Comparison of plasma ctDNA and tissue/cytology-based techniques for the detection of <Emphasis Type="Italic">EGFR</Emphasis> mutation status in advanced NSCLC: Spanish data subset from ASSESS

Purpose

The analysis of epidermal growth factor receptor (EGFR) mutations in many patients with advanced non-small-cell lung cancer (aNSCLC) has provided the opportunity for successful treatment with specific, targeted EGFR tyrosine kinase inhibitors. However, this therapeutic decision may be challenging when insufficient tumor tissue is available for EGFR mutation testing. Therefore, blood surrogate samples for EGFR mutation analysis have been suggested.

Methods

Data were collected from the Spanish cohort of patients in the large, non-interventional, diagnostic ASSESS study (NCT01785888) evaluating the utility of circulating free tumor-derived DNA from plasma for EGFR mutation testing. The incidence of EGFR mutation in Spain and the level of concordance between matched tissue/cytology and plasma samples were evaluated.

Results

In a cohort of 154 eligible patients, EGFR mutations were identified in 15.1 and 11.0% of tumor and plasma samples, respectively. The most commonly used EGFR mutation testing method for the tumor tissue samples was the QIAGEN Therascreen^® EGFR RGQ PCR kit (52.1%). Fragment Length Analysis?+?PNA LNA Clamp was used for the plasma samples. The concordance rate for EGFR mutation status between the tissue/cytology and plasma samples was 88.8%; the sensitivity was 45.5%, and the specificity was 96.7%.

Conclusions

The high concordance between the different DNA sources for EGFR mutation testing supports the use of plasma samples when tumor tissue is unavailable.

     

Protective effect of sulforaphane against cisplatin-induced mitochondrial alterations and impairment in the activity of NAD(P)H: Quinone oxidoreductase 1 and γ glutamyl cysteine ligase: Studies in mitochondria isolated from rat kidney and in LLC-PK1 cells

This work was designed to further study the mechanism by which sulforaphane (SFN) exerts a renoprotective effect against cisplatin (CIS)-induced damage. It was evaluated whether SFN attenuates the CIS-induced mitochondrial alterations and the impairment in the activity of the cytoprotective enzymes NAD(P)H: quinone oxidoreductase 1 (NQO1) and γ glutamyl cysteine ligase (γGCL). Studies were performed in renal epithelial LLC-PK1 cells and in isolated renal mitochondria from CIS, SFN or CIS + SFN treated rats. SFN effectively prevented the CIS-induced increase in reactive oxygen species (ROS) production and the decrease in NQO1 and γGCL activities and in glutathione (GSH) content. The protective effect of SFN on ROS production and cell viability was prevented by buthionine sulfoximine (BSO), an inhibitor of γGCL, and by dicoumarol, an inhibitor of NQO1. SFN was also able to prevent the CIS-induced mitochondrial alterations both in LLC-PK1 cells (loss of membrane potential) and in isolated mitochondria (inhibition of mitochondrial calcium uptake, release of cytochrome c, and decrease in GSH content, aconitase activity, adenosine triphosphate (ATP) content and oxygen consumption). It is concluded that the protection exerted by SFN on mitochondrial alterations and NQO1 and γGCL enzymes may be involved in the renoprotection of SFN against CIS.     

Prevalence of Hepatitis A and B Markers and Vaccine Indication in Cirrhotic Patients Evaluated for Liver Transplantation in Spain

Vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is generally recommended for patients with chronic liver disease and those evaluated for liver transplantation in the absence of immunity. HAV and HBV infections after liver transplantation are frequent and associated with a worse prognosis. The data suggest that the number of patients with chronic liver disease without naturally acquired immunity against HAV and HBV is substantial, and that new vaccination strategies are needed. The aim of this study was to determine the level of immunity from hepatitis A and B infections and the need for HBV and HAV vaccination among cirrhotic patients evaluated for liver transplantation. We studied HBV and HAV serological markers (HbsAg, anti-HBc, anti-HBs, IgG anti-HAV) in 451 cirrhotic patients evaluated for liver transplantation to investigate the association with gender, age, and etiology of cirrhosis. Negative HBV markers were observed in 57% of patients with 43% displaying one positive HBV marker: HBsAg (+), 9.5%; anti-HBc (+)/anti-HBs (−), 11.5%; anti-HBc (−)/anti-HBs(+), 4.2%; anti-HBc(+)/anti-HBs(+), 17.7%. HBV vaccine indication established in 68.5% of patients was greater among women and hepatitis C virus-negative patients. No differences were observed in age or cause of cirrhosis. HAV vaccination indicated in 6.7% of patients (IgG anti-HVA-negative) was greater among patients with negative HBV markers (9.3% vs 3.3%, P = .018) and younger patients (25.3% of patients ≤45 years). In conclusion, there are frequent indication, for HBV vaccine among cirrhotic patients evaluated for liver transplantation, as is time for HAV vaccine, especially among patients younger than 45 years of age.     

