Chong Bai

Isolated invasive Aspergillus tracheobronchitis: a clinical study of 19 cases.

Isolated invasive Aspergillus tracheobronchitis (iIATB) is an uncommon clinical form of invasive Aspergillosis in which Aspergillus infection is limited entirely or predominantly to the tracheobronchial tree. In the present study, we retrospectively analyzed the medical records of 19 patients who had histological documented iIATB in the Department of Respiratory Medicine of Changhai Hospital between October 2000 and February 2008. Malignancy was the most common underlying disease, which existed in 14 patients (73.7%) in our series. Most patients had impaired airway structures or defence functions, whereas the systemic immune status was relatively normal. Only three patients (15.8%) had neutropenia. The clinical manifestations and chest radiograph were nonspecific. We classified iIATB into four different forms according to the bronchoscopic features of intraluminal lesions: superficial infiltration type (Type I, n = 4), full-layer involvement type (Type II, n = 2), occlusion type (Type III, n = 6) and mixed type (Type IV, n = 7). Type IV was the largest group in our study, followed by Type III. All patients with iIATB of Type IV had definite airway occlusion. Fourteen patients (73.7%) had a good response to antifungal treatments and five (26.3%) died as a result of the progression of Aspergillosis, all of whom had full-layer invasion of the involved bronchi. In conclusion, we found that iIATB could occur in moderately or non-immunocompromised patients with impaired airway structures or defence functions and may be an early period of invasive pulmonary Aspergillosis. Most of the iIATB patients had a favourable prognosis with early diagnosis and effective antifungal treatment. The morphological features of intraluminal lesions might be of prognostic value.

miR-4782-3p Inhibited Non-Small Cell Lung Cancer growth via USP14

Background: Lung cancer is the leading cause of cancer-related mortality worldwide, with near 1.4 million deaths each year. NSCLC accounts for nearly 85% of all case of lung cancer. MiRNAs play important roles in regulation of gene expression at the post-transcriptional level. MiRNAs profiles may predict prognosis and disease recurrence in early-stage NSCLC. Our previous study proved that over-expression of ubiquitin specific peptidase 14 (USP14), a deubiquitinating enzyme, was associated with favorable prognosis in NSCLC patients and promoted tumor cells proliferation. Here, we tried to identify which miRNAs targeted USP14, and the roles of these miRNAs in NSCLC. Methods: MiR-4782-3p and its potential targeted genes were identified by bioinformatics algorithm. Dual luciferase reporter assay system was used to analyze the interaction between miR-4782-3p and targeted genes. Cell proliferation was assayed by MTT and BdU assay. MiRNAs and mRNA expression were assayed by qRT-PCR. USP14 protein level was assayed by Western blot. The role of miR-4782-3p in patients survival was revealed by Kaplan-Meier plot of overall survival. Results: Up-expression of miR-4782-3p in NSCLC cells decreased the USP14 expression. Down-expression of miR-4782-3p increased USP14 expression. In NSCLC specimen, Negative correlation between USP14 mRNA level and miR-4782-3p level was identified. Higher miR-4782-3p expression is associated with longer survival. USP14, ZEB2, XIAP overexpression reversed the inhibitory effect of miR-4782-3p. Conclusions: High expression of miR-4782-3p was associated with favorable prognosis in NSCLC patients. MiR-4782-3p inhibited cell proliferation in NSCLC by targeting USP14, ZEB2 and XIAP.

Over-expression of deubiquitinating enzyme USP14 in lung adenocarcinoma promotes proliferation through the accumulation of β-catenin.

The deubiquitinating enzyme USP14 has been identified and biochemically studied, but its role in lung cancer remains to be elucidated. The aim of this study was to evaluate the prognostic significance of USP14 in patients with lung adenocarcinoma and to define its role in lung cancer cell proliferation. USP14 mRNA levels in different non-small cell lung cancer (NSCLC) cell lines were detected by real-time qPCR. USP14 protein levels in surgically resected samples from NSCLC patients, and in NSCLC cell lines, were detected by immunohistochemistry or Western blot. The correlation of USP14 expression with clinical characteristics and prognosis was determined by survival analysis. After silencing USP14, cell proliferation was assessed by MTT assay and the cell cycle was measured by FACS assay. It was found that USP14 expression was upregulated in NSCLC cells, especially in adenocarcinoma cells. Over-expression of USP14 was associated with shorter overall survival of patients. Downregulation of USP14 expression arrested the cell cycle, which may be related to β-catenin degradation. Over-expression of USP14 was associated with poor prognosis in NSCLC patients and promoted tumor cell proliferation, which suggests that USP14 is a tumor-promoting factor and a promising therapeutic target for NSCLC.

