Digestive diseases
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Hepatocellular carcinoma (HCC) is a major health concern, and early HCC diagnosis is a primary radiological concern. The goal of imaging liver cirrhosis is the early identification of high-grade dysplastic nodules/early HCC since their treatment is associated with a higher chance of radical cure and lower recurrence rates. The newly introduced MRI contrast agent gadoxetic acid (gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid, Gd-EOB-DTPA) has enabled the concurrent assessment of tumor vascularity and hepatocyte-specific contrast enhancement during the hepatobiliary phase (HBP), which can help to detect and characterize smaller HCCs and their precursors. ⋯ Due to this capability of identifying the precursors and biological behavior of HCC, EOB-MRI has rapidly become a key imaging tool for the diagnosis of HCC and its precursors, despite the scarce MRI availability throughout Europe. With increasing experience, EOB-MRI may eventually be established as the diagnostic imaging modality of choice in this setting. Full recognition by the Western EASL-AASLD guidelines is expected.
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Biologics have revolutionized several areas of medical therapeutics, and dozens of them are used by millions of patients. Monoclonal antibodies are only one type of biologics, but more than 900 are now in different phases of development. These drugs are complex to make and not cheap. ⋯ Practical issues such as interchangeability and substitution remain unsolved, and it is very likely that there will be different solutions at the national level. Pharmacovigilance plans will be key for obtaining reliable data. Biosimilars are not better drugs, but can be clearly cheaper and may facilitate access to new treatments in many populations.
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The marijuana plant Cannabis sativa has been used for centuries as a treatment for a variety of ailments. It contains over 60 different cannabinoid compounds. Studies have revealed that the endocannabinoid system is involved in almost all major immune events. ⋯ Yet, in an additional study, low-dose cannabidiol did not have an effect on CD activity. In summary, evidence is gathering that manipulating the endocannabinoid system can have beneficial effects in IBD, but further research is required to declare cannabinoids a medicine. We need to establish the specific cannabinoids, as well as appropriate medical conditions, optimal dose, and mode of administration, to maximize the beneficial effects while avoiding any potential harmful effects of cannabinoid use.
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Adenosine triphosphate (ATP) is essential for the myriad of metabolic processes upon which life is based and is known widely as the universal energy currency unit of intracellular biologic reactions. ATP, adenosine diphosphate, adenosine, as well as other purines and pyrimidines also serve as ubiquitous extracellular mediators which function through the activation of specific receptors (viz. P2 receptors for nucleotides and purinergic P1 receptors for adenosine). ⋯ Increased understanding of mechanisms of extracellular ATP scavenging and specifically conversion to nucleosides by ectonucleotidases of the CD39 family have also led to novel insights into the exquisite balance of nucleotide P2-receptor and adenosinergic P1-receptor signaling in inflammatory and hepatic diseases. Further, CD39 and other ectonucleotidases exhibit genetic polymorphisms in humans which alter levels of expression/function and are associated with predisposition to inflammatory and immune diseases, diabetes and vascular calcification, amongst other problems. Development of therapeutic strategies targeting purinergic signaling and ectonucleotidases offers promise for the management of disordered inflammation and aberrant immune reactivity.
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Hepatocellular carcinoma (HCC) is heterogeneous in histopathology, pathogenesis and biological behavior. There is accumulating evidence that the expression of 'stemness'-related markers such as K19, EpCAM and CD133 in HCC is associated with an aggressive biological behavior and poor clinical outcome compared to conventional HCCs that do not express stemness-related markers. Compared to conventional HCCs, these tumors more frequently demonstrate infiltrative growth patterns, vascular invasion and more intratumoral fibrous stroma, and there is a spectrum of morphological and immunophenotypic features between HCCs with stemness-related marker expression, scirrhous HCCs and combined hepatocellular-cholangiocarcinoma with stem cell features. ⋯ These tumors have also been recognized as a specific subtype in recent molecular classifications, and increasing interest in the molecular pathogenesis of HCCs with stemness-related marker expression will shed light on the development of targeted therapy for these tumors. Therefore, it is important that pathologists identify HCCs expressing stemness-related markers such as K19 during routine pathological evaluation of surgically resected or biopsied HCC tissue, as it will help to identify a high-risk subgroup of HCCs characterized by increased chemoresistance, earlier recurrence after surgical and/or locoregional treatment, increased invasiveness/metastasis and poor overall survival. We will discuss the clinicopathological characteristics of a HCC subtype expressing stemness-related markers and its future perspectives.