Comparison of radiofrequency ablation combined with sorafenib or sorafenib alone in patients with ECOG performance score 1: identifying optimal candidates.

BACKGROUND: Sorafenib has been recommended as the first-line treatment and shown to prolong the median overall survival (OS) of patients with advanced unresectable hepatocellular carcinoma (HCC). Recently, a growing number of earlier studies showed the application of radiofrequency ablation (RFA) plus sorafenib in patients diagnosed at the advanced-stage HCC. This study aimed to compare the outcomes of RFA plus sorafenib versus sorafenib alone and identify prognostic factors related to OS for BCLC stage C patients with PS 1 but without vascular invasion or extrahepatic spread. METHODS: A total of 276 consecutive patients in BCLC stage C with PS 1 but without vascular invasion or extrahepatic spread were enrolled in this retrospective study. Survival analyses were performed using the Kaplan-Meier analysis, and the log-rank test examined the statistical differences between the transarterial chemoembolization (TACE) and sorafenib groups. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic factors for OS. RESULTS: Based on the Kaplan-Meier curves, patients treated with RFA plus sorafenib showed better OS than those undergoing sorafenib, with respective OS at 1, 3 and 5 years (84.0%, 43.1%, 22.8% vs. 55.6%, 29.6%, 4.8%, Log-rank P<0.001). The univariate analysis and multivariate analysis showed that tumor size, tumor number, treatment method, albumin, bilirubin, and the Child-Pugh score were associated with OS. According to the subgroups analyses based on the tumor size and tumor number, there were significant differences in OS among overall subsets except in patients with tumor number ≥4 between RFA plus sorafenib and sorafenib therapy. CONCLUSIONS: RFA plus sorafenib provided better prognostic performance than sorafenib, which should be suggested as an alternative treatment modality compared with sorafenib for BCLC stage C patients with PS 1 but without vascular invasion or extrahepatic spread.

Efficacy evaluation of the combination therapy of sorafenib and transarterial chemoembolization for unresectable HCC: a systematic review and meta-analysis of comparative studies.

BACKGROUND: Sorafenib and transarterial chemoembolization (TACE) are the standard treatments recommended by guidelines for unresectable hepatocellular carcinoma (HCC). Although previous studies have shown the combination therapy of sorafenib and TACE to be safe, there is no consensus regarding its efficacy. This systematic review and meta-analysis, which was based on the findings of comparative clinical trials, was conducted to provide up-to-date and comprehensive information about the efficacy of combination therapy versus TACE monotherapy in unresectable HCC. METHODS: Multiple databases were systematically reviewed to screen studies through particular inclusion criteria. Hazard ratio (HR) with 95% confidence intervals (95% CIs) was collected and analyzed by Revman 5.3 in a fixed or random effects meta-analysis model. Adverse events (AEs) were also evaluated. RESULTS: This review ultimately included 14 comparative studies focused on combination therapy versus TACE monotherapy. Of these: 5 studies conducted TACE plus sorafenib versus TACE with placebo; 9 studies provided overall survival (OS) in combination groups which ranged from 10.3 to 29.7 months; and 10 studies provided time to progression (TTP) in combination groups which ranged from 2.6 to 10.8 months. The disease control rate (DCR) in combination groups ranged from 9.7% to 89.2% in 7 of the studies. After performing a random effects meta-analysis model, our study showed that OS (HR =0.65, 95% CI: 0.54-0.79, P<0.0001) and TTP (HR =0.72, 95% CI: 0.59-0.88, P=0.001) have been significantly improved in the combination therapy group when compared with the TACE monotherapy group. AEs mainly included hand-foot skin reaction (HFSR), fatigue and diarrhea and the majority of these were in grade 1 or grade 2. CONCLUSIONS: Combination therapy has significant advantages over TACE monotherapy in terms of improving TTP and OS.

Prognostic value of the albumin-bilirubin grade in patients with hepatocellular carcinoma and other liver diseases.

