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Currently immunotherapy is considered a cutting edge pharmaceutical treatment for non-small cell lung cancer. Tumor profile plays a crucial role in identifying the correct patient group. Therefore, initial biopsies and re-biopsies are necessary in order to identify the expression of programmed death-ligand-1. This information is crucial and therefore all future immunotherapy studies have to be built upon a specific statistical model which associates the tumor profile and tumor profile expression along with treatment efficiency. We present a novel statistical methodology for future immunotherapy studies of non-small cell lung cancer.

The knowledge of airway length is the theoretical basis in the diagnosis and management of airway disease. The objective of this study is to measure the length of trachea and left and right main bronchus in Chinese Shanghai population. A total of 153 consecutive adult patients with minor pulmonary disease in Xinhua hospital were enrolled for bronchoscopy examination. Measurements were conducted on head and neck neutral position and height, weight and age for each patient were recorded either. Student t test and multiple linear regression was used to compare means between males and females and to analyze correlation among height, weight, sexual dimorphism and the lengths of the trachea and bronchus. The lengths of the trachea and left main bronchus are significantly different between male and female patients (P

Introduction: Immunotherapy is being used for the past five years either as first line or second line treatment with great results. Chemotherapy and radiotherapy have been also used as combination to immunotherapy to further enhance this type of treatment. Intratumoral treatment has been previously proposed as a treatment option for certain non-small cell lung cancer patients. Patients and Methods: We recruited in total seventy four patients with non-small cell lung cancer in their second line treatment who received only chemotherapy in their first line treatment with programmed death-ligand-1 ≤ 50. Only adenocarcinoma or squamous cell carcinoma, and all negative for epidermal growth factor receptor, anaplastic lymphoma kinase, proto-oncogene tyrosine-protein kinase-1 and proto-oncogene B-Raf. Data were first examined with descriptive statistics choosing frequencies for categorical variables and histograms for the continuous ones. Twenty five received only intravenous immunotherapy and forty-nine intravenous cisplatin with immunotherapy. Data were first examined with descriptive statistics choosing frequencies for categorical variables and histograms for the continuous ones. Results: The relationships between changes of performance status and disease progression were examined via a single correspondence analysis. The two-dimensional scores (coordinates) derived from the correspondence analysis were then regressed against the predictors to form distinct splits and nodes obtaining quantitative results. The best fit is usually achieved by lowering exhaustively the AICc criterion and looking in parallel the change of R2 expecting improvements more than 5%. both types of therapy are capable of producing best ameliorative effects, when either the programmed death-ligand-1 expression or parenchymal site in joint with low pack years are present in the sampling data. Conclusions: Intratumoral treatment combination with cisplatin plus immunotherapy indifferent of nivolumab or pembrolizumab combination is an effective choice. In specific for those with endobronchial lesions. Moreover; patients with programmed death-ligand-1 ≥ 50 had their performance status and disease progression improved over the eight month observation.

Introduction: Diagnosis of lung nodules is still under investigation. We use computed tomography scans and positron emission tomography in order to identify their origin. Patients and Methods: In our retrospective study, we included 248 patients with a single lung nodule or multiple lung nodules of size ≥1 cm. We used a radial-endobronchial ultrasound and a C-Arm. We used a 1.1 mm cryoprobe versus a 22G needle vs. forceps/brush. We compared the sample size of each biopsy method with the number of cell-block slices. Results: Central lesions indifferent to the method provided the same mean number of cell-block slices (0.04933–0.02410). Cryobiopsies provide less sample size for peripheral lesions due to the higher incidence of pneumothorax (0.04700–0.02296). Conclusion: The larger the lesion ≥2 cm, and central, more cell-blocks are produced indifferent to the biopsy method (0.13386–0.02939). The time of the procedure was observed to be less when the C-Arm was used as an additional navigation tool (0.14854–0.00089).

