Utility of medical thoracoscopy in diagnosis and treatment of hemothorax due to carcinoma: A case report.

Hemothorax cannot always be treated by thoracic surgeon. Rapidly improved interventional pulmonology broadens the application of medical thoracoscopy. We attempt to share our experiences of medical thoracoscopy for hemothorax and discuss the value of medical thoracoscopy in pleural diseases. We reported a 76-year-old male with hemothorax who was cured by medical thoracoscopy under local anesthesia together with argon plasma coagulation. Moreover, final pathological diagnosis was acquired as pleural sarcomatoid carcinoma. The unusual manifestation under medical thoracoscopy of such a relative rare disease was also described in this paper. The medical thoracoscopy could be used successfully for hemothorax instead of treating with surgeon, especially for those who cannot tolerate procedure of operation or surgical thoracoscopy.

Clinical efficacy of treatment for primary tracheal tumors by flexible bronchoscopy: Airway stenosis recanalization and quality of life.

The aim of the present study was to evaluate the effectiveness of interventional treatment of primary tracheal tumors through flexible bronchoscopy. The clinical data of 38 patients with primary tracheal tumours who underwent flexible bronchoscopy intervention therapy between January 2011 and January 2017 were retrospectively analyzed. The average time interval from onset of symptoms to the appearance of actual clinical manifestations in the 38 patients ranged from 0 to 60 months, with an average of 8.1±11.6 months and a median of 4.2 months. The rate of misdiagnosis at the first visit was 36.8% (14/38). After interventional treatment, the overall efficiency (complete + partial response) of airway stenosis recanalization in the 38 patients was 89.5%. In 3 patients with benign tumors, the anhelation score was reduced following treatment (1.00±0.77 vs. 3.13±1.21 at the pre-treatment stage; P<0.001). The overall survival rates of the 35 patients at 1, 3 and 5 years were 69.3, 48.7 and 20.3%, respectively. Therefore, flexible bronchoscopic intervention may effectively smoothen the airways of patients and relieve the symptoms of anhelation. Combining radiotherapy and chemotherapy may improve patient prognosis and safety.

Safety and complications of medical thoracoscopy in the management of pleural diseases.

BACKGROUND: Medical thoracoscopy is considered an overall safe procedure, whereas numbers of studies focus on complications of diagnostic thoracoscopy and talc poudrage pleurodesis. We conduct this study to evaluate the safety of medical thoracoscopy in the management of pleural diseases and to compare complications in different therapeutic thoracoscopic procedures. METHODS: A retrospective study was performed in 1926 patients, 662 of whom underwent medical thoracoscopy for diagnosis and 1264 of whom for therapeutic interventions of pleural diseases. Data on complications were obtained from the patients, notes on computer system, laboratory and radiographic findings. Chi-square test was performed to compare categorical variables and Fisher's exact test was used for small samples. RESULTS: The mean age was 51 ± 8.4 (range 21-86) years and 1117 (58%) were males. Diagnostic procedure was taken in 662 (34.4%) patients, whereas therapeutic procedure was taken in 1264 (65.6%) patients. Malignant histology was reported in 860 (44.6%) and 986 (51.2%) revealed benign pleural diseases. Eighty patients (4.2%) were not definitely diagnosed and they were considered as unidentified pleural effusion. One patient died during the creation of artificial pneumothorax, and the causes of death were supposed as air embolism or an inhibition of phrenic motoneurons and circulatory system. Complication of lung laceration was found in six patients (0.3%) and reexpansion pulmonary edema was observed in two patients (0.1%). Higher incidence of prolonged air leak was observed in bulla electrocoagulation group, in comparison with pleurodesis group. Moreover, pain and fever were the most frequently complications in pleurodesis group and cutaneous infection in entry site was the most frequently reported complication in pleural decortication of empyema group. CONCLUSIONS: Medical thoracoscopy is generally a safe and effective method, not only in the diagnosis of undiagnosed pleural effusions, but also in the management of pleural diseases. Mastering medical thoracoscopy well, improving patient management after the procedure and attempts to reduce the occurrence of post-procedural complications are the targets that physicians are supposed to achieve in the future.

