Pulmonary lymphoepithelioma-like carcinoma: a Surveillance,Epidemiology, and End Results database analysis

Background

Pulmonary lymphoepithelioma-like carcinoma (LELC) is one of the rare histological non-small cell lung cancers. Only a few case reports have been published. The knowledge of its characteristics and prognosis in western population is limited. Based on the data of the Surveillance, Epidemiology, and End Results database (SEER), an analysis was performed to fill the gap of our knowledge.

Methods

Characteristics, treatment and outcomes of all pulmonary LELC patients was extracted both from the SEER database from 1973 to 2011 using SEER*Stat 8.2.1 statistical analysis was performed using SPSS 16.0 and GraphPad Prism 5.

Results

A total of 62 patients with pulmonary LELC are identified and analyzed. The median age at diagnosis is 65. Among them, the majority was male (64.4%). Early stage patients account for the largest proportion (67.8%). The median survival of all LELC patients is 107 months [95% confidence interval (CI), 67–147]. The 1, 3 and 5 years survival rates of LELC are 85.6%, 74.5% and 55.2%. In the comparisons incorporating with other types of large cell lung cancer (LCC), adenocarcinoma (AD) and squamous cell lung cancer (SQ), the overall survival (OS) of LELC is superior to others. Most of the early stage (localized and regional) LELC patients (37/45, 82.2%) received surgical resection as the primary treatment. Patients older than 65 years predicted a worse prognosis.

Conclusions

Pulmonary LELC is a rare pathological type of lung cancer. In this cohort, most LELC cases were male and in early stage. Majority of early stage LELC patients have received surgical resection. Patients older than 65 years had worse survival. Unfortunately, no other prognostic factor has been identified in our study. In addition, we observed that LELC had an ideal prognosis comparing to other types of LCC, AD and SQ. In order to understand pulmonary LELC more thoroughly, more cases are required.     

Air pollution and COPD in China

Recently, many researchers paid more attentions to the association between air pollution and chronic obstructive pulmonary disease (COPD). Haze, a severe form of outdoor air pollution, affected most parts of northern and eastern China in the past winter. In China, studies have been performed to evaluate the impact of outdoor air pollution and biomass smoke exposure on COPD; and most studies have focused on the role of air pollution in acutely triggering symptoms and exacerbations. Few studies have examined the role of air pollution in inducing pathophysiological changes that characterise COPD. Evidence showed that outdoor air pollution affects lung function in both children and adults and triggers exacerbations of COPD symptoms. Hence outdoor air pollution may be considered a risk factor for COPD mortality. However, evidence to date has been suggestive (not conclusive) that chronic exposure to outdoor air pollution increases the prevalence and incidence of COPD. Cross-sectional studies showed biomass smoke exposure is a risk factor for COPD. A long-term retrospective study and a long-term prospective cohort study showed that biomass smoke exposure reductions were associated with a reduced decline in forced expiratory volume in 1 second (FEV₁) and with a decreased risk of COPD. To fully understand the effect of air pollution on COPD, we recommend future studies with longer follow-up periods, more standardized definitions of COPD and more refined and source-specific exposure assessments.     

A comparative analysis of lung cancer patients treated with lobectomy via three-dimensional video-assisted thoracoscopic surgery versus two-dimensional resection

Background

Three-dimensional (3D) vision systems are now available for thoracic surgery. It is unclear whether 3D video-assisted thoracic surgery (VATS) is superior to 2D VATS systems. This study aimed to compare the operative and perioperative data between 2D and 3D VATS lobectomy (VTL) and to identify the actual role of 3D VTL in thoracic surgery.

Methods

A two-institutional comparative study was conducted from November 2013 to November 2014 at Liaoning Cancer Hospital & Institute and the First Affiliated Hospital of Guangzhou Medical University, China, of 300 patients with resectable non-small cell lung cancer (NSCLC). Patients were assigned to receive either the 3D VATS (n=150) or 2D VATS (n=150) lobectomy. The operative and perioperative data between 2D VATS and 3D VATS were compared.

Results

Although there was no significant difference between the two groups regarding the incidence of each single complication, a significantly less operative time was found in the 3D VATS group (145 min) than in the 2D VATS group (176 min) (P=0.006). Postoperative mortality rates in 3D VATS and 2D VATS groups were both 0%.No significant difference was found between groups for estimated blood loss (P=0.893), chest drainage tube placement time (P=0.397), length of hospital stay (P=0.199), number of lymph nodes resected (P=0.397), postoperative complications (P=0.882) and cost of care (P=0.913).

Conclusions

Early results of this study demonstrate that the 3D VATS lobectomy procedure can be performed with less operative time. 3D VATS and 2D VATS lobectomy are both safe procedures in first-line surgical treatment of NSCLC.     

