Miki Ohe

Stromal micropapillary component as a novel unfavorable prognostic factor of lung adenocarcinoma

BackgroundPulmonary adenocarcinomas with a micropapillary component having small papillary tufts and lacking a central fibrovascular core are thought to result in poor prognosis. However, the component consists of tumor cells often floating within alveolar spaces (aerogenous micropapillary component [AMPC]) rather than invading fibrotic stroma observed in other organs like breast (stromal invasive micropapillary component [SMPC]). We previously observed cases of lung adenocarcinoma with predominant SMPC that was associated with micropapillary growth of tumors in fibrotic stroma observed in other organs. We evaluated the incidence and clinicopathological characteristics of SMPC in lung adenocarcinoma cases.Patients and MethodsWe investigated the clinicopathological characteristics and prognostic significance of SMPC in lung adenocarcinoma cases by reviewing 559 patients who had undergone surgical resection. We examined the SMPC by performing immunohistochemical analysis with 17 antibodies and by genetic analysis with epidermal growth factor receptor (EGFR) and KRAS mutations.ResultsSMPC-positive (SMPC(+)) tumors were observed in 19 cases (3.4%). The presence of SMPC was significantly associated with tumor size, advanced-stage disease, lymph node metastasis, pleural invasion, lymphatic invasion, and vascular invasion. Patients with SMPC(+) tumors had significantly poorer outcomes than those with SMPC-negative tumors. Multivariate analysis revealed that SMPC was a significant independent prognostic factor of lung adenocarcinoma, especially for disease-free survival of pathological stage I patients (p = 0.035). SMPC showed significantly higher expression of E-cadherin and lower expression of CD44 than the corresponding expression levels shown by AMPC and showed lower surfactant apoprotein A and phospho-c-Met expression level than corresponding expression levels shown by tumor cell components without a micropapillary component. Fourteen cases with SMPC(+) tumors (74%) showed EGFR mutations, and none of them showed KRAS mutations.ConclusionsSMPC(+) tumors are rare, but they may be associated with a poor prognosis and have different phenotypic and genotypic characteristics from those of AMPC(+) tumors.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9433341526290040.

Association of EPAS1 Gene rs4953354 Polymorphism with Susceptibility to Lung Adenocarcinoma in Female Japanese Non-Smokers

Introduction: Hypoxia-inducible factor-2&agr; (also called endothelial periodic acid–Schiff domain protein 1 [EPAS1]) seems to play an important role in some carcinogenesis, though there is no information on the relationship between single nucleotide polymorphism of EPAS1 and lung cancer development. The aim of this study was to explore a possible association of the EPAS1 gene rs4953354 polymorphism with susceptibility to lung cancer. Methods: A case–control study of 346 patients with non–small-cell lung carcinoma (adenocarcinoma = 249, squamous cell carcinoma = 97) and 247 healthy control subjects was carried out. A/G polymorphism within an intron 2 of the EPAS1 (rs4953354) was determined by direct sequencing. Results: A frequency of lung adenocarcinoma patients with a minor allele G (A/G or G/G genotype) at the rs4953354 was much higher than that of controls (odds ratio, 1.800; 95% confidence interval, 1.161–2.791; p = 0.008). This association was more evident when analyzed using female never-smokers (odds ratio, 3.31; 95% confidence interval, 1.21–9.01; p = 0.017). Mutations in epidermal growth factor receptor tended to be frequent in patients with G allele at the rs4953354, compared with those with other genotypes. Conclusion: The EPAS1 rs4953354 may be a potentially susceptible marker for development of lung adenocarcinoma, especially in female never-smokers.

