Comparison of a 22G Crown-Cut Needle with a Conventional 22G Needle with EBUS Guidance in Diagnosis of Sarcoidosis.

INTRODUCTION: Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a standard procedure in cases of enlarged mediastinal lymph nodes. Recently, new tools were developed aiming to improve the diagnostic yield. A novel crown-cut needle is considered to obtain tissue cores which can be beneficial for the evaluation by the pathologist. This study aimed to compare the novel 22G crown-cut needle with a conventional 22G needle with EBUS guidance in the diagnosis of sarcoidosis. METHODS: We designed a single-center prospective randomized clinical trial between March 2020 and January 2021 with 30 patients with mediastinal lymphadenopathy and suspected sarcoidosis. RESULTS: 24 patients (mean age 49.5 vs 54.1, mean FVC 73.7% vs 86.7%, mean DLCO 72.4% vs 72.5% for crown-cut needle vs conventional needle, respectively) were diagnosed with sarcoidosis. In the remaining six patients, sarcoidosis was reasonably excluded. The diagnostic yield for sarcoidosis was 77% with the crown-cut needle vs. 82% with the conventional needle (p > 0.05). In patients with histopathologic hallmarks typical of sarcoidosis (n = 19), the crown-cut needle was superior in detecting granulomas (8.3 vs 3.8 per cytoblock, p < 0.05) and histiocytes (502 vs 186 per cytoblock, p < 0.05). Four of seven bronchoscopists experienced difficulties passing through the bronchial wall with the crown-cut needle and one episode of bleeding occurred in this group which made interventions necessary. CONCLUSIONS: Despite equivalence in diagnostic accuracy, the crown-cut needle was superior to the conventional needle in detecting granulomas and histiocytes. This indicates greater potential for obtaining higher quality sample material with the crown-cut needle in cases of granulomatous inflammation.

[Recommendations for Performing Bronchoscopy in Times of the COVID-19 Pandemic - Update 12/2020]. / Empfehlungen zur Durchführung einer Bronchoskopie in Zeiten der COVID-19-Pandemie: Update 12/2020.

The SARS-CoV-19 pandemic continues to be globally related with significant morbidity and mortality, making protective measures to prevent transmission of the virus still necessary. Healthcare employees are exposed to a higher risk of infection and this is particularly true when performing aerosol-generating procedures such as bronchoscopy.Since the publication of recommendations for performing a bronchoscopy in the times of COVID-19 more than six months ago, the risk situation has not changed significantly, but due to the considerable gain in knowledge in the meantime, an update of the recommendations was necessary.The updated recommendations include the reduction of aerosol formation, the personal protection of the people involved in the procedure, as well as measures to better organize the processes in the endoscopy suite in order to perform bronchoscopic procedures securely even in times of COVID-19.

[Recommendations for Performing Bronchoscopy in Times of the COVID-19 Pandemic]. / Empfehlungen zur Durchführung einer Bronchoskopie in Zeiten der COVID-19-Pandemie.

COVID-19, caused by coronavirus SARS-CoV-2 is a new and ongoing infectious disease affecting healthcare systems worldwide. Healthcare worker are at high risk for COIVD-19 and many have been infected or even died in countries severely affected by COVID-19 like China or Italy. Bronchoscopy causes cough and aerosol production and has to be considered a significant risk for the staff to get infected. Particular recommendations should guide to prevent spreading COVID-19 and to protect healthcare worker when performing a bronchoscopy.

[Joint Statement of the German Respiratory Society and German Society of Thoracic Surgery in Cooperation with the German Radiological Society: Structural Prerequisites of Centers for Interventional Treatment of Emphysema]. / Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin und der Deutschen Gesellschaft für Thoraxchirurgie in Kooperation mit der Deutschen Röntgengesellschaft: Strukturvoraussetzungen von Zentren für die interventionelle Emphysemtherapie.

Interventional treatment of emphysema offers a wide range of surgical and endoscopic options for patientes with advanced disease. Multidsciplinary collaboration of pulmonology, thoracic surgery and imaging disciplines in patient selection, therapy and follow up ensures treatment quality. The present joint statement describes the required structural and quality prerequsites of treatment centres.

