FAM83H-AS1/miR-485-5p/MEF2D axis facilitates proliferation, migration and invasion of hepatocellular carcinoma cells.

BACKGROUND: Abundant evidence has manifested that long noncoding RNAs (lncRNAs) are closely implicated in human cancers, including hepatocellular carcinoma (HCC). Remarkably, lncRNA FAM83H antisense RNA 1 (FAM83H-AS1) has been reported to be a tumor-propeller in multiple cancers. However, its effect on HCC progression remains unknown. METHODS: FAM83H-AS1 expression was analyzed by RT-qPCR. Colony formation, EdU, and flow cytometry as well as transwell assays were implemented to analyze the biological functions of FAM83H-AS1 on HCC progression. Luciferase reporter, RIP and RNA pull-down assays were implemented to detect the interaction among FAM83H-AS1, microRNA-485-5p (miR-485-5p), and myocyte enhancer factor 2D (MEF2D) in HCC cells. RESULTS: FAM83H-AS1 expression in HCC cells was markedly elevated. FAM83H-AS1 accelerated cell proliferation, migration and invasion whereas inhibiting cell apoptosis in HCC. Besides, we confirmed that FAM83H-AS1 acts as a miR-485-5p sponge in HCC cells. Additionally, MEF2D was verified to be a direct target of miR-485-5p. FAM83H-AS1 could upregulate MEF2D expression via sponging miR-485-5p. Further, rescue experiments testified that MEF2D upregulation or miR-485-5p downregulation offset the repressive effect of FAM83H-AS1 depletion on HCC cell progression. CONCLUSIONS: FAM83H-AS1 facilitates HCC malignant progression via targeting miR-485-5p/MEF2D axis, suggesting that FAM83H-AS1 may be a promising biomarker for HCC treatment in the future.

Comparison of emergent versus elective laparoscopic common bile duct exploration for patients with or without nonsevere acute cholangitis complicated with common bile duct stones.

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) has already been established for the treatment of patients with common bile duct stones (CBDS) in elective situations. However, the effect of emergent LCBDE on those patients with nonsevere acute cholangitis has not been assessed. The aim of this study was to evaluate the effect of emergent LCBDE on patients with nonsevere acute cholangitis complicated with CBDS. METHODS: Seventy-two patients with CBDS admitted from January 2009 to December 2012 were included for this retrospective study. LCBDE of transductal approach for CBDS was performed to all patients. Thirty-seven patients underwent emergent LCBDE for nonsevere acute cholangitis and 35 patients underwent elective LCBDE. Duration of the procedure, complications, retained stone of bile duct, hospital stay, and total charges were compared between the two groups. In addition, the characteristics of patients underwent emergent LCBDE were also compared before and after surgery. RESULTS: There was no significant difference with regard to the diameter of common bile duct and number of CBDS from imaging and/or operative findings between the two groups. There was no conversion to open common bile duct exploration, no major bile duct injuries, and no mortality in both the group of patients. There was no significant difference in patients with or without acute or chronic cholecystitis, duration of surgery, overall hospital stay (16.41 ± 1.03 versus 14.54 ± 0.94, P > 0.05), and total charges (18,603 ± 1774.64 versus 14,951 ± 1257.09 Yuan in renminbi, P > 0.05) between the two groups. Four cases with retained stones were found in patients with emergent LCBDE and two in elective LCBDE patients. There were four cases of biliary leak in patients with emergent LCBDE and three cases in elective LCBDE group, respectively. However, there was no statistical difference between the two groups. The biliary leak was cured postoperatively after drainage. Control of septic symptoms was achieved in all patients after emergent LCBDE. CONCLUSIONS: Our data indicated that emergent LCBDE is as safe and effective as elective LCBDE for the treatment of patients with nonsevere acute cholangitis complicated with CBDS.

Effect of Low-Dose Aspirin Use After Thermal Ablation in Patients with Hepatocellular Carcinoma: A Retrospective Study.

