Synchronous Computed Tomography-Guided Percutaneous Transthoracic Needle Biopsy and Microwave Ablation for Highly Suspicious Malignant Pulmonary Ground-Glass Nodules.

INTRODUCTION: There is no consensus regarding the most appropriate management of suspected malignant pulmonary ground-glass nodules (GGNs). OBJECTIVE: We aimed to explore the feasibility and safety of synchronous computed tomography-guided percutaneous transthoracic needle biopsy (PTNB) and microwave ablation (MWA) for patients highly suspicious of having malignant GGNs. METHODS: We retrospectively reviewed medical records between July 2020 and April 2023 from our medical center. Eligible patients synchronously underwent PTNB and MWA (either MWA immediately after PTNB [PTNB-first group] or PTNB immediately after MWA [MWA-first group]) at the the physician's discretion. We analyzed the rate of definitive diagnosis and technical success, the length of hospital stay, the postoperative efficacy, and periprocedural complications. RESULTS: Of 65 patients who were enrolled, the rate of definitive diagnosis was 86.2%, which did not differ when stratified by the tumor size, the consolidation-to-tumor ratio, or the sequence of the two procedures (all p > 0.05). The diagnostic rate of malignancy was 83.1%. After the median follow-up duration of 18.5 months, the local control rate was 98.2% and the rate of completed ablation was 48.2%. The rate of perioperative minor and major complications was 44.6% and 6.2%, respectively. The most common adverse events included pain, cough, and mild hemorrhage. Mild hemorrhage took place significantly less frequently in the MWA-first group than in the PTNB-first group (16.7% vs. 45.5%, p < 0.05). CONCLUSION: Synchronous PTNB and MWA are feasible and well tolerated for patients highly suspicious of having malignant GGNs, providing an alternative option for patients who are ineligible for surgical resection.

Stent loaded with radioactive Iodine-125 seeds for adenoid cystic carcinoma of central airway: A case report of innovative brachytherapy.

Adenoid cystic carcinoma (ACC) of central airway is very rare. More than half of ACCs are unresectable for tumor extension. There's rare report on local ACCs only in central airway. We present a case of ACC in central airway who underwent an innovative brachytherapy. A 44-year-old woman was diagnosed with primary ACC in central airway without regional lymphadenopathy or metastatic disease. Stenosis was observed in lower trachea and both left and right main bronchi (stenosis in lumen ≥50%) with bronchoscopy. The tumor was unresectable due to local extension. A Y-shaped and stainless-steel stent loaded with radioactive 125I seeds was placed in the central airway using bronchoscope. The number and distribution of 125I seeds were planed using treatment planning system. The stent was removed three months later. The patient tolerated the procedure well. She was alive without relapse three years after removing the stent with 125I seeds. This case demonstrates the successful use of stent with radioactive 125I seeds for unresectable ACCs in central airway. In the procedure, the stent was placed with bronchoscope and under the vision from bronchoscope. This innovative brachytherapy is well-tolerated, safe, precise and individualized designed. The patient with unresectable ACCs could get a long-term relapse-free survival. Clinical trials could be taken to validate its effectiveness and tolerability in patients with ACCs of central airway.

Modified silicone stent for the treatment of post-surgical bronchopleural fistula: a clinical observation of 17 cases.

BACKGROUND: Bronchopleural fistula is a rare but life-threatening event with limited therapeutic options. We aimed to investigate the efficacy and safety of the modified silicone stent in patients with post-surgical bronchopleural fistula. METHODS: Between March 2016 and April 2020, we retrospectively reviewed the records of 17 patients with bronchopleural fistula and who underwent bronchoscopic placement of the Y-shaped silicone stent. The rate of initial success, clinical success and clinical cure, and complications were analyzed. RESULTS: Stent placement was successful in 16 patients in the first attempt (initial success rate: 94.1%). The median follow-up time was 107 (range, 5-431) days. All patients achieved amelioration of respiratory symptoms. The clinical success rate was 76.5%. Of the 14 patients with empyema, the daily drainage was progressively decreased in 11 patients, and empyema completely disappeared in six patients. Seven stents were removed during follow-up: four (26.7%) for the cure of fistula, two for severe proliferation of granulomatous tissue and one for stent dislocation. No severe adverse events (i.e. massive hemoptysis, suture dehiscence) took place. Seven patients died (due to progression of malignancy, uncontrolled infection, myocardial infarction and left heart failure). CONCLUSIONS: The modified silicone stent may be an effective and safe option for patients with post-surgical bronchopleural fistula patients in whom conventional therapy is contraindicated.

