Relationships Among Serological Indicators and In Vitro High-Throughput Drug Sensitivity Screening Results in Patients with Hepatocellular Carcinoma.

AIM: The purpose of this study was to analyze the relationship between serum indicators and high-throughput drug screening (HDS) results, aiming to achieve specific therapy for hepatocellular carcinoma (HCC). METHODS: This study recruited patients with HCC who underwent surgical resection at the Hepatobiliary Surgery Center of the First Affiliated Hospital of Chongqing Medical University from December 2019 to December 2021. HCC tissues were obtained from patients during surgery and subjected to in vitro cell culture, and then HDS testing was performed on the cultured tissue samples. We used Spearman's correlation analysis to examine the relationships between drug sensitivity results for anti-hepatocellular carcinoma drugs, other antitumor drugs, and serological indicators, the Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Systemic Immune Inflammatory Index (SII), Systemic Inflammatory Response Index (SIRI), Prognostic Nutritional Index (PNI), and Lymphocyte Monocyte Ratio (LMR). A significant correlation was considered when P<0.05 and |r|>0.40. Furthermore, linear regression analysis was conducted to elucidate the relationship between serological indicators and drug susceptibility, with significant results indicated by P<0.05 and R²≥0.50. RESULTS: In this study, 82 patients with HCC who had undergone hepatectomy and completed in vitro cell culture and HDS testing were evaluated. Using Spearman's correlation with a significance threshold of P<0.05 and |r|>0.40, we identified significant associations between serological indicators and specific drug regimens: NLR correlated with 5-Fluorouracil, 5- Fluorouracil+Calcium folinate (FOLFOX4), and Capecitabine + Cisplatin (XP); PLR with FOLFOX4; SII with XP, FOLFOX4, Doxorubicin + Oxaliplatin (ADM+L-OHP); and SIRI with XP and FOLFOX4. No correlations were found between PNI or LMR and any drug inhibition rates. A comprehensive evaluation using linear regression analysis-which included variables such as sex, age, hepatitis B virus and liver cirrhosis status, size and number of lesions, alphafetoprotein, total bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, and prothrombin time, alongside NLR, PLR, SII, and SIRI was conducted in relation to drug regimens. This analysis revealed that NLR, SII, and SIRI are significant predictors of FOLFOX4 inhibition rate, while NLR predicts the inhibition rate of XP effectively. However, no significant links were established between molecular targeted drugs, other antitumor drugs, and serological indicators. CONCLUSIONS: NLR, SII, and SIRI were correlated with FOLFOX4, and the higher the values of NLR, SII, and SIRI, the higher the in vitro inhibition of FOLFOX. Also, NLR was correlated with XP, and the higher the value of NLR, the higher the in vitro inhibition of XP.

Benefits of Hypothermic Oxygenated Perfusion Versus Static Cold Storage in Liver Transplant: A Comprehensive Systematic Review and Meta-analysis.

Background: The magnitude of potential benefits that hypothermic oxygenated perfusion (HOPE) may provide for liver transplantation (LT) patients compared to static cold storage (SCS) remains uncertain. In this systematic review and meta-analysis, we aimed to investigate the therapeutic effect that HOPE can offer LT recipients relative to SCS by synthesizing available evidence. Methods: A literature search was conducted in Embase, Medline, Web of Science, and the Cochrane database up to 1 June, 2023. The included studies were pooled for meta-analysis to synthesize their findings. Subgroup analysis was performed to investigate potential differences between HOPE and SCS for specific subgroups. Results: A total of 11 studies comprising 1765 patients were included. Compared with SCS, HOPE was associated with a significant reduction in the incidence of early allograft dysfunction (EAD) (OR: 0.36, 95% CI: 0.26-0.50), as well as a noteworthy decrease in graft loss rate within one year (OR: 0.57, 95% CI: 0.33-0.97) and a lower occurrence of Clavien-Dindo grade IIIa or higher complications (OR: 0.62, 95% CI: 0.43-0.89). Subgroup analysis revealed that HOPE significantly reduced the one-year mortality rate, any biliary complications incidence, and acute rejection of transplanted liver rate in patients who received organs from donation after cardiac death (DCD). Conclusions: HOPE has demonstrated efficacy in reducing the incidence of EAD after LT and shows some potential in diminishing postoperative complications such as biliary complications and acute rejection. This ultimately leads to improved patient prognosis, particularly among those receiving DCD grafts.

Analysis of Related Influencing Factors of Portal Vein Thrombosis After Hepatectomy.

Purpose: To analyze the related factors of portal vein thrombosis (PVT) after hepatectomy. Methods: A retrospective analysis was made on 1029 patients who underwent partial hepatectomy in the first affiliated Hospital of Chongqing Medical University from March 2018 to March 2023, including PVT group (n = 24) and non-PVT group (n = 1005). The general and clinical data of the two groups were collected. Univariate and multivariate logistic regression analysis was used to analyze the clinical information of the two groups. Result: The proportion of preoperative hepatitis B, liver cirrhosis, ascites, intraoperative blood transfusion, postoperative hemostatic drugs, preoperative prothrombin time, intraoperative portal occlusion time, operation time, international standardized ratio of prothrombin time on the first day after operation, D-dimer on the first day after operation, fibrin degradation products on the first day after operation and postoperative hospital stay in the PVT group were all higher than those in the control group (P < .05). The preoperative platelet and albumin in the PVT group were lower than those in the control group. Intraoperative blood transfusion, liver cirrhosis, ascites, international standardized ratio of postoperative prothrombin time, postoperative fibrin degradation products, hilar occlusion time and albumin were independent risk factors for PVT. Conclusion: There are many influencing factors of PVT after hepatectomy. Clinical intervention should be taken to reduce PVT. Clinical Registration Number: K2023-348.

