The role of microRNAs in liver cancer

Hepatocellular carcinoma and cholangiocarcinoma constitute the majority of primary malignant tumors located in the liver, with hepatocellular carcinoma accounting for approximately 80% of these tumors and cholangiocarcinoma representing the remaining 20%. Both are aggressive malignancies, heterogeneous in terms of biological activities and clinical behavior, with dismal outcomes and an increasing incidence worldwide. Radical surgical resection remains the gold standard to date, as adjuvant therapeutic modalities have failed to show a consistent and adequate curative response. However, radical surgical resection is not feasible in most of the patients with such tumors, as tumor size or functional status of the parenchyma does not permit extended hepatic resection. In addition, patients who undergo curative resection often have a high rate of relapse. Multimodal therapeutic approaches, such as the combination of invasive methods (surgical resection, radiofrequency ablation, and two-step or three-step procedures with intermittent portal vein embolization) with interferon-α, systemic chemotherapy, or transarterial catheter embolization, may prolong survival in some patients, but have, however, failed to demonstrate satisfactory results. Therefore, an obvious need emerges for the discovery of new biomarkers to understand the events leading to hepatocarcinogenesis, to relate different phenotypes with differences in clinical behavior and prognosis, and, if possible, to predict response rates to adjuvant therapeutic modalities or, furthermore, to establish novel mechanism-based treatments for hepatic tumors.     

Nilotinib as frontline and second-line therapy in chronic myeloid leukemia: open questions

Nilotinib is a second generation ABL tyrosine kinase inhibitor (TKI) that exerts major anti-leukemic effects in newly diagnosed patients with chronic myeloid leukemia (CML) as well as in most patients with imatinib-resistant CML. In freshly diagnosed patients, the anti-leukemic activity of nilotinib exceeds the efficacy of imatinib, and although long-term data for nilotinib are not available yet, the drug has recently been approved for firstline treatment of chronic phase CML in various countries. Still however, several questions concerning the optimal dose, follow-up parameters, long-term safety, and patient selection remain open. Likewise, it remains uncertain whether both Sokal low-risk and high-risk patients should receive nilotinib as frontline therapy in the future. Another question is whether nilotinib can completely eradicate CML in a subset of patients. Furthermore, it remains unclear whether and what comorbidity must be regarded as relative or absolute contra-indication for this TKI. To discuss these issues, the Austrian CML Working Group organized a series of meetings in 2010. In the current article, the outcomes from these discussions are summarized and presented together with recommendations for frontline use of TKIs in various groups of patients with CML. These recommendations should assist in daily practice as well as in the preparation and conduct of clinical trials.     

Outpatient evaluation and management of patients with ventricular premature beats or non-sustained ventricular tachycardia

In this survey, European physicians who deal with arrhythmia patients gave their opinions about diagnostic work up when they see patients with ventricular premature beats (VPBs) or non-sustained ventricular tachycardia (NSVT). In general, similar work-up regimens were used for these two arrhythmias except for coronary angiography, which was considered by one in four physicians when dealing with NSVT but by almost none for VPBs. The majority of physicians believe that it is acceptable to abstain from pharmacological therapy in an asymptomatic patient with VPBs. When considering second-line therapy almost half of the respondents would consider amiodarone in patients with NSVT whereas almost none would when dealing with VPBs. When the effect of therapy was evaluated, its influence on symptoms and arrhythmia burden were ranked highest.     

Cardiac resynchronization therapy is certainly cardiac therapy, but how much resynchronization and how much atrioventricular delay optimization?

Cardiac resynchronization therapy has become a standard therapy for patients who are refractory to optimal medical therapy and fulfill the criteria of QRS >120?ms, ejection fraction <35% and NYHA class II, III or IV. Unless there is some other heretofore unrecognized effect of pacing, the benefits of atrio-biventricular pacing on hard outcomes observed in randomized trials can only be attributed to the physiological changes it induces such as increases in cardiac output and/or reduction in myocardial oxygen consumption leading to an improvement in cardiac function efficiency. The term "Cardiac Resynchronization Therapy" for biventricular pacing presupposes that restoration of synchrony (simultaneity of timing) between left and right ventricles and/or between walls of the left ventricle is the mechanism of benefit. But could a substantial proportion of these benefits arise not from ventricular resynchronization but from favorable shortening of AV delay ("AV optimization") which cannot be termed "resynchronization" unless the meaning of the word is stretched to cover any change in timing, thus, rendering the word almost meaningless. Here, we examine the evidence on the relative balance of resynchronization and AV delay shortening as contributors to the undoubted clinical efficacy of CRT.