Regional delivery of mesothelin-targeted chimeric antigen receptor T-cell effectively and safely targets colorectal cancer liver metastases in mice.

Background: Liver metastasis is the major cause of colorectal cancer related death. Mesothelin (MSLN)-targeted chimeric antigen receptor (CAR) T-cell therapy has been illustrated effective and safe through regional delivery of breast cancer, ovarian cancer and malignant mesothelioma tumors. Herein, we investigated the safety, efficacy, and immune microenvironment of regional delivery of MSLN (CAR) T-cell in the treatment of colorectal carcinoma liver metastases (CRLM). Methods: Second-generation MSLN CAR T-cells were administered by portal vein (PV) or caudal vein (CV, systemic administration) delivery in an orthotopic MSLN+ CRLM nonobese diabetic (NOD)/severe combined immunodeficient (SCID)/γc-/- (NSG) mouse model. A total of 20 mice were randomly divided into control group, non-transduced T cell (NT)-CV group, NT-PV group, MSLN CAR T-cell CV (MSLN-CV) group, and MSLN CAR T-cell PV (MSLN-PV) group, with each group containing four mice to examine the safety and efficacy. The bioluminescence intensity (BLI) of tumor burden, tumor tissue macroscopic and microscopic observation were used to evaluate treatment efficacy. The safety was examined by body weight, survival time, and vital organ damage of mice. CAR T-cell infiltration and cytokine concentration were analyzed by flow cytometry, and immunostaining. The change of immune microenvironment between regional delivery and systemic delivery was investigated on an immune reconstructed CRLM patient-derived xenograft (PDX) model. Additionally, T cell subsets and immunosuppressive markers were examined. Results: PV administration of 1×107/100 µL MSLN CAR T-cells in 20 NSG mice was well tolerated, and no overt toxicity was observed. The tumor burden in the PV group was obviously alleviated. The BLI was (0.73±0.52)×109 in PV group and (1.97±0.11)×109 in CV group (P<0.05), CD8+ granzyme B (GB)+ T cell percentage (MSLN-CV 4.42%±0.47% vs. MSLN-PV 13.5%±4.67%, P<0.01) and cytokine concentration were obviously increased in the MSLN-PV group. In the immune reconstituted CRLM PDX model, intratumor (IT) delivery of MSLN CAR T-cells exhibited much more infiltration of CD4+ and CD8+ T cells accompanied with elevated expression levels of PD-1, LAG-3, and TIM-3. Conclusions: Regional delivery of MSLN-targeted CAR T-cell therapy has encouraging results in the orthotopic CRLM NSG mouse model and PDX model, and converts the tumor microenvironment from cold to hot. This study may provide a new therapeutic approach for CRLM. Further clinical study is needed.

Hypoxia-activated cascade nanovaccine for synergistic chemoembolization-immune therapy of hepatocellular carcinoma.

In this work, a promising treatment strategy for triggering robust antitumor immune responses in transarterial chemoembolization of hepatocellular carcinoma (HCC) is presented. The zeolitic imidazolate framework nanoparticles loaded with hypoxia-activated prodrug tirapazamine and immune adjuvant resiquimod facilitated in situ generation of nanovaccine via a facile approach. The nanovaccine can strengthen the ability of killing the liver cancer cells under hypoxic environment, while was capable of improving immunogenic tumor microenvironment and triggering strong antitumor immune responses by increasing the primary and distant intratumoral infiltration of immune cells such as cytotoxic T cells. Moreover, a porous microcarrier, approved by FDA as pharmaceutical excipient, was designed to achieve safe and effective delivery of the nanovaccine via transarterial therapy in rabbit orthotopic VX2 liver cancer model. The microcarrier exhibited the characteristics of excellent drug loading and occlusion of peripheral artery. The collaborative delivery of the microcarrier and nanovaccine demonstrated an exciting inhibitory effect on solid tumors and tumor metastases, which provided a great potential as novel combination therapy for HCC interventional therapy.

Pneumothorax and pulmonary hemorrhage after C-arm cone-beam computed tomography-guided percutaneous transthoracic lung biopsy: incidence, clinical significance, and correlation.

