In patients with unresectable hepatocellular carcinoma (HCC) without both macrovascular invasion and extrahepatic metastasis, the initial treatment choice recommended is transarterial chemoembolization (TACE). Before sorafenib came into wide use, TACE had been pointlessly carried out repeatedly. It was in the early 2010s that the concept of TACE refractory was advocated. Two retrospective studies from Japan indicated that conversion from TACE to sorafenib the day after patients were deemed as TACE refractory improved overall survival compared with continued TACE, according to the definition by the Japan Society of Hepatology. Nowadays, phase 3 trials have shown clinical benefits of several novel molecular target agents. Compared with the era of sorafenib, sequential treatments with these molecular target agents have gradually prolonged patients’ survival and have become major strategies in patients with HCC. Taking these together, conversion from TACE to systemic therapies at the time of TACE refractory, compared with before, may have a greater impact on survival and may be considered deeper in the decisions-making process in patients with unresectable HCC who are candidate for TACE. Up-to-date information on the concept of TACE refractory is summarized in this review. We believe that the survival of patients with unresectable HCC without both macrovascular invasion and extrahepatic metastasis may be dramatically improved by optimal timing of TACE refractory and switching to systemic therapies.

BACKGROUND: Recent studies indicate that the timing of introduction of potentially allergenic food is crucial for the development of food allergy in children. This cross-sectional study aimed to clarify the reality of allergen food intake in a general population of young children in Japan. METHODS: A questionnaire survey of caregivers was conducted at health checkups for 1.5-year (18-month)-old and 3-year-old children in the fall of 2020. The caregivers were asked about (1) the presence/absence of allergic disease symptoms based on the ISAAC questionnaire, and (2) foods that caregivers avoided giving their children. Ordinal logistic regression analyses were periformed to determine factors associated with food avoidance. RESULTS: Questionnaires were distributed to 1720 caregivers, and 1603 (93%) responded. The responders consisted of 771 and 832 caregivers who participated in 1.5-year-old and 3-year-old checkups, respectively. The prevalence of allergic diseases was comparable to recent epidemiological studies in Japan, indicating that the population may be representative. At 1.5 years old, more than 50% of the children were not exposed to peanuts, tree nuts, fish eggs, shellfish, and buckwheat. At 3 years old, the avoidance rates of the foods had decreased but were still between 18.8% and 32.0%. On the other hand, the avoidance rates of chicken egg and cow's milk, the top 2 common allergenic foods in Japan, were much lower at 2.8% and 1.5% at 1.5 years, and they decreased to 1.4% and 0.7% at 3 years old, respectively. Ordinal logistic analysis showed that avoidance of chicken egg, cow's milk, and wheat was associated with food allergy diagnosis and chicken egg avoidance with eczema, but avoidance of other foods showed no associations with any risk factors for food allergy. CONCLUSION Caregivers avoided giving various foods, independent of allergy risk factors, to their young children. Since delayed introduction of an allergenic food has been reported to increase the risk of developing an allergy to the food, the results warrant future investigation of the development of food allergies in relation to current eating habits and recommendations.
Female ; Animals ; Cattle ; Humans ; Cross-Sectional Studies ; Japan/epidemiology* ; Food Hypersensitivity/complications* ; Risk Factors ; Food ; Allergens