Bronchoscopic lung volume reduction (BLVR) is a novel approach for treatment of emphysema. Several techniques are available to accomplish BLVR including Bronchoscopic Vapor Thermal Ablation (BVTA). This technique is easy to perform and considered safe due to its gradual effect. We discuss BTVA in detail in this editorial.We discuss our experience with BTVA in detail including patient selection, equipment, procedure, post-procedural care and complications. We also review the literature to determine the pros and cons for its use. Other modalities such as endobronchial valves, coils and lung sealants are also briefly discussed.Vapor ablation is a novel and safe approach in inducing lung volume reduction in emphysema patients. The effects are gradual, and therefore potentially making it safer than other minimally invasive modalities. Pneumonitis and infection are common side effects. Just as in other BLVR techniques, a case by case evaluation is needed to determine the right candidate for BTVA. Further larger studies are needed before BTVA becomes standard of care in treatment of patients with emphysema.

Immunosuppressive chemoresistance is a major burden in lung cancer. Recent data reveal that long noncoding RNAs (lncRNAs) present in the lung tumor microenvironment are implicated in chemoresistant-related immune deregulation, and metastasis but their exact pathogenic role is still unknown. In this study, we investigate the role of lncRNA PCAT-1 in chemoresistant immunosuppression and its involvement in tumor stroma remodeling. Findings reveal PCAT-1 to regulate Kras-related lung chemoresistance through increased expression of the immunosuppressive micrornas miR-182/miR217 in lung tissues, thus promoting a pre-metastatic niche formation and a subsequent increase in lung metastatic burden. Elevated expression of PCAT-1 negative regulates p27/CDK6 expression by inducing G0/G1 cell cycle arrest through AMPK augmentation, contributing to a tumor-promoting status. Furthermore, PCAT-1 triggered fibroblast differentiation followed by CAF/myofibroblast secretion in TME triggering a CD133/SOX2-related stem cell phenotype. Subsequent PCAT-1 knockdown impaired CAF-mediated stromal activation, and reversed chemoresistance and tumor growth in vivo. Overall, these findings demonstrate the versatile roles of PCAT-1 in sustaining lung immunosuppressive neoplasia through tumor microenvironment remodeling and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumors.

Airway obstruction can be induced either by cancer or benign causes. Benign bronchus stenosis is being caused by: tuberculosis, sarcoidosis, vasculitis, and chronic inflammation due to smoking in c...

Stenosen der zentralen Atemwege durch bosartige Tumore konnen zu qualender Luftnot fuhren. Chemo- und Strahlentherapie wirken verzogert. Mit endoskopischer Dilatation, Gewebeabtragung durch Laser, Argonplasma-Koagulation (APC) oder Kryosonde sowie durch Einlage von Stents kann die Lebensqualitat sofort massiv verbessert werden. Gutartige Stenosen sind als Folge von lokalen Traumata wie Intubationen oder Entzundungen haufig. Sie werden oft erst spat bemerkt und beispielsweise als Asthma fehldiagnostiziert. Kurzstreckige narbige Stenosen konnen gut und langanhaltend endoskopisch mit Laser oder elektrischem Messer behandelt werden. Granulationsgewebe wird wie Tumorgewebe abgetragen, verbunden mit einer lokalen Gabe antiproliferativer Medikamente. Langstreckige, gutartige Strikturen kann man nur mit Stents erweitern. Man sollte aber unbedingt vorher die Moglichkeit der chirurgischen Resektion diskutieren, da langfristig mit Nebenwirkungen durch Stents zu rechnen ist. Individualisierte Stents konnten in naher Zukunft die therapeutischen Moglichkeiten verbessern.

