Once considered exceptionally rare,neuroendocrine tumors(NET)are increasingly common and therefore of growing relevance to both clinicians and researchers.Most patients with such tumors present with symptoms,and,of those,90％have secondary liver involvement.In the recent past,in-dividuals with metastatic liver disease were offered little in the way of therapy,or hope.Over the last few years,this fatalist approach has been rapidly replaced with a variety of new strategies for both systemic and loco-regional treatment options.Both sequential and parallel combined therapies,newly available drugs and a multi-disciplinary approach to patient management are all contributing to a revolution in the care and outcomes for this population.In this review,the reader will be oriented to the relevant statistics,nomenclature and diagnostic modalities for this confusing set of diseases.Most important is an update on the rapidly expanding treatment options available for optimizing care among patients with liver involvement.

Hepatocellular carcinoma(HCC)accounts for the vast majority of primary hepatic malignancies.The overall incidence of this disease has always been significant,but in recent years it has continued to rise,now making HCC one of the leading causes of cancer deaths worldwide.Fortunately,research into the mechanisms of carcinogenesis and treatment options for this disease has also been progressing rapidly.Although the future for new insights and therapies appears more promising than ever,it also remains important to understand both the nature of HCC and the current state-of-the-art for treating affected patients.Although surgery is often considered to be a first choice,many patients present with extensive disease and are therefore not operative candidates.Fortunately,significant clinical advances over the last decade have contributed a number of new or improved treatment options.Many of these treatments require expertise from a variety of different clinical subspecialties.Indeed,managing patients with HCC has rapidly become a multi-modality,multi-disciplinary endeavor in which the details of each in-dividual's circumstance can greatly impact outcomes,and strategies can be quite nuanced.The purpose of this review is to provide a perspective on the disease itself,the patients who become afflicted,the spectrum of currently available treatment options,and the strategies for their optimal implementation.Such knowledge can be critically important as new data become available on the research front.

Galectins(Gals)are evolutionarily conserved proteins that bind to β-galactoside containing glycans.Abnormal expression of Gals is associated with the development,progression,and metastasis of different types of cancer.Among the 11 Gals identified in humans,the roles of Gal-1 and Gal-3 have been extensively investigated in various tumors.Here,we summarize the roles of overly expressed Gal-1 and Gal-3 in the pathogenesis of hepatocellular carcinoma(HCC).The overexpression of Gal-1 and Gal-3 correlates with tumor growth,HCC cell migration and invasion,tumor aggressiveness,metastasis,and poor prognosis.A potentially promising future treatment strategy for HCC may include the combination of immunotherapy with Gal-1 inhibition.Additional research is warranted to investigate targeting Gal-1 and Gal-3 for HCC treatment.

The incidence of hepatocellular carcinoma(HCC)has been increasing for decades.This disease has now risen to become the sixth most common malignancy overall,while ranking as the third most frequent cause of cancer mortality.While several surgical interventions and loco-regional treatment options are available,up to 80％ of patients present with advanced disease not amenable to standard therapies.Indeed,traditional cytotoxic chemotherapeutic agents are notoriously ineffective and essentially play no role in the management of affected patients.This has led to an enormous need for more effective sys-temic therapeutic options.In recent years,immunotherapy has emerged as a potentially viable and exciting new alternative for the treatment of HCC.Although the current immunotherapeutic options remain imperfect,various strategies can be employed to further improve their efficacy.New findings have revealed epigenetic modulation can be effective as a new approach for improving HCC immuno-therapy.Studying the gut microbiome(gut-liver axis)can also be an interesting subject in this regard.Here,we explore the latest insights into the role of immunotherapy treating HCC,both mono and in combination with other agents.We also focus on the impact of epigenetic drugs and the microbiome in the overall effectiveness of HCC immunotherapy.