European Respiratory Society guidelines on transbronchial lung cryobiopsy in the diagnosis of interstitial lung diseases.

BACKGROUND: In patients with interstitial lung diseases (ILD), histopathological input is often required to obtain a diagnosis. Surgical lung biopsy (SLB) is considered the reference standard, but many patients are clinically unfit to undergo this invasive procedure, and adverse events, length of hospitalisation and costs are considerable. This European Respiratory Society (ERS) guideline provides evidence-based clinical practice recommendations for the role of transbronchial lung cryobiopsy (TBLC) in obtaining tissue-based diagnosis in patients with undiagnosed ILD. METHODS: The ERS Task Force consisted of clinical experts in the field of ILD and/or TBLC and methodological experts. Four PICO (Patient, Intervention, Comparator, Outcomes) questions and two narrative questions were formulated. Systematic literature searches were performed in MEDLINE and Embase (up to June 2021). GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology was applied. RESULTS: In patients with undiagnosed ILD and an indication to obtain histopathological data: 1) TBLC is suggested as a replacement test in patients considered eligible to undergo SLB, 2) TBLC is suggested in patients not considered eligible to undergo SLB, 3) SLB is suggested as an add-on test in patients with a non-informative TBLC, 4) no recommendation is made for or against a second TBLC in patients with a non-informative TBLC and 5) TBLC operators should undergo training, but no recommendation is made for the type of training required. CONCLUSIONS: TBLC provides important diagnostic information in patients with undiagnosed ILD. Diagnostic yield is lower compared to SLB, at reduced serious adverse events and length of hospitalisation. Certainty of the evidence is mostly "very low".

Transbronchial Lung Cryobiopsy in Interstitial Lung Diseases: Best Practice.

The lung biopsy in interstitial lung disease (ILD) represents an important diagnostic step when the clinical and radiological data are insufficient for a firm diagnosis. A growing body of evidence suggests the utility of transbronchial lung cryobiopsy (TBLC) in the diagnostic algorithm of ILD as it allows, compared to transbronchial lung biopsy with conventional forceps, a better identification of complex histological patterns - such as usual interstitial pneumonia - and can provide information which has a clinical impact on the multidisciplinary discussion similar to that provided by surgical lung biopsy. Performed correctly, it appears to have a better safety profile than surgery. The decision to perform a lung biopsy should be a multidisciplinary decision process where it is felt that there is sufficient diagnostic doubt after a careful clinical evaluation including review of the computed tomograms of the thorax. The presence of severe pulmonary hypertension (> 50 mm Hg), poor lung function (FVC < 50%), or dismissed gas transfer (DLCO of < 35%) are considered relative contraindications for TBLC. Anticoagulants and antiplatelet drugs should be discontinued for the minimum period required for the specific drugs. The greatest consideration should be given to ensure the biopsy is performed safely and we recommend the use of either an endotracheal tube or rigid bronchoscopy. Deep sedation or general anesthesia allow better control of the procedure and a better patient experience. Prophylactic balloon blockers should be used to tamponade any bleeding and also to prevent overspill of blood from the segment that is being sampled. The procedure should be performed under fluoroscopy to ensure that samples are ideally obtained about 10 mm from the pleural edge. The cryoprobe is activated for about 5 s for the first biopsy and then adjusted according to the sample size obtained. With a careful standardized approach it is possible to obtain good-quality lung specimens for diagnosis in a safe manner.

Esophageal Endosonography for the Diagnosis of Intrapulmonary Tumors: A Systematic Review and Meta-Analysis.