OBJECTIVE: This study aimed to assess the incidence and clinical significance of pneumothorax (PTX) and pulmonary hemorrhage (PH) after percutaneous transthoracic lung biopsy (PTLB) guided by C-arm cone-beam computed tomography (CBCT). Furthermore, this study aimed to examine the relationships between PTX and PH with demographics, clinical characteristics, imaging, and PTLB parameters. METHODS: A retrospective analysis was conducted on 192 patients who underwent PTLB at our hospital between January 2019 and October 2022. Incidences of PTX and PH were recorded. PTX was considered clinically significant if treated with chest tube insertion (CTI), and PH if treated with bronchoscopes or endovascular treatments. The various factors on PTX and PH were analyzed using the Chi-squared test and Student t-test. Logistic regression analyses were then used to determine these factors on the correlation to develop PTX and PH. RESULTS: PTX occurred in 67/192 cases (34.9%); CTI was required in 5/67 (7.5%). PH occurred in 63/192 cases (32.8%) and none of these cases required bronchoscopes or endovascular treatments. Lesion diameter (ORPTX = 0.822; ORPH = 0.785), presence of pulmonary emphysema (ORPH = 2.148), the number of samples (ORPH = 1.834), the use of gelfoam (ORPTX = 0.474; ORPH = 0.341) and ablation (ORPTX = 2.351; ORPH = 3.443) showed statistically significant correlation to PTX and PH. CONCLUSIONS: CBCT-guided PTLB is a safe and effective method for performing lung biopsies. The use of gelfoam has been shown to reduce the occurrence of PTX and PH. However, caution should be exercised when combining radiofrequency ablation with PTLB, as it may increase the risk of PTX and PH.

Microwave ablation combined with transarterial chemoembolization containing doxorubicin hydrochloride liposome for treating primary and metastatic liver cancers.

Aims: To determine the safety and efficacy of microwave ablation (MWA) and transarterial chemoembolization (TACE) with doxorubicin hydrochloride liposome (DHL) in patients with primary liver cancer (PLC) and metastatic liver cancer (MLC). Materials and methods: The medical records of patients with primary or metastatic liver cancer who underwent MWA combined with TACE containing DHL from March 2019 to March 2022 were collected and analyzed. Treatment-related adverse events (AEs) were recorded. Local tumor response was evaluated according to the modified RECIST criteria. Local tumor progression-free survival (LTPFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: Altogether, 96 patients with liver cancer were included (PLC, n â€‹= â€‹45; MLC, n â€‹= â€‹51). Forty (41.7%) patients experienced AEs during treatment, and eight (8.3%) patients developed grade 3 AEs. Compared to before treatment, the serum total bilirubin level and neutrophil to lymphocyte ratio significantly increased after treatment. The median LTPFS was 14.5 months in patients with PLC and 10.7 months in patients with MLC. The median OS was not reached in patients with PLC or MLC. The 1-month and 3-month disease control rates reached more than 80% in both groups. Conclusion: MWA combined with TACE with DHL may be a safe and effective method for the treatment of liver cancer.

Efficacy and Safety of Transarterial Chemoembolization with a Three-Stage Mixed Chemoembolic Regimen for Large Unresectable Hepatocellular Carcinoma.

Objective: This study aimed to assess the treatment response, survival outcomes, and safety of a novel transarterial chemoembolization (TACE) technique with a three-stage mixed chemoembolic regimen (M-TACE) in patients with large unresectable hepatocellular carcinoma (HCC) measuring more than 5 cm in maximum diameter. Methods: Between January 2017 and March 2023, a total of 82 patients were enrolled in this retrospective cohort study. Treatment response was assessed in the first month after M-TACE; progression-free survival and overall survival (OS) were evaluated. The prognostic factors associated with patient survival were statistically analyzed by the Cox regression model. Adverse events were recorded. Results: The maximum diameter of the tumors ranged from 5.3 cm to 20.0 cm (mean 10.71 cm). The objective response (OR) and disease control rates were 74.4 and 92.7%, respectively, at 1-month follow-up. The median survival time was 22 months (95% CI, 13.10-30.90 months). The OS rates were 82.0% at six months, 62.5% at one year, and 43.0% at two years. Targeted therapy and/or immunotherapy (P=0.001) and tumor response at one month (P=0.020) were protective factors for OS. In terms of safety, no major complications occurred and the only observed decrease within the normal range occurred in albumin and platelet levels one month after the embolization procedure. This decrease in levels did not show a significant relationship with the OR rates. Conclusion: M-TACE demonstrated a promising objective tumor response, making it a viable and effective treatment option for patients with large unresectable HCC.

