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Transarterial chemotherapy (TACE) is the standard treatment for patients with intermediate-stage hepatocellular carcinoma (HCC), defined as large, unresectable, or multinodular HCC in patients with good functional performance. The definition of TACE refractoriness is not well established. Generally, TACE refractoriness is defined as an insufficient response after two or more consecutive TACE. An increase in the number of liver lesions, continuously elevated tumor markers, vascular invasion, and extrahepatic spread also suggest TACE refractoriness. Timely switching to systemic therapy for TACE refractoriness should be considered to improve the outcome. Although data are sparse, the combination of anti-angiogenic and immune checkpoint inhibitor therapies shows promise for TACE-refractory patients. In this article, we review the role of systemic therapy in TACE refractory patients with HCC.

Background Adrenal insufficiency (AI) is associated with high morbidity and mortality. The aim of this systematic review was to enhance diagnostic approaches and summarize therapeutic strategies in the management of AI in patients with systematic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). Methods A literature search of PubMed and Medline databases was performed and 91 publications containing 105 cases were included for the final analysis. Results The following frequency of clinical signs and symptoms was noted: abdominal pain (39.04%) was the leading symptom, followed by fever (33.33%), vomiting (23.81%), and nausea (19.05%). APS was present in 73%, SLE in 17% of the patients, while 2% had a diagnosis of both, SLE and APS. ACTH stimulation test (ACTHst) was performed in 18% of cases and 76.6% of them were unresponsive towards stimulation. Variable treatment approaches were used: hydrocortisone was most commonly used (38.09%), followed by fludrocortisone (26.67%), prednisolone (20.00%) and volume replacement treatment (11.43%), respectively. Conclusions This analysis highlights the importance of an early diagnosis and initiation of therapeutic management when AI is suspected. In line, signs and symptoms related to autoimmune diseases in patients with AI should be reviewed crtitically.