The prognostic correlation of AFP level at diagnosis with pathological grade, progression, and survival of patients with hepatocellular carcinoma

The prognostic correlation of AFP level at diagnosis with pathological grade, progression, and survival of patients with hepatocellular carcinoma

The purpose of this study was to conduct a comprehensive study of the clinical correlation between the alpha-fetoprotein (AFP) level at diagnosis and pathological grades, progression, and survival of patients with hepatocellular carcinoma (HCC). A total of 78,743 patients in Surveillance, Epidemiology, and End Results Program (SEER)-registered HCC was analyzed. Multivariable Cox regression analyses identified AFP level as an independent predictor of survival risk of patients with HCC who did not undergo surgery (hazard ratio [HR], 1.660; 95% CI, 1.534–1.797; P < 0.001), and those who underwent surgery (HR, 1.534; 95% CI, 1.348–1.745; P < 0.001). The AFP level at diagnosis was an independent risk predictor associated with pathological grade, progression, and survival. More than 250,000 new cases of HCC occur annually, and approximately 500,000–600,000 patients die each year2,3. Approximately 50% of HCCs secrete AFP7,8, and a plasma AFP concentration >400 ng/ml is generally considered a reliable for supporting the diagnosis of HCC. Because the accuracy of the AFP concentration was challenged as well as a growing debate about its ongoing use for HCC surveillance programs, AFP was removed from updated international guidelines for HCC surveillance. However, many reports suggest a rationale for the continued use of AFP9,10,11.
To identify the clinical significance of AFP levels, in the present study we analyzed the comprehensive clinical relationship between the AFP levels and pathological grades, progression, and survival of patients with HCC using the data for patients with HCC that were deposited in the cancer registry of the Surveillance, Epidemiology, and End Results (SEER) Program from 1988 through 2013.

N-terminal gelsolin fragment potentiates TRAIL mediated death in resistant hepatoma cells

N-terminal gelsolin fragment potentiates TRAIL mediated death in resistant hepatoma cells

However, a combination of both CM and TRAIL reduced cell viability in HepG2 (~90%) and Huh7 (~70%) cells, indicating that CM sensitizes resistant hepatocytes to TRAIL mediated death. However, a combination of both CM and TRAIL reduced cell viability in HepG2 (~90%) and Huh7 (~70%) cells, indicating that CM sensitizes resistant hepatocytes to TRAIL mediated death.
p53 and Mdm2 phosphorylation was analyzed in CM, TRAIL, and CM + TRAIL treated HepG2 cells (panels A and B). p53 and Mdm2 phosphorylation was analyzed in CM, TRAIL, and CM + TRAIL treated HepG2 cells (panels A and B).
These results indicate that p53 functional activity may contribute to TRAIL mediated cell death in the presence of gelsolin, but is not the only mechanism by which decreased cell viability may occur via these ligands. These results indicate that p53 functional activity may contribute to TRAIL mediated cell death in the presence of gelsolin, but is not the only mechanism by which decreased cell viability may occur via these ligands.
On the other hand, cells treated with different concentrations of the gelsolin1–70 peptide together with TRAIL displayed significant loss of cell viability after 72 hours, while Hep3B cells displayed only a slight increase in cell death over cells treated with the gelsolin fragment alone (panel B), and TRAIL R1 modulation by gelsolin1–70 (panel C). On the other hand, cells treated with different concentrations of the gelsolin1–70 peptide together with TRAIL displayed significant loss of cell viability after 72 hours, while Hep3B cells displayed only a slight increase in cell death over cells treated with the gelsolin fragment alone (panel B), and TRAIL R1 modulation by gelsolin1–70 (panel C).
We observed in this study that the gelsolin fragment or CM reduced the level of activated Akt with increased cell death. We observed in this study that the gelsolin fragment or CM reduced the level of activated Akt with increased cell death.

Combining 18F-FDG positron emission tomography with Up-to-seven criteria for selecting suitable liver transplant patients with advanced hepatocellular carcinoma

Combining 18F-FDG positron emission tomography with Up-to-seven criteria for selecting suitable liver transplant patients with advanced hepatocellular carcinoma

Several studies have shown that a subset of patients with HCC exceeding standard criteria may benefit from LT.
Apart from that, we investigated whether the combination of the radiographic UTS criteria with 18F-FDG PET may be useful for predicting posttransplant tumor recurrence and, thus, for safely expanding the pool of suitable liver transplant patients.
Based on final pretransplant radiographic staging, patients were classified as Milan In (HCC meeting the MC; Milan In) or Milan Out (HCC exceeding the MC; Milan Out), and UTS In (HCC meeting the UTS criteria; UTS In) and UTS Out (HCC exceeding the UTS criteria; UTS Out), respectively.
Based on clinical staging, 66 patients were classified as Milan In (56.9%) and 50 patients as Milan Out (43.1%), whereas tumors were meeting and exceeding the UTS criteria in 85 (73.3%) and 21 (26.7%) patients, respectively.
In univariate analysis, AFP level, multiple tumor nodules, maximum tumor diameter, number of HCC nodules, UTS criteria and PET-status were significantly associated with risk of HCC recurrence.
RFS was comparable between UTS In and PET-negative beyond UTS patients (p = 0.534; Fig.
Tumor recurrence rate was 6.7% in non- 18F-FDG-avid patients, but 58.5% in those with PET+ tumors (p < 0.001; Table 6). In fact, the application of 18F-FDG PET was recently demonstrated to select suitable liver transplant patients with HCC beyond MC and UCSF criteria48,49,50,51. Rather, our data pointed out that the MC are excellent for selecting suitable liver transplant patients (Figs 1 and 2), whereas further biological tumor evaluation is necessary beyond the Milan boundaries (Table 5). Furthermore, outcome was not significantly different between patients meeting the UTS criteria and PET-negative patients exceeding them (Fig.