CDKN2A is a prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma.

Cyclin dependent kinase inhibitor 2A (CDKN2A) is an essential regulator of immune cell functionality, but the mechanisms whereby it drives immune infiltration in hepatocellular carcinoma (HCC) remain unclear. In the present study, we studied the association with CDKN2A expression and immune invasion with the risk of developing HCC. A totally of 2207 different genes were found between HCC and adjacent liver tissues from TCGA and GEO databases. CDKN2A was highly expressed in HCC and associated with poorer overall survival and disease-free survival. Notably, CDKN2A expression was positively correlated with infiltrating levels into purity, B cell, CD+8 T cell, CD+4 T cell, macrophage, neutrophil, and dendritic cells in HCC. CDKN2A expression showed strong correlations between diverse immune marker sets in HCC. These findings suggest that CDKN2A expression potentially contributes to regulation of tumor-associated macrophages and can be used as a prognostic biomarker for determining prognosis and immune infiltration in HCC.

Hepatocellular Carcinoma With Portal Vein Tumor Thrombus Treated With Transarterial Chemoembolization and Sorafenib vs. 125Iodine Implantation.

BACKGROUND AND AIMS: This study investigated the feasibility, safety, and efficacy of transarterial chemoembolization (TACE) combined with CT-guided 125iodine seed implantation for treatment of hepatocellular carcinoma (HCC) with first-branch portal vein tumor thrombosis (PVTT). METHODS: This prospective, controlled, multicenter study included HCC patients with Barcelona Clinic Liver Cancer stage C disease and PVTT in the right and/or left portal veins. Patients were treated with either TACE and sorafenib or TACE and CT-guided 125iodine seed implantation and regularly evaluated for clinical response and adverse events, with treatment termination resulting from declining clinical status, loss to follow-up, or death. RESULTS: This study demonstrated a significant between-group difference in median overall survival (OS); therefore, it was terminated early. A total of 123 patients were included in this study, with 52 patients in the TACE-sorafenib group and 71 patients in the TACE-125iodine group, without significant differences in baseline characteristics between groups. The median OS was 8.3 months (95% CI: 6.105-10.495) in the TACE-sorafenib group and 13.8 months (95% CI: 9.519-18.081) in the TACE-125iodine group. In a subgroup analysis of type IIa versus type IIb PVTT, the median OS was 17.5 months for type IIa and 7.1 months for IIb in the TACE-125iodine group. The median OS was 9.3 months for IIa and 4.0 months for IIb in the TACE-sorafenib group. Univariate and multivariate analyses confirmed that the PVTT type and treatment strategy were significant independent factors affecting OS. The objective response rates (ORR) for intrahepatic lesions and PVTT showed significant differences between groups. Most patients in both groups experienced minor adverse events related to TACE. The overall incidence of sorafenib-related adverse events or toxic effects was 90.4% in TACE-sorafenib group. In the TACE-125iodine group, the incidence of pneumothorax and minor hepatic subcapsular hemorrhage were 7.04% and 9.86%, respectively. CONCLUSIONS: This study showed that TACE-125iodine treatment significantly enhanced survival of patients with HCC and type II PVTT, especially subtype IIa, with minimal adverse events. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trials Database, identifier ChiCTR-ONN-16007929.

[Occurrence Characteristics and Health Risks of PAHs on the Surface of Buildings and Devices in the Coking Plant].

The occurrence characteristics of polycyclic aromatic hydrocarbons (PAHs) on the surfaces of buildings and devices in a typical coking plant were analyzed with the samples from different functional zones and materials. The health risk of PAHs was also evaluated. The results showed that PAHs concentrations ranged from 8.00×10-2-1.98×102 µg·dm-2, and 22.0% wiping samples exceeded the World Trade Center Task Group(WTCTG)standard (1.45 µg·dm-2), the highest rate beyond the standard in the samples was 135. The functional zones with the high PAHs concentration were mainly located in the coking and refinery zone. The PAHs concentration on the surfaces of buildings in the coking zone was 12.1 µg·dm-2, which was the highest in all functional zones. Among the surface materials, the antirust paint contained the highest concentrations of PAHs and were over the standard rate, whereas the glass had the lowest adsorption ability for PAHs. The US Superfund Risk Assessment Method was used to evaluate the health risk of PAHs. The evaluation results showed that PAHs in the coking and refinery zones were a risk for carcinogenicity, the total carcinogenic risk value to the exposed population (3.78×10-6-1.32×10-5) was higher than the lower limit of the US EPA standard (10-6). The results could provide the scientific basis for environmental management and remediation of contaminated sites.