Development and validation of a risk prediction algorithm for evaluating the efficacy of postoperative adjuvant TACE therapy for hepatocellular carcinoma.

BACKGROUND AND PURPOSE: There is a lack of a reliable outcome prediction model for patients evaluating the feasibility of postoperative adjuvant transarterial chemoembolization (PA-TACE) therapy. Our goal was to develop an easy-to-use tool specifically for these patients. METHODS: From January 2013 to June 2017, patients with hepatocellular carcinoma from the Liver Center of the First Affiliated Hospital of Chongqing Medical University received postoperative adjuvant Transarterial chemoembolization (TACE) therapy after liver cancer resection. A Cox proportional hazards model was established for these patients, followed by internal validation (enhanced bootstrap resampling technique) to further evaluate the predictive performance and discriminanceevaluate the predictive performance and discriminance, and compare it with other predictive models. The prognostic factors considered included tumour number, maximum tumor diameter, Edmondson-Steiner (ES) grade, Microvascular invasion (MVI) grade, Ki67, age, sex, hepatitis B surface antigen, cirrhosis, Alpha-fetoprotein(AFP), Albumin-bilirubin (ALBI) grade, Child-pugh grade, body mass index (BMI), Neutrophil-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR). RESULTS: The endpoint of the study was overall survival. The median overall survival was 36 (95%CI: 34.0-38.0 ) months, with 1-year, 2-year and 3-year survival rates being 96.3%, 84.0% and 75.3%, respectively. Tumour number, MVI grade, and BMI was incorporated into the model, which had good differentiation and accuracy. Internal validation (enhanced bootstrap ) suggested that Harrell's C statistic is 0.72. The model consistently outperforms other currently available models. CONCLUSION: This model may be an easy-to-use tool for screening patients suitable for PA-TACE treatment and guiding the selection of clinical protocols. But further research and external validation are required.

Comparison of different adjuvant therapy regimen efficacies in patients with high risk of recurrence after radical resection of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) has a high recurrence rate even after radical surgery. Postoperative adjuvant transhepatic arterial chemoembolization (PA-TACE), postoperative adjuvant hepatic arterial infusion chemotherapy (PA-HAIC), postoperative adjuvant radiotherapy (PA-RT), and postoperative adjuvant molecular targeted therapy have been demonstrated to be effective in reducing the postoperative recurrence rate. The present network meta-analysis was conducted to compare the effects of PA-TACE, PA-HAIC, PA-RT and postoperative adjuvant molecular targeted therapy on the overall survival (OS) and disease-free survival (DFS) in HCC patients after radical resection and to determine the optimal treatment strategy. METHODS: Network meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane Library, and Web of Science were used to collect eligible studies up to December 25, 2022. Studies related to PA-TACE, PA-HAIC, and postoperative adjuvant molecular targeted therapy after radical HCC resection was included. The endpoints were OS and DFS, and the effect size was determined using hazard ratio with a 95% confidence interval. R software and "gemtc" package were employed to analyze the results. RESULTS: A total of 38 studies involving 7079 patients with HCC after radical resection were ultimately enrolled to be analyzed. Four postoperative adjuvant therapy measures and two oncology indicators were evaluated. In this study, OS-related investigations validated that PA-Sorafenib and PA-RT markedly enhanced the OS rates in patients after radical resection when compared to PA-TACE and PA-HAIC. However, statistical analysis revealed no significant difference between PA-Sorafenib and PA-RT, as well as PA-TACE and PA-HAIC. In the DFS-related investigations, PA-RT demonstrated superior efficacy over PA-Sorafenib, PA-TACE, and PA-HAIC. Additionally, PA-Sorafenib displayed better efficacy than PA-TACE. Nevertheless, there was no statistical significance between PA-Sorafenib and PA-HAIC, as well as PA-TACE and PA-HAIC. We also performed a subgroup analysis of studies focusing on HCC complicated by microvascular invasion after radical resection. In terms of OS, both PA-RT and PA-Sorafenib demonstrated a noteworthy improvement over PA-TACE, whereas no statistical significance was detected between PA-RT and PA-Sorafenib. Likewise, for DFS, both PA-Sorafenib and PA-RT exhibited superior efficacy compared to PA-TACE. CONCLUSION: In patients with HCC after radical resection and a high risk of recurrence, both PA-Sorafenib and PA-RT significantly improved OS and DFS when compared to PA-TACE and PA-HAIC. Notably, PA-RT exhibited superior efficacy over PA-Sorafenib, PA-TACE, and PA-HAIC in terms of DFS. Similarly, PA-Sorafenib appeared to be more effective than PA-TACE for DFS.