The Efficacy of Hepatic Resection after Neoadjuvant Transarterial Chemoembolization (TACE) and Radiation Therapy in Hepatocellular Carcinoma Greater Than 5 cm in Size

In cases of large hepatocellular carcinoma (HCC), neoadjuvant treatment such as transarterial chemoembolization (TACE) and radiation therapy can be performed. The aim of this study was to evaluate the outcome of these treatments prior to hepatic resection. Between January 1994 and May 2007, 16 patients with HCC greater than 5 cm in size were treated with TACE and radiation therapy prior to hepatic resection. The clinicopathologic factors were reviewed retrospectively. Of the 16 patients, there were 14 men and two women, and the median age was 52.5 yr. TACE was performed three times in average, and the median radiation dosage was 45 Gy. The median diameter of tumor on specimen was 9.0 cm. The degree of tumor necrosis was more than 90% in 14 patients. The median survival time was 13.3 months. Five patients had survived more than 2 yr and there were two patients who had survived more than 5 yr. Although the prognosis of large HCC treated with neoadjuvant therapy is not satisfactory, some showed long-term survival loger than 5 yr. Further research will be required to examine the survival and disease control effect in a prospective randomized study

Update for the practicing pathologist: The International Consultation On Urologic Disease-European association of urology consultation on bladder cancer

The International Consultations on Urological Diseases are international consensus meetings, supported by the World Health Organization and the Union Internationale Contre le Cancer, which have occurred since 1981. Each consultation has the goal of convening experts to review data and provide evidence-based recommendations to improve practice. In 2012, the selected subject was bladder cancer, a disease which remains a major public health problem with little improvement in many years. The proceedings of the 2nd International Consultation on Bladder Cancer, which included a 'Pathology of Bladder Cancer Work Group,' have recently been published; herein, we provide a summary of developments and consensus relevant to the practicing pathologist. Although the published proceedings have tackled a comprehensive set of issues regarding the pathology of bladder cancer, this update summarizes the recommendations regarding selected issues for the practicing pathologist. These include guidelines for classification and grading of urothelial neoplasia, with particular emphasis on the approach to inverted lesions, the handling of incipient papillary lesions frequently seen during surveillance of bladder cancer patients, descriptions of newer variants, and terminology for urine cytology reporting

Structure-Function Studies of DNA Binding Domain of Response Regulator KdpE Reveals Equal Affinity Interactions at DNA Half-Sites

Expression of KdpFABC, a K+ pump that restores osmotic balance, is controlled by binding of the response regulator KdpE to a specific DNA sequence (kdpFABCBS) via the winged helix-turn-helix type DNA binding domain (KdpEDBD). Exploration of E. coli KdpEDBD and kdpFABCBS interaction resulted in the identification of two conserved, AT-rich 6 bp direct repeats that form half-sites. Despite binding to these half-sites, KdpEDBD was incapable of promoting gene expression in vivo. Structure-function studies guided by our 2.5 Å X-ray structure of KdpEDBD revealed the importance of residues R193 and R200 in the α-8 DNA recognition helix and T215 in the wing region for DNA binding. Mutation of these residues renders KdpE incapable of inducing expression of the kdpFABC operon. Detailed biophysical analysis of interactions using analytical ultracentrifugation revealed a 2∶1 stoichiometry of protein to DNA with dissociation constants of 200±100 and 350±100 nM at half-sites. Inactivation of one half-site does not influence binding at the other, indicating that KdpEDBD binds independently to the half-sites with approximately equal affinity and no discernable cooperativity. To our knowledge, these data are the first to describe in quantitative terms the binding at half-sites under equilibrium conditions for a member of the ubiquitous OmpR/PhoB family of proteins

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference