Lampros Reppas

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and presents a continuously growing incidence and high mortality rates worldwide. Besides advances in diagnosis and promising results of pre-clinical studies, established curative therapeutic options for HCC are not currently available. Recent progress in understanding the tumor microenvironment (TME) interactions has turned the scientific interest to immunotherapy, revolutionizing the treatment of patients with advanced HCC. However, the limited number of HCC patients who benefit from current immunotherapeutic options creates the need to explore novel targets associated with improved patient response rates and potentially establish them as a part of novel combinatorial treatment options. Glucocorticoid-induced TNFR-related protein (GITR) belongs to the TNFR superfamily (TNFRSF) and promotes CD8⁺ and CD4⁺ effector T-cell function with simultaneous inhibition of Tregs function, when activated by its ligand, GITRL. GITR is currently considered a potential immunotherapy target in various kinds of neoplasms, especially with the concomitant use of programmed cell-death protein-1 (PD-1) blockade. Regarding liver disease, a high GITR expression in liver progenitor cells has been observed, associated with impaired hepatocyte differentiation, and decreased progenitor cell-mediated liver regeneration. Considering real-world data proving its anti-tumor effect and recently published evidence in pre-clinical models proving its involvement in pre-cancerous liver disease, the idea of its inclusion in HCC therapeutic options theoretically arises. In this review, we aim to summarize the current evidence supporting targeting GITR/GITRL signaling as a potential treatment strategy for advanced HCC.

Echinococcosis or hydatid disease affecting the spine is an uncommon manifestation of Echinococcus granulosus infection of the spine. More commonly found in endemic areas, it causes significant morbidity and mortality as it grows slowly and produces symptoms mainly by compressing the spinal cord. As diagnostic methods are non-specific, diagnosis and management are usually delayed until the disease is advanced, thereby therapy is usually unlikely. Treatment is usually surgical, aiming at cyst excision, spinal cord decompression and spinal stabilization. This article summarizes the clinical findings of echinococcosis of the spine, discusses the specific laboratory and diagnostic findings, lists the current treatment options, and reviews the patients’ outcomes. The aim is to prompt clinicians to be aware of the possibility of echinococcosis as a possible diagnosis in endemic areas. Cite this article: EFORT Open Rev 2021;6:288-296. DOI: 10.1302/2058-5241.6.200130