Purpose: To determine the effect of aspirin on hepatocellular carcinoma (HCC) recurrence and survival after thermal ablation. Methods: A retrospective analysis was performed to evaluate the efficacy and safety of aspirin in combination with thermal ablation. The clinical data were collected for the enrolled patients. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed. Results: A total of 174 patients with HCC were enrolled. The median PFS was 11.1 (95% confidence interval [CI]: 8.1-14.0) months for patients who took aspirin and 8.6 (95% CI: 5.5-11.8) months for patients who did not take aspirin. The median OS of patients in the aspirin group was 76.7 (95% CI: 58.1-95.3) months and that in the non-aspirin group was 53.5 (95% CI: 42.7-64.3) months. In patients with non-viral HCC, OS was significantly better for the aspirin group (P = 0.03) after ablation. The PFS of patients who underwent ablation alone in the aspirin group was obviously superior to that of patients in the non-aspirin group (P = 0.002). Stratified Cox regression analysis demonstrated that aspirin use after ablation might be a protective factor in specific HCC patient subgroups. The incidence of major adverse events did not significantly differ between the two groups. Conclusion: Low-dose aspirin use was associated with better OS in patients with non-viral HCC after thermal ablation. In patients who received thermal ablation alone, the administration of low-dose aspirin could improve PFS. Aspirin use might be a protective factor in some patients after ablation.

Associations Between Single Nucleotide Polymorphisms of Hypoxia-Related Genes and Capsule Formation in Hepatocellular Carcinoma.

Purpose: Tumor capsule is an independent prognostic factor for patients with hepatocellular carcinoma (HCC) and used increasingly to guide clinical decision-making. Considering the genetic complexity for capsule formation and its potential association with hypoxia, the significance of the polymorphisms of hypoxia-related genes in capsule formation and HCC prognosis remains to be elucidated. Patients and Methods: Peripheral blood samples from HCC patients were collected in this study. Single nucleotide polymorphism (SNP) genotyping was conducted by the iPLEX chemistry on a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (Sequenom, Inc.). The demographic and clinical data for the patients were obtained through medical chart review and/or consultation with the treating physicians. SPSS 25.0, R 4.1.1, and PLINK toolset were used to perform statistical analysis. Results: A total of 183 patients were enrolled, including 88 patients assigned to the capsule group and 95 to the non-capsule group. SLC2A1 rs841858 T allele, SLC2A1 rs2297977 T allele, STAT1 rs1547550 C allele, and STAT1 rs34997637 G allele were associated with significantly increased risk of capsule formation. The genotypes of SLC2A1 rs841858, SLC2A1 rs2297977, STAT1 rs34997637, and STAT1 rs1914408 were significantly associated with the formation of HCC capsule. The polymorphisms of STAT1 rs2066802, STAT1 rs12693591, and HIF1A rs2057482 showed close relationship with the prognosis of HCC patients in the capsule group, while the genotype distributions of CTNNB1 rs4135385, IFNG rs1861494, and SERPINE1 rs2227631 were closely related to the survival of patients in the non-capsule group. Further haplotype analysis suggested that SLC2A1 block 1 and STAT1 block 2 were related to the susceptibility of HCC capsule. Conclusion: The polymorphisms of the hypoxia-related genes (HIF1A, SERPINE1, IFNG, STAT1, CTNNB1, and SLC2A1) were correlated with the formation of HCC capsule. Several SNPs in these genes also showed association with HCC prognosis except SLC2A1. Further functional studies are warranted to explore the underlying mechanisms.

D-dimer for assessment of treatment response, and survival to drug-eluting beads transarterial chemoembolization in hepatocellular carcinoma.

