Non-alcoholic fatty liver disease and hepatocellular carcinoma: Clinical challenges of an intriguing link

Non-alcoholic fatty liver disease(NAFLD)has emerged as the most common liver disorder worldwide mainly attributed to the epidemic spread of obesity and type 2 diabetes mellitus.Although it is considered a benign disease,NAFLD can progress to non-alcoholic steatohepatitis,liver cirrhosis and hepatocellular carcinoma(HCC).Most data regarding the epidemiology of NAFLD-related HCC are derived from cohort and population studies and show that its incidence is increasing as well as it is likely to emerge as the leading indication for liver transplantation,especially in the Western World.Although cirrhosis constitutes the main risk factor for HCC development,in patients with NAFLD,HCC can arise in the absence of cirrhosis,indicating specific carcinogenic molecular pathways.Since NAFLD as an underlying liver disease for HCC is often underdiagnosed due to lack of sufficient surveillance in this population,NAFLDHCC patients are at advanced HCC stage at the time of diagnosis making the management of those patients clinically challenging and affecting their prognostic outcomes.In this current review,we summarize the latest literature on the epidemiology,other than liver cirrhosis-pathogenesis,risk factors and prognosis of NAFLD-HCC patients.Finally,we emphasize the prevention of the development of NAFLD-associated HCC and we provide some insight into the open questions and issues regarding the appropriate surveillance policies for those patients.     

Tyrosine kinase inhibitors in sarcoma treatment

Sarcomas are a group of rare mesenchymal malignant tumors that arise from transformed cells of the mesenchymal connective tissue, which are challenging to treat. The majority of sarcomas are soft tissue sarcomas (STSs; 75%) and this heterogeneous group of tumors is further comprised of gastrointestinal stromal tumors (~15%) and bone sarcomas (10%). Although surgery remains the current primary therapeutic approach for localized disease, recurrent, metastatic and refractory sarcomas require cytotoxic chemotherapy, which usually yields poor results. Therefore the efficiency of sarcoma treatment imposes a difficult problem. Furthermore, even though progress has been made towards understanding the underlying molecular signaling pathways of sarcoma, there are limited treatment options. The aim of the present study was therefore to perform a systematic literature review of the available clinical evidence regarding the role of tyrosine kinase inhibitors (TKIs) in patients with recurrent or refractory STSs and bone sarcomas over the last two decades. Tyrosine kinases are principal elements of several intracellular molecular signaling pathways. Deregulation of these proteins has been implicated in driving oncogenesis via the crosstalk of pivotal cellular signaling pathways and cascades, including cell proliferation, migration, angiogenesis and apoptosis. Subsequently, small molecule TKIs that target these proteins provide a novel potential therapeutic approach for several types of tumor by offering significant clinical benefits. Among the eligible articles, there were 45 prospective clinical trials, primarily multicentric, single arm, phase II and non-randomized. Numerous studies have reported promising results regarding the use of TKIs, mainly resulting in disease control in patients with STSs. The lack of randomized clinical trials demonstrates the ambiguous efficiency of various studied treatment options, which therefore currently limits the approved drugs used in clinical practice. Research both in clinical and preclinical settings is needed to shed light on the underlying molecular drivers of sarcomagenesis and will identify novel therapeutic approaches for pretreated patients.     

Women veterans and menopause: Knowledge and preferences

The increasing number and older age of women Veterans receiving care at Veterans Health Administration (VHA) requires health-care providers to adjust to their changing patient population. We explored women Veterans’ self-reported knowledge of menopause, current/preferred sources of menopausal health information, and perceptions/barriers regarding treatment of menopausal symptoms. Three focus groups were conducted at two South Florida VHA facilities in 2014, which included 30 women Veterans (aged 45–60 years) who visited VHA primary care clinics at least once in the past year. Participants reported using various sources to obtain general and menopausal health information, particularly family, friends, and the internet. Some women also had discussions with their health-care providers, but believed not all VHA providers were knowledgeable about menopause. Most preferred older female providers, thinking they were better informed about menopausal issues. Women favored complementary/alternative therapies and were against using hormone therapy (HT) for symptom relief, although they felt they were insufficiently informed about HT. Menopausal-age women are the fastest growing group at VHA. To provide better care and enhance their experiences, the VHA must educate all primary care providers about menopausal care and strive to address women Veterans’ menopausal concerns and preferences.     

