Neuroendocrine carcinomas (NECs) are poorly differentiated and highly aggressive epithelial neuroendocrine neoplasms. The most common primary site is the lung, but they may arise in every organ. Approximately 37% of extrapulmonary NECs (EP-NECs) occur in the gastroenteropancreatic (GEP) tract, followed by the genitourinary (GU) system and gynecological tract. As a result of their rarity, there is scant evidence to guide treatment recommendations, and a multidisciplinary approach is essential for the management of such patients. Platinum-based chemotherapy currently represents the standard of care for EP-NECs of any site, mirroring the management of small-cell lung cancer (SCLC), but further approaches are still under investigation. Indeed, ongoing trials evaluating targeted therapies, immune checkpoint inhibitors (ICIs), and radionuclide therapy could provide potentially breakthrough therapeutic options. Given the relative dearth of evidence-based literature on these orphan diseases, the aim of this review is to provide an overview of the pathology and current treatment options, as well as to shed light on the most pressing unmet needs in the field.

During the last decade, a new therapeutic revolution has involved the management of hepatocellular carcinoma (HCC). This is made possible thanks to the documented efficacy of immunotherapy for this disease. In addition, new evidence demonstrated the role of the gut-liver axis and gut microbiota in host homeostasis, tumor development, and response to therapies. In particular, intestinal dysbiosis can alter the tumor microenvironment leading to the activation of intracellular signalling pathways that promote carcinogenesis. The composition of gut microbiota proved to influence the immune checkpoint inhibitors (ICIs) efficacy and drug toxicities. Therefore, this review aims to deepen knowledge about the immunomodulatory role of gut microbiota and its possible employment as diagnostic and predictive biomarkers in diagnosis and response to immunotherapy of HCC, respectively.