Malignant Pleural Effusion Supernatants Are Substitutes for Metastatic Pleural Tumor Tissues in EGFR Mutation Test in Patients with Advanced Lung Adenocarcinoma

Background Though the possibility of using malignant pleural effusions (MPEs) as alternatives for metastatic pleural tumor tissues (MPTTs) in epidermal growth factor receptor (EGFR) mutation test has been examined, due to the lack of studies comparing the results in matching MPEs and MPTTs, the clinical value of MPEs for advanced adenocarcinoma patients with pleural effusions is not confirmed. Methods EGFR mutation statuses in matching MPTTs, MPE supernatants and cell blocks, of 41 patients with advanced lung adenocarcinoma as diagnosed by thoracoscopy were analyzed using amplification refractory mutation system (ARMS). Results EGFR mutations were detected in 46.3% (19/41) of MPTTs, 43.9% (18/41) of MPE supernatants and 56.3% (18/32) of MPE cell blocks by ARMS analysis. Generally, the same EGFR statuses were identified in both MPTTs and matching MPE cell blocks of 81.3% patients (26/32), whereas MPTTs and matching MPE supernatants of 87.8% (36/41) patients shared the same EGFR status. Compared with EGFR mutation detection in MPTTs, the sensitivity of EGFR mutation detection in MPE-cell blocks was 87.5% (14/16), specificity was 75.0% (12/16), while the sensitivity of EGFR mutation detection in MPE-supernatants was 84.2% (16/19), specificity was 90.9% (20/22). Conclusions The high concordance of EGFR mutation statuses between MPEs and MPTTs in lung adenocarcinoma patients with pleural metastasis as determined by ARMS analysis suggests that MPEs, particularly MPE supernatants, may be substitutes for MPTTs in EGFR mutation test.

Necrotizing sarcoid granulomatosis with hemoptysis: a case report and literature review

We present a case of 39-year-old male with the symptoms of fever, cough, chest pain and bloody phlegm, whose chest CT showed multiple subpleural nodules and inflammatory infiltration. Video-Assisted Thoracic Surgery ( VATS ) for right subplural nodule was performed and confirmed the diagnosis of necrotizing sarcoid granulomatosis. Prednisolone was administered and the symptoms were under control untill the occurrence of intermittent hemoptysis after 10 months. Chest CT and bronchoscope revealed the right lower lobe nodule with intraluminal necrotic tissue in the right lower lobe posterior basal segment respectively. Fatal hemoptysis happened during endobronchial biopsy by flexible bronchoscope forcep. Based on this case, we reviewed the relevant literature and discussed the clinical features, pathological changes and prognosis of the disease.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1955868163936338

MicroRNA-34/449 targets IGFBP-3 and attenuates airway remodeling by suppressing Nur77-mediated autophagy