Predicting Parametrial Invasion in Cervical Carcinoma (Stages IB1, IB2, and IIA): Diagnostic Accuracy of T2-Weighted Imaging Combined With DWI at 3 T.

OBJECTIVE: The objective of our study was to retrospectively evaluate the efficacy of combined analysis of T2-weighted imaging and DWI in the diagnosis of parametrial invasion (PMI) in cervical carcinoma. MATERIALS AND METHODS: The clinical records of 192 patients with cervical carcinoma who met the study requirements were reviewed for this retrospective study. The signal intensities of suspicious PMI tissue were assessed on T2-weighted images, DW images, and apparent diffusion coefficient maps independently by two experienced radiologists. The radiologist observers predicted the presence of PMI by scoring T2-weighted imaging alone and then by scoring T2-weighted imaging and DWI combined. The results were compared with histopathologic findings. RESULTS: Histopathologic findings revealed PMI in 24 of 192 study subjects. In positively predicting the presence of PMI, T2-weighted imaging and DWI combined scored significantly better than T2-weighted imaging alone, as proven by high sensitivity (T2-weighted imaging alone vs T2-weighted imaging and DWI combined: observer 1, 75.0% vs 83.3% [p = 0.477]; observer 2, 66.7% vs 91.7% [p < 0.05]), high specificity (T2-weighted imaging alone vs T2-weighted imaging and DWI combined: observer 1, 84.5% vs 98.8% [p < 0.001]; observer 2, 85.7% vs 98.8% [p < 0.001]), and high accuracy (T2-weighted imaging alone vs T2-weighted imaging and DWI combined: observer 1, 83.3% vs 96.9% [p < 0.001]; observer 2, 83.3% vs 97.9% [p < 0.001]). The area under the ROC curve was also significantly higher for T2-weighted imaging and DWI combined (observer 1, 0.911; observer 2, 0.952) than for T2-weighted imaging alone (observer 1, 0.798; observer 2, 0.762). Although the interobserver agreement was good for T2-weighted imaging (κ = 0.695) and excellent for T2-weighted imaging and DWI combined (κ = 0.753), the improvement failed to achieve statistical significance (p = 0.28). CONCLUSION: Combined analysis of T2-weighted imaging and DWI enhances the accuracy of diagnosing PMI in patients with cervical cancer compared with T2-weighted imaging alone.

Transarterial chemoembolization combined with computed tomography-guided 125iodine implantation enhances survival in hepatocellular carcinoma patients with portal vein tumor thrombus.

We conducted a retrospective study to evaluate the safety and efficacy of transarterial chemoembolization (TACE) combined with computed tomography-guided 125iodine implantation (TACE-125iodine) in hepatocellular carcinoma (HCC) patients with type B portal vein tumor thrombus (PVTT). From medical records, we determined that 50 patients who received 125iodine implantation 4-7 days after the first TACE session showed better survival than 50 patients who received only TACE (median survival, 13.1 vs. 6.0 months; P<0.01). Moreover, the PVTT control rate was higher in the TACE-125iodine than TACE alone group (78% vs. 18%; P<0.01). Multivariate analysis demonstrated that the TACE-125iodine procedure was an independent prognostic factor for overall survival. We also observed that bilirubin levels were increased at 4 weeks, indicating that 125iodine seeding in the PVTT beneficially impacted the small bile duct, which is proximal to the portal vein. No severe adverse events were observed in patients that received 125iodine seed implantation, and the mild adverse events were successfully treated. This study shows that TACE-125iodine therapy enhances patient survival with minimal adverse events. It is also more affordable than sorafenib, which is currently the recommended therapy for advanced HCC patients with PVTT.