The influence of shunting left/right portal vein branch on post-TIPS hepatic encephalopathy: a study protocol for multicenter randomized blinded controlled trial.

INTRODUCTION: Gastroesophageal varices (GOV) bleeding is a common and serious complication of advanced liver cirrhosis with a median survival of less than 2 years. Multiple guidelines have pointed out that transjugular intrahepatic portosystemic shunt (TIPS) is the rescue treatment of acute variceal hemorrhage (AVB) after failure of standard therapy and an effective second-line treatment for preventing patients with high risks from rebleeding of GOV. The safety and stability of TIPS have been greatly improved due to the improvements of related technologies and the emergence of various novel devices, but the incidence of hepatic encephalopathy (HE) after shunting (10-50%) hindered the widespread use of TIPS. The target portal vein branch might affect the incidence of HE after TIPS. The aim of this study is to compare the rate of HE in patients with hepatitis B virus (HBV) related cirrhosis receiving TIPS either the left or right branch of the portal vein with 8mm Viatorr stent for preventing rebleeding from GOV. METHODS AND ANALYSIS: This study is a multicenter randomized controlled trial comparing the influence of shunting left or right portal vein branch on post-TIPS hepatic encephalopathy for preventing rebleeding from GOV in patients with HBV-related cirrhosis. A total of 130 patients will be recruited over a period of 24 months across 5 centers in China. Eligible patients will be stratified 1:1 to constructing either a left or right portal vein shunt with an 8-mm Viatorr stent. The primary objective was to compare the incidence of post-TIPS hepatic encephalopathy between the two groups. The secondary objectives were to compare the grade and duration of hepatic encephalopathy, the rate of shunt dysfunction, the rate of variceal rebleeding, the HE-free survival, the cumulative patency rate of the stent, and the overall survival at 12 months and 24 months between two groups. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of Zhongshan Hospital of Fudan University (No. B2018-292R) and was registered at ClinicalTrials.gov (NCT03825848). All participants give written informed consent. TRIAL REGISTRATION: ClinicalTrials.gov NCT03825848. Registered on January 31, 2019 TRIAL STATUS: The first patient was recruited into our study on June 19, 2019. A total of 55 patients were recruited till May 27, 2021 (27 and 28 patients assigned to shunting the left (L Group) and right (R Group) branches of the portal vein, respectively).

Development of a Costimulatory Molecule Signature to Predict Prognosis, Immune Landscape, and Response to Immune Therapy for Hepatocellular Carcinoma.

This work was aimed at investigating the predictive value on prognosis, response to immunotherapy, and association with the immune landscape of costimulatory molecules in HCC patients. We acquired the clinicopathological information and gene expression of HCC patients from public available database (TCGA and GEO). The prognostic model in TCGA database was established with LASSO regression and Cox regression analysis. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis, the enrichment analysis was implemented for analyzing the biological function and associated pathways. Immune microenvironment, immune escape, immune therapy, and tumor mutation were analyzed between both risk groups. TNFRSF4, the critical costimulatory molecule, was chosen for the in-depth investigation in vitro experiments. A novel risk signature based on 8 costimulatory molecules associated with prognosis was constructed from TCGA and proved in the database of GEO. The ROC and Kaplan-Meier curves confirmed that this risk model has good predictive accuracy. Our functional analysis demonstrated costimulatory molecular genes might associate with immune-related functions and pathways. Statistical differences were not shown between both groups, in the aspect of immune landscape, response to immune therapy, and tumor mutation. Knocking down TNFRSF4 expression significantly reduced the proliferation ability and increased the apoptosis ability. On the basis of the costimulatory molecule expression in HCC, a novel risk model was constructed and had an excellent value to predict prognosis, immune microenvironment, and response to immune therapy. TNFRSF4 was identified as an underlying oncogene in HCC and deserves further exploration.

Microwave ablation combined with lipiodol-microsphere mixed or conventional transarterial chemoembolization for the treatment of colorectal liver metastases: A retrospective study.