Erythromycin poudrage versus erythromycin slurry in the treatment of refractory spontaneous pneumothorax.

BACKGROUND: Refractory (recurrent or persistent) spontaneous pneumothorax with high recurrence rates required treatment either by continuous chest drainage or interventional approaches. Pleurodesis by sclerosing agents has become a significant therapy in the treatment of refractory spontaneous pneumothorax (RSP) on account of its high efficiency and safety. However, the efficacy, safety and appropriate mode of administration of intrapleural erythromycin for pleurodesis have not yet been realized in the treatment of RSP. METHODS: The trial was performed to compare thoracoscopic erythromycin poudrage with erythromycin slurry via a chest tube for patients with documented RSP. Fifty-seven patients with RSP were enrolled in this study with 30 patients for erythromycin poudrage and 27 patients for erythromycin slurry. Response to pleurodesis, complications and recurrences were recorded. Continuous variables were compared with t-test. Chi-square test was performed to compare categorical variables and Fisher's exact test was used for small samples. RESULTS: Twenty-four patients in the erythromycin poudrage group (80%) and sixteen in the erythromycin slurry (ES) group (59.26%) had an immediately successful pleurodesis within 5 days (P=0.087). Patients in erythromycin poudrage had shorter duration of postprocedural chest tube drainage (6.23±3.04 days) than patients in ES (10.67±9.81 days) (P=0.032). During the follow-up, there was no significant statistical difference in recurrence rates between the two groups. Common adverse reactions included fever and chest pain with no significant difference between the two groups. CONCLUSIONS: Erythromycin is an effective and safe sclerosing agent for pleurodesis in management of RSP. Both methods are safe but erythromycin poudrage is more effective than ES.

Microarray and network-based identification of functional modules and pathways of active tuberculosis.

Diagnose of active tuberculosis (TB) is challenging and treatment response is also difficult to efficiently monitor. The aim of this study was to use an integrated analysis of microarray and network-based method to the samples from publically available datasets to obtain a diagnostic module set and pathways in active TB. Towards this goal, background protein-protein interactions (PPI) network was generated based on global PPI information and gene expression data, following by identification of differential expression network (DEN) from the background PPI network. Then, ego genes were extracted according to the degree features in DEN. Next, module collection was conducted by ego gene expansion based on EgoNet algorithm. After that, differential expression of modules between active TB and controls was evaluated using random permutation test. Finally, biological significance of differential modules was detected by pathways enrichment analysis based on Reactome database, and Fisher's exact test was implemented to extract differential pathways for active TB. Totally, 47 ego genes and 47 candidate modules were identified from the DEN. By setting the cutoff-criteria of gene size >5 and classification accuracy ≥0.9, 7 ego modules (Module 4, Module 7, Module 9, Module 19, Module 25, Module 38 and Module 43) were extracted, and all of them had the statistical significance between active TB and controls. Then, Fisher's exact test was conducted to capture differential pathways for active TB. Interestingly, genes in Module 4, Module 25, Module 38, and Module 43 were enriched in the same pathway, formation of a pool of free 40S subunits. Significant pathway for Module 7 and Module 9 was eukaryotic translation termination, and for Module 19 was nonsense mediated decay enhanced by the exon junction complex (EJC). Accordingly, differential modules and pathways might be potential biomarkers for treating active TB, and provide valuable clues for better understanding of molecular mechanism of active TB.

Construction of protein interaction network involved in lung adenocarcinomas using a novel algorithm.

