Comparison of NK cell subsets, receptors and functions induced by radiofrequency ablation and microwave ablation in HBV-associated primary hepatocellular carcinoma.

Background: Topical therapy has been shown to induce an immune response in patients with hepatocellular carcinoma (HCC). In this study, a prospective parallel group control experiment was conducted to compare the differences between radiofrequency ablation and microwave ablation in inducing the immune regulation of NK cells. Methods: Sixty patients with clinically and pathologically confirmed hepatitis B-associated hepatocellular carcinoma (HCC) were selected for thermal ablation. Patients were randomly assigned into the MWA group (n = 30) and the RFA group (n = 30). Patient's peripheral blood was isolated on days D0, D7, and month M1. NK cell subsets, receptors, and killing function were detected by flow cytometry and LDH. Student t test and rank sum test were used to compare the statistical differences between the RFA (radio frequency) and MWA (microwave) groups. The Kaplan-Meier curve and log-rank test were used to calculate the difference between the two survival curves. Results: Comparison of the frequency of CD3-CD56+ and CD3-CD56+CD16+ in NK cells between the RFA and WMA groups showed that there was no difference in the D0, D7, M1, D7-D0, M1-D0, and M1-D7 groups. The changes of the inhibitory NK cell receptor CD159A were significantly different at D7 (P<0.05). CD107a were compared between the RFA and WMA groups, indicating that CD107a changes induced by NK cells were significantly different at D7-D0 (P<0.05). Comparison of NK cell lysis activity of target K562 cells between the RFA and WMA groups showed that there was no difference at D0, D7, D7-D0. There was no difference in recurrence-free survival (RFS) between the RFA and WMA groups (P=0.11). Conclusions: The difference between MWA and RFA-induced NK cell changes was mainly manifested in the inhibitory receptors CD159a and CD107a 1 week after surgery, with microwave-induced changes being more severe. Comparison of the NK cell lysis activity of the target K562 cells between the RFA and WMA groups showed that there was no difference in D0, D7, D7- D0. Survival analysis showed that these differences did not affect the recurrence-free survival (RFS) in the two groups.

Dynamic changes of phenotype and function of natural killer cells in peripheral blood before and after thermal ablation of hepatitis B associated hepatocellular carcinoma and their correlation with tumor recurrence.

BACKGROUND: Thermal therapy induces an immune response in patients with hepatocellular carcinoma (HCC), but the dynamic characteristics of the natural killer (NK) cell immune response post-thermal ablation remain unclear. We conducted a prospective longitudinal cohort study to observe the dynamic changes of phenotype and function of NK cells in peripheral blood before and after thermal ablation of hepatitis B-associated HCC and their correlation with tumor recurrence. METHODS: Fifty-six patients clinically and pathologically confirmed with hepatitis B-associated HCC were selected for thermal ablation. Peripheral blood was collected on day 0, day 7, and month 1. NK cell subsets, receptors, and killing function were detected by flow cytometry, and the LDH levels were examined. Overall recurrence and associated variables were estimated using Kaplan-Meier, log-rank, and Cox proportional-hazards analyses. RESULTS: The frequency of CD3-CD56+ cells was increased on day 7 (P < 0.01) without significant differences between D0 and M1. NKG2D, NKp44, NKp30, CD159a, and CD158a expression was increased on M1 (all P < 0.05). The granzyme B and IFN-γ expression in NK cells were higher on M1 vs. D0 (P < 0.05). On day 7, the NK cell lysis activity of the target K562 cells was increased (P < 0.01) but decreased on M1 (P < 0.05). Survival analysis showed that CD158a expression and IFN-γ and perforin release on day 0 were associated with the risk of HCC recurrence. Cox regression analysis showed that the expression changes in CD56, NKp46, granzyme B, and perforin (D7-D0) induced by thermal ablation were associated with recurrence-free survival (RFS) of patients with HCC. CONCLUSION: Thermal ablation increased the frequency and function of CD3-CD56+ NK cells in the peripheral blood of patients with HCC. These cells tended to be more differentiated and activated. Notably, expression levels of NK cell receptors NKp46, perforin, and granzyme B were associated with RFS.

Experimental Research on the Influence of Different Curved Rigid Boundaries on Electric Spark Bubbles.

