TACE with dicycloplatin in patients with unresectable hepatocellular carcinoma: a multicenter randomized phase II trial.

OBJECTIVES: To investigate the efficacy and safety of dicycloplatin as chemotherapeutic regimen in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). METHODS: In this randomized, open-label, phase II trial, patients with unresectable HCC who were TACE treatment-naïve or experienced recurrence after surgical resection or ablation were enrolled at 7 centers in China from March 2019 to November 2019. Participants were randomly assigned (1:1:1) to receive TACE with chemotherapeutic regimen of dicycloplatin alone (group A1), dicycloplatin plus epirubicin (group A2), or epirubicin alone (group B). The primary endpoint was objective response rate (ORR). The secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and safety. RESULTS: The ORR at 6 months in group A1 (n = 22) was significantly better than that in group B (p = 0.093; 90% confidence interval [CI], 1.03-9.45). The DCR in group A1 was significantly higher than that in group B (p = 0.045; 90% CI, 1.29-12.88). There was no significant difference in DOR among the groups (p = 0.271). The median PFS were 6.00 and 3.05 months in groups A2 (n = 25) and B (n = 24), respectively (p = 0.061). Grade 3 or worse adverse events were similar among groups in the safety population (p = 0.173). CONCLUSION: TACE with dicycloplatin was comparably safe and well tolerable as epirubicin alone in patients with unresectable HCC. Compared with epirubicin alone, significant improvement in ORR and DCR when dicycloplatin was applied, as well as prolonged PFS when dicycloplatin plus epirubicin was applied, was generated. KEY POINTS: • To our knowledge, this is the first multicenter randomized trial to assess the efficacy and safety of TACE with dicycloplatin in patients with unresectable HCC. • This phase II trial showed that TACE with dicycloplatin alone or plus epirubicin was comparably safe and well tolerable as epirubicin alone. • Significant improvements in ORR, DCR when dicycloplatin was applied, and prolonged PFS when dicycloplatin plus epirubicin was applied were recorded compared with epirubicin alone.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

Effectiveness of sharp recanalization of superior vena cava-right atrium junction occlusion.

BACKGROUND: Conventional recanalization techniques may fail in patients with completely occluded superior vena cava (SVC). AIM: To analyze the effectiveness and complications of sharp recanalization for completely occluded SVC. METHODS: This was a retrospective study of patients that underwent puncture and recanalization of the SVC between January 2016 and December 2017 at our hospital. Sharp recanalization was performed using the RUPS-100 system. The patients were followed for 12 mo. The main outcomes were the patency rate of SVC and arteriovenous fistula flow during dialysis. RESULTS: The procedure was successful in all 14 patients (100%). Blood pressure in the distal SVC decreased in all 14 cases (100%) from 26.4 ± 2.7 cmH2O to 14.7 ± 1.3 cmH2O (P < 0.05). The first patency rates of the SVC at 24 h and at 3, 6, 9 and 12 mo after sharp recanalization were 100%, 92.9%, 85.7%, 78.6% and 71.4%, respectively. There were two (14.3%) severe, one (7.1%) moderate and one (7.1%) minor complication. The severe complications included one case of pericardial tamponade and one case of hemothorax. CONCLUSION: The results suggest that sharp recanalization can be an additional tool to extend or renew the use of an occluded upper extremity access for hemodialysis. This could be of use in patients with long-term maintenance hemodialysis in whom the maintenance of central venous access is often a challenge.

CircC16orf62 promotes hepatocellular carcinoma progression through the miR-138-5p/PTK2/AKT axis.

Circular RNA (circRNAs) functions vital in the pathogenesis and progression of hepatocellular carcinoma (HCC). However, the expressions and functions of certain circRNAs on metastasis and proliferation of that cancer is still unclear. Bioinformation analysis and qRT-PCR indicated that CircC16orf62 was prominent upregulated in HCC of which the expression level was positively associated to cancer's malignant progression. Gain or loss-of-function studies indicated that the reduction of CircC16orf62 expression promotes the proliferation, invasion, and glycolysis of HCC in vitro and in vivo. The bioinformatic analysis found that miR-138-5p and PTK2 were the downstream target of CircC16or62. Then, the FISH(Fluorescence immunoin situ hybridization) and cell nucleoplasmic separation determined that CircC16orf62 located in the cell cytoplasm. Plasmid vectors or siRNAs were used to change the expression of CircC16orf62, miR-138-5p, and PTK2 in PC cell lines. CircC16orf62 functioned as a molecular sponge for miR-138-5p, and a competitive endogenous RNA for PTK2, promoting AKT/mTOR pathway activation. Our observations lead us to conclude that CircC16orf62 functions as an oncogene in HCC progression, behaving as a competitive endogenous RNA for miR-138-5p binding, thus activating the AKT/mTOR pathway. In conclusion, CircC16orf62 is an oncogene through the miR-138-5p/PTK2/Akt axis in HCC cells, indicating CircC16orf62 can be a therapeutic target with potentiality for liver cancer and a predictive marker for people with HCC.

Malic enzyme 2 promotes the progression of hepatocellular carcinoma via increasing triglyceride production.

The incidence and mortality of hepatocellular carcinoma (HCC) are gradually increasing during the past years. Recently, some studies have reported that malic enzyme (ME) plays an important role in cancer development, while the involvement of ME2 in HCC remains still undetermined. Here, we demonstrated that ME2 played an oncogenic role in HCC. ME2 was overexpressed in HCC tissues. TCGA database showed that the ME2 transcript level was inversely associated with the survival of HCC patients. Loss-of-function and gain-of-function assays showed that ME2 promoted HCC cell growth and migration. Furthermore, the xenografted tumorigenesis of MHCC97H cells was retarded by ME2 knockdown. ME2 silencing also suppressed the cell cycle process and induced apoptosis. Mechanistically, ME2 potentiated triglyceride synthesis, inhibition of which suppressed the proliferation and migration. We propose that ME2 promotes HCC progression by increasing triglyceride production.

Differential Diagnosis of Malignant Biliary Tract Cancer from Benign Tissues using Apparent Diffusion Coefficient Measurements with Diffusion Weighted Imaging in Asians.

BACKGROUND: The aim of this meta-analysis was to assess the efficacy of the apparent diffusion coefficient (ADC) value of diffusion-weighted MRI (DWI) for differentiating biliary tract cancer (BTC) from benign biliary tract diseases in Asians. MATERIALS AND METHODS: We systematically searched Embase and PubMed prior to December 2014. Eight studies conducted in Asians met our predetermined inclusion criteria. RESULTS: Our meta-analysis results showed that ADC values in BTC tissues were significantly lower than in benign biliary tract tissues (SMD = -1.54, 95%CI: -1.75~-1.33, P<0.001). Subgroup analysis based on the MRI machine type showed that the ADC values were consistent, accurate and reliable in the diagnosis of BTC when comparing cancer tissue vs. benign tissue under the Siemens 1.5 T/3.0 T, Philips 1.5 T/3.0 T, GE 1.5 T, and Toshiba 1.5 T types, respectively (all P<0.05). Further, ADC values were still consistent and accurate in the differential diagnosis of BTC under the b value of 800 and 1000 s/mm2 (all P<0.05). CONCLUSIONS: Our findings supported potential clinical applications of DWI ADC values in differentiating BTC from benign biliary tract diseases in Asians.