Studies that only assess differentially-expressed (DE) genes do not contain the information required to investigate the mechanisms of diseases. A complete knowledge of all the direct and indirect interactions between proteins may act as a significant benchmark in the process of forming a comprehensive description of cellular mechanisms and functions. The results of protein interaction network studies are often inconsistent and are based on various methods. In the present study, a combined network was constructed using selected gene pairs, following the conversion and combination of the scores of gene pairs that were obtained across multiple approaches by a novel algorithm. Samples from patients with and without lung adenocarcinoma were compared, and the RankProd package was used to identify DE genes. The empirical Bayesian (EB) meta-analysis approach, the search tool for the retrieval of interacting genes/proteins database (STRING), the weighted gene coexpression network analysis (WGCNA) package and the differentially-coexpressed genes and links package (DCGL) were used for network construction. A combined network was also constructed with a novel rank-based algorithm using a combined score. The topological features of the 5 networks were analyzed and compared. A total of 941 DE genes were screened. The topological analysis indicated that the gene interaction network constructed using the WGCNA method was more likely to produce a small-world property, which has a small average shortest path length and a large clustering coefficient, whereas the combined network was confirmed to be a scale-free network. Gene pairs that were identified using the novel combined method were mostly enriched in the cell cycle and p53 signaling pathway. The present study provided a novel perspective to the network-based analysis. Each method has advantages and disadvantages. Compared with single methods, the combined algorithm used in the present study may provide a novel method to analyze gene interactions, with increased credibility.

Gastropulmonary Route of Infection and the Prevalence of Microaspiration in the Elderly Patients with Ventilator-Associated Pneumonia Verified by Molecular Microbiology-GM-PFGE.

Gastropulmonary route of infection was considered to be an important mechanism of ventilator-associated pneumonia (VAP). However there is little evidence to support this assumption. Moreover, the prevalence of microaspiration in elderly ventilated patients was not well understood. To confirm gastropulmonary infection route and investigate the prevalence of microaspiration in elderly ventilated patients using genome macrorestriction-pulsed field gel electrophoresis (GM-PFGE). Patients over 60 years old, expected to receive mechanical ventilation longer than 48 h, were prospectively enrolled from October 2009 to January 2012. Clinical data were collected and recorded until they died, developed pneumonia, or were extubated. Samples from gastric fluid, subglottic secretion and lower respiratory tract (LRT) were collected during the follow-up for microbiological examination. To evaluate the homogeneity, GM-PFGE was performed on strains responsible for VAP that had the same biochemical phenotype as those isolated from gastric juice and subglottic secretions sequentially. Among 44 VAP patients, 76 strains were isolated from LRT and considered responsible for VAP. Twenty-two isolates had the same biochemical phenotype with the corresponding gastric isolates. The homology was further confirmed using GM-PFGE in 12 episodes of VAP. Nearly 30% of VAPs were caused by microaspiration based on the analysis of bacterial phenotype or GM-PFGE. In addition, 58.3% patients with gastric colonization developed VAP, especially late-onset VAP (LOP). Gastropulmonary infection route exists in VAP especially LOP in elderly ventilated patients. It is one of the important mechanisms in the development of VAP.

Serum albumin as a significant prognostic factor in patients with malignant pleural mesothelioma.

Our aim was to evaluate the prognostic role of the pretreatment serum albumin level in patients with malignant pleural mesothelioma (MPM) receiving platinum-based systemic chemotherapy. From 1995 to 2013, a total of 97 patients receiving platinum-based systemic chemotherapy for newly diagnosed MPM were enrolled. All clinical information and laboratory results were retrospectively collected from the medical records. The Kaplan-Meier method was used to calculate survival. The Cox proportional hazards model was used to identify significant independent prognostic factors for predicting survival. In total, 34 of the 97 patients (35.1 %) had hypoalbuminaemia (albumin ≤ 35 g/l). The 1-year overall survival rate was 44.1 % for patients with hypoalbuminaemia and 72.0 % for patients with a normal albumin level. Multivariate analysis indicated that pretreatment albumin was an independent prognostic factor in MPM. Patients with hypoalbuminaemia had a greater risk of death than those with a normal albumin level [hazard ratio (HR) 1.778; 95 % confidence interval (CI) 1.504-2.998; P = 0.031]. When albumin was entered as a continuous variable in the Cox regression model, the HR of death was significantly decreased by 9.8 % (95 % CI 0.851-0.956) for each 1-g/l increment. The pretreatment serum albumin level is a simple, inexpensive and easily measurable marker with prognostic significance in MPM patients treated with platinum-based systemic chemotherapy.