Modified silicone stent for difficult-to-treat massive hemoptysis: a pilot study of 14 cases.

BACKGROUND: Massive hemoptysis is a life-threatening event with limited therapeutic options. Bronchoscopic placement of stents may offer an alternative option for massive hemoptysis. However, traditional silicone stents have not been customized, making it difficult to tailor to individual patient's needs for achieving optimal hemostasis. To investigate the efficacy and safety of the modified silicone stent in patients with difficult-to-treat massive hemoptysis. METHOD: Between May 2016 and November 2018, we enrolled 14 patients who underwent bronchoscopic placement of the modified silicone stent, which was fabricated manually based on the Y-shaped silicone stent by tailoring and suturing on site. We recorded the technical success, clinical success, and complications. Patients were followed up for recording the recurrence of massive hemoptysis and complications. RESULTS: Placement of the modified silicone stent was successful in all 14 patients with a mean duration of 69.6 minutes (technical success rate: 100%). After stenting, no further massive hemorrhage episodes recurred in 12 patients (clinical success rate: 85.7%). Two cases suffered from recurrent hemoptysis in 4 and 6 days after stenting, respectively. The main complications were sputum plugging, granuloma proliferation and pulmonary infection such as pneumonia. There were no adverse events of stent migration and suture dehiscence. After a median follow-up of 5.8 (range, 0.3-21.3) months, three patients withdrew and seven patients succumbed. Only one patient died of uncontrolled pneumonia which was possibly related to stent placement. CONCLUSIONS: The modified silicone stent is an effective and safe gate-keeping therapeutic option for difficult-to-treat massive hemoptysis.

Extracellular mitochondrial DNA promote NLRP3 inflammasome activation and induce acute lung injury through TLR9 and NF-κB.

BACKGROUND: Extracellular mitochondrial DNA (mtDNA) was demonstrated to be capable of inducing pulmonary inflammation through TLR9 while its role in NLRP3 inflammation activation remains unknown. METHODS: C57BL/6 mice were challenged intratracheally with mtDNA. Pulmonary pathology, the NLRP3 and caspase-1 p20 in lung tissues were assayed. PMA-primed THP-1 macrophages were incubated with mtDNA in vitro and cell-free medium were concentrated to detect caspase-1 p20 subunit and NLRP3 by Western blotting. Additionally, IL-1ß, L-18, TNF-α and caspase-1 activity in culture were also analyzed by ELISA kits and activity assay kit. RESULTS: Intratracheal administration of mtDNA increased NLRP3 and caspase-1 p20 subunit in lung together with excessive inflammation and damage. Inhibition of caspase-1 substantially diminished mtDNA-induced lung injury and inflammation. Exposed to mtDNA in THP-1 macrophages resulted in significant up-regulation of NLRP3 and increased caspase-1 p20 subunit release in culture. It also led to significant increased transcripts of NLRP3, ASC, caspase-1 and release of IL-1ß, IL-18 and TNF-α in culture media. Futhermore, mtDNA exposure resulted in significant up-regulation of phosho -p38 MAPK and nucleus translocation of NF-κB. mtDNA-induced Transcripts of NLRP3 and ASC were inhibited by p38 siRNA inhibitor or NF-κB inhibitor. CONCLUSIONS: Extracellular mtDNA promote NLRP3 inflammasome activation, acute pulmonary inflammation and injury through TLR9, p38 MAPK and NF-κB pathways.

Assessing the clinical outcome of nab-paclitaxel in Chinese patients with advanced non-small-cell lung cancer.

