Size selection of intrahepatic lesions for cryoablation contributes to abscopal effect and long-term survival in patients with liver metastatic melanoma receiving PD-1 blockade therapy.

OBJECTIVES: In this study, we aimed to examine parameters of cryoablation, tumor characteristics, and their correlations with distant tumor response and survival of liver metastatic melanoma patients receiving cryoablation and PD-1 blockade (cryo-PD-1) combination treatment. MATERIALS AND METHODS: A retrospective study was conducted among 45 melanoma patients who received combined PD-1 blockade therapy and cryoablation for liver metastasis from 2018 to 2022. Cox regression was utilized to determine the associations between factors and overall survival (OS). Changes in cytokines and immune cell compositions in peripheral blood samples following the combined treatment were investigated, along with their correlations with treatment response. RESULTS: The mean cycle of cryo-PD-1 combination treatment was 2.2 (range, 1-6), and the 3-month overall response rate (RECIST 1.1 criteria) was 26.7%. Of the 21 patients who failed previous PD-1 blockade therapy after diagnosis of liver metastasis, 4 (19.0%) achieved response within 3 months since combination treatment. The diameter of ablated lesion ≤ 30 mm, metastatic organs ≤ 2, and pre-treatment LDH level ≤ 300 U/L were independent prognostic factors for favorable OS. Further analysis showed patients with intrahepatic tumor size of 15-45 mm, and ablated lesion size of ≤ 30 mm had significantly higher 3-month response rate (42.9% vs 12.5%; P = 0.022) and survival time (30.5 vs 14.2 months; P = 0.045) than their counterparts. The average increase in NLR among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 3.59 ± 5.01 and 7.21 ± 12.57, respectively. The average increase in serum IL-6 levels among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 8.62 ± 7.95 pg/ml and 15.40 ± 11.43 pg/ml, respectively. CONCLUSION: Size selection of intrahepatic lesions for cryoablation is important in order to achieve abscopal effect and long-term survival among patients with liver metastatic melanoma receiving PD-1 blockade therapy.

The relationship between the efficacy of thermal ablation and inflammatory response and immune status in early hepatocellular carcinoma and the progress of postoperative adjuvant therapy.

Hepatocellular carcinoma (HCC) is a highly heterogeneous disease. Thermal ablation has the advantages of being equivalent to surgical resection, minimally invasive, low cost and significantly reducing hospital stay. Therefore, it is recommended as one of the first-line radical treatment for early HCC. However, with the deepening of research on early HCC, more and more studies have found that not all patients with early HCC can obtain similar efficacy after radical thermal ablation, which may be related to the heterogeneity of HCC. Previous studies have shown that inflammation and immunity play an extremely important role in the prognostic heterogeneity of patients with HCC. Therefore, the inflammatory response and immune status of patients may be closely related to the efficacy of early HCC after curative thermal ablation. This article elaborates the mechanism of high inflammatory response and poor immune status in the poor prognosis after radical thermal ablation of early HCC, and clarifies the population who may benefit from adjuvant therapy after radical thermal ablation in patients with early HCC, which provides a new idea for the precise adjuvant treatment after radical ablation of early HCC in the future.

Transarterial Chemoembolization Followed by Hepatic Arterial Infusion Chemotherapy Combined a Tyrosine Kinase Inhibitor for Treatment of Large Hepatocellular Carcinoma.