Prognostic nutritional index predicts outcomes of malignant pleural mesothelioma.

PURPOSE: Nutritional status has been associated with long-time outcomes in cancer patients. We investigated whether the prognostic nutritional index (PNI), an indicator of nutritional status, affects overall survival in patients with malignant pleural mesothelioma (MPM). METHODS: We enrolled 121 patients with histologically confirmed MPM, who had successfully undergone biopsy by medical thoracoscopy in this study. Demographic, clinical and laboratory data were collected retrospectively. The PNI was calculated as 10× serum albumin value (g/dl) + 0.005 × total lymphocyte count (per mm(3)) in peripheral blood. Univariate and multivariate analyses were used to identify prognostic factors. RESULTS: Mean pretreatment PNI was 44.6. PNI was significantly associated with age (P = 0.031), smoking habits (P = 0.039) and weight loss (P = 0.029). Survival analysis showed PNI to be an independent prognostic factor in MPM. Patients with lower PNIs (PNI < 44.6) had greater risk of death than those with higher PNIs (PNI ≥ 44.6; hazard ratio: 2.290; 95 % confidence interval: 1.415-3.706; P = 0.001). These analyses were adjusted for patient age, gender, smoking habits, dyspnea, chest pain, weight loss, primary site of tumor, histology, platinum-based systemic chemotherapy, hospital and stage. CONCLUSIONS: Pretreatment PNI is a novel independent prognostic factor in MPM.

Endostatin, an angiogenesis inhibitor, ameliorates bleomycin-induced pulmonary fibrosis in rats.

BACKGROUND: Recent evidence has demonstrated the role of angiogenesis in the pathogenesis of pulmonary fibrosis. Endostatin, a proteolytic fragment of collagen XVIII, is a potent inhibitor of angiogenesis. The aim of our study was to assess whether endostatin has beneficial effects on bleomycin (BLM)-induced pulmonary fibrosis in rats. METHODS: The rats were randomly divided into five experimental groups: (A) saline only, (B) BLM only, (C) BLM plus early endostatin treatment, (D) BLM plus late endostatin treatment, and (F) BLM plus whole-course endostatin treatment. We investigated the microvascular density (MVD), inflammatory response and alveolar epithelial cell apoptosis in rat lungs in each group at different phases of disease development. RESULTS: Early endostatin administration attenuated fibrotic changes in BLM-induced pulmonary fibrosis in rats. Endostatin treatment decreased MVD by inhibiting the expression of VEGF/VEGFR-2 (Flk-1) and the activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). Endostatin treatment also decreased the number of inflammatory cells infiltrating the bronchoalveolar lavage fluid during the early inflammatory phase of BLM-induced pulmonary fibrosis. In addition, the levels of tumour necrosis factor-α (TNF-α) and transforming growth factor ß1 (TGF-ß1) were reduced by endostatin treatment. Furthermore, endostatin decreased alveolar type II cell apoptosis and had an epithelium-protective effect. These might be the mechanism underlying the preventive effect of endostatin on pulmonary fibrosis. CONCLUSIONS: Our findings suggest that endostatin treatment inhibits the increased MVD, inflammation and alveolar epithelial cell apoptosis, consequently ameliorating BLM-induced pulmonary fibrosis in rats.

Ethyl pyruvate reduces mortality in an endotoxin-induced severe acute lung injury mouse model.

