World Journal of Gastroenterology最新文献

Pancreatic cancer, a highly malignant gastrointestinal tumor, has a five-year survival rate of only 10%. With the increasing aging population, its incidence is rising across East Asia, North America, and Europe. Chemotherapy remains a basic strategy of the current treatment regimen for pancreatic cancer. However, the development of multidrug resistance poses a significant challenge, drastically reducing the efficacy of chemotherapy agents. The mechanisms underlying resistance in pancreatic cancer remain incompletely understood. To overcome this obstacle, scientists are dedicated to discovering new therapeutic strategies and addressing the issue of resistance. Plant-derived chemicals played essential roles in many documented ancient cultures, such as those in ancient China, ancient Egypt, ancient India, and ancient Babylon. Many modern medications are derived from plants, including paclitaxel, a widely used and effective chemotherapy agent originally derived from the Pacific yew tree. Although the development of plant-based compounds for cancer treatment is still under development, these compounds offer several advantages, including a long history of safe use, fewer side effects, lower costs, and improved patient acceptance. Recent studies have shown that plant-derived chemicals can significantly inhibit tumor cell proliferation and reversal drug resistance. Clinical trials have demonstrated promising therapeutic effects of these compounds in cancer treatment. This review summarizes recent research on the role of plant-derived compounds in overcoming drug resistance in pancreatic cancer. It provides insights into the mechanisms of drug resistance and highlights the potential of plant-based compounds as alternative therapeutic strategies. Considering the limitations of current therapies and the growing issue of drug resistance, plant-derived compounds offer a promising direction for enhancing treatment outcomes. This review aims to inform future research and promote the development of more effective, safer, and patient-friendly treatment options for pancreatic cancer.

Background: Liver transplantation is the only treatment for acute and chronic liver failure, but the global organ shortage has increased reliance on extended criteria donor livers, which are more susceptible to ischemia-reperfusion injury. While static cold storage is standard, these grafts often require improved preservation strategies.

Aim: To summarize the current state of small animal liver machine perfusion (MP), highlight variability in protocols, and emphasize the need for standardization to guide future research.

Methods: A comprehensive literature search of PubMed was conducted to identify studies on small animal (rat and mouse) ex vivo liver MP. Only English-language animal studies were included, with no restrictions on publication date. Relevant full-text articles were reviewed, and reference lists were screened to ensure completeness.

Results: Small animal liver MP provides a cost-effective model to explore dynamic preservation strategies. Rat perfusion studies face challenges including dual-vessel perfusion, maintaining physiological perfusate volumes, and lack of standardized protocols. Open- and closed-circuit setups have distinct advantages and limitations, and experimental designs vary widely across studies.

Conclusion: This review illustrates the wide variability in small animal liver MP protocols and underscores the urgent need for standardization. Addressing these inconsistencies will enhance reproducibility, facilitate comparison across studies, and support the development of optimized liver preservation strategies.

A major driver of hepatocellular carcinoma (HCC)'s aggressiveness is its ability to hijack the immune system, specifically by recruiting immunosuppressive tumor-associated macrophages. These M2-type macrophages are coerced into promoting tumor growth and metastasis. This study by Escobedo-Calvario et al reveals that the protein growth differentiation factor 11 can effectively "re-educate" these pro-tumoral macrophages by reducing classic M2 markers, rewiring cellular metabolism, and boosting production of reactive oxygen species, which ultimately switch the macrophages from a pro-tumor state toward an anti-tumor state. When applied to HCC cells, growth differentiation factor 11 also reduced the cancer cells' capacity to proliferate and migrate - key hallmarks of deadly metastasis. This two-pronged attack could represent a groundbreaking strategy to enhance current immunotherapies and control the aggressiveness of HCC, offering new hope for future treatments.

Pediatric inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), presents significant diagnostic challenges due to its heterogeneous clinical presentation and reliance on invasive procedures such as endoscopy. Recent studies highlight the potential of non-invasive biomarkers, particularly serum cytokines, for distinguishing pediatric IBD from non-IBD conditions. CXCL9, interleukin 8, and interleukin 22 have shown strong discriminatory ability, correlating with disease activity and aiding in the differentiation between CD and UC. These biomarkers may also inform disease progression and treatment needs, including the identification of patients likely to require biologic therapy. However, important gaps remain in translating biomarker findings into routine clinical practice, especially for predicting long-term treatment response. This editorial summarizes recent advances in non-invasive biomarkers for pediatric IBD, focusing on serum, fecal, and genetic markers, and discusses their integration with conventional diagnostic approaches. Ongoing validation in large pediatric cohorts is required to support clinical implementation and optimize biomarker-guided management strategies.

Chronic hepatitis B (CHB) infection is a global public health burden, affecting over 250 million persons globally, and is associated with substantial morbidity and mortality due to cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly common co-morbidity among patients with CHB, affecting an estimated 25%-40% of individuals. The physiologic and clinical impact of co-existing CHB and metabolic syndrome and/or MASLD [met-hepatitis B virus (HBV)] is poorly understood, although recent data suggest important associations with poorer antiviral response and clinical outcomes. This review summarizes current and emerging evidence addressing this relationship, and outline recommendations for the diagnosis, risk stratification, staging, and management of Met-HBV.

