Combination therapy in dyslipidemia: Where are we now?

Lowering low-density lipoprotein cholesterol (LDL-C) reduces the risk of cardiovascular disease: each 1.0 mmol/L (38.7 mg/dL) reduction in LDL-C reduces the incidence of major coronary events, coronary revascularizations, and ischemic stroke by approximately 20%. Statins are a well-established treatment option for dyslipidemia, with LDL-C reduction in the range of 27–55%.     

Renovascular hypertension in 2007: Where are we now?

Hypertension in patients with renovascular disease poses a major clinical challenge. Renal arterial disease accelerates hypertension by activation of multiple pressor systems. Although younger individuals with fibromuscular lesions often respond well to angioplasty with minor associated risks, care must be taken in cases of complex vascular anomalies, such as renal artery aneurysms. More than 85% of patients referred for revascularization have atherosclerotic renal artery stenosis; most are older patients with preexisting hypertension, diabetes, and vascular disease. The benefits of stent revascularization in this group are controversial. Antihypertensive therapy works best with drugs that block the renin-angiotensin system; however, most patients require multiple agents. Detailed analysis of the literature and small prospective trials failed to identify major benefits with renal artery angioplasty as compared with intensive drug therapy. The CORAL study and others seek to randomly assign subjects with high-grade renovascular lesions to optimal medical management with and without stenting.     

Treat-to-target in systemic lupus erythematosus: Where are we?

Systemic lupus erythematosus (SLE) is the most paradigmatic disorder within systemic autoimmune diseases. The concept and principles of treat-to-target (T2T) in SLE were established half a decade ago and, since then, remarkable advances have been made. An international consensus was organized in order to define and unify the term remission, although plurality, with subtle nuances still exists and has not been overcome. Also, lupus low disease activity state (LLDAS) was coined as an alternative and, perhaps, more realistic target. Both of them have proven to be meaningful in terms of improving several outcomes, and have opened the path for future research in clinical trials. This review arises from the need to summarize the current state of some of the recommendations of the T2T task force.     

Personalized medicine in gastric cancer: Where are we and where are we going?

Despite improvements in adjuvant therapies for gastric cancer in recent years, the disease is characterized by high recurrence rates and a dismal prognosis. The major improvement in the treatment of recurrent or metastatic gastric cancer in recent years has been the incorporation of trastuzumab, a monoclonal antibody that inhibits human epidermal growth factor receptor 2(HER2) heterodimerization, after the demonstrated predictive value of the overexpression and/or amplification of this receptor. Beyond HER2, other genetic abnormalities have been identified, and these mutations may be targetable by tyrosine kinase inhibitors or monoclonal antibodies. The demonstration of four distinct molecular subtypes of gastric cancer by the Cancer Genome Atlas study highlight the enormous heterogeneity of the disease and its complex interplay between genetic and epigenetic alterations and provide a roadmap to implement genome-guided personalized therapy in gastric cancer. In the present review, we aim to discuss, from a clinical point of view, the genomic landscape of gastric cancer described in recent studies, the therapeutic insights derived from these findings, and the clinical trials that have been conducted and those in progress that take into account tailored therapies for gastric cancer.     

Sedation in gastrointestinal endoscopy: Where are we at in 2014?

Gastrointestinal endoscopies are invasive and unpleasant procedures that are increasingly being used worldwide. The importance of high quality procedures(especially in colorectal cancer screening), the increasing patient awareness and the expectation of painless examination, increase the need for procedural sedation. The best single sedation agent for endoscopy is propofol which, due to its’ pharmacokinetic/dynamic profile allows for a higher patient satisfaction and procedural quality and lower induction and recovery times, while ma-intaining the safety of traditional sedation. Propofol is an anesthetic agent when used in higher doses than those needed for endoscopy. Because of this important feature it may lead to cardiovascular and respiratory depression and, ultimately, to cardiac arrest and death. Fueled by this argument, concern over the safety of its administration by personnel without general anesthesia training has arisen. Propofol usage seems to be increasing but it’s still underused. It is a safe alternative for simple endoscopic procedures in low risk patients even if administered by non-anesthesiologists. Evidence on propofol safety in complex procedures and high risk patients is less robust and in these cases, the presence of an anesthetist should be considered. We review the existing evidence on the topic and evaluate the regional differences on sedation practices.     

Hepatocellular adenoma: Where are we now?

Hepatocellular adenoma (HCA) is a benign hepatocellular neoplasm, commonly occurs in young women with a history of oral contraceptive use. Complications including hemorrhage and malignant transformation necessitate the need for a thorough understanding of the underlying molecular signatures in this entity. Recent molecular studies have significantly expanded our knowledge of HCAs. The well-developed phenotype-genotype classification system improves clinical management through identifying “high risk” subtype of HCAs. In this article, we attempt to provide updated information on clinical, pathologic and molecular features of each subtype of HCAs.     

Endoscopic ultrasound in chronic pancreatitis: Where are we now?

Endoscopic ultrasonography (EUS) is well suited for assessment of the pancreas due to its high resolution and the proximity of the transducer to the pancreas, avoiding air in the gut. Evaluation of chronic pancreatitis (CP) was an early target for EUS, initially just for diagnosis but later for therapeutic purposes. The diagnosis of CP is still accomplished using the standard scoring based on nine criteria, all considered to be of equal value. For diagnosis of any CP, at least three or four criteria must be...     

Immune therapies in pancreatic ductal adenocarcinoma: Where are we now?

Pancreatic ductal adenocarcinoma(PDAC)is one of the deadliest cancers,mostly due to its resistance to treatment.Of these,checkpoint inhibitors(CPI)are inefficient when used as monotherapy,except in the case of a rare subset of tumors harboring microsatellite instability(2%).This inefficacy mainly resides in the low immunogenicity and non-inflamed phenotype of PDAC.The abundant stroma generates a hypoxic microenvironment and drives the recruitment of immunosuppressive cells through cancerassociated-fibroblast activation and transforming growth factorβsecretion.Several strategies have recently been developed to overcome this immunosuppressive microenvironment.Combination therapies involving CPI aim at increasing tumor immunogenicity and promoting the recruitment and activation of effector T cells.Ongoing studies are therefore exploring the association of CPI with vaccines,oncolytic viruses,MEK inhibitors,cytokine inhibitors,and hypoxia-and stroma-targeting agents.Adoptive T-cell transfer is also under investigation.Moreover,translational studies on tumor tissue and blood,prior to and during treatment may lead to the identification of biomarkers with predictive value for both clinical outcome and response to immunotherapy.