Objective: To investigate the development of bronchoscopy in China and compare it with its application in the early 21st century. Methods: The data collection was based on questionnaires. Three hundred and nineteen hospitals, which distributed across 30 provinces and 130 cities, were included in the study. Data about the application of bronchoscopy in Shanghai and Hunan province in the early 21st century are also involved for comparison. Results: The median period of performing diagnostic and therapeutic bronchoscopy was 19.7±11.0 and 7.4±7.0 years, respectively. On average, about 155.2 cases and 28.4 cases received diagnostic and therapeutic bronchoscopy in each hospital per month. The average area and number of the examination room was 122.7m2 and 2.2m2, respectively. More examination items were performed in specialty hospitals than those in general hospitals (P0.05). On the other side, the whole amount of diagnosis and therapeutic items in teaching hospitals was slightly higher than that in non-teaching hospitals (P

Tumor immunotherapy is a key therapeutic paradigm for the treatment of several malignancies. However, in metastatic lung cancer, classical immunotherapy regimes are ineffective due to regulatory T cell (Treg)-related immunosuppression and tumor relapse.To address this issue, we designed specific biocompatible Treg-targeted nanocarriers (NCs) as a model of immune-based nanotherapy, in order to target Treg-related immunosuppression in the lung tumor microenvironment. This is achieved through the combination of Dasatinib and Epacadostat integrated into biodegradable nanosomes which can inhibit and reverse Treg-supporting immunosuppression. Flow cytometry and immunofluorescence analysis, PET/CT scan, PTT/PA imaging and the Balb/c tumor model were used to explore the anti-tumor effect of Treg-targeted NCs both in vitro and in vivo.Findings reveal that NC treatment triggered substantial tumor cell apoptosis and drastically decreased tumor volume followed by downregulation of Ki-67 antigen expression, respectively. Drug circulation time was also increased as shown by biodistribution analysis accompanied by greater accumulation in lung and peripheral tissues. Intratumoral Th1 cytokines' expression was also increased, especially TNF-A, IL-12 by 42%, and IL-6 by 18% compared to PBS treatment. In addition, the presence of mature CD80Overall, our findings present a novel nano-enabled platform for the inhibition of Treg-dependent immunosuppression in NSCLC and provide a novel nanotherapeutic strategy for the treatment of metastatic neoplasia.

Background: Inhaled drugs have been available in the market for several years and for several diseases. Drugs for chronic obstructive pulmonary disease, cystic fibrosis, and diabetes have been used for several years. In the field of drug modification, these drugs range from tablets to aerosol. Methods: Milling as used to break down the tablets to powder and nebulisers are used to produce aerosol droplets. A mastersizer was used to measure the mass median aerodynamic diameter of the aerosol droplets. Results: Apremilast produced mmad diameters (2.43 μm) without any statistical difference between the different jet-nebulizers. The residual cup B contributed to greater mmad diameters as the 95% interval of mean values, based on those the ANOVA mean square clearly indicated, followed by cups C and F. The previous interval plot is much better clarified when the interaction means between drug and residual cap are plotted. The residual cups B, C and F produce mmad between (2.0–3.2). Conclusion: In the current research study we demonstrated our methodology to create apremilast powder and produce apremilast aerosol droplets with different nebulisers and residual cups.

Lung cancer is diagnosed at a late stage due to lack of early disease symptoms. Therefore an efficient treatment is necessary for prolonged disease free survival.In our study we recruited 124 patients NSCLC patients with adenocarcinoma and squamus cell carcinoma. All recuited patients had Programmed death-ligand 1 expression ≥50 (PD-L1)with DAKO technique. Immunotherapy was administered with as first line treatment. Re-biopsies were performed in the main lung lesion every 4 months with the restaging of the patient and also in the metastastic sites in other organs that occurred during treatment. PD-L1 expressed was evaluated in the biopsies of the metastatic sites.It appears thereafter that the PD-L1 expression could easily be claimed as a promising bio-index with a cutoff value 65, below which a negative prognosis of the disease progress will be evident and above that value a positive continuation of the disease will be prominent.The findings of this study suggest that the PD-L1-65 index works adequately either concerning the neo-metastatic sites or the patient disease responses. Re-biopsies in new metastastic sites are necessary since we probably have a new cancer and chemotherapy should be added. More studies should confirm are results and change the NSCLC treatment approach of these patients.