Liu et al recently published research suggesting that multistrain probiotics significantly relieved bismuth quadruple therapy (BQT)-associated gastrointestinal symptoms without affecting eradication success. They conducted a rigorous randomized, double-blind, placebo-controlled trial, demonstrating that a 4-week regimen of a multistrain probiotic supplement significantly reduced symptoms such as reflux, dyspepsia, and diarrhea. The reduction in side effects and enhanced patient comfort highlight the clinical utility of probiotics as a safe and well-tolerated adjunct to BQT. Our contribution was about to involve the traditional Chinese medicine treating Helicobacter pylori-related chronic gastritis. They can have similar functions in regulating gut microbiota. Future research should build on this foundation to refine probiotic formulations, explore their long-term effects, and clarify their role in achieving higher eradication rates.

With the introduction of Janus kinase inhibitors like tofacitinib, the treatment landscape for ulcerative colitis (UC) is changing quickly. Response heterogeneity is still a significant clinical challenge in spite of its quick onset and oral convenience. Extending tofacitinib induction beyond the standard eight weeks can produce significant benefits in a subset of patients without sacrificing safety, according to evidence from pivotal trials and real-world studies. We review recent real-world evidence, highlight lessons learnt from extended induction therapy, and present a practical framework to help guide tailored treatment decisions in this editorial. After 16 weeks of prolonged induction, more than half of patients with moderate-to-severe UC experienced remission, with durable persistence and favorable safety, according to a multicenter 52-week real-world study published in this issue of the World Journal of Gastroenterology. Crucially, outcomes and maintenance dosing were impacted by modifiable factors like smoking and biologic exposure. Mechanistic findings support a response-guided rather than fixed-duration induction paradigm by indicating that immune kinetics, mucosal healing rates, and previous biologic exposure may account for delayed responses. An effective, patient-centered strategy that could maximize tofacitinib's therapeutic potential and assist in guiding refractory UC patients towards long-term remission is extended induction.

Background: Biologics are the preferred treatment for patients with moderate to severe Crohn's disease (CD). Four biologics included in China's National Reimbursement Drug List are available for CD treatment. Due to loss of response, patients need switching to another biologic, making it necessary to evaluate the cost-effectiveness of different biologic treatment sequences.

Aim: To assess the cost-effectiveness of sequential treatment strategies with National Reimbursement Drug List-included biologics for moderate to severe CD in China.

Methods: From a healthcare system perspective, a Markov model was constructed to evaluate the cost-effectiveness of four biologics [infliximab, adalimumab (ADA), ustekinumab (UST), and vedolizumab] applied in different treatment sequences for moderate to severe CD patients. Using one times the GDP per capita ($13444.68, 2024) in China as the willingness-to-pay threshold, the absolute net monetary benefit (NMB) and incremental cost-effectiveness ratio (ICER) were calculated. Both costs and utilities were discounted at an annual rate of 5%. Sensitivity analyses were conducted on key parameters.

Results: With $13444.68 as willingness-to-pay, among the 17 treatment sequences evaluated for biologic-naïve patients, sequence 3 (ADA-UST) yielded the highest absolute NMB of $35850.93. Compared with sequence 1 (vedolizumab-UST), sequence 3 had the most favorable ICER of $2285.38/quality-adjusted life year. For biologic-exposed patients, sequence 3 still demonstrated the optimal NMB and ICER results.

Conclusion: Adding biologic treatment lines provides greater health benefits for patients with moderate to severe CD. Among the various sequential strategies, the treatment sequence combining ADA and UST is more likely to be the optimal cost-effective option in China.

Background: The prognostic value of programmed death ligand-1 (PD-L1) expression in patients with gastric or gastroesophageal junction cancer (G/GEJC) at different stages remains unclear. We hypothesized that high PD-L1 expression is associated with poor survival in patients with pathological stage III (pIII) G/GEJC.

Aim: To investigate the relation between PD-L1 expression and survival outcomes in patients with pathological stage II (pII)-pIII G/GEJC.

Methods: In this retrospective cohort study, we collected the clinicopathological data of 388 consecutive patients with pII/pIII G/GEJC who underwent gastrectomy without neoadjuvant therapy at Nanfang Hospital, Southern Medical University. Postoperative tissue samples were collected to evaluate PD-L1 expression. Combined positive score (CPS) ≥ 1 was defined as PD-L1-positive, and CPS ≥ 5 as high PD-L1 expression. Survival outcomes were analyzed using Kaplan-Meier and Cox proportional hazards models.

Results: In pII G/GEJC, no significant differences were found in 3-year disease-free survival (DFS; 88.5% vs 87.9%, P = 0.939) or 3-year overall survival (OS; 92.3% vs 89.9%, P = 0.621) between PD-L1-positive and PD-L1-negative groups or between high and low PD-L1 expression groups (3-year DFS: 91.8% vs 84.2%, P = 0.138; 3-year OS: 94.2% vs 88.4%, P = 0.233). In pIII G/GEJC, PD-L1-positive patients had poorer 3-year DFS (52.2% vs 67.8%, P = 0.030) and 3-year OS (65.1% vs 78.2%, P = 0.007) than PD-L1-negative patients. High PD-L1 expression was associated with significantly inferior 3-year DFS (50.2% vs 64.8%, P = 0.023) and 3-year OS (64.0% vs 75.1%, P = 0.036) compared to low PD-L1 expression. Multivariate analysis revealed that high PD-L1 expression was independently associated with shorter DFS (HR = 1.624, P = 0.027) and OS (HR = 1.653, P = 0.043) in patients with pIII G/GEJC. Sensitivity analyses confirmed the robustness of the OS findings.

Conclusion: High PD-L1 expression serves as an independent adverse prognostic biomarker in stage III but not stage II G/GEJC. These findings indicate a stage-dependent prognostic value of PD-L1 expression in G/GEJC.