BACKGROUND: D-dimer exhibits a certain prognostic value in hepatocellular carcinoma (HCC) patients who underwent hepatectomy and microwave ablation, while its value in estimating the clinical benefit of drug-eluting beads transarterial chemoembolization (DEB-TACE) remains unclear. Hence, this study aimed to investigate the correlation of D-dimer with tumor features, response and survival to DEB-TACE in HCC patients. METHODS: Fifty-one HCC patients treated with DEB-TACE were recruited. Their serum samples at baseline and after DEB-TACE were collected and proposed for D-dimer detection by the immunoturbidimetry method. RESULTS: Elevated D-dimer levels were related to a higher Child‒Pugh stage (P = 0.013), tumor nodule number (P = 0.031), largest tumor size (P = 0.004), and portal vein invasion (P = 0.050) in HCC patients. Then, patients were classified by the median value of D-dimer, and it was observed that patients with D-dimer >0.7 mg/L achieved a lower complete response rate (12.0% vs. 46.2%, P = 0.007) but a similar objective response rate (84.0% vs. 84.6%, P = 1.000) compared to those with D-dimer ≤0.7 mg/L. The Kaplan‒Meier curve showed that D-dimer >0.7 mg/L (vs. ≤0.7 mg/L) was related to shorter overall survival (OS) (P = 0.013). Further univariate Cox regression analyses showed that D-dimer >0.7 mg/L (vs. ≤0.7 mg/L) was related to unfavorable OS [hazard ratio (HR): 5.524, 95% confidence interval (CI): 1.209-25.229, P = 0.027], but it failed to independently estimate OS (HR: 10.303, 95%CI: 0.640-165.831, P = 0.100) in multivariate Cox regression analyses. Moreover, D-dimer was elevated during DEB-TACE therapy (P<0.001). CONCLUSION: D-dimer may be helpful for monitoring prognosis to DEB-TACE therapy in HCC, while further large-scale-study validation is warranted.

Safety and efficacy of percutaneous microwave ablation using combined computed tomography and ultrasound-guided imaging in patients with hepatocellular carcinoma: A retrospective study.

Background: We retrospectively evaluated the safety and efficacy of percutaneous microwave ablation (MWA) using combined computed tomography (CT) and ultrasound (US)-guided imaging in patients with Barcelona Clinic Liver Cancer (BCLC)-A1-3 hepatocellular carcinoma (HCC). Methods: We included 88 consecutive patients with single HCC who were treated with transcatheter arterial chemoembolization (TACE) using our database. The patients were divided into three groups. The combination group received MWA under the guidance of nonenhanced CT and US, CT group received MWA under the guidance of nonenhanced CT alone and US group received MWA under the guidance of US alone. The study endpoints included the treatment time, number of puncture, local recurrence rate, and adverse events. Results: The median treatment time and mean puncture number were 38.6 (30-45) min, 1.2 (1-2) times (combination group); 45.8 (35-56) min, 4.2 (3-7) times (CT group); and 36.7 (30-47) min, 1.1 (1-2) times (US group), respectively. The median puncture number was significantly less than in the CT group. The local recurrence rate in the combination group was significantly inferior to that in the US group. There was a statistically significant difference between the combination group and CT group in Grade C complication rate. Conclusions: Combining CT-and US-guide MWA in patients with BCLC-A1-3 HCC appeared to be much better than the use of guidance of CT or US alone.

Treatment efficacy and safety of drug-eluting beads transarterial chemoembolization versus conventional transarterial chemoembolization in hepatocellular carcinoma patients with arterioportal fistula.