[Rebiopsy for Patients with Lung Cancer - Joint Opinion from both the Endoscopic and Thoracic Oncology Sections of the German Society of Pneumology (DGP)]. / Empfehlung der Sektionen 2 und 11 der DGP zur Rebiopsie bei Lungenkarzinomen.

Performing rebiopsies for primary lung cancer and/or their metastases is becoming more and more prominent in daily practice, as the therapeutical spectrum increases and some newer strategies are dependent on immunohistochemical and/or molecular factors. In general, nearly all recurrent lesions or metastases can be reached. However, frequently invasive procedures are necessary with the need to carefully weigh risks and benefits of rebiopsies for the patient in each case. In this review indications for recurrent and progressive disease as well as risks are discussed and alternatives to rebiopsies are shown. This work is the joint opinion from both the endoscopic and thoracic oncology sections of the German Society of Pneumology (DGP).

[Endobronchial Ultrasound (EBUS) - an Update 2017]. / Endobronchialer Ultraschall (EBUS) ­ Update 2017.

Endobronchial Ultrasound (EBUS) with the two modalities curved and radial EBUS significantly improved the diagnostics in several pulmonary diseases. The examination and staging of mediastinal and hilar lymph nodes in patients with known or suspected lung malignancy as well as the evaluation of unknown pulmonary or mediastinal lesions can be achieved with minimal invasive means when using EBUS. More invasive surgical procedures for diagnostic purposes can be omitted. The diagnostic yield also increases when EBUS is applied in sarcoidosis or mediastinal lymph node tuberculosis but only to some extend in case of lymphoma. Samples obtained by EBUS-TBNA should be handled efficiently to allow molecular analysis in lung cancer. EBUS is a safe procedure, and complication rate is extremely low. Further advances of the EBUS technology focus on improving analysis of the information provided by the ultrasound image and a better tissue sampling by developing of new EBUS bronchoscopes and TBNA-needles.

Heart dose exposure as prognostic marker after radiotherapy for resectable stage IIIA/B non-small-cell lung cancer: secondary analysis of a randomized trial.

Background: Heart exposure to ionizing irradiation can cause ischaemic heart disease. The partial heart volume receiving ≥5 Gy (heartV5) was supposed to be an independent prognostic factor for survival after radiochemotherapy for locally advanced non-small-cell lung cancer (NSCLC). But validation of the latter hypothesis is needed under the concurrent risks of lung cancer patients. Patients and methods: The ESPATUE phase III trial recruited patients with potentially operable IIIA(N2)/selected IIIB NSCLC between 01/2004 and 01/2013. Cisplatin/paclitaxel induction chemotherapy was given followed by neoadjuvant radiochemotherapy (RT/CT) to 45 Gy (1.5 Gy bid/concurrent cisplatin/vinorelbine). Operable patients were randomized to definitive RT/CT(arm A) or surgery (arm B) and therefore were treated at two different total dose levels of radiotherapy. HeartV5 and mean heart dose (MHD) were obtained from the 3D radiotherapy plans, the prognostic value was analysed using multivariable proportional hazard analysis. Results: A total of 161 patients were randomized in ESPATUE, heartV5 and MHD were obtained from the 3D radiotherapy plans for 155 of these [male/female:105/50, median age 58 (33-74) years, stage IIIA/IIIB: 54/101]. Power analysis revealed a power of 80% of this dataset to detect a prognostic value of heartV5 of the size found in RTOG 0617. Multivariable analysis did not identify heartV5 as an independent prognostic factor for survival adjusting for tumour and clinical characteristics with [hazard ratio 1.005 (0.995-1.015), P = 0.30] or without lower lobe tumour location [hazard ratio 0.999 (0.986-1.012), P = 0.83]. There was no influence of heartV5 on death without tumour progression. Tumour progression, and pneumonia were the leading causes of death representing 65% and 14% of the observed deaths. Conclusions: HeartV5 could not be validated as an independent prognostic factor for survival after neoadjuvant or definitive conformal radiochemotherapy. Tumour progression was the predominant cause of death. Register No: Z5 - 22461/2 - 2002-017 (German Federal Office for Radiation Protection).