PURPOSE: Nab-paclitaxel [nab-P, 130-nm albumin-bound paclitaxel particles] is a new solvent-free paclitaxel that allows for high intratumoral concentration and has been approved for use in various solid tumours. The aim of our study was to evaluate the efficacy and safety of nab-paclitaxel in the treatment of advanced non-small-cell lung cancer [NSCLC]. PATIENTS AND METHODS: We assessed 101 Chinese patients who were diagnosed with Stage IIIB or IV NSCLC from August 2009 to November 2014.The patients were injected with nab-paclitaxel [260 mg/m2 , day1] with or without platinum. Patients who completed more than two treatment cycles were assessed for response and survival. All patients were assessed for adverse events. RESULTS: The efficacy was evaluated in 79 patients; the overall response rate was 32.9%, and the disease control rate was 89.9%. Subgroup analysis found patients with squamous cell carcinoma, and combination therapies showed better outcomes. The median progression-free survival was 5.3 months [95%CI: 4.6-5.9], and the median overall survival was 8.9 months [95%CI: 6.1-11.6]. The main grades 3/4 adverse events were peripheral neuropathy [5.9%], leukopenia [5.0%], and anaemia [3.0%]. Additionally, severe abnormal hepatic function [2.0%], alopecia [2.0%], thrombocytopenia [1.0%] and fatigue [1.0%] could also be identified in some patients. CONCLUSION: The nab-paclitaxel chemotherapy could achieve significant tumour responses and encourage survival in advanced NSCLC patients with tolerable toxicities. Further clinical studies are needed to explore the optimal therapy regimen and target users.

Circulating long noncoding RNA GAS5 is a novel biomarker for the diagnosis of nonsmall cell lung cancer.

The recently discovered long noncoding RNAs have the potential to regulate many biological processes, which are aberrantly expressed in many tumor types. Our previous study showed that the long noncoding RNA-growth arrest-specific transcript 5 (GAS5) was decreased in lung cancer tissue, which contributed to the proliferation and apoptosis of nonsmall cell lung cancer (NSCLC). GAS5 was also associated with the prognosis of lung cancer patients. These results suggest that GAS5 may represent a novel prognostic indicator and a target for gene therapy in NSCLC. However, the expression and diagnosis significance of GAS5 in the plasma of NSCLC patients was unknown. The plasma samples were more readily available than the tissue samples in clinical, so we designed the study to investigate the diagnosis value of GAS5 in blood samples. In our study, 90 patients with NSCLC and 33 healthy controls were included. Blood samples were collected before surgery and therapy. We extracted the free RNA in the plasma and analyzed the expression of GAS5 with quantitative reverse transcription PCR. Suitable statistics methods were used to compare the plasma GAS5 levels of preoperative and postoperative plasma samples between the NSCLC patients and healthy controls. Receiver-operating characteristic curve analysis was used to evaluate the diagnostic sensitivity and specificity of plasma GAS5 in NSCLC. The results showed that GAS5 was detectable and stable in the plasma of NSCLC patients. Furthermore, the plasma levels of GAS5 were significantly down-regulated in NSCLC patients compared with healthy controls (P = 0.000). Moreover, GAS5 levels increased markedly on the seventh day after surgery compared with preoperative GAS5 levels in NSCLC patients (P = 0.003). GAS5 expression levels could be used to distinguish NSCLC patients from control patients with an area under the curve of 0.832 (P < 0.0001; sensitivity, 82.2%; specificity, 72.7%). The combination of the GAS5 and carcinoembryonic antigen could produce an area of 0.909 under the receiver-operating characteristic curve in distinguishing NSCLC patients from control subjects (95% confidence interval 0.857-0.962, P = 0.000). We have demonstrated that GAS5 expression was decreased in NSCLC Plasma. Plasma samples were more accessible than tissue samples in clinical; therefore, GAS5 could be an ideal biomarker for the diagnosis of NSCLC.