Inflammatory chemokines and their receptors in human visceral leishmaniasis: Gene expression profile in peripheral blood,splenic cellular sources and their impact on trafficking of inflammatory cells

Chemokines play an important role in determining cellular composition at inflammatory sites, and as such, influence disease outcome. In this study, we investigated the expression profile and splenic cellular source of various inflammatory chemokines and their receptors in human visceral leishmaniasis (VL). The expression of chemokines or their receptors was measured at the gene and protein level by employing real time qPCR and a cytometric bead array assay, respectively. In addition, the cellular source of chemokines and their receptors in the spleen was identified employing gene expression analyses in sequentially selected cell subsets. We identified elevated expression of CXCL10, CXCL9, CXCL8, and decreased CCL2 from VL patients. Further, we found reduced expression of the chemokine receptors CXCR1, CXCR2, CXCR3 and CCR2, but increased expression of CCR7 on VL PBMC, compared to endemic healthy controls. Additionally, splenic monocytes were found to be the major source of CXCL10, CXCL9 and CCR2, whereas T cells were the main source of CXCR3 and CCR7. We also report a strong association between plasma IFN-γ and CXCL-10, CXCL-9 levels. Enhanced parasite burden positively correlates with increased expression of CXCL10, CXCL9, IFN-γ and IL-10. Overall our result indicates that VL patients have an elevated inflammatory chemokine milieu which correlated with disease severity. However, expression of their chemokine receptors was significantly impaired, which may have contributed to reduced frequencies of blood monocytes and neutrophils in peripheral blood. In contrast, enhanced expression of CCR7 was associated with increased numbers of activated T cells in circulation. These findings highlight the importance of chemokines for recruitment of various cell populations in VL, and the knowledge gained may help in global understandings of the complex interaction between chemokines and pathological processes, and therefore will contribute towards the design of novel chemokine based immunological therapies against VL.     

miR-497 and miR-34a retard lung cancer growth by co-inhibiting cyclin E1 (CCNE1)

Cyclin E1, encoded by the CCNE1 gene, promotes G1/S transition, chromosome instability, and oncogenesis. Here, we show that miR-497 and miR-34a target the 3′-UTR of CCNE1. miR-497 and miR-34a are downregulated in cancer cells and their ectopic expression inhibited cell proliferation and colony formation in vitro, and inhibited tumor growth in a xenograft model. The effect of simultaneous overexpression of miR-497 and miR-34a on the inhibition of cell proliferation, colony formation, and tumor growth, and the downregulation of cyclin E1 was stronger than the effect of each miRNA alone. The synergistic actions of miR-497 and miR-34a partly correlated with cyclin E1 levels. When cells stably expressing CCNE1 were transfected with the Hi-miR-497/34a plasmid, there was no effect on colony formation, compared with that of cells transfected with either Hi-miR497 or Hi-miR34a. These results indicate cyclin E1 is downregulated by both miR-497 and miR-34a, which synergistically retard the growth of human lung cancer cells.     

Dust mite-derived Enterobacterial fimbriae H protein enforces the allergen specific immunotherapy in asthma mice

BackgroundThe mite alimentary canal contains plenty of microbiota. It is accepted that some of the microbial products function as adjuvants to speed up immune responses.ObjectivesWe identified five bacterial proteins from dust mite, and Enterobacterial fimbriae H (FimH) was one of them. This study aims to test a hypothesis that the FimH protein enforces immunotherapy in asthmatic mice.MethodsAsthmatic mice were treated by allergen specific immunotherapy (ASIT) with rDer f1/f2 or rDer f1/f2 plus FimH. Changes in inflammatory cell infiltration, airway hyperreactivity, frequency of Tregs, splenic CD4⁺IFN-γ⁺ cells, and serum levels of TGF-β, IL-10, IL-13 and IL-17A of asthmatic mice were checked.ResultsASIT with rDer f1/f2 plus FimH reduced inflammatory cell infiltration, airway hyperreactivity (AHR), and levels of IgE and IgG1 compared to ASIT with rDer f1/f2 alone, but the levels of IgG2a increased. Asthmatic mice that underwent ASIT with rDer f1/f2 plus FimH showed increased frequency of Tregs, splenic CD4⁺IFN-γ⁺ cells, serum levels of TGF-β and IL-10; and deceased splenic CD4⁺IL-4⁺ cells, and serum levels of IL-13 and IL-17A. In vitro study showed FimH triggered IL-10 expression in a concentration dependent manner and facilitated the differentiation of Tregs.ConclusionUsed as an adjuvant, FimH enforces the effect of ASIT in asthmatic mice via augmenting Tregs.     

Yield and cost effectiveness of mycobacterial infection detection using a simple IGRA-based protocol in UK subjects with inflammatory bowel disease suitable for anti-TNFα therapy

Background and aimsTesting for LTBI is recommended prior to anti-TNFα agents. This includes an assessment of TB risk factors, chest radiograph, and interferon-gamma release assay alone or with concurrent Tuberculin skin testing. Here we review our experience and cost-effectiveness of using T-SPOT.TB IGRA to detect mycobacterial infection in patients with IBD suitable for anti-TNFα therapy.MethodsThis was a single-centre, retrospective review and economic evaluation (compared to British Thoracic Society guidance) of 125 adult IBD patients (90 anti-TNFα naïve, 35 established on anti-TNFα) tested for LTBI using T-SPOT.TB IGRA.ResultsAll subjects had normal chest radiographs and no clinical evidence for TB. 109 (87%) were BCG vaccinated. 27 (22%) of all patients tested were not using immunomodulation at the time of testing. 66 (53%) were taking thiopurines, 22 (18%)corticosteroids, and 35 (28%) anti-TNFα agents. One hundred twenty two (98%) had a negative IGRA result, two (2%) had positive results, and one (1%) had an indeterminate IGRA. A strategy using IGRA to guide TB preventative treatment produced cost savings of £10.79 per person compared to the BTS guidance. Eighty eight percent of the anti-TNFα naïve group have subsequently received treatment with either infliximab or adalimumab (median follow-up of 24 months, IQR 18–30) with no cases of TB disease occurring.ConclusionsThe use of a simple screening protocol for LTBI incorporating T-SPOT.TB IGRA in place of TST in a largely BCG vaccinated population, many using immunomodulatory agents, appears to work well and is a cost-effective strategy in our IBD service.