OBJECTIVE: Evaluate the efficacy and safety of transarterial chemoembolization (TACE) sequential with hepatic arterial infusion chemotherapy (HAIC) and a tyrosine kinase inhibitor (TKI) for unresectable large hepatocellular carcinoma (HCC). METHODS: Patients with HCC size > 70 mm were included. They received 1-3 cycles of TACE and sequential HAIC every 3-6 weeks for 2-6 cycles, with each cycle given over a period of 48 hours (oxaliplatin plus fluorouracil/leucovorin). Patients also received sorafenib or lenvatinib beginning at the first TACE cycle and continuing until disease progression. Objective response rate (ORR) at 3 months was the primary endpoint. Progression-free survival (PFS) and safety were the secondary endpoints. RESULTS: From January 2020 to December 2020, 41 patients were included, who were divided into the drug-eluting bead TACE (DEB-TACE) group (n=13) and conventional TACE (cTACE) group (n=28). The overall ORR was 56.1% (23/41) using mRECIST criteria and 34.1% (14/41) using RECIST1.1 criteria. The median PFS of the cohort was 8 months. The ORR of the DEB-TACE group was 76.9% (10/13) vs. 46.4% (13/28) for the cTACE group (p = 0.06). The median PFS of the DEBTACE group was 12 months, and 6 months in the cTACE group (p = 0.09). Conversion hepatectomy was performed in 2 patients in the DEB-TACE group (15.4%), and in 3 patients in the cTACE group (10.7%). ALT/AST elevated, hypertension, nausea, and vomiting were the common treatment related adverse events. There was no treatment related death. CONCLUSION: TACE sequential with HAIC combined a TKI is a well-tolerated and promising tripletherapy for large, unresectable HCC.

Clinical Implications of Phenotypes of Hemodialysis Patients With Central Venous Occlusion or Central Venous Stenosis Defined by Cluster Analysis.

Objective: This study aims to investigate the association between clinical factors of patients with central (superior vena cava, brachiocephalic, or subclavian) venous occlusion or central venous stenosis (CVO/CVS) and the difficulty of interventional recanalization as well as the duration of postoperative patency. Methods: A total of 103 hemodialysis patients with CVO/CVS treated with endovascular treatment were enrolled. The two-step cluster analysis was selected to differentiate the cases into distinct phenotypes automatically. Differences in characteristics, the difficulty of interventional recanalization, and the duration of postoperative primary patency time between the two clusters were statistically compared. Results: The 103 cases were divided into distinct two clusters by the two-step cluster analysis with 48 (46.6%) in cluster 1 and 55 (53.4%) in cluster 2. Compared to cluster 2, patients in cluster 1 have a higher proportion of blunt stump, side branches, occlusion lesions >2 cm, calcification, or organization. Moreover, the above four factors were, in turn, the most critical four predictors distinguishing 103 patients into two clusters. The remaining six factors were, in turn, occlusion located in the superior vena cava (SVC), duration of central venous catheterization (CVC), lesion location, vessel diameter, number of CVC, and previously failed lesion. Of the four most important factors, with the exception of occlusion lesions exceeding 2 cm, there were significant differences in the length of procedure time between the groups grouped by the remaining three factors. And there was a significant difference in the primary patency rate between the group with blunt stump and the group without blunt stump and also between the group with occlusion lesions ≥ 2 cm and the group with occlusion lesions <2 cm. The operation time of cluster 1 was longer than that of cluster 2. In terms of postoperative patency time, the primary patency time was significantly longer in the patients of cluster 2 compared with cluster 1 (P = 0.025). Conclusion: Patients were divided into distinct two clusters. CVO/CVS of patients in cluster 1 was more challenging to be recanalized than that in cluster 2, and the primary patency time was significantly longer in the patients of cluster 2 compared with cluster 1. Blunt stump, side branches, occlusion lesions exceeding 2 cm, and calcification or organization are the four most critical predictors distinguishing 103 patients into two clusters.

Mediastinal Hepatoid Adenocarcinoma Treated With Arterial Interventional Therapy: A Case Report and Review of Literature.

Hepatoid adenocarcinoma (HAC) is an extremely rare extrahepatic carcinoma, which is pathologically featured by hepatocellular carcinoma (HCC) and marked by producing alpha-fetoprotein (AFP). HAC of mediastinum is extremely rare. For inoperable patients, the curative treatment options have not been established, and the outcome of HAC is usually poor. Here, we present a case of mediastinal HAC with normal serum AFP level who achieved well-controlled and good response after local-regional interventional approach combined with systemic PD-1 inhibitor. A 53-year-old male who complained of chest pain was admitted to our hospital in February 2021. A chest CT scan revealed several tumors in his mediastinum. The laboratory data showed normal serum AFP level. HAC was diagnosed through pathological assessment of biopsy. Surgery was not available due to the infiltration of sternum. Local regional FOLFOX chemotherapy was given by transarterial infusion, followed by transcatheter arterial chemoembolization, and thereafter combined with systemic anti-PD-1 treatment. The patient achieved favorable disease control and apparent symptom relief. So transarterial interventional therapy combined immunotherapy may be a possible and promising treatment for mediastinal HAC.