BACKGROUND: Biopsy-based diagnosis in patients with paraesophageal intrapulmonary tumors suspected of lung cancer is crucial for adequate treatment planning. OBJECTIVE: To evaluate the performance of transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in the diagnosis of intrapulmonary tumors located near or adjacent to the esophagus. METHODS: We performed a systematic review (PROSPERO, CRD42016033737) and searched MEDLINE, Embase, BIOSIS Previews, and Web of Science on September 22, 2016, without date or language restrictions. We included studies that evaluated the yield and/or sensitivity of EUS-FNA for diagnosing intrapulmonary tumors. Yield was defined as the number of patients in whom EUS-FNA made a biopsy-proven diagnosis (malignant or nonmalignant) relative to the total number of patients on whom EUS-FNA was performed. Sensitivity was defined as the number of patients in whom EUS-FNA made a biopsy-proven diagnosis of malignancy relative to the total number of patients in whom the tumor was found to be malignant. We performed a random-effects meta-analysis. RESULTS: Of 3,320 search results, 11 studies were included. Ten had a high risk of bias. The total number of patients was 313; the proportion of patients with malignancy ranged from 87 to 100% across these studies. The average yield was 0.90 (95% CI 0.82-0.95) and the average sensitivity was 0.92 (0.83-0.96). In the subgroup of prospective studies (n = 3), the average yield was 0.80 (0.56-0.93) and the average sensitivity was 0.83 (0.58-0.95). EUS-FNA-induced complications were reported for 5/256 patients (2.0%) for whom this information was available. CONCLUSIONS: Although the number of high-quality studies is limited, these findings suggest that EUS-FNA is safe and has a high yield for diagnosing intrapulmonary tumors.

Combined endobronchial and esophageal endosonography for the diagnosis and staging of lung cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline, in cooperation with the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS).

This is an official guideline of the European Society of Gastrointestinal Endoscopy (ESGE), produced in cooperation with the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS). It addresses the benefit and burden associated with combined endobronchial and esophageal mediastinal nodal staging of lung cancer. The Scottish Intercollegiate Guidelines Network (SIGN) approach was adopted to define the strength of recommendations and the quality of evidence.The article has been co-published with permission in the European Journal of Cardio-Thoracic Surgery and the European Respiratory Journal. Recommendations 1 For mediastinal nodal staging in patients with suspected or proven non-small-cell lung cancer (NSCLC) with abnormal mediastinal and/or hilar nodes at computed tomography (CT) and/or positron emission tomography (PET), endosonography is recommended over surgical staging as the initial procedure (Recommendation grade A). The combination of endobronchial ultrasound with real-time guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic (esophageal) ultrasound with fine needle aspiration, with use of a gastrointestinal (EUS-FNA) or EBUS (EUS-B-FNA) scope, is preferred over either test alone (Recommendation grade C). If the combination of EBUS and EUS-(B) is not available, we suggest that EBUS alone is acceptable (Recommendation grade C).Subsequent surgical staging is recommended, when endosonography does not show malignant nodal involvement (Recommendation grade B). 2 For mediastinal nodal staging in patients with suspected or proven non-small-cell peripheral lung cancer without mediastinal involvement at CT or CT-PET, we suggest that EBUS-TBNA and/or EUS-(B)-FNA should be performed before therapy, provided that one or more of the following conditions is present: (i) enlarged or fluorodeoxyglucose (FDG)-PET-avid ipsilateral hilar nodes; (ii) primary tumor without FDG uptake; (iii) tumor size ≥ 3 cm (Fig. 3a - c) (Recommendation grade C). If endosonography does not show malignant nodal involvement, we suggest that mediastinoscopy is considered, especially in suspected N1 disease (Recommendation grade C).If PET is not available and CT does not reveal enlarged hilar or mediastinal lymph nodes, we suggest performance of EBUS-TBNA and/or EUS-(B)-FNA and/or surgical staging (Recommendation grade C). 3 In patients with suspected or proven < 3 cm peripheral NSCLC with normal mediastinal and hilar nodes at CT and/or PET, we suggest initiation of therapy without further mediastinal staging (Recommendation grade C). 4 For mediastinal staging in patients with centrally located suspected or proven NSCLC without mediastinal or hilar involvement at CT and/or CT-PET, we suggest performance of EBUS-TBNA, with or without EUS-(B)-FNA, in preference to surgical staging (Fig. 4) (Recommendation grade D). If endosonography does not show malignant nodal involvement, mediastinoscopy may be considered (Recommendation grade D). 5 For mediastinal nodal restaging following neoadjuvant therapy, EBUS-TBNA and/or EUS-(B)-FNA is suggested for detection of persistent nodal disease, but, if this is negative, subsequent surgical staging is indicated (Recommendation grade C). 6 A complete assessment of mediastinal and hilar nodal stations, and sampling of at least three different mediastinal nodal stations (4 R, 4 L, 7) (Fig. 1, Fig. 5) is suggested in patients with NSCLC and an abnormal mediastinum by CT or CT-PET (Recommendation grade D). 7 For diagnostic purposes, in patients with a centrally located lung tumor that is not visible at conventional bronchoscopy, endosonography is suggested, provided the tumor is located immediately adjacent to the larger airways (EBUS) or esophagus (EUS-(B)) (Recommendation grade D). 8 In patients with a left adrenal gland suspected for distant metastasis we suggest performance of endoscopic ultrasound fine needle aspiration (EUS-FNA) (Recommendation grade C), while the use of EUS-B with a transgastric approach is at present experimental (Recommendation grade D). 9 For optimal endosonographic staging of lung cancer, we suggest that individual endoscopists should be trained in both EBUS and EUS-B in order to perform complete endoscopic staging in one session (Recommendation grade D). 10 We suggest that new trainees in endosonography should follow a structured training curriculum consisting of simulation-based training followed by supervised practice on patients (Recommendation grade D). 11 We suggest that competency in EBUS-TBNA and EUS-(B)-FNA for staging lung cancer be assessed using available validated assessment tools (Recommendation Grade D).

