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.

NK-92MI Cells Engineered with Anti-claudin-6 Chimeric Antigen Receptors in Immunotherapy for Ovarian Cancer.

Background: The application of chimeric antigen receptor (CAR) NK cells in solid tumors is hindered by lack of tumor-specific targets and inefficient CAR-NK cell efficacy. Claudin-6 (CLDN6) has been reported to be overexpressed in ovarian cancer and may be an attractive target for CAR-NK cells immunotherapy. However, the feasibility of using anti-CLDN6 CAR-NK cells to treat ovarian cancer remains to be explored. Methods: CLDN6 expression in primary human ovarian cancer, normal tissues and cell lines were detected by immunohistochemistry and western blot. Two types of third-generation CAR NK-92MI cells targeting CLDN6, CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) and CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB) were constructed by lentivirus transfection, sorted by flow cytometry and verified by western blot and qPCR. OVCAR-3, SK-OV-3, A2780, Hey and PC-3 cells expressing the GFP and luciferase genes were transduced. Subcutaneous and intraperitoneal tumor models were established via NSG mice. The ability of CLDN6-CAR NK cells to kill CLDN6-positive ovarian cancer cells were evaluated in vitro and in vivo by live cell imaging and bioluminescence imaging. Results: Both CLDN6-CAR1 and CLDN6-CAR2 NK-92MI cells could specifically killed CLDN6-positive ovarian cancer cells (OVCAR-3, SK-OV-3, A2780 and Hey), rather than CLDN6 negative cell (PC-3), in vitro. CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) exhibited stronger cytotoxicity than CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB). Furthermore, CLDN6-CAR1 NK cells could effectively eliminate ovarian cancer cells in subcutaneous and intraperitoneal tumor models. More importantly, CAR-NK cells combined with immune checkpoint inhibitors, anti-PD-L1, could synergistically enhance the antitumor efficacy of CLDN6-targeted CAR-NK cells. Conclusions: These results indicate that CLDN6-CAR NK cells possess strong antitumor activity and represent a promising immunotherapeutic modality for ovarian cancer.

The important role of whole-process computed tomography guidance for percutaneous gastrostomy in esophageal cancer patients who are unsuitable for or have had unsuccessful attempts with endoscopic and fluoroscopic gastrostomy.

PURPOSE: To explore the value of clinical application with the whole process computed tomography (CT) guided percutaneous gastrostomy in esophageal tumor patients. MATERIALS AND METHODS: A consecutive series of 32 esophageal tumor patients in whom endoscopic gastrostomy or fluoroscopy guided gastrostomy were considered too dangerous or impossible due to the esophagus complete obstruction, complicate esophageal mediastinal fistula, esophageal trachea fistula or severe heart disease. All of the 32 patients were included in this study from 2 medical center and underwent the gastrostomy under whole process CT guided. RESULTS: All of the gastrostomy procedure was finished successfully under whole process CT guided and the technical success rate was 100%. The average time for each operation was 27 min. No serious complications occurred and the minor complications occurred in 3 patients, including local infection, severe hyperplasia of granulation tissue and tube dislodgment. There were no procedure related deaths. CONCLUSION: The technical success rate of whole process CT guided percutaneous gastrostomy is high and the complication is low. This technique can be used feasible and effectively in some special patients.

Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

Local treatment of liver metastasis in a patient with advanced malignant melanoma: A case report.

Melanoma is a fatal malignant tumor with a high rate of metastasis. Liver metastasis of melanoma is always associated with insensitivity to immunotherapy and a poor prognosis. However, the combination of cryoablation, which is believed to stimulate the antitumor immune response in the body, with immunotherapy can improve the therapeutic response to this condition. Herein, we present the case of a 79-year-old woman with BRAF (B-Raf proto-oncogene) wild-type melanoma who later developed liver metastasis. The patient received intravenous antiprogrammed cell death 1 antibody, which showed poor efficacy, and subsequent treatment with immunotherapy combined with cryoablation yielded a partial response. However, after the second cryoablation, the patient refused further treatment due to a fear of bleeding. Therefore, only immunotherapy was provided, which resulted in disease progression. This report demonstrates the need to consider immunotherapy plus cryoablation for the treatment of liver metastases in patients with BRAF wild-type melanoma.