Nail psoriasis: a combined treatment with 8% clobetasol nail lacquer and tacalcitol ointment

Background   Nail involvement is a common and distressing feature in the course of psoriasis. Although much progress has been made in the treatment of the disease, the presence of psoriasis in the nail continues to pose a challenge. In recent years, vitamin D3 analogs and a new formulation containing 8% clobetasol-17-propionate in a colourless nail lacquer vehicle have produced good results for the control of nail psoriasis.
Objective   To determine the efficacy and safety of the combined treatment of 8% clobetasol-17-propionate in a lacquer vehicle and tacalcitol ointment in nail psoriasis.
Methods   Fifteen patients with both nail bed and nail matrix psoriasis were included in the study. They were treated with a colourless nail lacquer containing 8% clobetasol-17-propionate applied at bedtime at the weekend, and with tacalcitol ointment under occlusion on the remaining days, for 6 months.
Results   All 15 patients responded well to treatment. The therapeutic effect was very fast and directly related to the length of therapy. All nail alterations, including nail pain, were reduced, and the modified target Nail Psoriasis Severity Index fell by an average of 78% compared to baseline levels (±59.6, P  < 0.0001).
Conclusions   Combined treatment with tacalcitol ointment and 8% clobetasol-17-propionate in a nail lacquer is a safe, effective treatment for nail bed and nail matrix psoriasis.     

Colon cancer: p53 expression and DNA ploidy. Their relation to proximal or distal tumor site.

Overexpression of nuclear p53 and DNA ploidy were analyzed in a series of 65 colorectal adenocarcinomas and correlated with standard clinical and pathological variables (Dukes stage, tumor site, histological grade and type, and nature of the tumor margins). Immunohistochemical tests were done with the DO-7 monoclonal antibody, using formalin-fixed tissue samples and an antigen retrieval solution. Levels of p53 expression were evaluated using a semiquantitative grading system (CAS 200, BD). Nuclear staining of more than 15% of neoplastic cells was observed in 35 samples (53.8%), which were classified as p53-positive. DNA content was measured by flow cytometry in samples of fresh tissue. Tumor site had a significant direct relationship with DNA ploidy (p < 0.01) and p53 expression (p < 0.001). Proximal tumors were more frequently diploid than were distal tumors (78.6% vs 32%). Moreover, distal neoplasms showed more p53 expression than proximal tumors (64.6% vs 14.3%). However, there was no correlation between the other clinical or pathological variables and the pathological parameter p53 expression and DNA ploidy. Our data support the hypothesis that mechanisms of colorectal carcinogenesis may differ in proximal and distal neoplasms.     

Phenytoin-induced hemocytophagic histiocytosis indistinguishable from malignant histiocytosis

We have reported a case of phenytoin-induced hemocytophagic histiocytosis indistinguishable on clinical and histopathologic grounds from malignant histiocytosis. We emphasize the need to investigate for microbiologic causes and drug ingestion, even if the diagnosis of malignant histiocytosis is plausible. We think that reactive and malignant histiocytosis are not really two distinct entities with different etiologies, but a continuum of host responses to several insults with different degrees of aggressiveness depending on the host immune status.     

Osteogenesis imperfecta: presentation of a case

Osteogenesis Imperfecta constitutes a group of anomalies include between the lethal form of the disease and a condition in which the cortical bone is thiness and more breakable. It's frequently associated to dental abnormalities. It's possible to found serious bone alterations associated to regular dentition or on the contrary. The present article reports a clinical case with Osteogenesis Imperfecta Tarda.     

Relationship Between Capillary and Muscle Damage in Dermatomyositis

To assess the pathogenetic importance of capillary damage and its relationship with degenerating muscle fibers in dermatomyositis (DM), an electron microscope study of eight muscle biopsy specimens (adult and juvenile forms) and seven muscle specimens from patients with other neuromuscular diseases was conducted. There was a 49% reduction of capillaries in the muscle specimens of DM patients. Capillary damage also was more frequent in the DM group than in control group (p less than 0.001). We found a striking relation between capillary and muscle damage in the DM group (p less than 0.002) but not in the control group. The diagnostic value of undulating tubules within endothelial cells is also discussed.