Assessment of competence in simulated flexible bronchoscopy using motion analysis.

BACKGROUND: Flexible bronchoscopy should be performed with a correct posture and a straight scope to optimize bronchoscopy performance and at the same time minimize the risk of work-related injuries and endoscope damage. OBJECTIVES: We aimed to test whether an automatic motion analysis system could be used to explore if there is a correlation in scope movements and the operator's level of experience. Our hypothesis was that experienced bronchoscopists move less and keep the flexible scope straighter than less-experienced bronchoscopists while performing procedures. METHODS: Eleven novices, 9 intermediates and 9 experienced bronchoscopy operators performed 3 procedures each on a bronchoscopy simulator. The Microsoft Kinect system was used to automatically measure the total deviation of the scope from a perfectly straight, vertical line. RESULTS: The low-cost motion analysis system could measure the accumulated deviation of the scope precisely during the procedure. The deviations were greatest for the novices and smallest for the most experienced operators for all 3 procedures (p = 0.01, p = 0.01 and p = 0.04, respectively). The total deviation from the straight scope correlated negatively with the performance on the simulator (virtual-reality simulator score; p < 0.001). CONCLUSION: The motion analysis system could discriminate between different levels of experience. Automatic feedback on correct movements during self-directed training on simulators might help new bronchoscopists learn how to handle the bronchoscope like an expert.

Mental health effects of COVID-19 lockdowns: A Twitter-based analysis.

We use a distinctive methodology that leverages a fixed population of Twitter users located in France to gauge the mental health effects of repeated lockdown orders. To do so, we derive from our population a mental health indicator that measures the frequency of words expressing anger, anxiety and sadness. Our indicator did not reveal a statistically significant mental health response during the first lockdown, while the second lockdown triggered a sharp and persistent deterioration in all three emotions. Our estimates also show a more severe deterioration in mental health among women and younger users during the second lockdown. These results suggest that successive stay-at-home orders significantly worsen mental health across a large segment of the population. We also show that individuals who are closer to their social network were partially protected by this network during the first lockdown, but were no longer protected during the second, demonstrating the gravity of successive lockdowns for mental health.

Chest wall reconstruction in benign and malignant tumors with non-rigid materials: An overview.