Comparison of clinical management of young and elderly asthmatics by respiratory specialists and general practitioners

Abstract Background: Asthmatic death in the elderly is a serious problem worldwide. Differences in clinical skill between respiratory specialists (RS) and general practitioners (GP) are important in asthma control. The aim of this study was to compare asthma management between RS and GP. Methods: A cross-sectional survey was carried out in Shimane, Japan, in February 2009 using a questionnaire about patient background, treatment, asthma control test (ACT) and adherence to treatment. We secured the cooperation of 48 clinics (39 private clinics and 9 general hospitals). Asthmatics were divided into the elderly and young groups, and also into the RS and GP groups. Results: Clinical data of 779 patients were available for analysis. Elderly patients constituted 464 (RS group: 192, GP group: 272), while those of the young group were 315 (RS group: 207, GP group: 108). RS prescribed inhaled corticosteroids (ICSs) to their elderly and young patients more than GP. The total ACT score was higher in young RS group than in young GP group, but no such difference was noted in the elderly. Despite more asthma-related symptoms, the ACT showed that elderly GP asthmatics used fewer rescue inhalers than elderly RS. Self-assessment was higher in elderly GP than elderly RS asthmatics. Adherence to therapy was better in elderly patients than young patients. Conclusions: Elderly asthmatics treated by GPs underestimated the severity of their asthma and asthmatics seen by GPs were undertreated. The results stress the need to engage patients in educational activities, to adhere to guidelines, and to improve the coordination between GP and RS.

Comparison of Hemagglutination Inhibition Assay and Enzyme Immunoassay for Determination of Mumps and Rubella Immune Status in Health Care Personnel

Screening tests are available to determine immunity to vaccine‐preventable diseases, such as mumps and rubella. We aimed to define better assay for detecting immune status of health care personnel to vaccine‐preventable diseases.

Increased Expression Levels of Integrin α9β1 and CD11b on Circulating Neutrophils and Elevated Serum IL-17A in Elderly Aspiration Pneumonia

Background: Repeated aspiration pneumonia is a serious problem in the elderly. In aspiration pneumonia, neutrophils play an important role in acute lung injury, while CD18-independent neutrophil transmigration pathways have also been reported in acid-aspiration pneumonia animal models. However, the involvement of IL-17A and β1 integrin still remains unclear. The β1 integrin subfamily integrin α9β1 has been shown to be expressed on human neutrophils and to mediate adhesion to extracellular matrix proteins including the vascular cell adhesion molecule-1. Objectives: To elucidate the possible involvement of β1 integrin subfamily and IL-17A in aspiration pneumonia. Methods: We analyzed the expression levels of CD11b, CD18 and integrin α9β1 in circulating neutrophils and serum concentration of IL-17A, IL-22 and IL-23 in elderly aspiration pneumonia patients (n = 32, 14 males and 18 females, 78.8 ± 3.9 years old) at 2 time points (on the day of admission before starting antibiotics and the day after finishing antibiotics) and compared the results with those of a control group (n = 30, 13 males and 17 females, 76.1 ± 3.4 years old). Results: Recombinant IL-17A stimulated integrin α9β1 and CD11b expression levels in healthy human neutrophils in vitro. The expression levels of integrin α9β1 and CD11b in circulating neutrophils were significantly higher in pneumonia patients compared with the controls. In addition, serum IL-17A concentration was significantly increased in pneumonia patients. Integrin α9β1 levels positively correlated with serum IL-17A and CD18 expression levels. Conclusions: These findings suggest a potential role of integrin α9β1 expressed in neutrophils and elevated serum IL-17A in extravasation of neutrophils in cases of aspiration pneumonia.

Stromal micropapillary pattern predominant lung adenocarcinoma - a report of two cases