This study aimed to compare the treatment efficacy and tolerance between drug-eluting beads transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (cTACE) in hepatocellular carcinoma (HCC) patients with arterioportal fistula (APF). A total of 44 HCC patients with APF scheduled for DEB-TACE (N = 24, as DEB-TACE group) or cTACE (N = 20, as cTACE group) were recruited. Treatment response, hepatic function, and adverse events were assessed or recorded. Besides, progression-free survival (PFS) and overall survival (OS) were calculated. Total treatment response was better in the DEB-TACE group compared with the cTACE group (P = .012). Meanwhile, the objective response rate (87.5% versus 60.0%) was higher (P = .013), while the disease control rate (95.8% versus 85.0%) was similar in the DEB-TACE group compared to the cTACE group (P = .213). Besides, PFS (mean value: 12.2 (95%CI: 9.9-14.6) months versus 7.8 (95%CI: 5.6-10.0) months) (P = .037), but not OS (mean value: 20.0 (95%CI: 18.1-21.9) months versus. 18.6 (95%CI: 15.4-21.8) months) (P = .341) was prolonged in DEB-TACE group compared with cTACE group. Regarding the safety, Child-Pugh stage, albumin level, and bilirubin level after treatment were all similar between the DEB-TACE group and cTACE group (all P > .05); moreover, no difference was found in the occurrence of adverse events during or after treatment between the two groups (all P > .05). Moreover, subsequent analyses found that embolic materials for APF (microspheres) in the DEB-TACE group did not affect the treatment efficacy (all P > .05). DEB-TACE promotes treatment response and PFS compared with cTACE and shows good safety in HCC patients with APF.

Drug-eluting bead transarterial chemoembolization is an effective downstaging option for subsequent radical treatments in patients with hepatocellular carcinoma: A cohort study.

BACKGROUND: This study aimed to investigate the potential of drug-eluting bead transarterial chemoembolization (DEB-TACE) as downstaging therapy for subsequent radical treatment in patients with hepatocellular carcinoma (HCC). METHODS: Totally, 32 patients with unresectable HCC were enrolled, then they received DEB-TACE for down-staging therapy followed by radical treatments (surgery, radiofrequency ablation or microwave ablation). The rate of successful down-staging, treatment response (after DEB-TACE and radical therapy), alpha-fetoprotein (AFP), progression-free survival (PFS) and overall survival (OS) were assessed. RESULTS: After down-staging therapy with DEB-TACE, successful down-staging rate was 59.4%. With the followed radical treatment, the complete response was 81.3%. Subsequent analysis indicated that CNLC stage (IIb vs. IIa) was an independent risk factor for successful down-staging. Furthermore, AFP level presented a declined trend throughout the time points (before DEB-TACE, after DEB-TACE, and after radical treatment). Additionally, 1-year, 2-year and 3-year accumulating PFS were 68.8%, 40.6% and 31.3%, respectively; 1-year, 2-year and 3-year accumulating OS were 84.4%, 71.9% and 53.1%, respectively. Kaplan-Meier curves exhibited that successful down-staging was correlated with longer PFS and OS, then further Cox's regression analysis verified that successful down-staging was an independent factor for predicting increased OS but not PFS. Besides, child-Pugh stage (B vs. A), CNLC stage (IIb vs. IIa) and AFP abnormal after radical treatment were independent factors for decreased PFS or OS. CONCLUSIONS: DEB-TACE has potential as an additionally effective down-staging therapy for radical treatments, and successful down-staging treatment by DEB-TACE associates with favorable survival profiles in patients with unresectable HCC.

Hepatocellular carcinoma with type II-III portal vein tumour thrombosis: treatment using transarterial chemoembolisation and microwave ablation.