PURPOSE: To investigate the clinical outcomes of microwave ablation (MWA) combined with lipiodol-microsphere mixed transarterial chemoembolization (mTACE) or conventional TACE (cTACE) for patients with colorectal liver metastases (CRLM). MATERIALS AND METHODS: This retrospective study evaluated the medical records of patients with CRLM who underwent MWA combined with mTACE or cTACE from January 2018 to September 2021. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated during the follow-up. In addition, prognostic factors affecting survival were analyzed by univariate and multivariate methods. RESULTS: A total of 79 patients with CRLM were enrolled in the study (MWA-mTACE group, n = 38; MWA-cTACE group, n = 41). The patients who underwent MWA-mTACE had higher DCR (86.8% vs. 65.9%, P = 0.029) and better PFS (median, 8.1 vs. 5.5 months, P = 0.018) than those who underwent MWA-cTACE, but no significant difference was found in ORR (34.2% vs. 22.0%, P = 0.225) and OS (median, 15.7 vs. 13.0 months, P = 0.231). Further univariate and multivariate analyses indicated that MWA-mTACE was an independent positive factor for PFS, and abnormal carcinoembryonic antigen level was a hazard factor for OS. The postoperative laboratory tests and complications in patients who underwent MWA-mTACE were similar to those who underwent MWA-cTACE. CONCLUSION: Lipiodol-microsphere mixed TACE might be an effective and safe treatment to combine with microwave ablation for patients with colorectal liver metastases.

The Impact of Socioeconomic Status on Staging, Prognosis in Hepatocellular Carcinoma.

PURPOSE: We conducted this large population-based study to evaluate the impact of socioeconomic status (SES) factors on cancer-specific survival (CSS) of patients with hepatocellular carcinoma (HCC). We further assessed the value of a novel TNM-SES staging system, which incorporated these SES factors with TNM stage on staging and prognosis. METHODS: A total of 13,791 patients diagnosed with HCC from 2012 to 2016 were retrieved from one large population database. Cox proportional hazards regression model and Harrell's concordance index (C-index) were used to identify the SES factors associated with CSS and analyze the prognostic value of TNM-SES stage. Kaplan-Meier curves and Log rank test were performed to evaluate CSS. RESULTS: Four SES factors (marital status, insurance status, education, household income) were identified as the prognostic factors associated with CSS. The SES-2 (lower SES) stage was significantly correlated to unfavorable CSS of the patients with HCC, with a 32.0% increased risk (HR = 1.32, 95% CI (1.26-1.39), P < 0.001), after adjusting for several confounders. The C-index of the TNM-SES stage was 0.735 (95% CI (0.729-0.741)) which was higher than that of the TNM stage (0.718, 95% CI (0.712-0.724)), indicating a high accuracy of prognostic prediction. CONCLUSION: Our comprehensive study revealed that SES was significantly associated with prognosis of patients with HCC after adjusting several confounders. The novel TNM-SES staging system which combined TNM stage and SES stage had more superior predictive value than the traditional TNM stage. Disparity on SES should receive more attention for patients with HCC in clinical management.

Identification of Epithelial Mesenchymal Transition-Related lncRNAs Associated with Prognosis and Tumor Immune Microenvironment of Hepatocellular Carcinoma.

PURPOSE: The long noncoding RNAs (lncRNAs) play the important role in tumor occurrence and progression, and the epithelial to mesenchymal transition (EMT) is the critical process for tumor migration. However, the role of EMT-related lncRNA in hepatocellular carcinoma (HCC) has not been elucidated. METHODS: In this study, we selected the EMT-related lncRNAs in HCC by using data from The Cancer Genome Atlas database (TCGA). Two prognostic models of the overall survival (OS) and relapse-free survival (RFS) were constructed and validated through Cox regression model, Kaplan-Meier analysis, and the receiver-operating characteristic (ROC) curves. The unsupervised clustering analysis was utilized to investigate the association between EMT-lncRNAs with tumor immune microenvironment. ESTIMATE algorithm and gene set enrichment analysis (GSEA) were used to estimate tumor microenvironment and associated KEGG pathways. RESULTS: Two EMT-related lncRNA prognostic models of OS and RFS were constructed. Kaplan-Meier curves showed the dismal prognosis of OS and RFS in the group with high-risk score. The ROC curves and AUC values in two prognostic models indicated the discriminative value in the training set and validation set. Patients with HCC were clustered into two subgroups according the unsupervised clustering analysis. Lnc-CCNY-1 was selected as the key lncRNA. GSVA analysis showed that lnc-CCNY-1 was negatively associated with peroxisome proliferator-activated receptor (PPAR) signaling pathway and positively correlated with CELL cycle pathway. CONCLUSION: Two EMT-related lncRNA prognostic models of OS and RFS were constructed to discriminate patients and predict prognosis of HCC. EMT-related lncRNAs may play a role on prognosis of HCC by influencing the immune microenvironment. Lnc-CCNY-1 was selected as the key EMT-related lncRNA for further exploration.