Combination of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio is a useful prognostic factor in advanced non-small cell lung cancer patients.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) was recently shown to be a remarkable prognostic factor in tumors. Moreover, some studies have indicated that the combination of NLR and platelet to lymphocyte ratio (PLR) could be a better prognostic factor. As the combined prognostic value of NLR and PLR in non-small cell lung cancer (NSCLC) is not clear, we conducted this study to explore this further. METHODS: A total of 366 primary NSCLC patients with stage III or IV were finally included. The neutrophil, platelet, and lymphocyte counts were recorded before treatment was initiated. NLR and PLR were calculated and NLR > 2.68 or PLR > 119.50 was defined as elevated. Univariate and multivariate survival analyses were conducted to test their prognostic value. RESULTS: The median of NLR and PLR were 3.14 and 152.63, respectively, in all patients. It was indicated that PLR is linearly associated with NLR. PLR is associated with survival, but is not an independent prognostic factor. Removing NLR, PLR is an independent prognostic factor (overall survival [OS]: hazard ratio [HR] = 1.918, P = 0.003; progression-free survival [PFS]: HR = 1.822, P = 0.007 in condition of NLR ≤ 2.68). It was also indicated that elevated NLR is an independent prognostic factor (OS: HR = 1.778, P = 0.009; PFS: HR = 1.535, P = 0.022) in all patients. CONCLUSIONS: PLR is a useful complement of NLR, thus, advanced NSCLC patients could be divided into three prognostic groups prior to treatment: poor: NLR > 2.68; moderate: NLR ≤ 2.68 and PLR > 119.50; and good: NLR ≤ 2.68 and PLR ≤ 119.50.

Prognostic value of Twist in lung cancer: systematic review and meta-analysis.

BACKGROUND: Twist is identified as an epithelial-mesenchymal transition (EMT) regulator which has been considered to induce metastasis. However, the prognostic value of Twist in patients with lung cancer remains controversial. METHODS: A search of database including EMBASE, Medline, ISI Web of knowledge and PubMed was performed. Eligible articles studying on the prognostic significance of Twist were included in this meta-analysis. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were assessed to quantify the prognostic role. RESULTS: A total of five studies were included. The pooled HR for Twist was 1.949 (95% CI: 1.408-2.698, I(2)=42.7%, P<0.001), suggesting high Twist expression is associated with poor prognosis in lung cancer patients. Our sensitivity analyses suggested the robustness of the results. Neither Begg's test nor Egger's test found publication bias in any analysis. CONCLUSIONS: Overexpressed Twist in lung cancer tissue indicated poor prognosis.

Diagnostic Accuracy of CT-Guided Transthoracic Needle Biopsy for Solitary Pulmonary Nodules.

To evaluate the diagnostic accuracy of computed tomography (CT)-guided percutaneous lung biopsy for solitary pulmonary nodules. Three hundred and eleven patients (211 males and 100 females), with a mean age of 59.6 years (range, 19-87 years), who were diagnosed with solitary pulmonary nodules and underwent CT-guided percutaneous transthoracic needle biopsy between January 2008 and January 2014 were reviewed. All patients were confirmed by surgery or the clinical course. The overall diagnostic accuracy and incidence of complications were calculated, and the factors influencing these were statistically evaluated and compared. Specimens were successfully obtained from all 311 patients. A total of 217 and 94 cases were found to be malignant and benign lesions, respectively, by biopsy. Two hundred and twenty-five (72.3%) carcinomas, 78 (25.1%) benign lesions, and 8 (2.6%) inconclusive lesions were confirmed by surgery and the clinical course. The diagnostic accuracy, sensitivity, and specificity of CT-guided percutaneous transthoracic needle biopsy were 92.9%, 95.3%, and 95.7%, respectively. The incidences of pneumothorax and self-limiting bleeding were 17.7% and 11.6%, respectively. Taking account of all evidence, CT-guided percutaneous lung biopsy for solitary pulmonary nodules is an efficient, and safe diagnostic method associated with few complications.

A serum vitamin D level <25nmol/l pose high tuberculosis risk: a meta-analysis.

