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Accurate staging of non-small cell lung cancer (NSCLC) is crucial for allocation to surgical, medical or multimodal treatment. EUS and endobronchial ultrasound (EBUS) have gained ground in the diagnosis and staging of lung cancer in addition to radiological imaging (e.g., computed tomography, fluoroscopy, and magnetic resonance imaging), nuclear medicine techniques (e.g. positron emission tomography, PET), combined techniques (e.g., fluorodesoxyglucosepositron emission tomography scanning), and sonographic imaging including conventional transcutaneous mediastinal and lung ultrasound. By using one single echoendoscope in both the trachea and the esophagus, surgical staging procedures (e.g. mediastinoscopy and video assisted thoracoscopy) can be avoided in a considerable proportion of patients with NSCLC.

Background: According to guidelines, it is possible to biopsy lung tumors “immediately adjacent to the esophagus” with EUS-B-FNA. However, it is unknown what “immediately adjacent” exactly means. Objective: to investigate the possibility of achieving EUS-B-FNA biopsies from a lung tumor depending on the distance from the esophagus and to establish the maximal allowable distance between the tumor and the esophagus. Methods: In a prospective observational study, we included patients with a lung tumor located maximum 6 cm from the esophagus and indication of EUS-B-FNA from the tumor. The tumors were of different sizes. In a plot presenting the tumor size-distance relationship in cases with (biopsy) versus without (non-biopsy) successful EUS-B-FNA, a separation line representing the threshold between the groups were identified and a biopsy-index equation established. The maximal tumor-size corrected distance (TSCD) was calculated using the residuals to the separation line. Results: In total, 70 patients were included. EUS-B-FNA from the lung tumor was possible in 46 patients. All tumors with a distance from the esophagus below 19 mm could be biopsied. The maximal allowable esophagus-tumor distance depended on tumor size. From the separation line, a biopsy-index equation was established with the sensitivity of 93.5%, a specificity of 100%, and total accuracy of 95.7%. The TSCD was 31 mm (sensitivity: 95.7%, specificity 75.0%, and accuracy: 88.6%). Conclusion: We established a biopsy-index equation to predict the achievability of a lung tumor using EUS-B-FNA depending on distance to esophagus and tumor size. A general maximal TSCD was 31 mm.

Ultrasound-guided needle aspiration via the esophagus using the endobronchial endoscope (EUS-B-FNA) is increasingly being performed by the pulmonologist for the diagnosis of lung cancer, but we have little experience and data available in the literature especially with respect to staging of the disease. We present 2 cases of EUS-B-guided aspiration of malignant pericardial effusion performed in the same setting as bronchoscopy and endobronchial ultrasound. No complications were observed. We conclude that EUS-B-FNA may be safe and efficacious in the evaluation of pericardial effusion during lung cancer workup. Thus, EUS-B-FNA may save time in the diagnostic workup, improve cancer staging, and prevent transthoracic pericardiocentesis.

Die ultraschallgestützte Feinnadelaspiration mit Zugang über den Ösophagus unter Verwendung eines endobronchialen Endoskops (EUS-B-FNA) wird von Pneumologen zunehmend für die Diagnose von Lungentumoren angewendet. Bislang liegen uns jedoch nur wenige Erfahrungen und Daten aus der Literatur über das Staging der Erkrankung vor. Wir stellen hier 2 Fälle einer EUS-B-gestützten Aspiration eines malignen Perikardergusses vor, die unter denselben Bedingungen wie eine Bronchoskopie und endobronchiale Ultraschalluntersuchung durchgeführt wurden. Es traten keine Komplikationen auf. Wir ziehen den Schluss, dass es sich bei der EUS-B-FNA vermutlich um ein sicheres und wirksames Verfahren zur Beurteilung eines Perikardergusses im Rahmen der Lungentumor-Diagnostik handelt. Somit könnte die EUS-B-FNA bei der diagnostischen Abklärung Zeit sparen, das Tumorstaging verbessern und eine transthorakale Perikardpunktion überflüssig machen.