Combined iodine-125 seed strand, portal vein stent, transarterial chemoembolization, lenvatinib and anti-PD-1 antibodies therapy for hepatocellular carcinoma and Vp4 portal vein tumor thrombus: A propensity-score analysis.

Objective: To evaluate the safety and efficacy of interventional therapy (iodine-125[125I] seed strand and portal vein stent [PVS] implantation plus transarterial chemoembolization [TACE]) combined with systemic therapy (lenvatinib plus anti-PD-1 antibody) as first-line treatment for hepatocellular carcinoma (HCC) patients with Vp4 portal vein tumor thrombus (PVTT). Patients and methods: From December 2018 to October 2021, 87 HCC patients with Vp4 PVTT were included in this single-center retrospective study. Forty-seven patients underwent interventional therapy combined with lenvatinib and anti-PD-1 antibody (group A), while 40 cases underwent interventional therapy combined with lenvatinib only (group B). Overall response rate (ORR), stent occlusion rates (SOR), median overall survival (OS), median progression-free survival (PFS) and median stent patency time (SPT) were compared between the 2 groups. Results: The mean intended dose (r = 10 mm; z = 0; 240 days) was 64.9 ± 1.0 Gy and 64.5 ± 1.1 Gy in group A and B, respectively (p = 0.133). ORR and SOR were significantly different between group A and B (ORR, 55.3% vs 17.5%, p < 0.001; SOR, 12.8% vs 35.0%, p = 0.014). In the propensity-score matching (PSM) cohort, the median OS, median PFS and median SPT were significantly longer in group A compared with group B (32 PSM pairs; OS, 17.7 ± 1.7 vs 12.0 ± 0.8 months, p = 0.010; PFS, 17.0 ± 4.3 vs 8.0 ± 0.7 months, p < 0.001; SPT, not-reached vs 12.5 ± 1.1 months, p = 0.028). Conclusion: This interventional therapy combined with lenvatinib and anti-PD-1 antibody is safe and effective for HCC patients with Vp4 PVTT.

Microwave ablation and synchronous transarterial chemoembolization combined with PD-1 inhibitor in patients with hepatocellular carcinoma following tyrosine kinase inhibitor intolerance.

Purpose: To determine the safety and efficacy of microwave ablation (MWA) and synchronous transarterial chemoembolization (TACE) combined with or without PD-1 inhibitor in patients with hepatocellular carcinoma (HCC) following tyrosine kinase inhibitor (TKI) intolerance. Materials and methods: This study retrospectively enrolled TKI-intolerant HCC patients who underwent MWA-TACE combined with PD-1 inhibitor (MTP) or MWA-TACE (MT) from January 2019 to June 2021. MWA and TACE were performed simultaneously, and PD-1 inhibitor was administered intravenously at a dose of 200 mg once every three weeks after MWA-TACE. Adverse events (AEs) related to treatment were recorded during the follow-up. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups. Results: A total of 87 patients were included and classified into the MTP group (n =42) and MT group (n=45). Complications related to MWA-TACE in the MTP group were similar to that in the MT group (21.4% vs. 24.4%, P = 0.738). Moreover, 35 (83.3%) patients had eighty-four AEs related to PD-1 inhibitor in the MTP group, and 8 (19.0%) patients developed grade 3. Patients who underwent MWA-TACE combined with PD-1 inhibitor had better PFS (median, 10.0 vs. 4.7 months, P < 0.001) and OS (median, 17.0 vs. 8.5 months, P < 0.001) than those who underwent MWA-TACE alone. Treatment method and Child-Pugh class were independent prognostic factors for survival in the univariate and multivariate analysis. Conclusion: MWA and synchronous TACE combined with PD-1 inhibitor might be a favorable treatment option in TKI-intolerant HCC patients.

Development of a Novel Endovascular Brachytherapy Stent: A Proof-of-concept Study.