One of the most commonly used systems for grading liver function in hepatocellular carcinoma (HCC) patients is the Child-Pugh (CP) score. However, the CP scoring system is not without its shortcomings: for example, the cut-off values for the parameters are calculated arbitrarily and the assessment of ascites and hepatic encephalopathy is subjective. More recently, an alternative to traditional CP grade has emerged in the form of albumin-bilirubin (ALBI) grade. The predictive value provided for HCC patients by the ALBI grade is comparable to that of the CP grade; however, it can also surpass CP grade by greatly reducing subjectivity and further subdividing CP A patients into several different groups, thus improving the prognosis judgment and helping to inform clinicians' optimal decision-making. The application of the ALBI grade into currently used HCC staging systems such as the Barcelona Clinic Liver Cancer (BCLC) staging system, the Cancer of the Liver Italian Program (CLIP) staging system, and the Japan Integrated Staging (JIS) score, etc., as well as newly produced systems like the ALBI-PLT grade, the ALBI and progression disease (ALBI-PD) grade and Modified Intermediate Stage of Liver Cancer (MICAN) criteria, greatly elevates prognostic power.

Molecular Pathological Markers Correlated With the Recurrence Patterns of Glioma.

PURPOSE: Glioma is one of the most common tumors of the central nervous system, and many patients suffer from recurrence even after standard comprehensive treatment. However, little is known about the molecular markers that predict the recurrence patterns of glioma. This study aimed to demonstrate the correlations between molecular markers and glioma recurrence patterns, which included local/nonlocal recurrence and paraventricular/nonparaventricular recurrence. METHODS: Immunohistochemical techniques were used to assess the molecular markers of 88 glioma tissues following surgical resection. The recurrence patterns were divided into local recurrence, marginal recurrence, distant recurrence, multirecurrence, and subarachniod recurrence, with the last four recurrence patterns being collectively called nonlocal recurrence. According to whether the recurrence invaded ventricles, the nonlocal recurrence patterns were divided into paraventricular and nonparaventricular recurrence. Then, we compared the different recurrence patterns and their clinical characteristics, focusing on the expression of molecular markers. RESULTS: More patients in the nonlocal recurrence group received combined radiotherapy and chemotherapy than patients in the local recurrence group (p=0.019). Sex, age, extent of surgery, time to recurrence, tumor location, size, and WHO grade were not different in the defined groups (P>0.05). Recurrent tumor volume and WHO grade were significantly different between the paraventricular and nonparaventricular recurrence groups (p=0.046 and 0.033). The expression of Ki-67, P53, and PCNA in the nonlocal recurrence group was significantly higher than that in the local recurrence group (p=0.015, 0.009, and 0.037), while the expression of S-100 in the nonlocal recurrence group was significantly lower than that in the local recurrence group (p=0.015). Cox regression indicated hazard ratio (HR) for high expression level of PCNA associated with non-local recurrence was 3.43 (95% CI, 1.15, 10.24), and HR for high expression level of MGMT associated with paraventricular recurrence was 2.64 (95% CI, 1.15,6.08). CONCLUSIONS: Ki-67, P53, PCNA, and MGMT might be important clinical markers for nonlocal recurrence and paraventricular recurrence.

In vitro cell behaviors of bone mesenchymal stem cells derived from normal and postmenopausal osteoporotic rats.

Postmenopausal osteoporosis (PMO) increases bone fragility and the risk of fractures, and impairs the healing procedure of bone defects in aged women. The stromal cell­derived factor-1α (SDF-1α)/CXC chemokine receptor type 4 (CXCR4) axis helps to maintain the biological and physiological functions of bone marrow mesenchymal stem cells (BMSCs) and increase the homing efficiency of BMSCs. The present study aimed to provide insights into the possible association between migration and osteogenic ability and the SDF-1α/CXCR4 axis in BMSCs derived from a rat model of PMO. In order to do this, the general and SDF-1α/CXCR4-associated biological characteristics as well as associated molecular mechanisms in BMSCs isolated from a PMO rat model (OVX-BMSCs) and normal rats (Sham­BMSCs) were investigated and compared. In comparison with Sham-BMSCs, OVX-BMSCs exhibited an impaired osteo-genic ability, but a stronger adipogenic activity as well as a higher proliferative ability. In addition, OVX-BMSCs presented a lower chemotactic activity towards SDF-1α, lower expression levels of CXCR4 and reduced levels of phosphorylated AKT (p-AKT). Therefore, the lower expression levels of CXCR4 and p-AKT may be responsible for the impaired osteogenic ability and lower chemotactic activity towards SDF-1α of OVX-BMSCs.