BACKGROUND: Ethyl pyruvate (EP) was recently identified as an experimental therapeutic agent in a wide variety of model systems for inflammation-mediated tissue and cellular injury. OBJECTIVE: To evaluate the effect of ethyl EP on improving the survival in mice with LPS-induced acute lung injury (ALI). METHODS: ALI was induced by administering lipopolysaccharide (LPS) intratracheally. The mice were treated intraperitoneally (i.p.) with 100, 50 and 10 mg/kg EP immediately before intratracheal instillation of LPS, and 100 mg/kg EP was administered 0, 12, 24 and 48 hours after induction of ALI. The mortality rate was recorded and analyzed by the Kaplan-Meier method. Serum tumor necrosis factor (TNF)-alpha, interleukin (IL) -6 and IL-1 beta were measured in bronchial alveolar lavage fluid using an enzyme-linked immunosorbent assay. High-mobility group box 1 levels were measured by Western immunoblotting. RESULTS: Treatment with EP significantly inhibited the release of HMGB1, TNF-alpha, IL-6 and IL-1beta into bronchoalveolar lavage (BAL) fluids of ALI mice, and reduced the permeability index of the injured lung. High EP doses reduced the mortality from ALI and the permeability index (100 mg/kg and 50 mg/kg EP versus control; P < 0.0001). Early administration of high-dose EP significantly increased survival rate (0, 12 and 24 h versus control; P < 0.0001, P < 0.0001 and P = 0.01 respectively by log-rank test). There was no survival advantage when EP was initiated at 48 h. CONCLUSION: Ethyl pyruvate improves survival and reduces the lung permeability index in mice with LPS-induced ALI.

Serum high mobility group box protein 1 as a clinical marker for non-small cell lung cancer.

AIM: The role of high mobility group box protein 1 (HMGB1) in non-small cell lung cancer (NSCLC) is unknown. We investigated the contributions of HMGB1 in NSCLC, and analyze the correlation between HMGB1 and clinicopathologic outcomes. PATIENTS AND METHODS: A total of 145 patients with diagnosed NSCLC, and 77 patients with diagnosed chronic obstructive pulmonary disease (COPD) (51 chronic bronchitis and 26 obstructive pulmonary emphysema), and 49 healthy volunteers were enrolled from January 2005 through July 2008. HMGB1 levels were analyzed by Western blot analysis. RESULTS: The mean value of serum HMGB1 levels in 145 patients with lung cancer was 76.1+/-37.0ng/ml and was significantly higher than those in 77 COPD patients (39.8+/-10.8ng/ml), and 49 healthy control (7.7+/-6.1ng/ml, p<0.0001, respectively); The serum HMGB1 levels were 30.2+/-5.9ng/ml, 60.9+/-22.5ng/ml, 99.0+/-23.1ng/ml and 133.4+/-18.9ng/ml in patients with NSCLC of TNM stage I, II, III, and IV. There were significant differences among four groups (p<0.0001). Moreover, the significant positive correlation between the levels of serum HMGB1 and the size of tumor (r=0.799, p<0.001); The serum HMGB1 levels were 57.2+/-28.8ng/ml in patients with NSCLC before operation, and 26.5+/-14.7ng/ml one month after operation (p<0.0001). CONCLUSIONS: Our study suggests that HMGB1 may be a useful clinical marker for evaluating the NSCLC progression and is of potential prognostic value.

[Experimental study on effect of Qidan granule in treatment of pulmonary fibrosis in rats].