BACKGROUND: Low serum Vitamin D is considered to be associated with tuberculosis while the "dangerous" level was not clear. The aim of this study was to identify the association between tuberculosis and serum Vitamin D levels via synthesis of available evidence. METHODS: A search of EMBASE, Medline, ISI Web of knowledge, and Pubmed was conducted. The number of subjects of tuberculosis and no-tuberculosis groups in four Vitamin D range. Meta-analyses were performed and presented by odds ratios (ORs) and corresponding 95% confidence intervals (CIs). RESULTS: A total of 15 studies involving 1440 cases and 2558 controls were included. A significantly increased risk of tuberculosis was found in two ranges: ≤ 12.5 nmol/L: pooled OR = 4.556, 95% CI = 2.200-9.435; 13-25 nmol/L: pooled OR = 3.797, 95% CI = 1.935-7.405. No statistically significant risk of tuberculosis was found in the range of 26-50 nmol/L (pooled OR = 1.561, 95% CI =0.997-2.442). In range 51-75 nmol/L, no positive association was found (pooled OR =1.160, 95% CI = 0.708-1.900). CONCLUSIONS: This study found that a serum Vitamin D level ≤ 25 nmol/L was significantly associated with an increased risk of tuberculosis while the range of 51-75 nmol/L was not. The range 26-50nmol/L posed potential high tuberculosis risk. Future large-scale, well-designed studies are needed to verify these results.

Intratracheal administration of mitochondrial DNA directly provokes lung inflammation through the TLR9-p38 MAPK pathway.

An increasing number of studies have focused on the phenomenon that mitochondrial DNA (mtDNA) activates innate immunity responses. However, the specific role of mtDNA in inflammatory lung disease remains elusive. This study was designed to examine the proinflammatory effects of mtDNA in lungs and to investigate the putative mechanisms. C57BL/6 mice were challenged intratracheally with mtDNA with or without pretreatment with chloroquine. Changes in pulmonary histopathology, cytokine concentrations, and phosphorylation levels of p38 MAPK were assayed at four time points. In in vitro experiments, THP-1 macrophages were pretreated or not pretreated with chloroquine, TLR9 siRNA, p38 MAPK siRNA, or SB203580 and then incubated with mtDNA. The levels of cytokines and p-p38 MAPK were detected by ELISA and Western blot, respectively. The intratracheal administration of mtDNA induced infiltration of inflammatory cells, production of proinflammatory cytokines (including IL-1ß, IL-6, and TNF-α), and activation of p38 MAPK. The chloroquine pretreatment resulted in an abatement of mtDNA-induced local lung inflammation. In vitro experiments showed that the exposure of THP-1 macrophages to mtDNA also led to a significant upregulation of IL-1ß, IL-6, and TNF-α and the activation of p38 MAPK. And these responses were inhibited either by chloroquine and TLR9 siRNA or by SB203580 and p38 MAPK siRNA pretreatment. The intratracheal administration of mtDNA induced a local inflammatory response in the mouse lung that depended on the interactions of mtDNA with TLR9 and may be correlated with infiltrating macrophages that could be activated by mtDNA exposure via the TLR9-p38 MAPK signal transduction pathway.

The treatment strategy for tracheoesophageal fistula.

With the development of endoscopic techniques, the treatment of tracheoesophageal fistula (TEF) has made marked progress. As surgical intervention is often not an advisable option due to advanced malignancy and poor performance status of the patients, bronchoscopic intervention provides a good choice to palliate symptoms and reconstruct the airway and esophagus. In this review, we focus on the application of interventional therapy of TEF, especially the application of airway stenting, and highlight some representative cases referred to our department for treatment.

Prognostic value of FGFR1 gene copy number in patients with non-small cell lung cancer: a meta-analysis.