[Tracheal injuries, fistulae from bronchial stump and bronchial anastomoses and recurrent laryngeal nerve paralysis : management of complications in thoracic surgery]. / Tracheaverletzungen, Insuffizienz von Bronchusstumpf/-anastomose und Rekurrensparese : Management der Komplikationen in der Thoraxchirurgie.

BACKGROUND: Complications cannot always be avoided and their treatment is an integral component of a high quality medical treatment. Complications of the central airways are rare but necessitate supportive treatment by an experienced thoracic surgeon. OBJECTIVE: The reader should become acquainted with measures to prevent complications, to recognize and treat complications early and should understand the necessity for an interdisciplinary approach. MATERIAL AND METHODS: A selective literature research was supplemented by personal experiences and complemented with prospectively collected photographs. RESULTS: There are risk constellations for the appearance of all the mentioned complications which the surgeon needs to know in order to be able to take measures for early detection of complications. Iatrogenic tracheal injuries and bronchial stump fistulae are rare (< 5 %) whereas recurrent laryngeal nerve palsy after left-sided pneumonectomy occurs in up to 30 % of cases. DISCUSSION: After the occurrence of complications at the latest, it is very important to include experienced thoracic surgeons and other specialists when necessary to protect the patient from further damage.

HER2 expression and markers of phosphoinositide-3-kinase pathway activation define a favorable subgroup of metastatic pulmonary adenocarcinomas.

OBJECTIVES: Pulmonary adenocarcinomas (ADC) can be sub-grouped based on dominant oncogenic drivers. EGFR mutations define an entity of metastatic ADC with favorable prognosis and high susceptibility to EGFR tyrosine kinase inhibition. In contrast, the clinical impact of additional ERBB family members in ADC is less defined. To this end we prospectively studied HER2 expression, gene amplification, and mutation in relation to outcome of patients with advanced or metastatic ADC. MATERIALS AND METHODS: Diagnostic tumor biopsies from 193 sequential patients with stage III/IV ADC were prospectively studied for HER2 expression by immunohistochemistry (IHC). Cases with IHC scores 2+ or 3+ were analyzed by HER2 chromogenic in situ hybridization (CISH), and sequencing of HER2 exons 20 and 23. Additional prospectively determined biomarkers included PTEN, cMET, pAKT, and pERK expression, KRAS, EGFR, BRAF and PIK3CA mutations, and ALK fluorescence ISH (FISH). RESULTS AND CONCLUSION: HER2-IHC was feasible in 176 (91.2%) cases. Of 53 (30%) cases with IHC scores 2+/3+, 45 (85%) could be studied by CISH and 34 (64%) by sequencing. The lower number of HER2-mutational analyses resulted from exhaustion of tumor tissue and DNA following mutational analysis of KRAS, EGFR, BRAF and PIK3CA. HER2 amplification was detected in 4 cases (2.3%), while no mutation was found. HER2 expression correlated with expression of pAKT and cMET. Expression of HER2 and pAKT was associated with favorable overall survival in stage IV disease. HER2-expressing ADC more frequently harbored KRAS mutations, while HER2 expression was absent in all 4 cases with BRAF mutation. HER2-IHC was not predictive of HER2 gene amplification or mutation, which both were rare events in prospectively studied patients with advanced or metastatic ADC. Expression of HER2 and pAKT define a population of patients with stage IV ADC with a distinct disease course, who could benefit from specifically tailored pharmacotherapies.

Efficient utilization of EBUS-TBNA samples for both diagnosis and molecular analyses.