It is well known that the bubble dynamics and load characteristics of cavitation bubbles depend to a great extent on their proximity to the boundary. The purpose of this study is to explore the relationship between the boundary curvature and bubble dynamics, as well as the load characteristics, and summarize the relevant change laws. This study takes three hemispheres of different curvatures and one flat board as its main research boundaries. The hemisphere was chosen as the curved surface boundary because the hemisphere represents the simplest type of curved surface boundary. This method allowed us to easily observe the experimental results and summarize the change laws of bubble dynamics and load characteristics. A high voltage electricity of 400 V was used to produce stable and repeatable electric spark bubbles in this experiment. Since the pulsation time of the bubbles is very short, we used a high-speed camera to acquire the necessary photographs. We also used a Hopkinson bar (HPB) to measure the bubble collapse load. Suppose that the dimensionless parameter of curvature is ζ and the dimensionless parameter of the explosion distance is γ. By summarizing the 44 groups of the experimental results under different combinations of ζ and γ, we found that the cavitation bubble dynamics and loading characteristics are affected by ζ. With an increase of ζ, the shockwave load and bubble collapse load will decrease. In addition, in terms of load characteristics, this study further verified the change trend of the shockwave load and bubble collapse load with γ. For the bubble shrink shape, this paper illustrates the relationship between the bubble's shrink shape and its shrinkage speed. Four typical bubble shrink shapes are summarized. The effects of different ζ and γ values on the jet are preliminarily explored using the experimental results, and, by considering the experimental results, the developmental trends of the time of the bubble's first pulsation period are discussed.

Efficacy of ultrasound-, computed tomography-, and magnetic resonance imaging-guided radiofrequency ablation for hepatocellular carcinoma.

PURPOSES: This study aimed to investigate the efficacy of ultrasound (US)-, computed tomography (CT)-, and magnetic resonance imaging (MRI)-guided radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 141 patients with HCC who were treated with US-guided (n = 29), CT-guided (n = 50), or MRI-guided RFA (n = 62). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), technique success (TS), and technique efficacy (TE). Cox model and logistic regression were used to determine the risk factors for tumor recurrence and TE. RESULTS: The US, CT, and MRI groups did not show a significant difference in terms of baseline variables. The three groups did not differ significantly in PFS rate (P = 0.072) and OS rate (P = 0.231). The PFS rates at 3 years for the US, CT, and MRI groups were 40.90%, not reached, and 14.80%, respectively. The OS rates at 3 years were 94.70%, 97.50%, and 85.50% for US, CT, and MRI groups, respectively. No significant differences were observed between the three groups in terms of TS rate (P = 0.113) and TE rate (P = 0.682). In multivariate analysis, liver cirrhosis (P = 0.001), level of alpha-fetoprotein (AFP, P = 0.004), and number of tumors (P = 0.012) were independent risk factors for PFS. For TE, the level of AFP (P = 0.018) was an independent factor. CONCLUSION: US-, CT-, and MRI-guided RFA was effective for treating HCC patients. Liver cirrhosis, AFP level, and tumor number were associated with tumor recurrence, and the level of AFP was an independent risk factor affecting TE.

Novel mutations found in the ATP7B gene in Chinese patients with Wilson's disease.

BACKGROUND: Wilson's disease (WD) is an autosomal recessive genetic disease caused by mutations in ATP7B and characterized by copper metabolism disorders. METHODS: Direct sequencing of the ATP7B gene is the most sensitive and widely used confirmatory testing method. Fourteen probands with WD and 12 family members participated in this study. The ATP7B gene was analyzed by direct sequencing. RESULTS: Twenty-nine different variants (27 substitutions, 1 duplication, 1 deletion) were found. Of the 23 reported variants, nine nondisease variants, 11 disease variants, one silent variant, and two variants with uncertain functions were identified. The six novel variants included c.1875T>A, c.2306T>C, c.3028A>G, c.3243G>A, c.3437_3438 delTG, and c.3903+5G>A. CONCLUSION: These findings will assist in the diagnosis of WD. The novel variants have enriched the WD database.

Identification of miRNA and mRNA expression profiles by PCR microarray in hepatitis B virus­associated hepatocellular carcinoma.

The present study aimed to identify differentially expressed microRNAs (miRNAs) and mRNAs in hepatitis B virus­associated hepatocellular carcinoma (HCC). A total of five HCC tissues and paired adjacent non­tumor tissues were screened to identify the differentially expressed miRNAs and target mRNAs using polymerase chain reaction microarrays. The interaction between differential miRNA and mRNA expression was concurrently analyzed using bioinformatics methods. A total of 32 differentially expressed miRNAs (four upregulated miRNAs and 28 downregulated miRNAs) and 16 differentially expressed mRNAs (11 upregulated mRNAs and five downregulated mRNAs) were identified. Among these, upregulated hsa­miRNA (miR)­96­5p and hsa­miR­18b­5p suppressed their target mRNAs forkhead box O1 and MET transcriptional regulator MACC1 (MACC1). Downregulation of hsa­miR­199a­5p led to upregulation of its target mRNAs, cyclin dependent kinase 4 and insulin like growth factor 2 (IGF2). The high­level expression of IGF2 mRNA and cyclin E1 mRNA was due to the low­level expression of hsa­miR­145­5p, hsa­miR­181a­5p, hsa­miR­199a­5p and hsa­miR­223a­3p, and hsa­miR­26a­5p and hsa­miR­26b­5p, respectively. The low­level expression of coronin 1A mRNA and MACC1 mRNA was due to overexpression of hsa­miR­517a­3p and hsa­miR­18a­5p, and hsa­miR­18b­5p, respectively. Numerous gene ontology terms were associated with oncogenesis. The most enriched pathways targeted by the dysregulated miRNAs and mRNAs were associated with cancer and oncogenesis pathways. The present data suggested that differential miRNA and mRNA expression is present in HCC. Thus, interactions between certain miRNAs and mRNAs may be involved in the pathogenesis of HCC.