OBJECTIVE: To investigate the therapeutic effect and mechanism of Qidan granule on blemycinA5-induced pulmonary fibrosis in rats. METHODS: A total of 70 SD rats were randomly divided into normal group, the model group, Qidan group and hydrocortisone group and observed for 28 days and 42 days, respectively. Rat pulmonary fibrosis was induced by intrabronchial injection of blemycinA5. Treatment started from day 14 to day 42 with Qidan granule and Hydrocortisone for 14 days (day 28 group) and for 28 days (day 42 group), respectively. The lung pathological grades were observed by hematoxylin and eosin (HE) staining and expressions of transforming growth factor beta (TGF-beta(1)) protein and tumor necrosis factor alpha (TNF-alpha) protein were tested by the immunohistochemical technique. RESULTS: (1) Lung pathobiology fibrosis were alleviated was alleviated significantly in Qidan granule group compared with those in model group and hydrocortisone group (p < 0.01). (2) In Qidan group and hydrocortisone group, the expression of TGF-beta(1) protein was 1.71 +/- 0.17 and 1, 78 +/- 0.17 in day 28 group and day 42 group, respectively. The expression of TNF-aprotein was 2.16 +/- 0.40 and 1.98 +/- 0.33 in day 28 group and day 42 group, respectively. The expression of TGF-beta(1) and TNF-alpha protein was significantly difference from those in the model group and the hydrocortisone group (p < 0.01). CONCLUSIONS: Qidan granule ameliorate the pulmonary fibrosis by decreasing expressions of TGF-beta(1) and TNF-alpha proteins in lung tissue.

[The value of thoracoscopy for diagnosis and management of refractory hepatic hydrothorax].

OBJECTIVE: To study the value of thoracoscopy for diagnosis and management of refractory hepatic hydrothorax (HH). METHODS: Twenty-six patients with refractory HH were enrolled in this study. Twenty-four of them underwent therapeutic thoracoscopy to achieve pleurodesis by application of talc poudrage. RESULTS: Nineteen of the 26 patients had dilated chest wall veins, 6 had dilated azygos veins, and 16 had diaphragm blebs. Of the 24 patients who received pleurodesis via thoracoscope, 14 cases showed complete response, and 8 showed partial response. Mild chest pain and temperature elevation were the most complaints during or after the procedure. Liver function abnormalities were the most serious side effects after pleurodesis. During the follow-up period ranging from 6 months to 3 years, 1 patient died of upper gastrointestinal hemorrhage and encephalopathy in 1 month, 3 patients died of hemorrhage in 6, 12, 18 months respectively, and 1 case experienced recurrence in 18 months. CONCLUSIONS: Defects in the diaphragm seemed to be the main cause for the development of HH. Pleurodesis achieved by thoracoscopy and talc poudrage was effective in the treatment of HH, but complications and impaired liver functions should be considered.

[The relationship between transforming growth factor-beta1, platelet derived growth factor and airway remodeling in eosinophilic bronchitis].

OBJECTIVE: To study the relationship between the expression of transforming growth factor-beta(1) (TGF-beta(1)) and platelet derived growth factor (PDGF) and airway remodeling in eosinophilic bronchitis (EB). METHODS: Bronchial biopsy specimens were obtained from 12 patients with EB (A group), 10 asthmatic patients (B group) and 10 patients (C group) with peripheral lung cancer in early stage. The subepithelial basement membrane (SBM) thickness was measured by light microscopy using HE staining. The expressions of TGF-beta(1) and PDGF in the bronchial mucosa were examined by immunostaining. RESULTS: The SBM of A group [(6.3 +/- 1.4) micro m] was significantly thicker than that of C group [(4.1 +/- 1.2) micro m, P < 0.05], but significantly thinner than that of B group [(8.2 +/- 1.5) micro m]. The numbers of positive cells for TGF-beta(1) and PDGF in A group (59 +/- 9, 47 +/- 7 respectively) and B group (85 +/- 12, 76 +/- 11, respectively) were significantly higher than those in C group (31 +/- 4, 20 +/- 3, respectively), and were positively correlated with SBM thickness (r = 0.76, 0.52, P < 0.05). CONCLUSION: These results suggest that TGF-beta(1) and PDGF expressions in bronchial mucosa may play a role in bronchial subepithelial fibrosis in EB patients.