Postoperative lenvatinib + PD-1 blockade reduces early tumor recurrence in hepatocellular carcinoma with microvascular invasion (Barcelona Clinic Liver Cancer stage 0 or A): a propensity score matching analysis.

BACKGROUND: This study aimed to determine the effectiveness of postoperative adjuvant lenvatinib + PD-1 blockade for patients with early-stage hepatocellular carcinoma (HCC) with microvascular invasion (MVI). METHODS: A total of 393 patients with HCC (Barcelona Clinic Liver Cancer stage 0 or A) who underwent curative hepatectomy with histopathologically proven MVI were enrolled according to the inclusion and exclusion criteria and assigned to 2 groups: surgery alone (surgery-alone group) and surgery with lenvatinib and PD-1 blockade (surgery + lenvatinib + PD-1 group) to compare recurrence-free survival (RFS), overall survival (OS), recurrence type, and annual recurrence rate after the application of propensity score matching (PSM). The Cox proportional hazards model was used for univariate and multivariate analyses. RESULTS: Overall, 99 matched pairs were selected using PSM. Patients in the surgery + lenvatinib + PD-1 group had significantly higher 3-year RFS rates (76.8%, 65.7%, and 53.5%) than patients in the surgery-alone group (60.6%, 45.5%, and 37.4%) (P = .012). The 2 groups showed no significant difference in recurrence types and OS. Surgery alone, MVI-M2, and alpha-fetoprotein of ≥200 ng/mL were independent risk factors for RFS (P < .05), and history of alcohol use disorder was an independent risk factor for OS (P = .022). CONCLUSION: Postoperative lenvatinib + PD-1 blockade improved the RFS in patients with HCC with MVI and was particularly beneficial for specific individuals.

The Role of Nuclear Receptors in the Pathogenesis and Treatment of Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a global health burden closely linked to insulin resistance, obesity, and type 2 diabetes. The complex pathophysiology of NAFLD involves multiple cellular pathways and molecular factors. Nuclear receptors (NRs) have emerged as crucial regulators of lipid metabolism and inflammation in NAFLD, offering potential therapeutic targets for NAFLD. Targeting PPARs and FXRs has shown promise in ameliorating NAFLD symptoms and halting disease progression. However, further investigation is needed to address side effects and personalize therapy approaches. This review summarizes the current understanding of the involvement of NRs in the pathogenesis of NAFLD and explores their therapeutic potential. We discuss the role of several NRs in modulating lipid homeostasis in the liver, including peroxisome proliferator-activated receptors (PPARs), liver X receptors (LXRs), farnesoid X receptors (FXRs), REV-ERB, hepatocyte nuclear factor 4α (HNF4α), constitutive androstane receptor (CAR) and pregnane X receptor (PXR).The expanding knowledge of NRs in NAFLD offers new avenues for targeted therapies, necessitating exploration of novel treatment strategies and optimization of existing approaches to combat this increasingly prevalent disease.

Does inclusion of bioactive n-3 PUFAs in parenteral nutrition benefit postoperative patients undergoing liver surgery? A systematic review and meta-analysis of randomised control trials.

OBJECTIVES: This meta-analysis aims to evaluate the effect of n-3 polyunsaturated fatty acids (PUFAs) as a part of parenteral nutrition in patients undergoing liver surgery. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, the Cochrane Central Register of Controlled Trials, Springer link, Web of Science, China National Knowledge Infrastructure and VIP Database. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) and evaluated the outcomes of liver function, inflammatory reaction, the influence of certain markers of the immune system, and specific clinical indexes for patients undergoing liver surgery and receiving parenteral nutrition with n-3 PUFAs. DATA EXTRACTION AND SYNTHESIS: The Cochrane Collaboration's tool was used to assess the risk of bias for each study. Findings were summarised in Grades of Recommendation, Assessment, Development and Evaluation evidence profiles and synthesised qualitatively. RESULTS: Eight RCTs, including 748 patients (trial: 374; control: 374), were included in the meta-analysis. Compared with patients in the control group, the patients in the n-3 PUFA group who underwent liver surgery had significantly lower aspartate aminotransferase (mean difference, MD -42.72 (95% CI -71.91 to -13.52); p=0.004), alanine aminotransferase (MD -38.90 (95% CI -65.44 to -12.37); p=0.004), white cell count (MD -0.93 (95% CI -1.60 to -0.26); p=0.007) and IL-6 (MD -11.37 (95% CI -14.62 to -8.13); p<0.00001) levels and a higher albumin level (MD 0.42 (95% CI 0.26 to 0.57); p<0.00001). They also had fewer infection complications (OR 0.44 (95% CI 0.28 to 0.68); p=0.0003) and a shorter duration of hospital stay (MD -2.17 (95% CI -3.04 to -1.3); p<0.00001) than the controls. However, there were no significant differences in terms of total bilirubin, TNF-α, IL-2, IgA, IgG, IgM and CD3, biliary leakage and mortality between the two groups. CONCLUSIONS: We found that n-3 PUFAs can benefit patients undergoing liver surgery by improving liver function and certain clinical indexes and decreasing related inflammation factors. However, there are limited RCTs on the application of n-3 PUFAs for patients undergoing liver surgery. Further evidence of the benefit of n-3 PUFAs in these patients warrants further exploration.