Generally, adenocarcinomas with micropapillary pattern, featuring small papillary tufts lacking a central fibrovascular core, are thought to have poor prognosis. This pattern has been described in various organs. However, tumor cells with micropapillary pattern of lung adenocarcinoma are more often seen to float within alveolar spaces (aerogenous micropapillary pattern, AMP) than in fibrotic stroma like other organs (stromal micropapillary pattern, SMP) and SMP predominant lung adenocarcinoma (SMPPLA) has not been well described yet. We presented two cases of SMPPLA which were found in the last four years. Both the cases showed more than 50% of SMP in the tumor area. The majority of the stromal micropapillary clusters expressed MUC1 and epithelial membrane antigen along the outer surface of cell membrane. On the other hand, connective tissues surrounding stromal micropapillary clusters showed no reactivity for epithelial markers (thyroid transcription factor-1 and cytokeratin) or endothelial marker (D2-40 and CD34). It means clusters of SMP do not exist within air space or lymphatic or vessel lumens. The tumors with SMP often presented lymphatic permeation and vessel invasion, and intriguingly, one of the two cases showed metastasis to the mediastinal lymph node. Additionally, both the cases showed EGFR point mutations of exon 21. These results suggest that SMPPLA might be associated with poor prognosis and effective for EGFR tyrosine kinase inhibitors.

Comparative analysis of a complement fixation assay and enzyme immunoassay to determine the seroprevalence of measles and varicella in a survey of healthcare workers

Objective Seroprevalence surveys of healthcare workers for vaccine-preventable diseases, including measles and varicella, are essential for disease prevention and infection control programmes. The purpose of this study was to compare the complement fixation (CF) assay and an enzyme immunoassay (EIA) to determine the prevalence of immunoglobulin G antibodies directed against measles and varicella viruses in healthcare workers. Methods Antimeasles and antivaricella antibody titres were measured simultaneously in serum samples from healthcare workers employed at a Japanese university hospital, using the CF assay and an EIA. Results Serum samples were obtained from 898 healthcare workers. Seropositivity rates determined using the CF assay and EIA were 67.8% versus 94.0%, respectively, for measles, and 83.2% versus 97.6% for varicella. Compared with EIA, a nine- and 22-fold higher number of seronegative subjects was identified by the CF assay for measles and varicella, respectively. Conclusion Differences between the CF assay and EIA in detecting seronegative or seropositive healthcare workers for measles and varicella suggest that undertaking a seroprevalence survey using an EIA, rather than a CF assay, would more accurately determine susceptibility to vaccine-preventable diseases, in healthcare settings.

Up-regulated integrinα4β1 on systemic lymphocytes and serum IL-17A in interstitial pneumonia

In interstitial pneumonia (IP), lymphocytes play an important role in lung injury and the involvement of integrinα4β1 on leukocytes has previously been reported in animal models. Although the integrinα4β1 expression level is known to be up‐regulated by inflammatory cytokines, the involvement of interleukin (IL)‐17A is unclear. The purpose of this study is to address the possible involvement of integrinα4β1 on circulating lymphocytes and its correlation with serum IL‐17A in interstitial lung diseases (ILDs).

Multiple logistic regression analysis of risk factors in elderly pneumonia patients: QTc interval prolongation as a prognostic factor

BackgroundAcute pneumonia is a serious problem in the elderly and various risk factors have already been reported, but the involvement of QTc interval prolongation remains uncertain. The aim of this study was to elucidate the prognostic factors for the development of pneumonia in elderly patients and to study the possible involvement of QTc interval prolongation.MethodsThe subjects were 249 hospitalized pneumonia patients more than 65 years old in Aki-Ohta Hospital from January 2010 to December 2013. Community-acquired pneumonia patients and nursing care and healthcare-associated pneumonia patients were included in the study. The pneumonia severity index, vital signs, blood chemistry data and ECG findings were retrospectively compared using multiple logistic regression analysis.Results39 patients died within 30 days from onset. The clinical features related to poor prognosis were: advanced age, past history of cerebral vascular disease and/or diabetes mellitus, decreased serum albumin level, higher CURB-65 or PORT index scores and QTc interval prolongation. Patients showing a prolonged QTc interval had a higher mortality than those with a normal QTc interval. A prolonged QTc interval was not related to serum calcium concentration and/or treatment with QTc prolongation drug, clarithromycin or azithromycin, but related to age, lower albumin concentration and past history of diabetes mellitus.ConclusionsThese findings suggest potential prognostic factors for pneumonia in elderly patients, including a prolonged QTc interval (> 0.44 seconds).