The study aimed to explore the effect of a bronchoscopic simulator-based comprehensive teaching method in the training of flexible bronchoscope-guided intubation for suspected lung cancer patients for doctors without bronchofibroscopic operation background.We designed a prospective self-control study involved in 35 trainees from the Navy Military Medical University's affiliated hospital to evaluate flexible bronchoscope-guided intubation's training outcome. Before and after the practice training, we recorded the flexible bronchoscope passing time from nasal to visible glottis and carina, tracheal placement tube, and ventilation.All 35 trainees could complete flexible bronchoscope-guided intubation independently after training.The bronchial diagnosis for suspected lung cancer patients and treatment-based model can be widely applied in tracheal intubation training.

Airway stenting has been practiced for several decades. It is one of the most common procedures performed by interventional pulmonologists. Typically, these stents are implanted to maintain the tubular patency of the tracheobronchial tree. They are only considered as a temporizing measure, or when a surgical option cannot be pursued. Through the past few decades, a number of metallic airway stents have been introduced into the market. First generation stents were comparatively simplistic and crafted from stainless steel. The latest generation of metallic airway stents are hybrid in nature and constructed with complex alloys. As airway stenting become more widely practiced, concerns arose regarding their safety. However, with improved understanding of stent-airway interactions, advancements in biomedical engineering, and a larger emphasis on post procedural care, the use of metallic endobronchial stents has been resurrected. We present the history, technological advancement, and contemporary indications of metallic airway stents.

A fifty year old male was diagnosed with bronchial HPV. He was treated with local interventional treatment argon plasma coagulation and subcutaneous injections bevacizumab. Spraying of the regions followed with a specially designed catheter with interferon-α (2b). Systematic treatment of esomeprazole was also administered. After six months the patient is disease free and on close follow-up.

Background/introduction In contrast to patients who present with advanced stage lung cancer and associated poor prognosis, patients with early-stage lung cancer may be candidates for curative treatments. The results of the NELSON lung cancer screening trial are expected to stimulate the development and implementation of a lung cancer screening strategy in most countries. Widespread use of chest computed tomography scans will also result in the detection of solitary pulmonary nodules. Because reliable biomarkers to distinguish between malignant and benign lesions are lacking, tissue-based histopathological diagnostics remain the gold standard. In this study, we aimed to establish a test to assess the predictive ability of DNA hypermethylation of SHOX2 and PTGER4 in plasma to discriminate between patients with 1.) lung cancer, 2.) benign lesions, and 3.) patients with chronic obstructive pulmonary disease (COPD). Patients and methods We retrospectively analysed SHOX2 and PTGER4 methylation in 121 prospectively collected plasma samples of patients with lung cancer (group 1A), benign lesions (group 1B), and COPD without nodules (group 2). Results PTGER4 DNA hypermethylation was more frequently observed in patients with lung cancer than in controls (p = 0.0004). Results remained significant after correction for tumour volume, smoking status, age, and eligibility for the NELSON trial. Conclusions Detection of methylated PTGER4 in plasma DNA may serve as a biomarker to support clinical decision-making in patients with pulmonary lesions at lung cancer screening in high-risk populations. Further exploration in prospective studies is warranted.

Introduction: Novel technologies are currently used for lung cancer diagnosis. EBUS-TBNA 22G is considered one of the most important tools. However; there are still issues with the sample size.Patients and Methods: 223 patients underwent EBUS-TBNA with a 21G Olympus needle, 22GUS Mediglobe and 22GUB Mediglobe. In order to evaluate the efficiency of 22GUB novel needle design. In order to evaluate the sample size of each needle, we constructed cell blocks and measured the different number of slices from each biopsy site. Results: The 22GUB novel needle had similar and larger number of slices from each biopsy site compared to 21G needle. Discussion: Firstly as a novel methodology we used the number of slices from the constructed cell blocks in order to evaluate the sample size. Secondly, we should seek novel needle designs and not only concentrate on the volume of the sample size.