BACKGROUND: The assessment of an increasing number of molecular markers is becoming a standard requirement from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimens. However, it is unclear how many needle passes should be performed and the amount of lung cancer cells that should be sent for molecular analyses. The objective of this study was to determine if it is feasible to divide the material obtained by EBUS-TBNA to allow for molecular analysis without compromising the accuracy of mediastinal staging. OBJECTIVE: We aimed to determine if dividing EBUS-TBNA specimens has a negative impact on either histopathological diagnosis or molecular analysis. METHODS: EBUS-TBNA was performed in 249 enlarged lymph nodes. Negative or ambiguous histopathological results were confirmed by surgical means and clinical follow-up over 6 months. The tissue obtained by EBUS-TBNA was placed onto a glass slide and divided for histopathological workup and molecular analysis. The number of passes was recorded. Both the accuracy of the mediastinal lymph node staging and the applicability of the sample division for molecular analysis were assessed. RESULTS: Each lymph node was punctured an average of 3.18 times and division of the obtained material for diagnosis and molecular analysis was feasible in all cases. The sensitivity and accuracy of the mediastinal lymph node staging were 96.6% and 97.6%, respectively. A cytokeratin (CK)-19-mRNA concentration-based molecular test was feasible in 74.1% of cases. CONCLUSION: Dividing EBUS-TBNA samples for both histopathological diagnosis and molecular testing is feasible and does not compromise the accuracy of mediastinal staging. This method may be an alternative to taking additional needle passes for molecular analyses.

[Role of pretherapeutic biomarkers in lung cancer with special regards to bronchoscopic procedures]. / Prätherapeutische Biomarker des Lungenkarzinoms unter besonderer Berücksichtigung der Bronchoskopie.

Molecular biomarkers are becoming increasingly significant in the workup of lung carcinoma patients. They assist in diagnosis, selecting the most adequate therapy and determining prognosis. Obtaining blood based biomarkers or volatile markers in exhaled breath may provide a less invasive method in the future. For the time being, bronchoscopy is still the method of choice to obtain specimen and assess tissue based biomarkers. The techniques how specimen are collected and processed for analysis are of paramount importance.

Assessment of SHOX2 methylation in EBUS-TBNA specimen improves accuracy in lung cancer staging.

BACKGROUND: Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) is a well-established method to assess mediastinal lymph nodes for lung cancer. However, a proportion of patients require further investigation, due to the low negative predictive value (NPV). The objective of this study was to determine whether the assessment of short stature homeobox 2 (SHOX2) DNA methylation level in lymph node tissue obtained by EBUS-TBNA improves the accuracy of mediastinal staging. PATIENTS AND METHODS: EBUS-TBNA was carried out for suspicious lymph nodes of 154 patients. Negative or ambiguous histological results were confirmed by surgical means and clinical follow-up over 6 months. EBUS-TBNA was assessed on 80 positive and 85 negative classified lymph nodes and compared with the result of the SHOX2 DNA methylation real-time PCR analysis. Relative methylation measured by delta-delta cycle threshold (ΔΔCt) was used to classify the samples. Clinical performance of the EBUS-TBNA procedure with and without the additional SHOX2 assessment was calculated against the final classification according to the gold standard. RESULTS: Based on data from 105 patients, an average 80-fold increase in the SHOX2 methylation level was measured for positive compared with negative lymph nodes. SHOX2 results with a ΔΔCt value of <6.5 indicate positive lymph nodes. Applying this molecular analysis to EBUS-TBNA cases, not diagnosed by pathologic assessment, the sensitivity of staging was improved by 17%-99%. The NPV increased from 80% to 99%. CONCLUSIONS: The combination of EBUS-TBNA and SHOX2 methylation level strongly improves the assessment of the nodal status by identifying additional malignant lesions and confirming benign nodes and therefore avoiding invasive follow-up procedures.

2-diethylaminoethyl-dextran methyl methacrylate copolymer nonviral vector: still a long way toward the safety of aerosol gene therapy.