To biopsy centrally located lung tumors is a challenge, especially in patients with severe respiratory insufficiency. The endobronchial ultrasound guided fine needle aspiration performed through the esophagus (EUS-B-FNA) makes it possible to attain tissue samples without entering the airways, but safety in patients with respiratory insufficiency has not earlier been investigated.Therefore, this study aimed at assessing feasibility and safety of EUS-B-FNA from centrally located lesions suspected of lung cancer in patients with respiratory insufficiency.Method: patients with indication for EUS-B-FNA of a centrally located tumor and existing respiratory insufficiency defined as mMRC≥3, saturation ≤90% or need of continuous oxygen supply were included prospectively from three centers. Any adverse events (AE) were recorded during procedure and one-hour recovery. AEs were defined as hypoxemia (saturation

Background: In patients with suspected or proven lung cancer, assessment of regional nodal and distant metastases is key before treatment planning. By introducing the endobronchial ultrasound (EBUS)-guided scope into the esophagus and stomach (EUS-B), liver lesions and celiac nodes can be visualized. To date, the utility of EUS-B in diagnosing liver lesions and retroperitoneal lymph nodes is unknown. Objectives: To assess the feasibility, safety, and diagnostic yield of sampling of liver lesions and retroperitoneal nodes by EUS-B fine-needle aspiration (FNA) in a lung cancer staging setting. Method: Consecutive patients suspected of lung cancer in 2 Danish centers between 1 January 2015 and 31 December 2017 were included retrospectively when a lesion in the liver or a retroperitoneal lymph node was visualized and biopsied with EUS-B-FNA. Results: 23 left liver lobe lesions and 19 retroperitoneal lymph nodes were sampled by EUS-B-FNA. Sensitivity and diagnostic yield of sampled liver lesions were 86 and 83%, respectively. In 19/23 patients, there was a cytopathological diagnosis of malignancy. Sensitivity and diagnostic yield from retroperitoneal lymph node samples were 83 and 63%, respectively. In 10/19 patients, the diagnosis was malignancy. No complications were observed. Conclusion: EUS-B-FNA enables safe sampling of left liver lobe lesions and retroperitoneal lymph nodes. EUS-B should be considered as a minimally invasive technique to provide tissue proof of distant metastases lung cancer patients.

Background: Diagnosing centrally located lung tumors without endobronchial abnormalities and not located near the major airways is a diagnostic challenge. Tumors near or adjacent to the esophagus can be aspirated and detected with esophageal ultrasound (EUS) using gastrointestinal endoscopes. Objective: To assess the feasibility and diagnostic yield of endoscopic ultrasound with bronchoscope-guided fine needle aspiration (EUS-B-FNA) in paraesophageally located lung tumors and its added value to bronchoscopy and endobronchial ultrasound (EBUS). Methods: Retrospective, multicenter international study (from January 1, 2015 until January 1, 2018) of patients with suspected lung cancer, undergoing bronchoscopy, EBUS, and endoscopic ultrasound bronchoscopy (EUS-B) in one session by a single operator (pulmonologist), in whom the primary lung tumor was detected and aspirated by EUS-B. In the absence of malignancy following endoscopy, transthoracic ultrasound needle aspiration, clinical and radiological follow-up of at least 6 months was performed. The yield and sensitivity of EUS-B-FNA and its added value to bronchoscopy and EBUS was assessed. Results: 58 patients were identified with the following diagnosis: non-small-cell lung cancer (n = 43), small-cell lung cancer (n = 6), mesothelioma (n = 2), metastasis (n = 1), nonmalignant (n = 6). The yield and sensitivity of EUS-B-FNA for detecting lung cancer was 90%. In 26 patients (45%), the intrapulmonary tumor was exclusively detected by EUS-B. Adding EUS-B to conventional bronchoscopy and EBUS increased the diagnostic yield for diagnosing lung cancer in para­esophageally located lung tumors from 51 to 91%. No EUS-B-related complications were observed. Conclusion: EUS-B-FNA is a feasible and safe technique for diagnosing centrally located intrapulmonary tumors that are located near or adjacent to the esophagus. EUS-B should be considered in the same endoscopy session following nondiagnostic bronchoscopy and EBUS.

Background: Several studies have reported the efficacy of esophageal ultrasound-guided fine needle aspiration (EUS-FNA) for the detection of metastases in the left adrenal gland (LAG) in patients with lung cancer. Currently we have only limited evidence based on small studies on the usefulness of EUS-B [endobronchial ultrasound (EBUS) scope into the esophagus] to provide tissue proof of suspected LAG metastases. The objectives of this study are to investigate feasibility, safety and diagnostic yield of EUS-B-FNA in LAG analysis in patients with proven or suspected lung cancer.Methods: In two Danish hospitals, a systematic search in the electronic database for patients who underwent EUS-B-FNA of the LAG for suspected or proven lung cancer was performed retrospectively between January 1st, 2015 and December 31st, 2017. Computed tomography (CT), positron emission tomography-CT, endoscopy, pathology and follow-up data were acquired.Results: One hundred and thirty-five patients were included; the prevalence of biopsy proven LAG malignancy was 30% (40/135). A total of 87% (117/135) of EUS-B-FNA samples were adequate (i.e., containing adrenal or malignant cells). No complications were observed.Conclusions: We present the largest cohort of patients ever reported showing that EUS-B-FNA of the LAG is a safe and feasible procedure and should therefore be used for staging purposes in patients with lung cancer and a suspicious LAG.