Immunosuppressive chemoresistance is a major barrier in lung cancer treatment. However, the immunosuppressive mechanisms responsible for lung cancer cell chemoresistance and tumor relapse are still unknown. In this study, we introduce a model of precise immunosuppressive-based nanotherapy by designing and delivering biocompatible MDSC-targeted nanocarriers (NCs) into the lung tumor microenvironment. This is accomplished by conjugating l-Norvaline and Sunitinib integrated into biodegradable nanosomes in order to facilitate inhibition of tumor-supporting immunosuppression. Findings show that treatment with NCs increased apoptosis and significantly reduced tumor volume and Ki-67 antigen expression respectively. Biodistribution analysis revealed an increase in drug circulation time, as well as a greater accumulation in lung and peripheral tissues. Furthermore, an upregulation of tumor infiltrating lymphocytes expression was observed, especially CD8+ T cells by 27%, and CD4+ T cells by 7% compared to PBS treatment. The presence of CD161+ (NK1.1) cells revealed NK cell activation followed by decreased MDSC infiltration and MDSC subsets were characterized by the reduction of Gr/CD11b cell population in blood and tissue samples. In addition, these nanospheres, showed increased PTT efficiency and tumour targeting ability as evidenced by highly efficient tumour ablation under near infrared (NIR) exposure. Significant tumor reduction was observed due to recruitment of cytotoxic T-lymphocytes, followed by downregulation of immunosuppressive Foxp3+ Treg cells. Taken together, our findings provide a novel nanodrug delivery strategy for the inhibition of MDSC-related immunosuppression in lung tumor microenvironment and provide a new approach for the efficient treatment of metastatic cancer.

Introduction: Non-small cell lung cancer is still diagnosed at a late stage although we have new diagnostic equipment such the radial endobronchial ultrasound, convex probe endobronchial ultrasound, and electromagnetic navigation. The diagnostic techniques have been upgraded with rapid on-site evaluation (ROSE) and currently from 2014 real-time elastography is being evaluated as a ROSE technique.Areas covered: A thorough search was performed on PubMed and Scopus with the following key words: elastography, strain ratio, convex probe EBUS, endoscopic ultrasound (EUS), elastography. In the current mini review, we will focus on published data regarding elastography with the convex probe endobronchial ultrasound in two different systems and comment on this future ROSE technique. Elastography, strain ratio, and factors such as(I) margin (indistinct or distinct); (II) shape (oval or round); (III) short-axis size less or more than 1 cm; (IV) presence or absence of central hilar structure (CHS); (V) echogenicity (homogeneous or heterogeneous); and (VI) presence or absence of coagulation necrosis sign are presented in our review based on published literature.Expert opinion: Current data indicate that we can have up to 93% sensitivity and specificity of real-time elastography and strain ratio for the evaluation of benignancy and malignancy; however, sample biopsy is still necessary. For now, we can only reduce the number of punctures.

Foreign body removal is a challenging procedure. Firstly we have to identify properly the foreign body and the position of the obstruction. Secondly we have to choose the proper removal equipment and finally the appropriate method of patient ventilation during the procedure. In our case report we present a challenging procedure with the removal of a metallic needle with minimum resources and equipment in a young girl in Djibouti, Africa. Keywords: Foreign body, Bronchoscopy, Biopsy forceps

We report herein on two cases where high-risk osseous foreign bodies that incarcerated or penetrated the bronchial wall. The foreign bodies were unable to be removed via flexible bronchoscope (FB), with the foreign bodies close to the pulmonary artery and aortic artery. After preoperative evaluation and planning with the virtual bronchoscopic navigation (VBN) system, the airway foreign bodies were extracted effectively and safely using advanced therapeutic endoscopic technique by rigid bronchoscope (RB), thus avoiding the surgical thoracotomy. Keywords: Virtual bronchoscopic navigation, LungPoint, Foreign body, High risk, Rigid bronchoscope, Removal, Artery