C-arm Lipiodol CT in transcatheter arterial chemoembolization for small hepatocellular carcinoma.

AIM: To investigate the value of C-arm Lipiodol computed tomography (CT) for intra-procedural hepatocellular carcinoma (HCC) lesion detection during transcatheter arterial chemoembolization (TACE). METHODS: Forty patients (37 male, 3 female; mean age, 52.6 ± 12.5 years, age range: 25-82 years) diagnosed with HCC were enrolled in this study. All patients underwent 64-slice CT 1-2 wk before TACE. During the procedure, hepatic angiography was performed first. Following diagnostic embolization with Lipiodol injected into the hepatic artery, a C-arm CT scan was immediately conducted (C-arm Lipiodol CT). If new HCC lesions were confirmed, gelfoam particles were super-selectively injected into the tumor-nourishing blood vessel. A Lipiodol CT scan was performed 7-14 d after TACE. All images acquired from 64-slice CT, digital subtraction angiography (DSA), C-arm Lipiodol CT and Lipiodol CT were retrospectively reviewed by four radiologists and the number of detected lesions in each examination was counted, respectively. The results of Lipiodol CT were taken as the diagnostic reference. Alpha-fetoprotein values were examined both before and after TACE. This study only takes into account the lesions that were not found or were considered suspicious on 64-slice CT before TACE. RESULTS: Preprocedural 64-slice CT detected a total of 13 suspicious lesions in the 40 patients. DSA detected ten definite and four suspicious lesions. C-arm Lipiodol CT detected 71 lesions in total and Lipiodol CT confirmed 67 lesions with a diameter range of 3-12 mm. Four false-positive lesions, which were detected by C-arm Lipiodol CT, were considered to be hepatic artery-portal vein fistulas. The average alpha-fetoprotein values before and after TACE were significantly different (452.3 ± 192.6 ng/mL vs 223.8 ± 93.2 ng/mL; P = 0.039). CONCLUSION: C-arm Lipiodol CT has a higher diagnostic sensitivity for small HCC lesions. This technique may help physicians make intraprocedural decisions to provide patients with earlier treatment.

Complete remission of multiple lung metastases after ablation of hepatocellular carcinoma by transarterial infusion with the p53 gene.

We describe the case of a 68-year-old man who presented with a massive lesion in the right liver. It was confirmed by preoperative aspiration biopsy to be a case of moderately differentiated hepatocellular carcinoma, and the patient was shown by immunohistochemistry to have a mutation in the p53 gene. The hepatic lesion showed complete necrosis after arterial embolization combined with microwave ablation. During a re-examination 3 months after ablation, the α-fetoprotein level was found to have increased markedly. Bilateral pulmonary metastases were shown by a lung computed tomography scan, with a focal diameter smaller than 1 cm. Hepatic and bronchial intra-arterial infusion with the recombinant adenovirus p53 gene (rAd-p53) was performed twice. The second time the infusion was administered, interleukin-2 was used in combination with rAd-p53. After 2 months of treatment, the bilateral pulmonary lesions had almost disappeared. After 7 months of treatment, the bilateral pulmonary metastases disappeared completely, and no further recurrence has been identified in the lungs and liver.

Comparison of diagnostic sensitivity of C-arm CT, DSA and CT in detecting small HCC.

BACKGROUND/AIMS: To compare the detection rate of 64-slice CT, digital subtraction angiography (DSA) and C-arm computed tomography (C-arm CT) in small lesions with a diameter ≤3.0 cm of hepatocellular carcinoma (HCC). METHODOLOGY: Sixty-six patients with HCC underwent 64-slice CT, DSA, and C-arm CT, and were followed up by lipiodol CT two weeks after transcatheter arterial chemoembolization (TACE). Whose result was used as diagnostic reference. The number of detected lesions with diameter ≤3.0 cm in each imaging modality was counted independently by 4 radiologists. RESULTS: A total of 174 lesions out of the 66 patients were confirmed by lipiodol CT, among which 47.7% were detected by 64-slice CT, 82.2% by DSA, and 97.1% by C-arm CT. McNemar test showed the statistical difference in detection rate between each two methods of CT, DSA and C-arm CT (all p<0.0001). All lesions were further classified into 3 groups (group A, B, C) according to the diameter (≤1cm, 1-2cm, 2-3cm), where C-arm CT showed significantly higher diagnostic sensitivity in group A and B. CONCLUSIONS: Compared to 64-slice CT and DSA, C-arm CT has the best sensitivity by detecting small lesions of HCC, and thus may play a guiding role in TACE procedure.