The use of the endobronchial ultrasound (EBUS) endoscope in the oesophagus, the so‐called EUS‐B procedure, for the diagnosis and staging of thoracic malignancy is quickly gaining ground. Pleural lesions located close to the oesophagus can be inaccessible to transthoracic biopsy and endoscopic procedures can be the only option. We here present two cases demonstrating that EUS‐B‐guided fine needle aspiration (EUS‐B‐FNA) of pleural lesions is possible. The first case demonstrates a EUS‐B‐FNA with malignant mesothelioma of a pleural lesion in a 70‐year‐old patient. In the second case, EUS‐B‐FNA diagnosed a pleural metastasis from adenoid cystic adenocarcinoma in a 75‐year‐old‐patient. In conclusion, we hereby demonstrate that EUS‐B‐FNA from pleural lesions is feasible and appears to be safe., Endoscopic ultrasound (EUS) via the oesophagus can be performed either with the use of a conventional gastrointestinal endoscope (EUS‐fine needle aspiration (FNA)) or by using the endobronchial ultrasound (EBUS) endoscope in the oesophagus (EUS‐B‐FNA). The use of EUS‐B for the diagnosis and staging of thoracic malignancy is quickly gaining ground. We here present two cases demonstrating that EUS‐B‐guided FNA (EUS‐B‐FNA) of pleural lesions is possible.

Flexible bronchoscopy and endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) are the pulmonologists´ basic procedures for the biopsy of suspicious lung lesions. If inconclusive, other guiding-modalities for tissue sampling are needed, computed tomography performed by a radiologist, or - if available - radial EBUS or electromagnetic navigation biopsy. We wanted to investigate if same-day X-ray fluoroscopy-guided transthoracic fine-needle aspiration biopsy (F-TTNAB) performed by the pulmonologist immediately after bronchoscopy and EBUS is a feasible alternative. We retrospectively identified consecutive patients in whom F-TTNAB followed a bronchoscopy and EBUS in the same séance. Patients in whom the suspicion of malignancy was invalidated after complete work up were followed for six months to identify false-negative cases. In total 125 patients underwent triple approach (bronchoscopy, EBUS and F-TTNAB) during the same séance. Malignancy was diagnosed in 86 (69%), and 77 of these (90%) were primary lung cancers. The diagnostic yield of F-TTNAB for malignancy was 77%, and sensitivity was 90%. Pneumothorax occurred in 35 (28%) patients, and was administered with pleural drainage in 22 (18% of all patients). No cases of prolonged haemoptysis were observed. The risk of pneumothorax differed insignificantly with lesion size ≤2.0 cm (27%) versus >2.0 cm (29%). We conclude that it is feasible for pulmonologist to perform F-TTNAB immediately after endoscopy as a combined triple approach in a fast-track workup of suspected lung cancer.

Background: Diagnosing centrally located lung tumors without endobronchial abnormalities is a diagnostic challenge. Tumors located adjacent to the esophagus can be aspirated and detected with EUS using GI endoscopes. The feasibility and yield of EUS-B (use of the EBUS scope in the esophagus) is unknown. Objective: To assess the feasibility and diagnostic yield of EUS-B-FNA in centrally located lung tumors and its added value to bronchoscopy and EBUS. Methods: Retrospective multicentre international analysis (from 01-2015 until 12-2017) of patients with suspected lung cancer, undergoing a bronchoscopy, EBUS and EUS-B in one session by a single operator (pulmonologist), in which the primary lung tumor was detected and aspirated by EUS-B. In the absence of malignancy following endoscopy, clinical and radiological follow-up of 6 months was performed. The yield and sensitivity of EUS-B-FNA and its added value to bronchoscopy and EBUS was assessed. Results: 58 patients were identified with the following diagnosis: NSCLC (n=43), SCLC (n=6), Mesothelioma (n=2), metastasis (n=1), non-malignant (n=6). The diagnostic yield and sensitivity of EUS-B-FNA for detecting lung cancer was 90%. In 26 patients (45%), the intrapulmonary tumor was exclusively detected by EUS-B. Adding EUS-B to conventional bronchoscopy and EBUS increased the diagnostic yield for diagnosing lung cancer in centrally located lung tumors from 51% to 90%. No EUS-B related complications were observed. Conclusion: EUS-B-FNA is a feasible and safe technique for diagnosing centrally located intrapulmonary tumors that are located near or adjacent to the esophagus. EUS-B should be considered in the same endoscopy session following a non-diagnostic bronchoscopy and EBUS

