Research progress of Yttrium-90 microsphere selective internal radiation therapy in downstaging and conversion of hepatocellular carcinoma

The incidence and mortality of hepatocellular carcinoma (HCC) in China are among the highest in the world, imposing a heavy social burden. Liver resection and liver transplantation are the primary radical treatments for HCC, although most patients are no longer able to meet the surgical requirements at initial diagnosis. Yttrium-90 microsphere selective internal radiation therapy (90Y-SIRT) has the advantages of shrinking tumors, enlarging residual liver, regressing portal vein tumor thrombus and improving the quality of life, which can be used for conversion, downstaging and bridging therapy for HCC before surgical treatment, enabling patients regain the chance of radical treatment and reducing the postoperative recurrence rate. This review focuses on the clinical application and progress of 90Y-SIRT in this field

Dual pH-sensitive nanodrug blocks PD-1 immune checkpoint and uses T cells to deliver NF-κB inhibitor for antitumor immunotherapy

A potent drug delivery strategy promotes tumor infiltration of T cells and unleashes antitumor immunity.</jats:p

High Expression of Ten Eleven Translocation 1 Is Associated with Poor Prognosis in Hepatocellular Carcinoma

Background. DNA methylation patterns have been found to be distinct between tumor and normal patients. However, the effect of DNA demethylation enzymes, ten eleven translocation (TET) proteins, has not been comprehensively characterized in liver cancer. In this research, we sought to unravel the linkage of TET proteins with prognosis, immune characteristics and biological pathways in hepatocellular carcinoma (HCC). Materials and Methods. Four independent datasets with gene expression data and clinical data of HCC samples were downloaded from public databases. CIBERSORT, single sample Gene Set Enrichment Analysis (ssGSEA), MCP-counter, and TIMER were implemented to evaluate immune cell infiltration. limma was employed to screen differentially expressed genes (DEGs) between two groups. The demethylation-related risk model was established by using univariate Cox regression analysis, the least absolute shrinkage and selection operator (LASSO), and stepwise Akaike information criterion (stepAIC). Results. TET1 was significantly higher expressed in tumor samples than that in normal samples. HCC patients with advanced stages (III+IV) and grades (G3+G4) had higher TET1 expression compared to early stages (I+II) and grades (G1+G2). HCC samples with high TET1 expression had worse prognosis than that with low expression. High and low TET1 expression groups had distinct immune cell infiltration and response to immunotherapy and chemotherapy. We identified 90 DEGs related to DNA demethylation in high vs. low TET1 expression groups. Furthermore, we established a risk model based on 90 DEGs containing seven key prognostic genes (SERPINH1, CDC20, HACD2, SPHK1, UGT2B15, SLC1A5, and CYP2C9) with effectiveness and robustness in predicting HCC prognosis. Conclusions. Our study suggested TET1 as a potential indicator in HCC progression. TET1 was closely involved in immune infiltration and activation of oncogenic pathways. The DNA demethylation-related risk model was potential to be applied for predicting HCC prognosis in clinics

Particle-Swarm-Optimization-Based Operation of Secondary Heat Supply Networks

Urban centralized heating systems, as a crucial component of the energy transition, face new challenges in terms of reliable and balanced operation, energy-saving performance, and optimized control. Based on the accurate quantification of user heat load, an operational optimization method for secondary heating networks is proposed. By accurately analyzing the actual heating demands of different users according to building characteristics and climatic conditions and integrating the hydraulic and thermal modeling of a pipeline network, a Particle Swarm Optimization (PSO) algorithm is employed to optimize the valve opening degrees of users and the secondary side, achieving the optimal operating state of the secondary network that matches user load and obtaining the optimal valve regulation strategy. The results of a case analysis show that, after optimization, the overall variance of return water temperature for heat users decreased by 12.16%, and the electricity consumption of the secondary network circulation pump was reduced by 16.46%, demonstrating the effectiveness and practicality of the proposed optimization method. On the basis of ensuring hydraulic balance in the heating system, the method meets the individual heating demands of users, effectively improves user thermal comfort, and reduces energy consumption, addressing the issues of excessive and uneven heat supply

Risk Factors, Patterns, and Long-Term Survival of Recurrence After Radiofrequency Ablation With or Without Transarterial Chemoembolization for Hepatocellular Carcinoma