Selective Organ-Targeting Hafnium Oxide Nanoparticles with Multienzyme-Mimetic Activities Attenuate Radiation-Induced Tissue Damage.

Radioprotective agents hold clinical promises to counteract off-target adverse effects of radiation and benefit radiotherapeutic outcomes, yet the inability to control drug transport in human organs poses a leading limitation. Based upon a validated rank-based multigene signature model, radiosensitivity indices are evaluated of diverse normal organs as a genomic predictor of radiation susceptibility. Selective ORgan-Targeting (SORT) hafnium oxide nanoparticles (HfO2 NPs) are rationally designed via modulated synthesis by α-lactalbumin, homing to top vulnerable organs. HfO2 NPs like Hensify are commonly radioenhancers, but SORT HfO2 NPs exhibit surprising radioprotective effects dictated by unfolded ligands and Hf(0)/Hf(IV) redox couples. Still, the X-ray attenuation patterns allow radiological confirmation in target organs by dual-beam spectral computed tomography. SORT HfO2 NPs present potent antioxidant activities, catalytically scavenge reactive oxygen species, and mimic multienzyme catalytic activities. Consequently, SORT NPs rescue radiation-induced DNA damage in mouse and rabbit models and provide survival benefits upon lethal exposures. In addition to inhibiting radiation-induced mitochondrial apoptosis, SORT NPs impede DNA damage and inflammation by attenuating activated FoxO, Hippo, TNF, and MAPK interactive cascades. A universal methodology is proposed to reverse radioenhancers into radioprotectors. SORT radioprotective agents with image guidance are envisioned as compelling in personalized shielding from radiation deposition.

Clinical application of radiofrequency ablation-assisted coaxial trocar biopsies for pulmonary nodules at a high risk of bleeding.

Context: The purpose of this study was to assess computed tomography (CT)-guided puncture biopsy of pulmonary nodules at a high risk of bleeding. First, a coaxial trocar technique was used to radiofrequency ablate small blood vessels in the puncture area, followed by a biopsy of the pulmonary nodule. Aim: This study aimed to evaluate the effectiveness and safety of this procedure. Methods: In this retrospective research, we assessed the relevant data of 45 patients who had undergone needle biopsy of pulmonary nodules at a high risk of bleeding. Twenty-five of these patients had CT-guided coaxial radiofrequency ablation (RFA)-assisted biopsy (group A). The remaining 20 had undergone conventional CT-guided needle biopsy (group B). We equated the technical success rate and the incidence of complications such as bleeding, pneumothorax, and pain in the two groups of needle biopsies. Results: Both groups had a 100% success rate with puncture biopsy. The incidences of pneumothorax in groups A and B were 10% (2/20) and 24% (6/25), respectively; this difference is not significant (P > 0.050). The rates of bleeding in groups A and B were 10% (2/20) and 44% (11/25), respectively, and the rates of pain were 30% (6/20) and 60% (15/25), both of which were statistically significant (P = 0.030; P = 0.045, respectively). Conclusions: CT-guided coaxial trocar technique for RFA-assisted biopsy of pulmonary nodules at a high risk of bleeding is effective and safe and can significantly reduce the risk of biopsy-induced pulmonary hemorrhage.

Identification of prognosis-related cyclin-dependent kinases and potential response drugs in hepatocellular carcinoma.