Autophagy plays critical roles in airway inflammation and fibrosis-mediated airway remodeling and many factors including proinflammatory cytokines and inflammation related pathways are involved in the process. The aim of the present study was to examine the role of epithelial microRNAs (miRNAs) in autophagy-mediated airway remodeling and to identify the factors involved and the underlying mechanisms. Serum miR-34/449, inflammatory factors, and autophagy and fibrosis-related proteins were determined by real-time PCR, enzyme-linked immunosorbent assay and western blotting in 46 subjects with asthma and 10 controls and in the lung epithelial cell line BEAS-2B induced with IL-13 and treated with miRNA mimics. Luciferase assays were used to verify IGFBP-3 as a target of miR-34/449, and immunohistochemistry, immunofluorescence and co-immunoprecipitation were used in vitro and in vivo study. miR-34/449 were downregulated in patients with asthma in parallel with the upregulation of autophagy-related proteins. Proinflammatory factors and fibrosis-related proteins were significantly higher in asthma patients than in healthy controls. IL-13 induction promoted autophagy and upregulated miR-34/449 in BEAS-2B cells, and these effects were restored by IGFBP-3 silencing. miR-34/449 overexpression suppressed autophagy, decreased fibrosis, activated Akt, downregulated fibrosis-related factors, and downregulated proinflammatory cytokines and nuclear factor κB by targeting IGFBP-3. In vivo experiments showed that miR-34/449 overexpression was associated with Nur77 nuclear translocation and IGFBP-3 downregulation in parallel with decreased airway remodeling by decreased autophagy. miR-34/449 are potential biomarkers and therapeutic targets in asthma. miR-34/449 may contribute to airway inflammation and fibrosis by modulating IGFBP-3 mediated autophagy activation.

Endobronchial ultrasound convex probe for lymphoma, sarcoidosis, lung cancer and other thoracic entities. A case series

Endobronchial ultrasound endoscopy is a state of the art diagnostic endoscopic procedure for the thorax. Firstly it was designed mainly for the staging of lung cancer and of course for the diagnosis of suspicious findings in large central airways. The main limitation of the equipment is the diameter of the instrument and therefore it can only be guided through large airways. However; the diameter of the working channel also provides a large tissue sample nowadays with the 19G biopsy needle. We will provide our experience with the 22G needle of the endobronchial convex-probe in several medical situations of the thorax.

A new mode of ventilation for interventional pulmonology. A case with EBUS-TBNA and debulking

Lung cancer is still underdiagnosed mainly due to lack of symptoms. Most patients are diagnosed in a late stage where unfortunately only systematic therapy can be applied. Fortunately in the last five years several novel therapies and combinations have emerged. However; in certain situations local therapeutics modalities have to be applied in order to solve emergency problems as in the case that we will present. Convex-EBUS probe was used along with a novel method of ventilation which keeps PCO2 concentration satisfyingly low.

Immunotherapy “Shock” a case series of PD-L1 100% and pembrolizumab first-line treatment

In this decade a “bloom” of novel therapies has been observed for non-small cell lung cancer. We have new tools for the diagnosis of lung cancer and also we can re-biospy easier than before in different lesions and obtain tissue samples in order to investigate whether a patient can receive new targeted therapies. Immunotherapy has been well established previously for other forms of cancer, and nowadays it is also available for lung cancer. There are two immunotherapies for now nivolumab and pembrolizumab which can be administered as second line treatment, the second can also be administered as first-line if there is a programmed death-ligand 1 ≥50% expression.

Comparison of the efficacy of four endobronchial ablation techniques in dogs

The present study aimed to evaluate the safety and efficacy of four commonly used ablation techniques, namely neodymium-doped yttrium aluminium garnet (Nd:YAG) laser therapy, argon plasma coagulation (APC), high-frequency electrocautery and CO2 cryotherapy. The techniques were performed at various powers or impedance settings, and for various durations, on the trachea of beagle dogs. Pathological changes of the tracheal wall were assessed by bronchoscopy. The endoscopic gross appearance of lesions induced by ablation treatments was consistent with the histopathological changes. The results suggested that cryotherapy was relatively safe, whereas APC induced superficial tissue coagulative necrosis. Furthermore, Nd:YAG laser therapy was the most efficient technique and showed the greatest penetration potential. In general, tissue injury was exacerbated with extended application time, at constant power or impedance. The safest application parameters were 20 W for ≤1 sec for Nd:YAG laser therapy, 40 W for ≤3 sec for electrocautery, 40 W for ≤5 sec for APC and 100 Ω for ≤120 sec for cryotherapy. At the maximum times, these settings resulted in identical pathological changes. Healing of the lesions following ablation was achieved within 3 weeks. The Nd:YAG laser, APC, electrocautery and cryotherapy endobronchial ablation techniques differed according to their potential and limitations for application on the trachea. However, when applied at specific combinations of power or impedance and duration, they exhibited similar efficacies.