ObjectivesTo classify hepatocellular carcinoma (HCC) recurrence patterns after radiofrequency ablation (RFA) or transarterial chemoembolization (TACE) combined with RFA (TACE-RFA) and analyze their risk factors and impacts on survival.MethodsWe retrospectively evaluated the medical records of HCC patients who underwent RFA or TACE-RFA from January 2006 to December 2016. HCC recurrences were classified into four patterns: local tumor progression (LTP), intra-segmental recurrence, extra-segmental recurrence, and aggressive recurrence. Risk factors, overall survival (OS), and post-recurrence survival of each pattern were evaluated.ResultsA total of 249 patients with a single, hepatitis-B virus (HBV)-related HCC ≤ 5.0 cm who underwent RFA (HCC ≤ 3.0 cm) or TACE-RFA (HCC of 3.1-5.0 cm) were included. During follow-up (median, 53 months), 163 patients experienced HCC recurrence: 40, 43, 62 and 18 patients developed LTP, intra-segmental recurrence, extra-segmental recurrence, and aggressive recurrence, respectively; the median post-recurrence survival was 49, 37, 25 and 15 months, respectively (P &amp;lt; .001); the median OS was 65, 56, 58 and 28 months, respectively (P &amp;lt; .001). Independent risk factors for each pattern were as follows: tumor sized 2.1-3.0 cm undergoing RFA alone and insufficient ablative margin for LTP, periportal tumor and non-smooth tumor margin for intra-segmental recurrence, HBV-DNA ≥ 2000 IU/mL for extra-segmental recurrence, and periportal tumor and α-fetoprotein ≥ 100 ng/mL for aggressive recurrence. Recurrence pattern (P &amp;lt; .001) and Child-Pugh class B (P = .025) were independent predictors for OS.ConclusionsBased on our classification, each recurrence pattern had different recurrence risk factors, OS, and post-recurrence survival.</jats:sec

Mechanisms and therapeutic strategies to combat the recurrence and progression of hepatocellular carcinoma after thermal ablation

Thermal ablation (TA), including radiofrequency ablation (RFA) and microwave ablation (MWA), has become the main treatment for early-stage hepatocellular carcinoma (HCC) due to advantages such as safety and minimal invasiveness. However, HCC is prone to local recurrence, with more aggressive malignancies after TA closely related to TA-induced changes in epithelial-mesenchymal transition (EMT) and remodeling of the tumor microenvironment (TME). According to many studies, various components of the TME undergo complex changes after TA, such as the recruitment of innate and adaptive immune cells, the release of tumor-associated antigens (TAAs) and various cytokines, the formation of a hypoxic microenvironment, and tumor angiogenesis. Changes in the TME after TA can partly enhance the anti-tumor immune response; however, this response is weak to kill the tumor completely. Certain components of the TME can induce an immunosuppressive microenvironment through complex interactions, leading to tumor recurrence and progression. How the TME is remodeled after TA and the mechanism by which the TME promotes HCC recurrence and progression are unclear. Thus, in this review, we focused on these issues to highlight potentially effective strategies for reducing and preventing the recurrence and progression of HCC after TA

Sintilimab plus bevacizumab as maintenance therapy for patients with unresectable hepatocellular carcinoma treated with transarterial chemoembolization: A phase Ib study.

e16165 Background: Sintilimab (a PD-1 inhibitor) plus bevacizumab (Sin-Bev) has been demonstrated to confer a significant survival benefit over sorafenib in patients with unresectable hepatocellular carcinoma (uHCC). This phase Ib study (NCT04592029) aimed to evaluate the safety and efficacy of Sin-Bev for patients with uHCC who received transarterial chemoembolization (TACE). Methods: The key eligibility criteria were: age ≥ 18 years; BCLC B/C stage uHCC; no prior systemic therapy and non-curative local treatments; Child-Pugh score ≤7; ECOG PS ≤1. This study included dose escalation and dose expansion stages. In the dose escalation stage, a 3+3 design was employed to determine the safety of a standard dose of sintilimab (200 mg Q3W) plus two possible doses of bevacizumab (group A: 7.5 mg/kg Q3W; group B: 15.0 mg/kg Q3W) after TACE. In the dose expansion stage, additional 30 patients were randomized 1:1 to each group. Sintilimab and bevacizumab was started at 3-7 days after the first TACE (TACE was repeated on demand). The primary endpoints were the incidence of adverse events (AEs) and progression free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: At the time of data cutoff (January 20th, 2022), 36 patients were enrolled (18 in each group). One patient in group A withdrew from the study after the first cycle of treatment. Of the remaining 35 patients, 20 (57.1%) had disease at BCLC C stage, 15 (42.9%) had macroscopic vascular invasion and 11 (31.4%) had extrahepatic metastasis. The mean largest tumor size was 10.5±5.2 cm. The median follow-up was 9.57 (range, 4.4-15.6) months. Thirty-one patients (86.1%, n=36) had treatment-related AEs (83.3% in group A vs. 88.9% in group B, P=1.000). All the AEs were mild (&lt;grade 2) and manageable. During follow-up, 19 patients (54.3%) experienced disease progression (per RECIST 1.1 or mRECIST). The median PFS was 7.2 (95% CI 3.6-10.8) months (6.7 [95% CI 4.7-8.8] months in group A vs. 8.4 [95% CI 3.9-12.8] months in group B, P=0.832). The median PFS in this report was immature due to some later enrolled patients were censored. Thus, it is likely to improve with longer follow-up. The ORR per RECIST 1.1 and mRECIST was 37.1% (41.2% in group A vs. 33.3% in group B, P=0.733) and 80.0% (88.2 in group A vs. 72.2% in group B, P=0.402), respectively. The DCR per RECIST 1.1 or mRECIST was 91.4% (94.1% in group A vs. 88.9% in group B, P=1.000). The median OS was not reached. Conclusions: Sin-Bev showed preliminary clinical benefits and an acceptable safety profile in uHCC patients treated with TACE. The study is still ongoing and further follow-up is required to obtain the final survival results. Clinical trial information: NCT04592029. </jats:p