OBJECTIVE: To evaluate the use of transarterial chemoembolisation (TACE) combined with microwave ablation (MWA) to treat patients with hepatocellular carcinoma (HCC) and type Ⅱ-Ⅲ portal vein tumour thrombosis (PVTT) intolerant to targeted drug (TG) therapy. METHODS: A total of 18 patients with HCC and type Ⅱ-Ⅲ PVTT intolerant to TG were enrolled between June 2015 and December 2019, who were treated with TACE + MWA (MWA group). 24 patients were treated with TACE + TG (TG group; control cohort). Time to progression and overall survival (OS) were analysed along with the incidence of adverse events. RESULTS: The median follow-up time was 19.0 months (9.0-32.0 months). The median OS was 17.0 months (8.3-29.3 months; MWA group) and 13.5 months (5.5-22.5 months; TG group) and was not significantly different. The 1- and 2 year OS was also comparable (MWA group: 66.7%, 44.4% vs Target group: 41.7%, 29.2%). Time to progression showed no distinct differences (MWA group: 11.5 months; TG group: 9.0 months) between the two groups. Moreover, the incidence of major Grade 3-4 adverse events in the MWA group (5.6%) was similar to those in the TG group (8.3%). CONCLUSION: TACE + MWA and TACE + TG were comparable in their safety and efficacy in patients with HCC, type Ⅱ-Ⅲ PVTT, and intolerance to TG. ADVANCES IN KNOWLEDGE: TACE + MWA can be used as a palliative treatment alternative for TACE + TG in patients with HCC, type Ⅱ-Ⅲ PVTT, and intolerance to TG.

Imaging features and outcomes in patients with ruptured hepatocellular carcinoma following transcatheter arterial chemoembolization: a retrospective clinical study.

OBJECTIVE: To summarize and analyze the imaging features and outcomes of patients with ruptured hepatocellular carcinoma (HCC) following transcatheter arterial chemoembolization (TACE). METHODS: We investigated all consecutive patients with HCC who received standardized TACE based on our hospital database. Ruptured HCCs were divided into three types according to their relationship with the liver capsule, determined by computed tomography or magnetic resonance imaging scans: Type I, portion of tumor cambered outwards ≤30%; Type II, portion of tumor cambered outwards >30% and <50%; and Type III, portion of tumor cambered outwards ≥50%. RESULTS: There were 54, 40, and 26 patients with Type I, II, and III HCCs, respectively. Among these, eight patients developed ruptured tumors within 2 weeks after TACE, including one, two, and five patients with type I, II, and III ruptured HCCs, respectively. Patients with type III HCCs had a shorter median survival time than patients with type I-II HCCs. CONCLUSIONS: Patients with type III HCCs might have a higher re-rupture rate and benefit less from emergency arterial embolization procedures than patients with type I-II HCCs.

Drug-eluting beads-transarterial chemoembolization plus microwave ablation is an effective and safe treatment strategy in treating hepatocellular carcinoma adjacent to gallbladder.

The present study aimed to compare the efficacy and safety of drug-eluting beads-transarterial chemoembolization (DEB-TACE) plus microwave ablation (MWA) versus (vs.) surgery in treating patients with hepatocellular carcinoma (HCC) adjacent to gallbladder. Totally 54 patients with HCC adjacent to gallbladder were included and divided into two groups: DEB-TACE plus MWA group (n = 24) and surgery group (n = 30). Treatment response, relapse-free survival (RFS), progression-free survival (PFS), overall survival (OS) and adverse events were assessed and documented. For DEB-TACE plus MWA group, complete response rate, objective response rate and disease control rate were 79.2%, 95.8% and 100.0% after one-month post treatment, respectively. In terms of survival profiles, DEB-TACE plus MWA group presented similar RFS (28.2 (95% CI: 12.5-43.9) months vs. 26.6 (95% CI: 19.2-34.1) months) (P = 0.930), PFS (21.2 (95% CI: 1.6-40.8) months vs. 26.6 (95% CI: 19.2-34.1) months) (P = 0.541), and OS (41.4 (95% CI: 35.0-47.9) months vs. 59.7 (95% CI: 51.7-67.7) months) (P = 0.138) compared with surgery group, and further multivariate Cox's regression analysis validated that, after adjustment of confounding factors, DEB-TACE plus MWA group exhibited no difference of RPS, PFS or OS compared with surgery group. Regarding safety, the intraoperative adverse event incidence was higher in DEB-TACE plus MWA group compared with surgery group (P = 0.008), while two groups exhibited no difference of postoperative adverse event incidence (P = 0.618). In conclusion, DEB-TACE plus MWA presents to be an optional treatment strategy in patients with HCC adjacent to gallbladder.