Several materials and techniques have been described for the procedure of chest wall reconstruction: the choice of using a technique or a material over another relies mainly on the surgeon's experience as well as thoracic defect localization and dimension, local availability of materials, and costs. From a technical point of view, autologous and alloplastic reconstruction are available, and, in both cases, rigid and non-rigid prostheses are found. Each material has its peculiarities, with advantages and disadvantages; thus, it is mandatory to be confident when planning the intervention to foresee possible complications and minimize them. We have reviewed the literature on chest wall reconstruction in chest wall tumors (both malignant and non malignant) with non-rigid prosthetic materials, focusing on safety outcomes.

COVID-19-Related Pericarditis with Pericardial Clotting as a Hallmark: Two Cases and a Review.

The prevalence of pericardial effusion and its clinical significance is not well understood in COVID-19 patients. We report two cases of COVID-19-related pericardial effusion complicated by intrapericardial clot formation. The final outcome was favorable, but intrapericardial clot remained mostly unchanged at 6-month follow-up. The treatment approach and the long-term consequences are still unclear. We propose a review of this particular cardiovascular complication in COVID-19 patients.

Diagnosis and staging of lung cancer with the use of one single echoendoscope in both the trachea and the esophagus: A practical guide.

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.

Radial endobronchial ultrasound-assisted transbronchial needle aspiration for pulmonary peripheral lesions in the segmental bronchi adjacent to the central airway.

BACKGROUND: Tissue samples from lesions located in the 3rd to 5th segmental bronchi are challenging to obtain. In this retrospective study, we aimed to evaluate the diagnostic rate of pulmonary peripheral lesions located in the 3rd to 5th segmental bronchi, near the inner field of lung on the computed tomography (CT) image and outside the bronchus, using radial endobronchial ultrasound (REBUS) followed by transbronchial needle aspiration (TBNA). METHODS: This retrospective study enrolled patients whose preoperative CT examinations showed a lesion located in the segmental bronchi (3rd to 5th), yet adjacent to the inner field of lung on the CT image. REBUS followed by TBNA was used to acquire tissue samples from these lesions. A bronchoscope was used to reach the bronchi surrounding the lesion, and an ultrasound probe was used to determine the lesion's location. Then, the ultrasound probe was withdrawn, and puncture was performed at the location that was determined by ultrasound. The tissue specimens obtained were subjected to pathological examination. RESULTS: Nineteen patients were enrolled in this study including 15 males and 4 females with an average age of 55 years old. Of the enrollees, 8 patients (42.1%) were successfully diagnosed with samples obtained through TBNA, including 6 cases of lung cancer, 1 case of non-specific inflammation, and 1 case of cryptococcal infection. The diagnostic rate was 42.1%. No post-procedural complications were observed among the patients. There was no significant difference in nodule diameter between patients with a diagnostic sample and those in whom TBNA failed to provide a diagnosis (2.99±0.96 vs. 2.26±1.27 cm, P=0.20). CONCLUSIONS: With the assistance of REBUS, TBNA can acquire sufficient samples to achieve a reasonably diagnostic rate for parenchymal lung lesions located near the inner field of lung on the CT image without intrabronchial invasion.

Comparison between closed pleural biopsy and medical thoracoscopy for the diagnosis of undiagnosed exudative pleural effusions: a systematic review and meta-analysis.