Context and Aims: Which cyclin-dependent kinases (CDKs) involved in the progress of hepatocellular carcinoma (HCC) need to be further clarified. To identify prognostic-relevant biomarkers in HCC through a systematic investigation of the prognostic value of CDKs. Methods and Material: We explored the relationship between CDKs expression and the prognosis of patients with HCC using multiple online databases. In addition, their biological functions and correlation with the immune system and drug response were investigated. Results: Among the 20 CDKs (CDK1 ~20) altered in HCC, the significantly high expression of CDK1 and CDK4 in patients with HCC was significantly associated with worse prognosis. Interestingly, CDK1 had significant co-occurrence with CDK4 and CDK1-related and CDK4-related signaling pathways are closely related to hepatitis virus-related HCC. We identified multiple transcription factors of CDK1 and CDK4; of those, only four (E2F1, PTTG1, RELA, and SP1) were significantly associated with the prognosis of HCC patients. Genetic alterations in CDKs were significantly correlated with disease-free and progression-free survival, which may be associated with aberrant expression of progesterone receptor. Moreover, we found a significantly positive correlation between CDK1 and CDK4 expression and tumor-infiltrating activated CD4+ T cell and exhausted T cell-related signature. Finally, we identified drugs with good potential prognostic value predicted by CDK1 and CDK4 levels. Conclusions: CDK1 and CDK4 may be potential prognostic biomarkers for HCC. Moreover, targeting four transcription factors (E2F1, PTTG1, RELA, and SP1) combined with immunotherapy may be a new therapeutic strategy for treating HCC patients with high CDK1 and CDK4 expression, especially hepatitis-related HCC.

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 Combined With Apatinib Plus PD-1 Inhibitors for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Multicenter Retrospective Study.

INTRODUCTION: The aim of this study was to compare transarterial chemoembolization (TACE) combined with apatinib and PD-1 inhibitors (TACE-AP) with TACE combined with apatinib alone (TACE-A) in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) and to explore the prognostic factors affecting the survival of patients. METHODS: This retrospective study analyzed data of patients with HCC with PVTT who were treated with TACE-AP or TACE-A between December 2018 and June 2021. The primary end points of the study were progression-free survival (PFS) and overall survival (OS), and the secondary end points were objective response rate (ORR) and adverse events (AEs). Propensity score matching (PSM) and stabilized inverse probability weighting (sIPTW) analyses were used to reduce patient selection bias, and Cox regression analysis was used to analyze prognostic factors affecting patient survival. RESULTS: Sixty-nine and 40 patients were included in the TACE-A and TACE-AP groups, respectively. After PSM and IPTW analyses, the median PFS and median OS in the TACE-AP group were significantly higher than those in the TACE-A group (PFS: after PSM, 6.9 vs 4.0 months, P < 0.001, after IPTW, 6.5 vs 5.1 months, P < 0.001; OS: after PSM, 14.6 vs 8.5 months P < 0.001, after IPTW, 16.1 vs 10.5 months, P < 0.001). After PSM and IPTW analyses, the tumor ORR in the TACE-AP group was significantly higher than that in the TACE-A group (PSM, 53.6% vs 17.9%, P = 0.005; IPTW, 52.5% vs 28.6%, P = 0.013). All treatment-related AEs were observed to be tolerated. Multivariate Cox regression analysis showed that the main prognostic factors affecting the survival of patients were tumor number, PVTT type, alpha-fetoprotein, and treatment mode. DISCUSSION: In the treatment of patients with HCC with PVTT, TACE-AP significantly improved PFS, OS, and ORR, and the AEs were safe and controllable.

SurvivalPath:A R package for conducting personalized survival path mapping based on time-series survival data.

The survival path mapping approach has been proposed for dynamic prognostication of cancer patients using time-series survival data. The SurvivalPath R package was developed to facilitate building personalized survival path models. The package contains functions to convert time-series data into time-slices data by fixed interval based on time information of input medical records. After the pre-processing of data, under a user-defined parameters on covariates, significance level, minimum bifurcation sample size and number of time slices for analysis, survival paths can be computed using the main function, which can be visualized as a tree diagram, with important parameters annotated. The package also includes function for analyzing the connections between exposure/treatment and node transitions, and function for screening patient subgroup with specific features, which can be used for further exploration analysis. In this study, we demonstrate the application of this package in a large dataset of patients with hepatocellular carcinoma, which is embedded in the package. The SurvivalPath R package is freely available from CRAN, with source code and documentation hosted at https://github.com/zhangt369/SurvivalPath.

Transarterial chemoembolization combined with apatinib with or without PD-1 inhibitors in BCLC stage C hepatocellular carcinoma: A multicenter retrospective study.