First episode of shellfish contamination by palytoxin-like compounds from Ostreopsis species (Aegean Sea, Greece).

In order to investigate the toxicity of Ostreopsis species present in Greek coastal waters, cultures of Ostreopsis sp. and Ostreopsis ovata, mixed Ostreopsis field populations and shellfish collected from coastal waters of North Aegean Sea during late summer and autumn periods of 2004, 2005 and 2006 were examined by both mouse bioassay (MBA) and hemolysis neutralization assay (HNA). MBA testing was based on two different extraction protocols, while HNA also included the use of ouabain, a known palytoxin (PLT) antagonist. Results indicated the presence of a compound in both Ostreopsis cells and shellfish tissues, which was strongly toxic to mice. This compound exhibited characteristic symptomatology in mice (death, numbness, waddling gait and blindness) to that of PLT, as well as delayed hemolytic activity, which was neutralized by ouabain. HNA indicated that Ostreopsis cells contained a PLT-like compound (putative PLT, p-PLT) at concentrations ranging between 0.4 and 0.9 pg/cell, whereas concentration in shellfish tissues was estimated to range from about 33.3 to 97.0 microg p-PLT/kg tissue. To our knowledge, this is the first report of p-PLT contamination of shellfish by natural Ostreopsis species populations in European coastal waters and possibly globally, and also the first evidence on Ostreopsis cells' toxicity in the Eastern Mediterranean Sea.     

Evaluation and management of alveolitis and interstitial lung disease in scleroderma

PURPOSE OF REVIEW: In the fibrosing alveolitis of systemic sclerosis, treatment decisions depend on prognostic evaluation, which continues to excite considerable interest and debate. Advances in the staging of fibrosing alveolitis of systemic sclerosis and recent therapeutic studies are discussed in this review. RECENT FINDINGS: The decision about whether to start treatment is often the most difficult clinical challenge, because many patients have limited pulmonary fibrosis that will not necessarily progress. The estimation of disease extent (using high-resolution CT) and disease severity (using pulmonary function tests) is pivotal. Factors reducing the threshold for treatment, in addition to severe disease, include evidence of recent deterioration, a short duration of systemic disease, antitopoisomerase antibody positivity, and, in some cases, bronchoalveolar lavage findings (although the role of bronchoalveolar lavage remains contentious). Histologic appearances at surgical biopsy have little prognostic value, with the great majority of patients having nonspecific interstitial pneumonia. Best current initial treatment consists of either oral or intravenous cyclophosphamide, usually administered with low-dose corticosteroid therapy, although the risk of scleroderma renal crisis with low-dose steroid therapy requires further evaluation. SUMMARY: Careful prognostic evaluation, including the staging of disease severity and the definition of longitudinal disease behavior (by serial imaging and pulmonary function tests), is central to the formulation of a logical management plan in fibrosing alveolitis of systemic sclerosis. Cyclophosphamide, the best initial treatment currently, is associated with significant toxicity, justifying therapeutic studies of other immunosuppressive agents and a wide range of anticytokine and antifibrotic agents.     

Effects of a new soy/beta-sitosterol supplement on plasma lipids in moderately hypercholesterolemic subjects

Our aim was to test the hypocholesterolemic effect of a low-dose formulation of soy proteins supplemented with isolated b-sitosterol in a ratio of 4:1 in 20 moderately hypercholesterolemic subjects. The study has been divided in three different periods of forty days each: a stabilization diet period, then a treatment period during which all subjects assumed 10 g one time a day of the tested product and, finally, a wash out period. From the end of the stabilization diet period to the end of the soy protein added in b-sitosterol supplementation we observed a 0.45±0.30 mmol/L, 0.09±0.31 mmol/L and 0.17±0.22 mmol/L mean±SE decrease in respectively LDL-C, TG and apoB levels, associated with a 0.12±0.25 and 0.03±0.51 mg/dL mean increase respectively in HDL-C and apoA plasma concentrations. According to this recommends, low doses of soy protein added in b-sitosterol seems to be a practical and safe alternative for patients seeking modest reductions in LDL-C (<15%). J Am Diet Assoc. 2002;102:1807-1811.