Personal comorbidities and their subsequent risks for liver,gallbladder and bile duct cancers

Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously diagnosed comorbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The 13 comorbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the considered comorbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers.     

Layer-specific and whole wall global longitudinal strain predict major adverse cardiovascular events in patients with stable angina pectoris

The International Journal of Cardiovascular Imaging - Global longitudinal strain (GLS) has proven to be a powerful prognostic marker in various patient populations, but the prognostic value of...     

Synthesis and automated fluorine-18 radiolabeling of new PSMA-617 derivatives with a CuAAC radiosynthetic approach

In the last decade, the development of new radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research, especially focusing on the prostate-specific membrane antigen (PSMA), an antigen which is upregulated in prostate, as well as in other tumor cells. A large variety of PSMA ligands have been radiolabeled, to date. Among the various derivatives, PSMA-617 resulted to be one of the most interesting in terms of interaction with the antigen and clinical properties, and its lutetium-177 labeled version has recently been approved by regulatory agencies for therapeutic purposes. For this reasons, the radiolabeling with fluorine-18 of a PSMA-617 derivative might be of interest. Beside other methodologies to radiolabel macromolecules with fluorine-18, the “click-chemistry” approach resulted to be very useful, and the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is considered one of most efficient and reliable. This paper proposes the synthesis of a suitable precursor for the radiolabeling with fluorine-18 of a new PSMA-617 derivative. The whole radiosynthetic procedure has been fully automated, and the final product, which proved to be stable in plasma, has been obtained with radiochemical yield and purity suitable for subsequent preclinical studies.     

Principles of environmentally-sustainable anaesthesia: a global consensus statement from the World Federation of Societies of Anaesthesiologists

The Earth’s mean surface temperature is already approximately 1.1°C higher than pre-industrial levels. Exceeding a mean 1.5°C rise by 2050 will make global adaptation to the consequences of climate change less possible. To protect public health, anaesthesia providers need to reduce the contribution their practice makes to global warming. We convened a Working Group of 45 anaesthesia providers with a recognised interest in sustainability, and used a three-stage modified Delphi consensus process to agree on principles of environmentally sustainable anaesthesia that are achievable worldwide. The Working Group agreed on the following three important underlying statements: patient safety should not be compromised by sustainable anaesthetic practices; high-, middle- and low-income countries should support each other appropriately in delivering sustainable healthcare (including anaesthesia); and healthcare systems should be mandated to reduce their contribution to global warming. We set out seven fundamental principles to guide anaesthesia providers in the move to environmentally sustainable practice, including: choice of medications and equipment; minimising waste and overuse of resources; and addressing environmental sustainability in anaesthetists’ education, research, quality improvement and local healthcare leadership activities. These changes are achievable with minimal material resource and financial investment, and should undergo re-evaluation and updates as better evidence is published. This paper discusses each principle individually, and directs readers towards further important references.     

Nanotherapy: New Approach for Impeding Hepatic Cancer Microenvironment via Targeting Multiple Molecular Pathways

Objective: Hepatocellular carcinoma (HCC) microenvironment has been recognized as a key contributor for cancer progression, metastasis, and drug resistance. The crosstalk between tumor cells, the vascular endothelial growth factor (VEGF), and the chemokine (C-C motif) ligand 2 (CCL2) signaling networks mediates immunoinhibitory impact and facilitates tumor angiogenesis. The current investigation aimed at exploring the potent anti-cancer activity of the newly designed nano-based anti-cancer therapy comprising anti-VEGF drug, avastin (AV), and CCR2 antagonist (CR) to counteract HCC and tracking its mode of action in vivo. Methods: The prepared AV, CR, and AVCR nanoprototypes were characterized by nanoscale characterization techniques in our previous work. Here, they are applied for unearthing their anti-cancer properties / mechanisms in hepatic cancer-induced rats via analyzing protein levels and genetic expression of the elements incorporated in the angiogenesis, apoptosis, and metastasis signalling pathways. Results: The present results revealed a significant down-regulation in the angiogenesis, survival and metastasis indices along with up-regulation in the pro-apoptotic mediators upon treatment of hepatic cancer-bearing rats with the novel synthesized nanomaterials when compared with the untreated counterparts. We showed across HCC model that anti-VEGF in combination with CCR2 antagonism therapy leads to sensitization and enhanced tumor response over anti-VEGF or CCR2 antagonism monotherapy, particularly in its nanoscale formulation. Conclusion: The present approach provides new mechanistic insights into the powerful anti-hepatic cancer advantage of the novel nanoprototypes which is correlated with modulating critical signal transduction pathways implicated in tumor microenviroment such as angiogenesis, apoptosis and metastasis. This research work presents a substantial foundation for future studies focused on prohibiting cancer progression and recovery by targeting tumor microenviroment.     

Mesenchymal neoplasms with NTRK and other kinase gene alterations

Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications.     

Effect of the Lipid Fraction of Microalgae on Biochemical Parameters in Female C57BL/6 Mice

Bulletin of Experimental Biology and Medicine - We studied the effect of microalgae of various systematic groups added to the ration on the biochemical parameters of blood serum and liver and...