Arsenic trioxide intravenous infusion combined with transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with pulmonary metastasis: Long-term outcome analysis.

OBJECTIVE: To evaluate the safety, clinical efficacy, and long-term outcome of arsenic trioxide (As2 O3 ) intravenous infusion for pulmonary metastases in patients with HCC. MATERIALS AND METHODS: Sixty consecutive patients who were diagnosed with advanced hepatocellular carcinoma (HCC) with pulmonary metastasis were randomized 1:1 into the treatment and control groups. Treatment group underwent transcatheter arterial chemoembolization (TACE) for the primary liver tumor and then underwent As2 O3 treatment, whereas control group underwent TACE alone. The treatment group underwent a continuous 5-h intravenous infusion of 10 mg/day As2 O3 . The course of As2 O3 treatment was initiated 3-5 days after TACE (to allow liver and gastrointestinal function to recover) and continued for 14 consecutive days. All patients in the treatment group underwent at least four treatment courses. Response to treatment was evaluated after four treatment courses. RESULT: In treatment group, two patients had a complete response (CR), six had a partial response (PR), 10 had stable disease (SD), and 12 had progressive disease. A clinically effective rate (CR + PR) was achieved in 26.7%, and the clinical benefit rate (CR + PR + SD) was 60%. In the control group, no patients had a CR or PR, five had SD, and 25 had progressive disease. The clinically effective rate was 0%, and the clinical benefit rate was 16.7%. The overall 1-year survival was 56.7% in treatment group and 36.7% in control group. The overall 2-year survival was 16.7% in treatment group and 3.3% in control group. CONCLUSION: Transcatheter arterial chemoembolization plus an intravenous infusion of As2 O3 effectively controlled pulmonary metastasis and prolonged overall survival in patients with HCC compared with TACE alone.

Effect of intravenous gadolinium-DTPA on diffusion-weighted imaging of brain tumors: a short temporal interval assessment.

PURPOSE: To determine the effect of intravenous administration of gadolinium (Gd) contrast medium (Gd-DTPA) on diffusion-weighted imaging (DWI) for the evaluation of normal brain parenchyma vs. brain tumor following a short temporal interval. MATERIALS AND METHODS: Forty-four DWI studies using b values of 0 and 1000 s/mm(2) were performed before, immediately after, 1 min after, 3 min after, and 5 min after the administration of Gd-DTPA on 62 separate lesions including 15 meningioma, 17 glioma and 30 metastatic lesions. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and apparent diffusion coefficient (ADC) values of the brain tumor lesions and normal brain tissues were measured on pre- and postcontrast images. Statistical analysis using paired t-test between precontrast and postcontrast data were obtained on three brain tumors and normal brain tissue. RESULTS: The SNR and CNR of brain tumors and the SNR of normal brain tissue showed no statistical differences between pre- and postcontrast (P > 0.05). The ADC values on the three cases of brain tumors demonstrated significant initial increase on the immediate time point (P < 0.01) and decrease on following the 1 min time point (P < 0.01) after contrast. Significant decrease of ADC value was still found at 3min and 5min time point in the meningioma group (P < 0.01) with gradual normalization over time. The ADC values of normal brain tissues demonstrated significant initial elevation on the immediately postcontrast DWI sequence (P < 0.01). CONCLUSION: Contrast medium can cause a slight but statistically significant change on the ADC value within a short temporal interval after the contrast administration. The effect is both time and lesion-type dependent.

Proton magnetic resonance spectroscopy predicts radiotherapy response and time-to-progression in high-grade gliomas after surgery.