We use pulmonary interventional procedures for the diagnosis of pulmonary diseases either for benign or malignant lesions. Flexible bronchoscopy with or without radial endobronchial ultrasound, convex-probe endobronchial ultrasound and electromagnetic navigation are procedures performed in centers with experience in diagnostic pulmonary medicine. The method of sedation and ventilation is very important in order to avoid or handle with success complications. Proper respiration during pulmonary (or other interventional) procedures is a key factor. Apart from the proper sedation method we have to choose the proper ventilation method which decides respiratory movement. Superimposed high-frequency jet ventilation (SHFJV) is supposed to be safe and effective in clinical practice. Although this perception is commonly accepted, there is no study proving its safety on the basic of reliable data. We analyzed the data of 100 patients in different interventional settings (bronchoscopy with or without navigational approach, left atrial appendage closure (LAAC) or intracardiac catheterization) using nasal SHFJV. Mainly analyzed were capillary ABG-Data at the beginning and end of the intervention under sedation. The aim was to analyze if a risk scenario for the patient by using the nasal SHFJV can be derived by measuring the changes of pCO2, pO2, cBase Excess, cHCO3 and PH. Due to our data we conclude that this method of ventilation can be easily and safely used in interventional medicine for patients with all kind of comorbidities such as; chronic respiratory disease, lung cancer, interstitial lung disease, structural heart disease and heart failure. CA extern

Juergen Hetzel,1 Michael Boeckeler,1 Marius Horger,2 Ahmed Ehab,1 Christopher Kloth,2 Robert Wagner,3 Lutz Freitag,4 Dirk-Jan Slebos,5 Richard Alexander Lewis,6 Maik Haentschel1 1Division of Haematology, Oncology, Rheumatology, Immunology and Pulmonology, Department of Internal Medicine, 2Department of Diagnostic and Interventional Radiology, 3Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University Tuebingen, Tuebingen, Germany; 4Division of Pulmonology, University Hospital Zurich, Zurich, Switzerland; 5Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 6National Pollen and Aerobiology Research Unit, Institute of Science and the Environment, University of Worcester, Worcester, UK Background: Lung volume reduction (LVR) improves breathing mechanics by reducing hyperinflation. Lobar selection usually focuses on choosing the most destroyed emphysematous lobes as seen on an inspiratory CT scan. However, it has never been shown to what extent these densitometric CT parameters predict the least deflation of an individual lobe during expiration. The addition of expiratory CT analysis allows measurement of the extent of lobar air trapping and could therefore provide additional functional information for choice of potential treatment targets. Objectives: To determine lobar vital capacity/lobar total capacity (LVC/LTC) as a functional parameter for lobar air trapping using on an inspiratory and expiratory CT scan. To compare lobar selection by LVC/LTC with the established morphological CT density parameters. Methods: 36 patients referred for endoscopic LVR were studied. LVC/LTC, defined as delta volume over maximum volume of a lobe, was calculated using inspiratory and expiratory CT scans. The CT morphological parameters of mean lung density (MLD), low attenuation volume (LAV), and 15th percentile of Hounsfield units (15%P) were determined on an inspiratory CT scan for each lobe. We compared and correlated LVC/LTC with MLD, LAV, and 15%P. Results: There was a weak correlation between the functional parameter LVC/LTC and all inspiratory densitometric parameters. Target lobe selection using lowest lobar deflation (lowest LVC/LTC) correlated with target lobe selection based on lowest MLD in 18 patients (50.0%), with the highest LAV in 13 patients (36.1%), and with the lowest 15%P in 12 patients (33.3%). Conclusion: CT-based measurement of deflation (LVC/LTC) as a functional parameter correlates weakly with all densitometric CT parameters on a lobar level. Therefore, morphological criteria based on inspiratory CT densitometry partially reflect the deflation of particular lung lobes, and may be of limited value as a sole predictor for target lobe selection in LVR. Keywords: emphysema, chronic obstructive pulmonary disease, high-resolution computed tomography, lung volume reduction

