Analysis of KRAS Mutations of Exon 2 Codons 12 and 13 by SNaPshot Analysis in Comparison to Common DNA Sequencing

Due to the call for fast KRAS mutation status analysis for treatment of patients with monoclonal antibodies for metastatic colorectal cancer, sensitive, economic, and easily feasible methods are required. Under this aspect, the sensitivity and specificity of the SNaPshot analysis in comparison to the commonly used DNA sequencing was checked. We examined KRAS mutations in exon 2 codons 12 and 13 with DNA sequencing and SNaPshot analysis in 100 formalin-fixed paraffin-embedded tumor tissue samples of pancreatic carcinoma, colorectal carcinoma, and nonsmall cell lung cancer specimens of the primary tumor or metastases. 40% of these samples demonstrated mutated KRAS genes using sequencing and SNaPshot-analysis; additional five samples (45/100) were identified only with the SNaPshot. KRAS mutation detection is feasible with the reliable SNaPshot analysis method. The more frequent mutation detection by the SNaPshot analysis shows that this method has a high probability of accuracy in the detection of KRAS mutations compared to sequencing

Primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma: A case report

Primary ovarian carcinoid tumors are exceptionally rare entities accounting for approximately 0.1% of all ovarian neoplasms. This report describes a primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma in a 65 year-old woman. Macroscopically, the unilateral adnexal tumor was composed of cystic, solid and mucinous elements which resolved into a dual component lesion histologically. The majority of the tumor displayed an organoid architecture with mild to moderate pleomorphism and no discernible mitotic activity, while approximately 10% consisted of sheets and groups of cells with highly pleomorphic nuclei, necrosis and occasional mitoses. Features of a mature cystic teratoma were seen very focally. Immunohistochemistry revealed strong, diffuse positivity for CD56 and synaptophysin. Chromogranin immunonegativity was noted and there was an absence of nuclear β-catenin accumulation. Ki-67 index was 10–12%. Although there is no established diagnostic framework for primary ovarian carcinoid tumors, this case was diagnosed as a well-differentiated neuroendocrine tumor, Grade 2 (intermediate grade), arising in association with a mature cystic teratoma/dermoid cyst. This case highlights the need to develop ovarian diagnostic criteria in this area

Environmental Isocyanate-Induced Asthma: Morphologic and Pathogenetic Aspects of an Increasing Occupational Disease

Occupational diseases affect more and more people every year. According to the International Labour Organization (ILO), in 2000 an estimated amount of at least 160 million people became ill as a result of occupational-related hazards or injuries. Globally, occupational deaths, diseases and injuries account for an estimated loss of 4% of the Gross Domestic Product. Important substances that are related to occupational diseases are isocyanates and their products. These substances, which are used in a lot of different industrial processes, are not only toxic and irritant, but also allergenic. Although the exposure to higher concentrations could be monitored and restricted by technical means, very low concentrations are difficult to monitor and may, over time, lead to allergic reactions in some workers, ending in an occupational disease. In order to prevent the people from sickening, the mechanisms underlying the disease, by patho-physiological and genetical means, have to be known and understood so that high risk groups and early signs in the development of an allergic reaction could be detected before the exposure to isocyanates leads to an occupational disease. Therefore, this paper reviews the so far known facts concerning the patho-physiologic appearance and mechanisms of isocyanate-associated toxic reactions and possible genetic involvement that might trigger the allergic reactions

Preneoplastic lesions of the lung

Lung cancer is the leading cause of cancer deaths worldwide. If we can define and detect preneoplastic lesions, we might have a chance of improving survival. The World Health Organization has defined three preneoplastic lesions of the bronchial epithelium: squamous dysplasia/carcinoma in situ; atypical adenomatous hyperplasia; and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. These lesions are believed to progress to squamous cell carcinoma, adenocarcinoma and carcinoid tumors, respectively. In this review we summarize the data supporting the preneoplastic nature of these lesions, and delve into some of the genetic changes found in atypical adenomatous hyperplasia and squamous dysplasia/carcinoma in situ

Stepping down the dose of inhaled corticosteroids for adults with asthma

BACKGROUND: Asthma is a condition of the airways affecting more than 300 million adults and children worldwide. National and international guidelines recommend titrating up the dose of inhaled corticosteroids (ICS) to gain symptom control at the lowest possible dose because long-term use of higher doses of ICS carries a risk of systemic adverse events. For patients whose asthma symptoms are controlled on moderate or higher doses of ICS, it may be possible to reduce the dose of ICS without compromising symptom control. OBJECTIVES: To evaluate the evidence for stepping down ICS treatment in adults with well-controlled asthma who are already receiving a moderate or high dose of ICS. SEARCH METHODS: We identified trials from the Specialised Register of the Cochrane Airways Group and conducted a search of ClinicalTrials.gov (www.ClinicalTrials.gov) and the World Health Organization (WHO) trials portal (www.who.int/ictrp/en/). We searched all databases from their inception with no restriction on language. We also searched the reference lists of included studies and relevant reviews. We performed the most recent search in July 2016. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of at least 12 weeks' duration and excluded cross-over trials. We looked for studies of adults (aged ≥ 18 years) whose asthma had been well controlled for a minimum of three months on at least a moderate dose of ICS. We excluded studies that enrolled participants with any other respiratory comorbidity.We included trials comparing a reduction in the dose of ICS versus no change in the dose of ICS in people with well-controlled asthma who a) were not taking a concomitant long-acting beta agonist (LABA; comparison 1), and b) were taking a concomitant LABA (comparison 2). DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results for included studies, extracted data on prespecified outcomes of interest and assessed the risk of bias of included studies; we resolved disagreements by discussion with a third review author. We analysed dichotomous data as odds ratios (ORs) using study participants as the unit of analysis and analysed continuous data as mean differences (MDs). We used a random-effects model. We rated all outcomes using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) system and presented results in 'Summary of findings' tables. MAIN RESULTS: We included six studies, which randomised a total of 1654 participants (ICS dose reduction, no concomitant LABA (comparison 1): n = 892 participants, three RCTs; ICS dose reduction, concomitant LABA (comparison 2): n = 762 participants, three RCTs). All included studies were RCTs with a parallel design that compared a fixed dose of ICS versus a 50% to 60% reduction in the dose of ICS in adult participants with well-controlled asthma. The duration of the treatment period ranged from 12 to 52 weeks (mean duration 21 weeks; median duration 14 weeks). Two studies were performed in the setting of primary care, two were performed in the secondary care setting and two reported no information on setting.Meta-analysis was hampered by the small number of studies contributing to each comparison, combined with heterogeneity among outcomes reported in the included studies. We found the quality of synthesised evidence to be low or very low for most outcomes considered because of a risk of bias (principally, selective reporting), imprecision and indirectness. Although we found no statistically significant or clinically relevant differences between groups with respect to any of the primary or secondary outcomes considered in this review, the data were insufficient to rule out benefit or harm. AUTHORS' CONCLUSIONS: The strength of the evidence is not sufficient to determine whether stepping down the dose of ICS is of net benefit (in terms of fewer adverse effects) or harm (in terms of reduced effectiveness of treatment) for adult patients with well-controlled asthma. A small number of relevant studies and varied outcome measures limited the number of meta-analyses that we could perform. Additional well-designed RCTs of longer duration are needed to inform clinical practice regarding use of a 'stepping down ICS' strategy for patients with well-controlled asthma