Revealing the lung tumor genome has directed the current treatment strategies toward targeted therapy. First line treatments targeting the genome of lung tumor cells have been approved and are on the market. However, they are limited by the small number of patients with the current investigated genetic mutations. Novel treatment administration modalities have been also investigated in an effort to increase the local drug deposition and disease control. In the current study, we investigated the safety of the new nonviral vector 2-diethylaminoethyl-dextran methyl methacrylate copolymer (DDMC; Ryujyu Science), which belongs to the 2-diethylaminoethyl-dextran family by aerosol administration. Thirty male BALBC mice, 2 month old, were included and divided into three groups. However, pathological findings indicated severe emphysema within three aerosol sessions. In addition, the CytoViva technique was applied for the first time to display the nonviral particles within the pulmonary tissue and emphysema lesions, and a spectral library of the nonviral vector was also established. Although our results in BALBC mice prevented us from further investigation of the DDMC nonviral vector as a vehicle for gene therapy, further investigation in animals with larger airways is warranted to properly evaluate the safety of the vector.

[Hemoptysis--targets in diagnostic and therapy]. / Hämoptoe--diagnostische und therapeutische Ziele.

Hemoptysis (coughing up blood) is an extremely alarming situation for the patient, caused by various different underlying diseases. First of all, a peripheral venous catheter should be placed and oxygen should be supplied as patients are threatened by impaired gas exchange caused by the bleeding. Bronchoscopy should be performed immediately, although computed tomography of the thorax may give valuable diagnostic information and should be performed if permitted by the clinical situation. Rigid bronchoscopy should be performed as it allows a broader spectrum of therapeutic options.

[Diagnosis of pulmonary tuberculosis using Ziehl-Neelsen stain and polymerase chain reaction]. / Diagnostik der Lungentuberkulose mit Ziehl-Neelsen-Färbung und Polymerasekettenreaktion.

BACKGROUND: Definitive diagnosis of unclear pulmonary lesions is mainly based on morphological methods. In addition to a neoplasm, inflammatory reactions, in particular tuberculosis (TB), have to be considered in most cases. Therefore, the aim of this work was to determine whether established methods used in general pathology can be efficiently used with cytological material. MATERIALS AND METHODS: An established polymerase chain reaction (PCR) protocol for the detection of Mycobacterium tuberculosis complex (Mtc) DNA in fixed specimens was conducted on fixed material available as an assay for liquid-based cytology (LBC). CytoLyt®-fixed material of 45 patients with clinically suspected TB or other mycobacteriosis were selected and were initially tested cytologically. In cases of absent tumor cells, PCR for detection of Mtc DNA and Ziehl-Neelsen stain (ZN) were performed. RESULTS: In 9 patients (20 %), Mtc DNA was found by PCR. The following methods were used to obtain material: catheter biopsy (5), needle biopsy (2), transbronchial needle aspiration (1), and bronchoalveolar lavage (1). Cytologically an inflammatory reaction was observed in all cases. In 2 patients, a history of TB, in 2 further cases either silicosis or a posttransplant situation was known. In cases with a positive PCR, 7 patients (78 %) were positive in ZN and 3 patients (33.3 %) in TB culture (15.5 % vs. 6.7 % of the total cohort); however, the material used for investigation was not always from identical sources, respectively. In 36 out of 45 patients, both PCR and ZN were negative for the detection of Mtc DNA. CONCLUSION: The material intended for LBC can be used for detection of TB with ZN and Mtc PCR.

[Rapid on-site evaluation (ROSE) in cytological diagnostics of pulmonary and mediastinal diseases]. / "Rapid on-site evaluation" (ROSE) in der zytologischen Diagnostik von Lungen- und Mediastinalerkrankungen.

Endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA) has become an important tool in the diagnosis and staging of malignant tumors of the lungs and mediastinum. Rapid on-site evaluation (ROSE) denotes a cytomorphological diagnostic procedure that allows assessment of the adequacy and accuracy of the material obtained during bronchoscopy within a few minutes in or near the bronchoscopy suite (on-site) using a quick staining of smears. This results in a significant decrease in the number of repeated bronchoscopy procedures required to recover an adequate biopsy sample and is therefore both time and cost effective. The obtained material can be further assessed as conventional cytological specimens or alternatively using the thin-prep technique for definitive cytopathology diagnosis and/or embedded in paraffin for immunohistochemical or molecular analyses such as DNA sequencing or flow cytometry.