RESUMEN
Purpose@#This study aimed to assess the incidence of and factors associated with major complications, delayed discharge, and emergency room (ER) visits or readmission after percutaneous radiofrequency ablation (RFA) for single hepatocellular carcinoma (HCC) <3 cm in a recent cohort at a tertiary cancer center. @*Methods@#A total of 188 patients with treatment-naïve single HCCs <3 cm who underwent RFA between January 2018 and April 2021 were included in the analysis. Univariable and multivariable logistic regression analyses were performed to identify the factors associated with major complications, delayed discharge, and ER visits or readmission. Local tumor progression (LTP) and overall survival were estimated using the Kaplan-Meier method and Cox proportional-hazards regression analysis. @*Results@#Major complications occurred in 3.2% (6/188) of the patients. The longest diameter of the ablation zone was significantly larger in patients with major complications (P=0.023). Delayed discharge occurred in 5.8% (9/188) of the patients, for which albumin-bilirubin grade 3 was identified as an important determinant. No variables other than major complications were significantly associated with ER visits or readmission, which occurred in 7.0% (13/188) of the patients. Major complications, delayed discharge, and ER visits or readmission were not substantially related to the post-treatment outcomes of LTP and overall survival. @*Conclusion@#This study confirmed RFA as a highly safe procedure for single HCCs <3 cm, despite the rapidly changing RFA techniques in the most recent cohort. A large ablation zone and poor liver function were predictors of major complications and delayed discharge, respectively.
RESUMEN
Mast cells (MCs) are systemically distributed and secrete several allergic mediators such as histamine and leukotrienes to cause type I hypersensitivity. Dasatinib is a type of anti-cancer agent and it has also been reported to inhibit human basophils. However, dasatinib has not been reported for its inhibitory effects on MCs or type I hypersensitivity in mice. In this study, we examined the inhibitory effect of dasatinib on MCs and MC-mediated allergic response in vitro and in vivo. In vitro, dasatinib inhibited the degranulation of MCs by antigen stimulation in a dose-dependent manner (IC 50 , ~34 nM for RBL-2H3 cells; ~52 nM for BMMCs) without any cytotoxicity. It also suppressed the secretion of inflammatory cytokines IL-4 and TNF-α by antigen stimulation. Furthermore, dasatinib inhibited MC-mediated passive cutaneous anaphylaxis (PCA) in mice (ED 50 , ~29 mg/kg). Notably, dasatinib significantly suppressed the degranulation of MCs in the ear tissue. As the mechanism of its effect, dasatinib inhibited the activation of Syk and Syk-mediated downstream signaling proteins, LAT, PLCγ1, and three typical MAP kinases (Erk1/2, JNK, and p38), which are essential for the activation of MCs. Interestingly, in vitro tyrosine kinase assay, dasatinib directly inhibited the activities of Lyn and Fyn, the upstream tyrosine kinases of Syk in MCs. Taken together, dasatinib suppresses MCs and PCA in vitro and in vivo through the inhibition of Lyn and Fyn Src-family kinases. Therefore, we suggest the possibility of repositioning the anti-cancer drug dasatinib as a treatment for various MC-mediated type I hypersensitive diseases.