BACKGROUND: Reliable early prediction response to therapy and time-to-progression (TTP) remain an important goal of high-grade gliomas (HGGs) research. Proton magnetic resonance spectroscopy ((1)H-MRS) has been applied with variable success in clinical application, and we hypothesize that (1)H-MRS in predictive value should perform well as a marker of TTP in patients treated with radiotherapy (RT) after surgery. METHODS: (1)H-MRS was performed before surgery on 25 patients who had undergone resection of HGGs; then the ratios of lipid/creatine (Lip/Cr) and myo-inositol/creatine (mI/Cr) were determined in the solid tumor. RT response was classified as follows: complete resolution (CR), partial response (PR), stable disease (SD), and progressive disease (PD) by comparison of pre-treatment and post-radiotherapy scans. TTP was defined at the time to radiographic progression by MacDonald criteria. Correlation was evaluated between the ratios of Lip/Cr, mI/Cr and treatment response, TTP. The chi-square test and Pearson correlation test were used for data analyses. RESULTS: Multivariate analysis revealed that the prognostic value of spectroscopic variables was independent of age, sex, WHO histologic grade, extent of surgery, and Karnofsky score (KPS). The correlation between the ratios of lipid/Cr and TTP was significant (r = 0.894, P = 0.000), and between the ratios of mI/Cr and TTP was also significant (r = 0.891, P = 0.000). As predicted, RT response correlated significantly with TTP (r = 0.59, P = 0.002): median TTP was 49.9 days for patients with PD compared with 202.7 days for SD, 208.0 days for PR, and 234.5 days for CR. CONCLUSION: The ratios of Lip/Cr and mI/Cr of the solid tumor region before surgery could provide important information in predicting RT response and TTP in patients with HGGs treated by radiation alone after surgery.

Comparison of computed tomography versus magnetic resonance imaging in assessing radiofrequency ablation margins after radiofrequency ablation in patients with hepatocellular carcinomas.

OBJECTIVE: To assess the diagnostic value of magnetic resonance imaging (MRI) in the follow-up of patients with hepatocellular carcinomas treated with radiofrequency ablation (RFA) and to compare it with that of computed tomography (CT). METHODS: From December 2009 to September 2011, 40 patients (47 hepatocellular carcinomas) were treated with RFA after transcatheter arterial chemoembolization and underwent MRI and CT for follow-up. RFA margins were assessed on a five-point scale with receiver operating characteristic curve analysis. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were evaluated. RESULTS: The interobserver agreement rate for MRI was significantly higher (Kappa=0.935) than for CT (Kappa=0.714; P < 0.05). The scores of 1 and 5 points for MRI, which confirms the presence or absence of residual tumor, accounted for 89.4% (84/94), while for CT accounting for only 31.9% (30/94). The area under the receiver operating characteristic curve of MRI was significantly higher than that of CT (P < 0.05), as were the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of detection rate (mean, 100%, 96.4%, 76.9%, 100%, and 96.8% for MRI, respectively, vs. 30.0%, 57.1%, 10.3%, 87.7%, and 63.8% for CT). CONCLUSION: MRI is superior to CT in assessing the RFA margins in terms of the diagnostic accuracy and detection rate .

[The clinical therapeutic effects of arsenic trioxide combined with transcatheter arterial chemoembolization in treating primary liver cancer with pulmonary metastases].

OBJECTIVE: To observe the therapeutic effects of arsenic trioxide combined with transcatheter arterial chemoembolization on treatment of primary liver cancer with pulmonary metastases. METHODS: Sixty patients were randomly divided into two groups: group A (treatment group, n = 30) and group B (control group, n = 30). Group A was received periodic transcatheter arterial chemoembolization (TACE) and 10 mg arsenic trioxide by intravenous infusion for 5 hours per day, 3 days after TACE. Each cycle consisted of 14 days' administration, and repeated after 2 weeks. Each patient was received 3-4 successive cycles. Group B was received periodic TACE alone. OBJECTIVE: efficiency, benefit rate, quality of life and the correlates with metastatic tumor size and number in the both groups were recorded. RESULTS: The objective efficiency was 26.7% (8/30), and the benefit rate was 60.0% (18/30) in group A, while they were 0 and 16.7% (5/30) in group B with significant statistics differences (χ(2) = 7.067, P = 0.008; χ(2) = 11.915, P = 0.001). The quality of life was improved in 4 patients and stable in 18 of group A, while no patient was improved and 13 were stable in group B (χ(2) = 9.669, P = 0.008). There was a significantly positive correlation between the tumor burden and therapeutic effect (Kendall r = -0.765, P < 0.001; Spearman r = -0.821, P < 0.001). CONCLUSION: Arsenic trioxide combined TACE is an effective treatment method in treating primary liver cancer with pulmonary metastases.