Transradial versus Transfemoral Access for Patients with Liver Cancer Undergoing Hepatic Arterial Infusion Chemotherapy: Patient Experience and Procedural Complications.

PURPOSE: To determine whether transradial access (TRA) is a more favorable and safe method for hepatic arterial infusion chemotherapy (HAIC) than transfemoral access (TFA). MATERIALS AND METHODS: Retrospective and prospective cohorts of patients with liver cancer were included. Sixty-seven patients in the retrospective cohort were divided into 2 groups: (a) TRA-HAIC (n = 24) and (b) TFA-HAIC (n = 43). Another 33 patients were prospectively enrolled to receive both TRA and TFA for HAIC in a crossover design. Prolonged arterial access was required for up to 48 hours. The primary endpoint was quality of life (QOL) using the visual analog scale. The secondary endpoints mainly included procedural success, adverse events, and operation time. RESULTS: Patient QOL measures revealed significantly lower scores of indices in the TRA-HAIC group than in the TFA-HAIC group in the retrospective cohort (all P < .001). The significant improvement of the QOL indices by TRA-HAIC, such as overall discomfort (P = .019) and pain at the access site (P = .018), was validated in the prospective cohort. The satisfaction scores were significantly higher in the TRA-HAIC group than in the TFA-HAIC group, and patients preferred TRA-HAIC (P < .001). Radial artery occlusion (RAO) as an access-related adverse event occurred more frequently in both the retrospective and prospective cohorts (38% and 33%, P < .001 and P = .001, respectively). Notably, the multivariate analysis of RAO-associated factors showed that enoxaparin use was significantly correlated with a reduced risk of postprocedural RAO (P = .036). CONCLUSIONS: TRA was superior to TFA in patient experience. However, because of the high incidence of access-related adverse events, especially for RAO with a total incidence of 35%, strategies should be optimized for patients to benefit from TRA in future procedures.

microRNA-375 inhibits the malignant behaviors of hepatic carcinoma cells by targeting NCAPG2.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. Emerging evidence has revealed the vital functions of microRNAs (miRNAs) in cancer malignant progressions. miR-375 has been verified to serve as an antioncogene in tumorigenesis and a potential therapeutic target in various types of cancer. In this study, we aimed to determine the role of miR-375 in the regulation of chemoresistance and metastasis of HCC. Differentially expressed miR-375 and NCAPG2 were externally validated using expression data from The Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression levels of miR-375 in HCC tissues and cell lines. miR-375 mimics and NCAPG2-overexpression were transfected into HepG2 and Huh7 cells to establish miR-375 overexpression models. Cell Counting Kit-8, Transwell, and flow cytometry experiments were conducted to monitor cell proliferation, migration, and apoptosis. The targeting relationship between miR-375 and non-SMC condensin II complex subunit G 2 (NCAPG2) was determined by qRT-PCR, western blot, and luciferase reporter gene assay. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted using Gene Set Enrichment Analysis (GSEA). The pathway enrichment analysis was used to predict the potential pathways for further study. miR-375 was significantly downregulated in HCC tissues and cells compared to adjacent tissue and normal hepatocyte cell line respectively while NCAPG2 was upregulated. The targeting relationship was verified by luciferase reporting assay, and miR-375 could target the 3'UTR of NCAPG2 mRNA and effectively suppress NCAPG2 protein expression. Replenishing of miR-375 significantly repressed HCC cell proliferation and migration, and induced cell apoptosis. Overexpression of NCAPG2 recovered those biological abilities in miR-375 overexpressed cells. Collective data suggested that miR-375 served as a tumor suppressor via regulating NCAPG2. Replenishing of miR-375 or knockout of NCAPG2 could be therapeutically exploited for HCC.