BACKGROUND: Exudative pleural effusion (EPE) is a common diagnostic challenge. The utility of medical thoracoscopy (MT) and closed pleural biopsy (CPB) to aid in the diagnosis of EPE has been reported in many published studies. Herein, we perform a systematic review and meta-analysis to compare the diagnostic yield and safety of CPB and MT in EPE. METHODS: Four databases were searched for studies reporting the diagnostic yield of CPB and MT for EPE. The quality of the included studies was evaluated according to the quality assessment of diagnostic accuracy studies (QUADAS) tool. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and complication risks were compared between the two groups. RESULTS: Ten studies dealing with CPB and twenty-three studies dealing with MT for the diagnosis of EPE were included in this meta-analysis. Pooled sensitivity, specificity, PLR, NLR and DOR of CPB group was 77%, 99%, 32.55, 0.22, 165.71, respectively, while pooled sensitivity, specificity, PLR, NLR and DOR of MT group was 93%, 100%, 10.82, 0.08, 162.81, respectively. The area under the summary receiver operating characteristic (SROC) curve of CPB and MT were both 0.97. The ability of CPB to diagnose non-malignant diseases was like MT (69% vs. 68%), while the ability was lower than that of MT to diagnose malignant diseases (72% vs. 92%). The pooled diagnostic accuracy of CPB and MT for mesothelioma was 26% (95% CI, 14-38%) and 42% (95% CI, 22-62%) (P<0.001), respectively. The rate of complications with CBP was lower than that reported for MT. CONCLUSIONS: CBP is a relatively accurate tool with a lower complication rate compared to MT in the diagnosis of EPE, especially in diagnosing non-malignant diseases. We confirm the utility of MT in the diagnostic workup of malignancy (especially mesothelioma); however, in selected cases, CPB could be used as the first diagnostic approach with a favorable safety profile.

Does transbronchial lung cryobiopsy give useful information in asthmatic patients?

INTRODUCTION: Lung biopsy in asthmatic patients is justified in case of atypical presentations of asthma, when other differential diagnoses, such as hypersensitivity pneumonitis or eosinophilic granulomatosis with polyangiitis, could be possible or for research purposes. AIM: We aim to describe the utility and the safety of TBLC (transbronchial lung cryobiopsy) in asthmatic patients, providing data on the pathological changes occurring in the airways and in the lung parenchyma. METHODS: We reviewed asthmatic patients that underwent TBLC, that eventually had only a final diagnosis of asthma. RESULTS: Three patients were detected. TBLC described pathological abnormalities in peribronchiolar and alveolar spaces already well identified with SLB (surgical lung biopsy); the pathological information provided could be useful to better understand the pathobiology of the disease. Finally, we had no complications, confirming a satisfactory safety profile of TBLC. CONCLUSION: We suggest the potential role of TBLC in asthmatic patients: its safety and its acceptable diagnostic accuracy lead to consider this procedure instead of SLB when histological changes in lung parenchyma are needed for the differential diagnosis. Furthermore, TLBC could be useful for research in the pathobiology of asthma and severe asthma.

Biopsy needles for mediastinal lymph node sampling by endosonography: current knowledge and future perspectives.

Due to the increasing role of endosonography [endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and esophageal ultrasound-guided fine needle aspiration (EUS-FNA)] in the diagnosis of several lung diseases, the knowledge of technical aspects is mandatory to optimize the success of the procedure. Among those technicalities related to the procedure, the choice of a needle over another one-either in terms of dimension and type-may have a role in the diagnostic process, especially in some diseases such as lymphoproliferative disorders. In this review, we analyze the current knowledge about the biopsy needle for endosonography, providing also some hints for the future.

Usefulness of Medical Thoracoscopy in the Management of Pleural Effusion Caused by Chronic Renal Failure.

INTRODUCTION: Although pleural effusion (PE) can be caused by several pathologies like congestive heart failure, infections, malignancies, and pulmonary embolism, it is also a common finding in chronic kidney disease (CKD). Diagnostic thoracentesis is of limited value in the differential diagnosis, and the role of more invasive investigations like medical thoracoscopy (MT) is still unclear. AIM: To evaluate the usefulness of MT in unexplained PE in CKD. MATERIALS AND METHODS: In the electronic database of our Institution, we retrospectively searched for patients with CKD who underwent MT for unexplained PE between January 2008 and August 2016. RESULTS: Ten patients were included in the present study. The average age was 72.4 years, the male:female ratio 9:1 and the average blood creatinine value 5.96 mg/dL. The average follow-up was 18 months.A thoracentesis showed an exudate was found in 9 patients and in 1 case pleural fluid characteristics were not recorded for technical reasons; in none of them the cytologic or microbiological analyses were considered diagnostic.The clinical suspicion was a neoplastic (5) or an infectious disease (5). In 4 patients with recurrent PE, MT was performed to obtain talc pleurodesis.No immediate procedure-related complications were recorded; 1 patient developed empyema after 2 months. In 6 cases final diagnosis was chronic uremic pleuritis, hydrothorax in 2, and chronic lymphocytic pleurisy in 2. CONCLUSIONS: MT represents a safe and effective diagnostic and therapeutic procedure in patients with CKD, that itself is a common cause of exudative effusion, and those patients may not require MT.