BACKGROUND: A number of studies have investigated the relationship between fibroblast growth factor receptor1 (FGFR1) gene copy number and survival in non-small cell lung cancer (NSCLC) patients. However, conclusions reported by different parties seem to be inconsistent, especially regarding the differences among different histopathologic subtypes. To derive a more precise estimate of the prognostic significance of FGFR1 gene copy number, we have reviewed published studies and carried out a meta-analysis. METHODS: The meta-analysis was conducted in accordance with PRISMA guidelines. The required data for estimation of individual hazard ratios (HRs) for survival were extracted from the publications and an overall HR was calculated. RESULTS: We identified 6 eligible studies, all dealing with NSCLC. The global quality score ranged 32.5-80%, with a median of 53.33%. For FGFR1 amplification in three studies including differed according to histological type, the overall RR was 0.86 which 95% confidence interval (CI) was 0.75 to 0.99 and P value was 0.048. Combined HR for the six evaluable studies was 1.17 (95% CI: 0.95 to 1.43). In the subgroup of squamous cell lung cancer (SQCC), the combined HR was 1.24 (95% CI: 0.89 to 1.73). For the Asian populations' studies, the combined HR was 1.67 (95% CI: 1.1 to 2.52). CONCLUSIONS: FGFR1 amplification significantly was more frequent in SQCC. FGFR1 was not associated with poorer survival in patients with NSCLC. Furthermore studies will be needed in terms of survival implications.

Diagnostic and prognostic significance of lysophosphatidic acid in malignant pleural effusions.

BACKGROUND: Lysophosphatidic acid (LPA) is an important extracellular signal transmitter and intracellular second messenger in body fluids. It can be detected in the ascitic fluid of patients with ovarian cancer. Increasing evidence shows that LPA can stimulate cancer cell proliferation and promote tumor invasion and metastasis. Our study aimed to evaluate the diagnostic value of LPA in differentiating between malignant pleural effusions (MPEs) and benign pleural effusions (BPEs) and to evaluate the association between the level of LPA in MPE and the prognosis of lung cancer patients. PATIENTS AND METHODS: The level of LPA in the pleural effusions (PEs) of 123 patients (94 MPE, 29 BPE) with lung cancer was evaluated using an enzyme-linked immunosorbent assay. The performance of LPA was analyzed by standard Receiver operator characteristic curve (ROC) analysis methods, using the area under the curve (AUC) as a measure of accuracy. Overall survival (OS) curves and progression-free survival (PFS) curves were based on the Kaplan-Meier method, and the survival differences between subgroups were analyzed using the log-rank or Breslow test (SPSS software). A multivariate Cox proportional hazards model was used to assess whether LPA independently predicted lung cancer survival. RESULTS: The levels of LPA differed significantly between MPE (22.08±8.72 µg/L) and BPE (14.61±5.12 µg/L) (P<0.05). Using a cutoff point of 18.93 µg/L, LPA had a sensitivity of 60% and a specificity of 83% to distinguish MPEs from BPEs with an AUC of 0.769±0.045 (SE) (P=0.000) (95% CI, 0.68-0.857). In the three pathological types of lung cancer patients with MPE, there were no significant associations between LPA levels and the length of PFS and OS (P=0.58 and 0.186, respectively). Interestingly, in the patients with MPE caused by lung adenocarcinoma there were significant associations between the LPA levels and the PFS and OS (P=0.018 and 0.026, respectively). Multivariate analysis showed that the LPA level was an independent prognostic factor for PFS in lung adenocarcinoma. CONCLUSIONS: Our results indicate that LPA can be used as a new biomarker for the diagnosis of MPE caused by lung cancer and that higher levels of LPA are related to shorter PFS in adenocarcinoma of the lung.

[Vascular normalization and cancer immunotherapy].

Immunotherapies, as a promising anticancer therapy stratrgy, has been paid more and more attentions. However, the abnormal tumor vasculature creates a hypoxic microenvironment that make immune cells toward immune suppression. The immunosuppressive microenvironment seems to impede the development of immunotherapies. Hence, normalization tumor vascular by anti-angiogenesis properly could improve the immunosuppressive miroenvironment. Consequently, the efficacy of the immunotherapies was enhanced. Here, we discuss the effects of vascular normalizing on tumor immunity and propose a potentially strategy to re-engineer the tumor-immune microenvironment and improve cancer immunotherapy.