The state of female hepato-pancreato-biliary (HPB) surgeons in China: see us in operation theater with great prospects.

OBJECTIVE: This study aims to investigate the proportion and distribution of female HPB surgeons in China, describe their current status, and analyze the possible barriers and challenges in their careers. METHOD: Tertiary hospitals with the division of HPB in mainland China in 2021 were enrolled and surgeon demographic information was collected through the review of official websites and/or telephone interviews. RESULTS: The majority of female HPB surgeons (72.92%) were located in the first or second-tier cities in mainland China, with an increasing number of new female HPB surgeons entering the field annually, particularly after 2005 (from 27 to 52 per 5 years). Despite no significant difference in academic backgrounds, female HPB surgeons initiated their careers at an earlier age and took a longer time to obtain chief titles (P < 0.05). Interestingly, female HPB surgeons performed laparoscopic complex HPB cases at a similar rate (95.42%) to their male counterparts and were more likely to specialize in endoscopic surgery (P = 0.021), with a similar ratio of obtaining administrative positions. CONCLUSION: Minimally invasive surgery may provide females with unprecedented opportunities in the HPB surgery field. However, despite the increasing numbers of female HPB surgeons, the proportion remains low in China.

Anatomical Resection Improved the Outcome of Intrahepatic Cholangiocarcinoma: A Propensity Score Matching Analysis of a Retrospective Cohort.

Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common liver malignancy after hepatocellular carcinoma (HCC), with a dismal prognosis and high heterogeneity. The oncological advantages of anatomical resection (AR) and nonanatomical resection (NAR) in HCC have been studied, but surgical strategies for ICC remain controversial with insufficient investigations. Materials and Methods: From Jan 2013 to Dec 2016, 3880 consecutive patients were retrospectively reviewed from a single center. Patients with ICC undergoing AR or NAR have been enrolled according to inclusion and exclusion criteria. Propensity score matching (PSM) analysis was performed between two groups with a 1 : 1 ratio. The primary endpoint was overall survival (OS), and the secondary endpoints included disease-free survival (DFS), intraoperative patterns, postoperative morbidity, mortality, complications and recurrence. A prognostic nomogram was developed by a multivariate Cox proportion hazard model. Results: After PSM, 99 paired cases were selected from 276 patients enrolled in this study. Patients in the AR group achieved better 1-, 3-, and 5-year OS (70%, 46%, and 34%, respectively) and DFS (61%, 21%, and 10%, respectively) than patients in the NAR group with statistical significance after PSM analysis. The postoperative complications and recurrence patterns were comparable between the two groups. Multivariate analysis identified NAR, tumor size >5 cm, multiple tumors, and poor differentiation as independent risk factors for OS (p < 0.05). Selected patients can benefit most from AR, according to subgroup analysis. A prognostic nomogram based on six independent risk factors for OS and factors with clinical significance was constructed to predict OS in ICC patients. Conclusion: AR improved the long-term survival of ICC with comparable postoperative complications and similar recurrence patterns. AR is suggested in ICC patients with sufficient remnant liver volume. In addition to surgery strategy, malignant characteristics of tumors are risk factors for ICC prognosis.