Background: The evaluation of patients with lung lesions is challenging. The nature of the lesion can be determined by pathological evaluation of biopsies. The pulmonologists will be met by increasing demands with regard to biopsy techniques including ultrasound-guided transthoracic needle biopsy (US-TTNB).Objective: The aim of this paper is to present the pulmonologist to a systematic step-by-step guide for performing US-TTNB and to assess the evidence for this approach. Method/results: Indications, contraindications and a step-by-step guide for the techniques used when performing US-TTNB are presented, and major complications and handling of these are described. Conclusion: US-TTNB performed by pulmonologists is a safe and feasible procedure.

Introduction: Mediastinal lymph node (LN) short axis diameter of >10 mm at CT scan is the radiological cut-off for abnormality. LN size is one of several ultrasonographical estimates performed during endobronchial ultrasound guided (EBUS). Objective: To evaluate if EBUS measured LN size was associated with benign cytology, adequacy of sampling or procedure-related features. Method: Consecutive patients undergoing EBUS TBNA for suspected malignancy in our unit Sep/13 – Feb/14. We recorded LN variables (size, border, heterogeneity, hilus), needle passes, LN contact, aspired blood, clot formation, smear (number, visible cell rich aspirate, anthracosis). Cytopathological diagnosis for each LN sample was considered Adequate or Inadequate (lymphatic tissue present resp. not present). Diagnosis of adequate samples was either benign, malignant, non-necrotic granuloma (sarcoidosis). Results: Totally 640 samples were obtained during 219 EBUS procedures. Size was noted in 632 (≤10 mm: n=355; 56%) samples, and of these 558 (88%) were adequate. LN diagnoses were benign/malignant /sarcoidosis in 339(61%)/184(33%)/35(6%). Size ≤10 mm was significantly associated to benign result, yet 15% was malignant. Conversely, 86 (34%) of enlarged LNs were benign. Size ≤10 mm was negatively associated with adequate sampling and formation of cell blocks, and positively associated with antracosis. Conclusions: Using the traditional cut-off of ≤10 mm for normal mediastinal LN size during EBUS does not accurately predict cytopathological outcome in a population referred for mediastinal workup for suspected malignancy.

The acyl glucuronide metabolites of endogenous as well as of xenobiotic compounds may undergo isomerization in vitro as well as in the human body. The parent acyl glucuronide and the isomerization products may react with endogenous protein to form products which in worst cases may act as antigens and thus create an allergic response. In the present paper new methods based on micellar electrokinetic or microemulsion electrokinetic chromatography for the separation of all isomerization products as well as the hydrolysis product of acyl glucuronides are described. In order to perform the separation at lower pH values in a reasonable time dynamically coated capillaries were used. This enables the electroosmotic flow to be high and constant even at low pH. The methods were developed using S-naproxen-beta-1-O-acyl glucuronide as the model substance. The assignment of the single peaks in the electropherogram was performed tentatively based on the sequential appearance of the isomerization products with time.

A method for the simultaneous determination of pyrimethamine, sulfadiazine and its metabolite N -acetyl-sulfadiazine in small plasma samples from neonates in treatment for congenital toxoplasmosis has been developed. In this method only 25 μl of plasma is used and a simple sample preparation based on protein precipitation and centrifugation provides highly reliable data as the recovery is about 100% and the precision is good. The analysis is performed using high performance liquid chromatography with UV and mass spectrometric (MS) detection. Pyrimethamine was found to give a linear response using MS detection in the range 0.02–5 μg/ml. Sulfadiazine and its metabolite N -acetyl-sulfadiazine were preferably analysed by UV at 269 nm in the concentration ranges 0.2–200 μg/ml for sulfadiazine and 0.2–50 μg/ml for N -acetyl-sulfadiazine.

The use of one single ultrasound echoendoscope in both the trachea (EBUS) and the oesophagus (EUS-B) gives a fast, safe and precise diagnosis and stage of the patient with suspected lung cancer. There is solid evidence for simulator-based training in EBUS concerning safety and diagnostic outcome, but this is currently not an option in EUS-B and needs development. In this review, we recommend evidence-based simulator training and certification in EBUS and when available also in EUS-B before practicing on patients.