BACKGROUND AND AIMS: Endovascular implantation of iodine-125 (125I) seeds strand combined with stent is an effective method of treatment for portal vein tumor thrombosis. The aim of this study was to develop a novel endovascular brachytherapy stent (EVB-Stent) and to evaluate its feasibility of use. METHODS: An EVB-Stent was implanted into the main portal vein (MPV) in a live porcine model via the percutaneous transhepatic route. Blood samples were collected and tested before and after operation, as well as before euthanasia. Single-photon emission computed tomography (SPECT) combined with CT (SPECT/CT) scan were performed directly after operation and CT scan was performed 2 months after implantation. After the CT scan was performed, all animals were euthanized and histologically examined. RESULTS: The novel stent was successfully positioned in all six pigs. No deterioration of liver function was observed during the 2-month follow-up period. SPECT/CT revealed the uniform distribution of radiation around the seeds strand, and the hottest spot was near the center of the MPV. The patency of the stented MPV was confirmed using CT scans. The tissue-accumulated absorbed dose was 31,822.11 mGy at 10 mm transversely away from the midpoint of the 125I seeds strand, with a half-life of 59.4 days. Pathological examination results showed no significant atrophy or inflammation of adjunct liver tissue, and no obvious intima thickening or thrombosis were detected in the stented MPV. CONCLUSIONS: A liver porcine model was used to demonstrate that the transhepatic placement of a novel endovascular brachytherapy stent, EVB-Stent, is both technically feasible and safe.

Embolization of the Transhepatic Tract after Percutaneous Portal Vein Interventions: Single-Centre Retrospective Study Comparing n-butyl Cyanoacrylate Versus Coils.

PURPOSE: The aim of this study was to compare the safety and efficacy of transhepatic puncture tract embolization with n-butyl cyanoacrylate (n-BCA) versus coils after percutaneous transhepatic portal vein interventions in patients with hepatocellular carcinoma (HCC). It was also the aim of the study to evaluate the extent of artifacts in CT exams during FU. METHODS: Single-center retrospective study from 2017-2019 in 190 patients who underwent percutaneous transhepatic portal vein interventions. The transhepatic puncture tracts were embolized with n-BCA in 88 patients (Group A) and with coils in 102 patients (Group B). Procedure-related complications and image noise around coils and n-BCA were compared between the groups. No significant differences were noted at baseline between both groups (platelets, coagulation, liver disease, types of procedures, liver function, liver tumors). RESULTS: All patients underwent transhepatic puncture tract embolization. Procedure-related complications were only observed in patients from Group B: subcapsular hemorrhage (n = 2; 1.96%), hepatic artery hemorrhage (n = 1; 0.98%), and pseudoaneurysms combined with hemobilia occurred (n = 1; 0.98%). In Group A, the distal part of the punctured portal vein branch was embolized with n-BCA in 1 patient (1.14%). Four major complications in Group B Vs 0 in Group A were observed, respectively (p < 0.0001). The image noise around n-BCA was significantly lower than that around coils (10.7 ± 1.7 HU vs. 54.3 ± 15.0 HU, p < .001). CONCLUSIONS: n-BCA tract embolization is more effective than using coils, with fewer bleeding events, at the cost of a higher potential for unintended embolization of portal vein branches.

Nomogram for Predicting the Prognosis of Patients with Hepatocellular Carcinoma Presenting with Pulmonary Metastasis.

BACKGROUND: Only a few studies have investigated the clinical features and outcomes of patients with pulmonary metastasis from hepatocellular carcinoma (HCC) at the initial diagnosis. This study aimed to evaluate the prevalence, risk factors and prognostic factors related to pulmonary metastasis and then construct a nomogram to predict the outcomes of patients with HCC presenting with pulmonary metastasis. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to select patients. A total of 25,236 eligible patients diagnosed with HCC from 2010 to 2015 were selected. Then, 897 patients with HCC presenting with pulmonary metastasis at the initial diagnosis were included in the primary set (n=598) and validation set (n=299). Logistic and Cox regression analyses were used to determine the risk factors and prognostic factors for pulmonary metastasis. A nomogram predicting the prognosis of patients with HCC presenting with pulmonary metastasis was constructed based on independent prognostic factors identified in Cox regression analyses. Both internal and external validations of the nomogram were performed using discrimination and calibration plots. RESULTS: The prevalence of pulmonary metastasis was 3.6% (897/25,236) in the entire cohort diagnosed with HCC as the initial diagnosis. Age, race, Edmonson-Steiner classification grade I/III, higher T stage, N stage, alpha fetoprotein(AFP) levels, brain metastasis, bone metastasis and intrahepatic metastasis were positively correlated with the development of HCC with pulmonary metastasis at the initial diagnosis. Prognostic factors incorporated in the nomogram were sex, T stage, bone metastasis, AFP levels, treatment, radiation and chemotherapy. The concordance index (C-index) of the nomogram in the primary set was 0.661 (95% CI: 0.633-0.688), indicating considerable predictive accuracy. The calibration curves showed consistency between the nomogram and the actual observations. When the nomogram was applied to the validation set, the results also remained reconcilable, and the C-index of the nomogram was 0.657 (95% CI: 0.626-0.698). CONCLUSION: A list of risk factors associated with pulmonary metastasis occurrence in patients with HCC was selected, and the nomogram accurately predicted the prognosis of patients with HCC presenting with pulmonary metastasis at the initial diagnosis.