Background: Despite the proof of principle that gene therapy can cure various monogenic diseases, limited clinical progress has been noted for gene therapy of the respiratory system. Certain anatomic features of the lungs, along with the suboptimal gene delivery vehicles utilized up to now, have significantly delayed successful clinical practice. Thus, the need for additional improvements towards safety and efficacy of the procedure is indispensable. Objective: The objective of this work was to review the progress and limitations of gene therapy in the treatment of lung disease with a focus on monogenic disease, chronic obstructive pulmonary disease and asthma and to present studies that provide a proof of principle that it works in different model systems and in patients. Method: A thorough search was performed on the aforementioned topic using Pubmed in order to identify relevant manuscripts. Several gene therapy studies for monogenic disorders affecting other organs or systems were also taken into consideration. Results: A hundred and thirty one papers were included. Inclusion criteria regarded novel gene transfer technologies of the past decade, as well as publications outlining the pitfalls that precluded earlier successful implementation of gene therapy for pulmonary diseases. Conclusion: Current gene transfer protocols and vector design require additional amelioration. The rapidly evolving and much promising technology of CRISPR/Cas9 might possibly overcome the hurdles posed to date for effective implementation of gene therapy and become the basis for the onset of new clinical trials.

Introduction: Stents have been used for quite some time for the treatment of benign and malignant airway stenosis. Silicon stents are preferred for benign situations, whereas metallic self-expanding stents are preferred for malignant comorbidities. Patient and methods: In general, stents can be placed in different approach directions, although in pulmonary medicine it is logical to apply only antegrade techniques – until now. A 63-year-old patient, 168 cm height and 53 kg weight on referral, suffered chronical diseases. The patient was diagnosed with a papillary thyroid carcinoma in 1989, which was treated by resection and radiotherapy. In the following years, she developed a stenosis of the esophagus. The decision to try endobronchial stenting was made upon the plan to close that fistula with a pedicled omentum majus replacement through the diaphragmal opening of the esophagus. This surgical plastic needed an abutment and a secured continuous airway replacement above the tracheostoma level. A Freitag stent (FS), 11 cm in length (110–25–40) and an inner diameter of 13 mm, was placed successfully retrograde into the trachea and completely bridged the big fistula. Unfortunately the patient passed away due to pulmonary infections after several weeks. Discussion: In this case report, a successful but unusual case of retrograde stent placement of a modified FS is presented. OA gold

Immunosuppressive chemoresistance is a major challenge in lung cancer treatment. Exosomes present in the tumor microenviroment are implicated in chemoresistant-related immune suppression, and metastasis but the exact pathogenic role of lung-derived exosomes is still uncertain. Recent reports reveal that lung cancer pathogenesis is strictly associated with a exosomal tumor supportive status and a dysfunctional immune system. In this study, we investigate the role of Kras-derived exosomes in chemoresistant immunosuppression in which neoplastic cells create a metabolic-sustained microenvironment. Findings reveal that Kras-derived exosomes induce regulation of SMARCE1/NCOR1 chromatin remodeling genes promoting pre-metastatic niche formation in naive mice and consequently increase lung metastatic burden. Furthermore, exosomal Kras inhibition downregulated transcription factor BACH2/GATA-3 expression in lung tumor tissues by shifting pyruvate/PKM2 dependent metabolism, contributing to a tumor-restraining status. Further co-treatment with carboplatin triggered RIP3/TNFa dependent necroptosis in ex vivo cells accompanied by differential expression of immunosuppressive miR-146/miR-210 regulators in metastatic lung cancer patients. Overall, these findings demonstrate the multifaceted roles of Kras-derived exosomes in sustaining lung immunosuppressive metastasis and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumors.

Hemoptysis is a frequently encountered symptom in many clinical settings, and etiologic diagnosis can sometimes prove challenging. Bronchoscopy may not promptly reveal the source or the cause of bleeding and few reports have focused so far on the abnormalities of bronchial mucosa vasculature that may unveil the underlying pathophysiology. In this special feature article, we present a series of cases presenting with hemoptysis after angiographic interventions in the thoracic vessels. Localized hyperemia and vascular dilatations in the bronchial mucosa observed during bronchoscopy as unique findings became clues enabling the correct diagnosis and management. We suggest the relevant pathophysiological mechanisms and discuss the available published experience on similar clinical entities.

