Systemic immune-inflammation index predicts prognosis of sequential therapy with sorafenib and regorafenib in hepatocellular carcinoma.

BACKGROUND: Regorafenib has shown promising results as a second-line therapy for patients with hepatocellular carcinoma (HCC) who progressed on sorafenib. Although there have been several data regarding the efficacy of sequential therapy with sorafenib and that of regorafenib in real-life, specific inflammation markers for predicting the prognosis have not been studied. This study aimed to investigate prognostic value of systemic inflammatory markers in patients with HCC who received sorafenib-regorafenib sequential therapy. METHODS: We retrospectively analyzed medical data of patients who received regorafenib for the treatment of HCC after sorafenib failure. Progression free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier survival curves. Univariate and multivariate analyses were performed to analyze the factors associated with survival. RESULTS: A total of 58 patients who received at least one dose of regroafenib and fulfilled the eligibility criteria, good performance status (Eastern Cooperative Oncology Group [ECOG] 0-1) and preserved liver function (Child-Pugh-A), were included in the analysis. The median PFS was 3 months (95% confidence interval [CI] = 0.981-5.019) and the median OS was 8 months (95% CI = 5.761-10.239). Elevated systemic immune-inflammation index (SII ≥340) was independently associated with poor OS. In multivariate analysis, the SII (hazard ratio [HR] = 2.211, 95% CI = 1.089-4.489, P = 0.028) and alpha-fetoprotein (AFP) (HR = 2.750, 95% CI = 1.259-6.010, P = 0.011) were independent predictors of OS. CONCLUSION: Elevated SII is associated with poor OS in patients with HCC who received sequential therapy with sorafenib and regorafenib. In addition, when selecting a treatment strategy, the SII can be used in combination with the AFP level as a promising prognostic tool for HCC.

Complete Regression of Recurrent Advanced Hepatocellular Carcinoma After Liver Transplantation in Response to Sorafenib Treatment: A Case Report.

Liver transplantation is a potentially curative treatment for hepatocellular carcinoma. However, patients with recurrent hepatocellular carcinoma after liver transplantation have few treatment options and local treatment may not be feasible. Sorafenib, an orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma, significantly improves progression-free and overall survival. However, only a few studies have evaluated the efficacy of sorafenib in patients with recurrent hepatocellular carcinoma following liver transplantation. Here, we report a case of a patient with recurrent advanced hepatocellular carcinoma after living donor liver transplantation who achieved complete remission in response to sorafenib treatment. The patient has survived for more than 4 years post-transplantation.

Expression of brain-derived neurotrophic factor in catecholaminergic neurons of the rat lower brainstem after colchicine treatment or hemorrhage.

Widespread brain-derived neurotrophic factor messenger RNA expression has been detected in the region of catecholamine groups of the rat lower brainstem, while few brain-derived neurotrophic factor-immunoreactive cells were found in this area. In the present study, a double-color immunofluorescence technique for brain-derived neurotrophic factor and tyrosine hydroxylase after colchicine treatment was employed to evaluate the possible presence of brain-derived neurotrophic factor immunoreactivity in the catecholaminergic cells of the rat lower brainstem. We detected many new brain-derived neurotrophic factor-immunoreactive cells in the A1, A2, A4, A6-A10 and C1-C3 cell groups and in the other lower brainstem nuclei where, without colchicine treatment, brain-derived neurotrophic factor messenger RNA was expressed, but not brain-derived neurotrophic factor immunoreactivity. In addition, the catecholaminergic neurons were found to express brain-derived neurotrophic factor immunoreactivity with the co-existence being greatest, in percentage terms, in medullary catecholaminergic cell groups. Hypotensive hemorrhage, which activates medullary catecholaminergic neurons, induced the expression of brain-derived neurotrophic factor immunoreactivity in catecholaminergic neurons (A1/C1 and C2). The results demonstrate that brain-derived neurotrophic factor is regulated by neuronal activity in medullary catecholaminergic cell groups involved in central cardiovascular regulation.