Transradial Access Chemoembolization for Hepatocellular Carcinoma Patients.

Transarterial chemoembolization (TACE) is the most common modality for treatment of hepatocellular carcinoma (HCC) at the intermediate stage. TACE is typically performed via transfemoral access (TFA). However, transradial access (TRA) is preferred in coronary artery interventions due to decreased complications and mortality. Whether the advantages of TRA can be applied to TACE required investigation. Patients receiving TRA TACE at a single center were retrospectively enrolled for study. Procedural details, technical success, radial artery occlusion (RAO) rate, and access site-related bleeding complications were evaluated. From October 2017 to October 2018, 112 patients underwent 160 TRA TACE procedures. The overall technical success rate was 95.0% (152/160). The rate of crossover from TRA to TFA was 1.9%. No access site-related bleeding complications were found in any cases. Asymptomatic RA occlusion occurred in three patients (2.7%). Compared with TFA, TRA can increase safety and patient satisfaction while decreasing access site-related bleeding complications. Moreover, TRA interventions can benefit patients with advanced age, obesity, or a high risk of bleeding complications.

A Preclinical Porcine Model of Portal Vein Thrombosis in Liver Cirrhosis.

BACKGROUND: This study aimed at presenting a novel method of developing a porcine model of portal vein thrombosis (PVT) in cirrhosis by intravenous administration of thrombin and insertion of a fibered coil. We further investigated changes of biochemical parameters, coagulation, and proinflammatory cytokine expression in the cirrhosis-PVT group. METHODS: Twelve male pigs were randomized into the control group (n = 3) and cirrhosis group (n = 9). In cirrhotic pigs, three were randomly selected to establish PVT by ultrasound-guided percutaneous puncture of the main portal vein (MPV) followed by intravenous thrombin administration and fibered coil insertion. Thrombosis in the MPV was detected by abdominal enhanced computer tomography (CT). The changes of hepatic function, coagulation system, and inflammation cytokines were compared among normal, cirrhosis, and cirrhosis with PVT groups. RESULTS: As manifested by the presence of a filling defect in MPV on portal venous-phase CT angiography, fibrin thrombi were formed in the MPV in cirrhotic pigs within one week and persisted for four weeks. Five weeks after surgery, abnormal liver functions occurred in association with PVT formation in cirrhosis. Both coagulation and thromboelastography parameters showed that cirrhosis-PVT pigs exhibited a procoagulant state through hyperfunction of platelets and clotting factors. Interleukin 6 (IL-6) as a potential inflammatory marker stimulated PVT-mediated inflammation activation in cirrhosis. CONCLUSIONS: Our study provides in vivo evidence that intravenous injection of a coil and thrombin into MPV under interventional guided devices enables a feasible method in thrombus creation. Further exploration and validation of large-sample cases are required to characterize utilities of this model.

Update on Preoperative Embolization of Bone Metastases.

Management of patients with bone metastasis is complex and should include different specialties. Goals of therapy should be identified for each individual patient prior to the start of treatment. Preoperative embolization has generally been considered a safe and effective means of reducing intraoperative blood loss with recent studies and advances in technique reported. Update on indications, contraindications, technique, and efficacy, as well as prognostic factors and complications of preoperative embolization of bone metastases will be reviewed. New trends such as transradial arterial access and usage of liquid embolic agents will be discussed. Large tumor size, increased preprocedural tumor vascularity, longer embolization-to-surgery interval, and radical surgical procedures are associated with greater intraoperative blood loss and prolonged operative time. An accurate, noninvasive method to evaluate tumor vascularity prior to angiography is needed to identify patients who are most likely to benefit from preoperative embolization. Particular attention will be paid to skeletal metastases and spinal metastases as each has its own set of complexity.