The earlier, the better: The beneficial effect of different timepoints of the preoperative transarterial embolization on ameliorating operative blood loss and operative time for carotid body tumors.

BACKGROUND: To explore the effect of the optimal time interval from preoperative transarterial embolization to surgery of carotid body tumors by analyzing surgery-related indicators. METHODS: This single-center retrospective review included 103 patients and 108 carotid body tumor resections performed between June 2010 and June 2020. All carotid body tumors were divided into three groups based on interval time between transarterial embolization and surgery: 1-day group (G1), 2-day group (G2), and 3-day group (G3). Demographics, inflammatory biomarkers, periprocedural details, and postoperative outcomes were analyzed. RESULTS: Among 103 patients, 48.54% were women, and the mean age was 37.07 years. The tumor sizes were 43.83, 44.31, and 42.84 mm in G1, G2, and G3, respectively, and the blood loss and operative time were 163.68, 331.54, and 683.68 mL, and 182.32, 216.31, and 280.79 mins with the prolonged time interval, respectively. Compared with pretransarterial embolization, the expression of white blood cells (109/L) and neutrophils (109/L) were obviously increased post-transarterial embolization in the three groups (G1: white blood cells 6.81 vs 9.32; neutrophils 0.54 vs 0.74, all P < .05. G2: white blood cells 7.19 vs 10.01, P = .118; neutrophils 0.54 vs 0.77, P < .05. G3: white blood cells 7.08 v. 12.37; neutrophils 0.59 vs 0.80, all P < .05), and those in G3 were significantly higher than those in G1. The incidences of revascularization, which was 30.26%, 53.85%, and 42.10%, and adverse events (26.32%, 30.77%, and 21.05%) were not significantly different among G1, G2, and G3. CONCLUSION: The optimal time interval between preoperative transarterial embolization and surgical resection resulted as 1 day as patients in this group showed obvious lower blood loss and shorter duration of operation than patients in other groups. Both inflammation and recanalization provided support for these results at some extent.

Prognostic value of splenic volume in hepatocellular carcinoma patients receiving transarterial chemoembolization.

BACKGROUND: Liver function is a key determinant for the survival of hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE). However, establishing robust prognostic indicators for liver insufficiencies and patient survival remains an unmet demand. This retrospective study evaluated the prognostic value of splenic volume (SV) in HCC patients undergoing TACE. METHODS: A total of 67 HCC patients who underwent at least two consecutive TACE procedures were retrospectively included in this study. Comprehensive clinical information and follow-up data were collected, and the SV was measured based on dynamic contrast enhanced images. Risk factors of SV enlargement were assessed. The prognostic value of SV on survival was analyzed and compared with Child-Pugh (CP) classification and albumin-bilirubin (ALBI) grade. RESULTS: The baseline SV was 299.74±143.63 cm3, and showed a moderate and statistically significant correlation with CP classification (R=0.31, P<0.05). The SV increased remarkably after the first and second TACE procedures (330.16±155.38 cm3, P<0.01, and 355.63±164.26 cm3, P<0.01, respectively). In survival analysis, the optimal cut-off value of SV was determined as 373 cm3 using X-tile software, and the patients were divided into the small SV group and the large SV groups accordingly. Based on the pre-TACE SV, the median overall survival (mOS) for patients in the small SV group and the large SV group was 458 days and 249 days, respectively (P<0.05). After the first and second TACE, the mOS in the small SV group and the large SV group were 454 vs. 266 days (P<0.05) and 526 vs. 266 days (P<0.05), respectively. No prognostic value of CP classification and ALBI grade was identified for these patients. Furthermore, there were no significant differences between the small and large SV groups in age, tumor stage, and ALBI grade, except for CP classification (P<0.05). CONCLUSIONS: SV was correlated with CP classification and was a robust predictor for HCC patients undergoing TACE treatment.