Effect of microwave ablation on platelet and coagulation function in patients with BCLC-A hepatocellular carcinoma.

AIM: To preliminarily evaluate the effect of microwave ablation (MWA) alone on platelet (PLT) and coagulation function in patients with BCLC-A hepatocellular carcinoma (B-A-HCC) using a retrospective method. MATERIALS AND METHODS: A total of 36 patients with 48 B-A-HCCs were radically treated with MWA alone under the guidance of ultrasound between April and October 2018. PLT coagulation indexes were measured before and after MWA at 1 day, 3 days, 1 week, and 2 weeks, and blood samples (after morning fasting) were collected from cubital veins. Coagulation indexes included prothrombin time (PT), prothrombin activity (PTA), thrombin time (TT), Activated Partial Thromboplastin Time (APTT), international standardized ratio (INR), plasma fibrinogen (FIB), plasma antithrombin III (AT-III), and D dimer (DD). Overall survival (OS), recurrence-free survival (RFS), local tumor progression (LTP), and adverse reactions were also recorded. RESULTS: All patients were radically treated with MWA alone. The median size of the lesion was 2.6 (1.5-7.0) cm3. On the first day after MWA, the level of PLT decreased significantly compared with the values before MWA and gradually returned to preoperative levels one week after MWA. One day after MWA, the levels of PT, INR, and AT-III increased markedly and the level of PTA decreased significantly, all of them gradually returned to baseline after 3 days to a week of time. 1, 3, and 7 days after MWA, the levels of FIB, and DD increased significantly, and the level of TT decreased significantly; all of them gradually returned to baseline at 2 weeks. At 6 months posttreatment, the OS and RFS rates were 100% and 91.7%, the LTP rates was 5.6%, no significant adverse reactions. CONCLUSION: PLT and coagulation indexes were abnormal in patients with B-A-HCC who were radically treated with MWA alone after treatment; without specific treatment, they all gradually returned to baseline within a week or two.

Reduced Syntactic Processing Efficiency in Older Adults During Sentence Comprehension.

Researchers have frequently reported an age-related decline in semantic processing during sentence comprehension. However, it remains unclear whether syntactic processing also declines or whether it remains constant as people age. In the present study, 26 younger adults and 20 older adults were recruited and matched in terms of working memory, general intelligence, verbal intelligence and fluency. They were then asked to make semantic acceptability judgments while completing a Chinese sentence reading task. The behavioral results revealed that the older adults had significantly lower accuracy on measures of semantic and syntactic processing compared to younger adults. Event-related potential (ERP) results showed that during semantic processing, older adults had a significantly reduced amplitude and delayed peak latency of the N400 compared to the younger adults. During syntactic processing, older adults also showed delayed peak latency of the P600 relative to younger adults. Moreover, while P600 amplitude was comparable between the two age groups, larger P600 amplitude was associated with worse performance only in the older adults. Together, the behavioral and ERP data suggest that there is an age-related decline in both semantic and syntactic processing, with a trend toward lower efficiency in syntactic ability.

Age-related temporal-spatial dynamic ERP changes during sentence comprehension.

The aim of the present study was to investigate whether age-related brain response alterations during sentence comprehension exist when verbal fluency and intelligence are controlled for. Twenty-four younger and twenty-four older adults with matched verbal fluency, verbal intelligence, years of education, and gender ratio were recruited. They were asked to read congruent (CON) and incongruent (INCON) sentences to make semantic acceptability judgments. A significant group by condition interaction on accuracy was found, showing a significant congruency effect in younger, but not older adults. The ERP results revealed a dynamic temporal-spatial change in older adults. The congruency related N400 effect was reduced and delayed significantly in the older adults compared to the younger adults, and accompanied by different distribution patterns across time windows. The late positive component with more positive-going in the INCON condition than the CON condition was found in older adults only, which did not correlate with the performance, however. The results suggest that with age, there is a decline in semantic processing during sentence comprehension.