Airway stenting has been practiced for several decades. It is one of the most common procedures performed by interventional pulmonologists. Typically, these stents are implanted to maintain the tubular patency of the tracheobronchial tree. They are only considered as a temporizing measure, or when a surgical option cannot be pursued. Through the past few decades, a number of metallic airway stents have been introduced into the market. First generation stents were comparatively simplistic and crafted from stainless steel. The latest generation of metallic airway stents are hybrid in nature and constructed with complex alloys. As airway stenting become more widely practiced, concerns arose regarding their safety. However, with improved understanding of stent-airway interactions, advancements in biomedical engineering, and a larger emphasis on post procedural care, the use of metallic endobronchial stents has been resurrected. We present the history, technological advancement, and contemporary indications of metallic airway stents.

Lung cancer remains the leading cause of cancer-related deaths and despite extensive research, the survival rate of lung cancer patients remains significantly low. Recent data reveal that aberrant Kras signaling drives regulatory T cells (Tregs) present in lung tumor microenvironment to establish immune deregulation and immunosuppression but the exact pathogenic mechanism is still unknown. In this study, we investigate the role of oncogenic Kras in Treg-related immunosuppression and its involvement in tumor-associated metabolic reprogramming. Findings reveal Tregs to prompt GATA3/NOS2-related immunosuppression via STING inhibition which triggers a decline in CD4+ T infiltration, and a subsequent increase in lung metastatic burden. Enhanced Treg expression was also associated with low T/MDSC ratio through restriction of CD8+CD44+CD62L- T effector cells, contributing to a tumor-promoting status. Specifically, TIM3+/LAG3+ Tregs prompted Kras-related immunosuppressive chemoresistance and were associated with T cell dysfunction. This Treg-dependent immunosuppression correlated with CD8 T cell exhaustion phenotype and ILC2 augmentation in mice. Moreover, enhanced Treg expression promoted activation-induced cell death (AICD) of T lymphocytes and guided lymph node metastasis in vivo. Overall, these findings demonstrate the multifaceted roles of Tregs in sustaining lung immunosuppressive neoplasia through tumor microenvironment remodeling and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumors.

There is a paucity of data concerning the benefit of bronchoalveolar lavage (BAL) for the diagnosis of suspected peripheral lung cancer (PLC). The aim of this study was to investigate the diagnostic value of BAL for the diagnosis of suspected PLC.All flexible bronchoscopies that included BAL among other modalities (brush, forceps, washing) for the diagnosis of a suspected PLC performed between 2009 and 2013 were analyzed in this retrospective study.A total of 260 patients were included. Malignancy was present in 61%. BAL's sensitivity for the diagnosis of malignancy was 29%, and overall diagnostic yield of BAL was 46%. However, only 1% of cancer diagnoses would have been missed in the absence of BAL. In the multivariable analysis, the size of lesion (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.02-1.33; P = .023), the presence of bronchus sign (OR, 4.73; 95% CI, 1.06-21.08; P = .042), and the presence of mediastinal/hilar lymphadenopathy (OR, 3.37; 95% CI, 1.53-7.41; P = .002) were associated with improved BAL true-positive ratio relating to diagnosis of malignancy. However, the effect of lesion size on sensitivity was small (area under the curve, 0.31; 95% CI, 0.23-0.40; P .001). Ground-glass lesions were not associated with improved BAL diagnostic value. The number needed to test for BAL for the diagnosis of malignancy or pulmonary infection was 37.Conventional BAL has a low diagnostic value for the diagnosis of suspected PLC, and the low number needed to test does not qualify BAL as a recommended routine investigation for the diagnosis of suspected PLC for either solid or ground-glass lesions.