Objective: We evaluated the efficacy and safety of transarterial chemoembolization (TACE) combined with apatinib plus PD-1 inhibitors (TACE-AP) compared with TACE combined with apatinib (TACE-A) in patients with advanced hepatocellular carcinoma (HCC) and to explore the prognostic factors affecting patient survival. Methods: Data from patients with unresectable HCC who received TACE-AP or TACE-A from December 2018 to June 2021 were collected retrospectively. The main outcome of the study was overall survival (OS) and prognostic factors affecting survival, while the secondary outcomes were progression-free survival (PFS), the objective response rate (ORR), and treatment-related adverse events (TRAEs). Propensity score matching (PSM) analysis was used to reduce patient selection bias, and the random survival forest (RF) model was employed to explore prognostic factors affecting patient survival. Results: We enrolled 216 patients, including 148 and 68 patients in the TACE-A and TACE-AP groups, respectively. A total of 59 pairs of patients were matched using PSM analysis. Before and after PSM, the OS, PFS, and ORR in the TACE-AP group were significantly higher than in the TACE-A group (before, OS: 22.5 months vs. 12.8 months, P < 0.001; PFS: 6.7 months vs. 4.3 months, P < 0.001; ORR: 63.2% vs. 34.5%, P < 0.001; after, OS: 22.5 months vs. 12.0 months, P < 0.001; PFS: 6.7 months vs. 4.3 months, P < 0.001; ORR: 62.7% vs. 30.5%, P = 0.003). Multivariate Cox regression and RF models before and after PSM analysis revealed that the main prognostic factors affecting survival were tumor number, portal vein tumor thrombus (PVTT) invasion, alpha-fetoprotein (AFP) levels, total bilirubin (TBIL) level, and treatment. There was no significant difference in TRAEs between the two groups (P > 0.05). Conclusion: Compared with TACE-A, TACE-AP significantly improved OS, PFS, and ORR in patients with advanced HCC. The number of tumors, PVTT invasion, AFP levels, TBIL level, and treatment were significant prognostic factors associated with patient survival. All observed TRAEs were mild and controllable.

Prospective study of TACE combined with sorafenib vs TACE combined with 125I seed implantation in the treatment of hepatocellular carcinoma with portal vein tumor thrombus and arterioportal fistulas.

Purpose: To compare the efficacy of TACE combined with sorafenib and TACE combined with 125I seed implantation in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) combined with arterioportal fistulas (APFs), and discuss the efficacy and safety of TACE combined with 125I seed implantation. Patients and methods: Between January 2017 and December 2018, the clinical data of patients with HCC complicated with PVTT and APFs who were admitted to the Affiliated Cancer Hospital of Zhengzhou University, First Affiliated Hospital of Zhengzhou University, and Henan Provincial People's Hospital were prospectively collected. The patients were divided into the TACE+sorafenib (TACE-S) group based on their treatment willingness. There were 26 and 32 patients in the TACE-S and TACE-125I groups, respectively. Both groups of patients underwent APFs occlusion during TACE therapy. The embolization effect of APFs was observed and recorded in the two groups, the efficacy of intrahepatic lesions and PVTT was evaluated, and the effects of different treatment methods on the efficacy were analysed. Results: All patients completed the 3 months follow-up. The improvement rates of APFs in TACE-S and TACE-125I groups were 30.77% (8/26) and 68.75% (22/32), respectively, and difference was statistically significant (χ2 = 8.287, P=0.004). The median survival time of TACE-S and TACE-125I groups was 8.00 months and 12.8 months, respectively (χ2 = 7.106, P=0.008). Multivariate analysis showed that the PVTT subtype (IIa/IIb) and treatment method (TACE-S or TACE-125I) were independent factors affecting the recanalization of APFs in patients (P<0.05). Conclusion: For patients with HCC with PVTT and APFs, TACE combined with 125I seed implantation can effectively treat portal vein tumor thrombus, thereby reducing the recanalization of APFs and prolonging the survival time of patients.

Plasma arginase-1 as a predictive marker for early transarterial chemoembolization refractoriness in unresectable hepatocellular carcinoma.

