Journal of gastrointestinal and liver diseases : JGLD最新文献

Colorectal cancer is a prevalent malignancy, with advanced and metastatic forms exhibiting poor treatment outcomes and high relapse rates. To enhance patient outcomes, a comprehensive understanding of the pathophysiological processes and the development of targeted therapies are imperative. The high heterogeneity of colorectal cancer demands precise and personalized treatment strategies. Colorectal cancer organoids, a three-dimensional in vitro model, have emerged as a valuable tool for replicating tumor biology and exhibit promise in scientific research, disease modeling, drug screening, and personalized medicine. In this review, we present an overview of colorectal cancer organoids and explore their applications in research and personalized medicine, while also discussing potential future developments in this field.

Background and aims: Systemic therapy is mainly recommended for advanced hepatocellular carcinoma (HCC). Considering the variety of treatments available for HCC, there is a need to understand their relative benefits and risks, especially for the newly approved combination of immune checkpoint inhibitors and vascular endothelial growth factor inhibitors represented by atezolizumab in combination with bevacizumab. A reticulated meta-analysis was used to evaluate the efficacy and safety of atezolizumab-bevacizumab combination therapy compared with other first-line systemic therapies for the treatment of patients advanced HCC.

Methods: PubMed, The Cochrane Library, Web of Science, and Embase databases were searched from the time of library construction to 01 December 2022, and the data were extracted and analyzed using Stata16.0 for Meta-analysis. The data were extracted separately, and a meta-analysis was performed using the software Stata16.0.

Results: 16 clinical studies with 8,779 subjects were identified from 13,417 records and were used to build the evidence network for all trials. TThe combination therapy of atezolizumab and bevacizumab has the advantage of prolonging the OS of patients when treating advanced HCC [HR=5.71, 95%CI (4.30, 7.12), p<0.05] Also, the combination therapy has the advantage of prolonging the patient's progression free survival [HR=1.60, 95%CI (0.89, 2.49), p<0.05].

Conclusions: Atezolizumab-bevacizumab combination therapy can improve clinical outcomes such as OS and PFS in patients with advanced HCC.

Background and aims: This meta-analysis was performed to compare the efficacy and safety of a triple therapy, involving transcatheter arterial chemoembolization (TACE) + apatinib combined with a programmed-cell death protein-1 (PD-1) inhibitor versus TACE + apatinib, a dual therapy with apatinib and PD-1 inhibitor, and TACE alone for the treatment of advanced primary hepatocellular carcinoma (HCC).

Methods: A computerized systematic search of databases, such as PubMed, Embase, the Cochrane Library, CNKI, Wanfang Data, and VIP e-Journals was performed to retrieve studies comparing TACE + apatinib combined with a PD-1 inhibitor versus a non-triple therapy for the treatment of advanced primary HCC. The literature search, quality assessment, and data extraction were performed independently by two researchers. Stata 16.0 software was employed to analyze the data. Heterogeneity was assessed utilizing the I2 statistic and p-value, followed by conducting sensitivity analysis.

Results: A total of 2,352 patients were enrolled from 8 studies, including 900 patients in the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor, 877 patients in the TACE + apatinib group, 52 patients in the apatinib + a PD-1 inhibitor group, and 112 patients in the TACE group. The results revealed that the objective response rate (ORR) was significantly higher in the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor than that in the non-triple therapy group [odds ratio (OR)=2.47, 95% confidence interval (95%CI): 1.61-3.78]. Besides, disease control rate (DCR) was greater in the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor than that in the non-triple therapy group (OR=1.87, 95%CI: 1.44-2.44). Patients in the triple therapy group experienced a significant extension of overall survival (OS) (HR=0.42, 95%CI: 0.36-0.49). In addition, there was no significant difference in the overall rate of adverse events (AEs) between the two groups (OR=1.05, 95%CI: 0.89-1.22).

Conclusions: Compared with the non-triple therapy group, the triple therapy group of TACE + apatinib combined with a PD-1 inhibitor outperformed in terms of tumor response and long-term survival with manageable AEs.

Background and aims: The burnout syndrome (BOS) is commonly seen in healthcare professionals, particularly in physicians who are exposed to a high level of stress at work and has a negative impact on the medical activity. Physicians with BOS manifest a negative attitude, a reduction in compassion at work, and suboptimal patient care experiences. These all can lead to absenteeism, poor performance and more frequent medical errors. We aimed to assess the level of BOS in a tertiary gastroenterology university center in Romania.

Methods: This observational study involved 40 physicians from a tertiary gastroenterology university center. An online questionnaire assessed the presence of BOS using the Maslach Burnout Inventory.

Results: A total of 40 physicians responded to the questionnaire. The prevalence of overall BOS of 87.5%. In terms of high burnout, 15 doctors (37.5%) had emotional exhaustion, 10 doctors (25%) had depersonalization, and 30 doctors (80%) scored low for personal achievement. Men presented more frequently emotional exhaustion and women lower personal achievement scores, but there was no significant statistical difference. No significant relationship was found between marital status or the number of children and BOS. We identified multiple risk factors associated to BOS, the most important one being strict internal regulations.

Conclusions: Physicians presented an increased risk for BOS. The high rate of BOS among physicians found in our study requires careful attention. Further studies aiming to identify other factors that contribute to BOS and to identify measures to combat this syndrome are necessary.

Background and aims: The incidence and mortality of hepatocellular carcinoma (HCC) are increasing. It is urgent to develop more effective HCC biomarkers for diagnosis and treatment. This project intends to verify the expression of enhancer of zeste 1 polycomb repressive complex 2 subunit (EZH1) and its mechanism in HCC.

Methods: This study integrates global microarray and high-throughput sequencing datasets, combined with internal immunohistochemistry, to analyze the expression and prognostic value of EZH1 in HCC. Functional enrichment analysis was conducted to investigate transcriptional targets, which were achieved by intersecting HCC over-expressed genes, EZH1 co-expressed genes and putative transcriptional targets. The relationship between EZH1 and anticancer drugs was detected by drug sensitivity analysis.

Results: In this study, 84 datasets from 40 platforms (3,926 HCC samples and 3,428 non-cancerous liver tissues) were included to show the high expression of EZH1 in HCC. Immunohistochemistry with 159 HCC samples and 62 non-HCC samples confirmed the high expression level. HCC patients with high EZH1 expression had worse survival prognoses. Gene ontology and Reactome analysis revealed that metabolism-related pathways, including autophagy, are critical for HCC. Interestingly, as one of the EZH1 potential transcriptional targets, autophagy-related 7 (ATG7) appeared in the above pathways. ATG7 was positively correlated with EZH1, upregulated in HCC, and mediated poor prognosis. Upregulation of EZH1 was found to be in contact with HCC anti-tumor drug resistance.

Conclusions: The upregulation of EZH1 expression can promote the occurrence of HCC and lead to poor clinical progression and drug resistance; these effects may be mediated by regulating ATG7.