 12 serum biomarkers was subsequently selected and a supervised learning model was developed to classify patients.

Results: The study included 246 pediatric patients, who had a median age of 13.03 years and were 37.4% female (103 CD, 52 UC, 91 controls). In univariate analyses, C-X-C motif chemokine ligand 9 (CXCL9) was the only biomarker significantly elevated in IBD vs controls (P < 0.001). A multivariable model achieved an area under the receiver operating characteristic of 0.861 for distinguishing IBD from controls. Interleukin 8 (IL-8) emerged as a key biomarker alongside CXCL9 and IL-22 in the model. The random forest model identified CXCL9 with the greatest diagnostic accuracy (area under the curve [AUC] = 0.81), followed by IL8 and IL22 (AUC = 0.737 and 0.68, respectively). CXCL9 and IL-18 showed higher levels in CD (P = 0.016), whereas CXCL1 levels predicted progression to biologic therapy within 1 year (P = 0.039). However, the model did not effectively predict disease subclassification or progression to biologic therapy.

Conclusion: Serum biomarkers, particularly CXCL9, IL-8, and IL-22, can aid in the diagnosis of pediatric IBD. CXCL9 and IL18 were found to be significant predictors of CD, and CXCL1 differed between patients requiring biologic therapy vs those who did not.

In recent years, hepatology has undergone a transformative evolution driven by significant advancements in diagnostic and therapeutic technologies. The expanding integration of endoscopic modalities into hepatology has enforced the diagnosis, staging, management of liver diseases beside integration into transplantation. This review highlights the evolving discipline of "endo-hepatology", where endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, and novel interventional tools are employed to address the critical challenges in chronic liver disease. The review provides a comprehensive synthesis of current evidence and different clinical applications, while also exploring future directions including revolution of artificial intelligence-assisted endoscopies and enhanced imaging endoscopies. By bridging the anatomical and functional interface between the gastrointestinal lumen and the liver, endo-hepatology is not only improving diagnostic accuracy and therapeutic precision but also reshaping multidisciplinary paradigms in hepatology practice.

Liver fibrosis remains a major global health challenge with limited therapeutic options. In their recent study, Wang et al report that levodopa, a dopamine precursor widely used in Parkinson's disease, significantly attenuates carbon tetrachloride-induced liver fibrosis in rats by enhancing dopamine receptor D1 expression and activating the Hippo signaling pathway, leading to phosphorylation and inactivation of yes-associated protein 1. This discovery links G-protein-coupled receptor signaling to Hippo pathway regulation in hepatic fibrosis. The work highlights the dopamine receptor D1-Hippo/yes-associated protein 1 axis as a promising antifibrotic mechanism and introduces levodopa as a potential repurposing candidate for chronic liver disease. With its established safety and affordability, levodopa offers a rapidly translatable strategy that warrants validation in human tissues and diverse fibrosis models. Here, we place these findings in the broader context of G-protein-coupled receptor regulation of hepatic stellate cell activation, discuss translational opportunities for levodopa in liver fibrosis, and propose future directions to validate this pathway across disease models and clinical settings.

Background: ChatGPT was developed in November 2022 with studies showing its impressive performance in academic examinations, serving as a promising tool to answer questions even on controversial topics. Artificial intelligence (AI) achieving surface-level performance does not necessarily equate to a deep understanding of human cognition. The development of artificial wisdom, therefore, necessitates a shift from simply mimicking intelligent behavior to modeling the underlying mechanisms of human wisdom, including emotional understanding, ethical considerations, and contextual awareness. Several theories exist behind the death of Alexander the Great, but no definitive conclusion has been made.

Aim: To evaluate whether a hybrid approach, combining generative AI (ChatGPT) with human clinical judgment, can meaningfully reassess the cause of death of Alexander the Great.

Methods: This is a cross-sectional study using ChatGPT (version 4 Pro). A search was performed with search terms describing the symptoms experienced by Alexander the Great and possible causes of his death: West Nile virus (WNV) encephalitis, poisoning, acute pancreatitis due to excessive alcohol consumption, typhoid fever, and malaria. The historical data and symptomatology were analyzed, weighing evidence and context in a manner akin to human wisdom.

Results: The most likely cause of death of Alexander the Great, as generated by ChatGPT, was typhoid fever complicated by Guillain-Barré syndrome (GBS). The hypothesis was based on the alignment between Alexander's reported symptoms, such as prolonged high fever, severe abdominal pain, neurological decline, and the known clinical presentation of typhoid fever. However, after carefully reviewing the sources mentioned by ChatGPT, many did not back up the idea that typhoid caused GBS and instead pointed to Campylobacter jejuni as the more likely trigger. Other possible causes of death suggested by ChatGPT including acute pancreatitis from excessive alcohol consumption, infectious causes (WNV encephalitis, malaria), and poisoning were less likely.

Conclusion: While ChatGPT initially concluded typhoid fever with GBS as the most plausible cause of death, expert reappraisal of the sources and pathophysiology suggested that C. jejuni-associated GBS was more likely. This study exemplifies how incorporating AI's pattern recognition with human scrutiny can yield responsible interpretations of historical records.

Background: Basal cell carcinoma (BCC) is the most prevalent skin cancer, characterized by indolent growth and low metastatic rates. When metastatic BCC (mBCC) does occur, it most commonly involves lymph nodes, lungs, and bones, with metastases to other sites being exceptionally rare. This case reports the first documented instance of mBCC to the stomach, highlighting the importance of considering atypical metastatic sites, and the challenges associated with diagnosis and management.

Case summary: A 52-year-old male with recurrent BCC and known mBCC to the bone presented with progressive dysphagia, cranial neuropathies and generalized weakness. He had been treated with immune checkpoint inhibitors, with intermittent therapy modifications due to treatment related toxicities. His past history was notable for malignant perineural invasion, radiotherapy for osseous metastases, immune checkpoint inhibitor-induced enteritis, and osteonecrosis of the jaw. Gastroscopy revealed subepithelial gastric lesions, and biopsies confirmed mBCC - a previously unreported site of disease dissemination. A multidisciplinary team involving gastroenterology, oncology, neurology, and palliative care guided his management. Given his declining functional status and poor prognosis, he was ultimately transitioned to hospice care.

Conclusion: Clinicians should consider atypical metastatic sites in advanced BCC. A multidisciplinary approach remains essential for timely diagnosis and coordinated management.