Impact of EBUS-TBNA on PET-CT Imaging of Mediastinal Nodes.

BACKGROUND: Positron emission tomography-computed tomography (PET-CT) with fluorine-18-fluorodeoxyglucose has a high sensitivity in detecting malignancy in patients suspected of lung cancer but a low specificity as inflammatory reactions can also result in metabolic activity. Furthermore, it is assumed that invasive pulmonary procedures with biopsies from benign lesions can induce metabolic activity resulting in false-positive results. However, this hypothesis lacks solid evidence. We aimed to evaluate how often endobronchial ultrasound (EBUS) with biopsies from benign lesions are followed by false-positive results. METHODS: Patients with suspected or proven lung cancer admitted for invasive pulmonary procedures in a 6-year period were retrospectively reviewed. Patients who had at least 1 nonmalignant mediastinal lymph node (MLN) biopsied 1 to 13 days before PET-CT were included. The number of false-positive and true-negative results shortly after EBUS biopsy of nonmalignant MLN was reviewed. RESULTS: Of 1025 patients, 216 patients were referred for PET-CT 1 to 13 days after biopsy. Of these, 107 patients had at least 1 MLN biopsied. From a total of 198 biopsied MLNs, we found 62% without metabolic activity (benign) and 38% with metabolic activity. In 5% the metabolic activity could be explained by an infection or inflammatory disorder, in 15% no cytologic follow-up was available, in 1% malignancy was confirmed at follow-up, and in 3% the patients were not possible to follow-up. In the remaining 14%, no other reasonable explanation for the metabolic activity was found other than the biopsy. CONCLUSIONS: EBUS with biopsy do not necessarily result in PET activity. Therefore, PET-positive results should always be taken seriously, even when PET is performed shortly after biopsies.

Bronchoscopy as a supplement to computed tomography in patients with haemoptysis may be unnecessary.

BACKGROUND: Haemoptysis is a common symptom and can be an early sign of lung cancer. Careful investigation of patients with haemoptysis may lead to early diagnosis. The strategy for investigation of these patients, however, is still being debated. OBJECTIVES: We studied whether the combination of computed tomography (CT) and bronchoscopy had a higher sensitivity for malignant and non-malignant causes of haemoptysis than CT alone. METHODS: The study was a retrospective, non-randomised, two-centre study and included patients who were referred from primary care for the investigation of haemoptysis. RESULTS: A total of 326 patients were included in the study (mean age 60.5 [SD 15.3] years, 63.3% male). The most common aetiologies of haemoptysis were cryptogenic (52.5%), pneumonia (16.3%), emphysema (8.0%), bronchiectasis (5.8%) and lung cancer (4.0%). In patients diagnosed with lung cancer, bronchoscopy, CT and the combination of bronchoscopy and CT had a sensitivity of 0.61, 0.92 (p<0.05) and 0.97 (p=0.58), respectively. In patients with non-malignant causes of haemoptysis, most aetiologies were diagnosed by CT and comprised mainly pneumonia, emphysema and bronchiectasis. Bronchoscopy did not reveal these conditions and the sensitivity to these conditions was not increased by combining CT and bronchoscopy. CONCLUSIONS: CT can stand alone as a diagnostic workup for patients with haemoptysis referred to an outpatient clinic. Bronchoscopy does not identify any malignant aetiologies not already diagnosed by CT. Combining the two test modalities does not result in a significant increase in sensitivity for malignant or non-malignant causes of haemoptysis.