Objective: To explore the relationship between plasma arginase-1 (ARG1) and early transarterial chemoembolization (TACE) refractoriness in patients with hepatocellular carcinoma (HCC) and develop nomograms for predicting early TACE refractoriness. Methods: A total of 200 patients with HCC, treated with TACE, were included in the study, including 120 in the training set and 80 in the validation set. Pre-treatment enzyme-linked immunosorbent assay was used to detected the plasma ARG1 levels of the patient, and independent predictors of early TACE refractoriness were determined using a multivariate logistic regression model, based on which a predictive model was developed using a nomogram. Results: Risk of early TACE refractoriness was negatively correlated with plasma ARG1 levels, and multivariate logistic analysis showed tumour size (OR = 1.138, 95% CI = 1.006-1.288, P = 0.041), multiple tumors (OR=4.374, 95% CI = 1.189-16.089, P = 0.026), platelet count (OR = 0.990, 95% CI = 0.980-0.999, P = 0.036), and plasma ARG1 levels (OR = 0.209, 95% CI = 0.079-0.551, P = 0.002) to be independent prognostic factors for early TACE refractoriness.The AUC value for the nomogram of the training cohort was 0.786 (95% CI = 0.702-0.870), and the validation set AUC value was 0.833 (95% CI = 0.791-0.875).The decision curve analysis suggested that the nomogram had good clinical utility. Conclusion: High plasma ARG1 expression was associated with a lower incidence of early TACE refractoriness. The nomogram constructed based on four independent prognostic factors could facilitate an individualised prediction of the incidence of early TACE refractoriness.

Clinical practice guidelines on image-guided thermal ablation of primary and metastatic lung tumors (2022 edition).

The main contents of the Clinical Practice Guidelines on Image-Guided Thermal Ablation (IGTA) of Primary and Metastatic Lung Tumors (2022 Edition) include the following: epidemiology of primary and metastatic lung tumors; the concepts of the IGTA and common technical features; procedures, indications, contraindications, outcomes evaluation, and related complications of IGTA on primary and metastatic lung tumors; and limitations and future development.

Local ablation of pulmonary malignancies abutting pleura: Evaluation of midterm local efficacy and safety.

Objective: To retrospectively evaluate the efficacy and safety of local ablation treatment for adjacent pleural lung tumors. Materials and methods: Sixty-two patients who underwent pulmonary nodule ablation at the Affiliated Cancer Hospital of Zhengzhou University were enrolled between January 2016 and December 2020. All patients were followed up with enhanced computed tomography or magnetic resonance imaging within 48 h after treatment and 2, 4, 6, 9, and 12 months after treatment. All patients were followed for at least 12 months. Results: A total of 84 targeted tumors (62 patients) underwent 94 ablations. In the 12-month follow-up images, 69 of the 84 targeted tumors were completely ablated, 15 had incomplete ablation, and the 12-month incomplete ablation rate was 17.8% (15/84). Of the 15 incompletely ablated tumors, six had partial responses, five had stable disease, and four had progressive disease. The most common adverse event was pneumothorax, with an incidence of 54.8% (34/62). The second most common complication was pleural effusion, with an incidence rate of 41.9% (26/62). The incidence of needle-tract bleeding was 21% (13/62) and all patients were cured using hemostatic drugs. Serious complications were bronchopleural fistula in four patients (6.5%, 4/62) and needle tract metastasis in one patient. Four cases of bronchopleural fistula were found in the early stages and were cured after symptomatic treatment. Conclusion: Local ablation is effective for the treatment of adjacent pleural lung tumors, and its operation is safe and controllable.

Cryoablation reshapes the immune microenvironment in the distal tumor and enhances the anti-tumor immunity.

As one of the local treatments, cryoablation plays an increasingly important role in the comprehensive treatment of malignant tumors with its advantages of less trauma, high reproducibility, and minimally invasive. Activation of anti-tumor immunity, another characteristic of cryoablation, has attracted more and more attention with the extensive application of immunotherapy. Unfortunately, the mechanism by which cryoablation enhances anti-tumor immunity is still unclear. In this study, we applied a multi-omics approach to investigate the effects of local cryoablation in the distal tumor microenvironment. The results revealed that large amounts of tumor antigens were released post-cryoablation, leading to a sterile inflammatory response in distant tumors. During this period, activated lysosome-related pathways result in over-expression of SNAP23 (Synaptosome associated protein 23) and STXBP2 (Syntaxin binding protein 2), activation of immune effector cells, suppression of the release of immunosuppressive factors, and finally enhancement of anti-tumor immunity, which shows a broad prospect in combined immunotherapy.

Benefits of step-by-step debulking microwave ablation for huge unresectable hepatocellular carcinoma patients after transcatheter arterial chemoembolization refractoriness.

OBJECTIVES: To compare the safety and efficacy of step-by-step debulking Microwave Ablation (MWA) with Transarterial Chemoembolization (TACE) monotherapy for huge (≥10 cm in diameter) unresectable hepatocellular carcinoma (HCC) after TACE refractoriness. METHODS: This is a multi-center retrospective study carried out on 599 patients with huge unresectable HCC who received TACE as first-line therapy at five hospitals from January 2009 to December 2018. A total of 103 patients with TACE refractoriness were divided into two cohorts: monthly step-by-step debulking MWA (n = 52) or continued TACE (n = 51). Overall survival (OS) and progression-free survival (PFS) after refractory TACE were evaluated. Residual liver and tumor volume were recorded for the MWA group. RESULTS: Median follow-up period was 24.3 months and median OS and PFS were significantly longer in the MWA group than in the TACE group (OS 21.0 vs. 11.7 months, PFS 6.1 vs. 3.0 months, both p < 0.001). The one-, two-, and three-year OS rates in the MWA and TACE groups were 73.1%, 46.6%, and 37.2% versus 43.1%, 15.5%, and 2.9%, respectively. Furthermore, the 0.5-, 1-, and 2-year PFS rates in the MWA and TACE groups were 51.9%, 36.5%, and 25.0% versus 27.5%, 11.8%, and 0, respectively. Multivariate analyses confirmed that switching to debulking MWA treatment was an independent favorable prognostic factor for PFS and OS. In the MWA group, the average additions of residual liver volume/total liver volume were 7.7% ± 6.7%, 7.2% ± 10.2%, and 10.1% ± 8.8% after the first, second, and third MWA procedure. CONCLUSION: Step-by-step debulking MWA can significantly improve long-term OS and PFS in patients with huge unresectable HCCs compared with repeated TACE after TACE refractoriness. Key PointThe debulking MWA therapy provides significantly longer OS and PFS than continued TACE for patients with huge unresectable HCCs after TACE-refractory, especially with complete tumor ablation.The most common complications were fever (48.1%) and pain (46.2%) in the MWA group. Two major complications (abdominal infection) were recorded in the MWA group, which recovered after symptomatic treatment.During the course of repeated MWAs, liver hyperplasia appeared mainly after the second MWA procedure and the average maximum increased RLV/TLV rate was 16.3%±12.7%.

Feasibility and efficacy of superconducting open-configuration magnetic resonance-guided microwave ablation of malignant liver tumors with real-time imaging sequences.

Objective: To evaluate the safety and effectiveness of open superconducting magnetic resonance (MR)-guided microwave ablation of liver tumors and explore feasibility of real-time imaging sequence-guided needle insertion technique. Materials and Methods: Medical records of December 2019-May 2021 of microwave ablations of liver tumors under MR guidance in XX University Cancer Center were reviewed. Real-time imaging-guided puncture technique refers to real-time insertion and adjusting the position of a microwave applicator under a fast imaging sequence. The safety and efficacy of the procedure among the enrolled patients were assessed. Results: Twenty-six patients underwent 27 procedures, with 30 lesions ablated (long diameter: 1.51 ± 0.81 cm, short diameter: 1.30 ± 0.61 cm). There were 20 cases of primary liver cancer and 10 of liver metastases. All lesions were identified by MR imaging (MRI), and all procedures were successfully performed using the finger positioning method for puncture sites. Five patients underwent real-time guided needle insertion techniques. Further, the microwave applicators reached the target position at once, and the entire insertion process was completed within 3 min. The completion rate of the real-time guided needle insertion technology was 100%, and 25 (92.6%) patients had minor complications. No severe complications were observed, and the technical success rate of 30 MRI-guided lesions was 100%. Finally, the complete ablation rate of the MRI-guided ablation after the first procedure was 93.1%. Conclusion: Open MR-guided microwave ablation is safe and effective in treating liver tumors. Furthermore, real-time imaging sequence-guided puncture technique under MRI is feasible and efficient.