Sara Colella

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).

Combined endobronchial and oesophageal 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)

New guidelines for combined endobronchial and oesophageal mediastinal nodal staging of lung cancer http://ow.ly/MwM4H

Endoscopic ultrasound in the diagnosis and staging of lung cancer

We reviewed the role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and esophageal ultrasound guided fine needle aspiration (EUS-FNA) in the pretherapeutic assessment of patients with proven or suspected lung cancer. EUS-FNA and EBUS-TBNA have been shown to have a good diagnostic accuracy in the diagnosis and staging of lung cancer. In the future, these techniques in combination with positron emission tomography/computed tomographic may replace surgical staging in patients with suspected and proven lung cancer, but until then surgical staging remains the gold standard for adequate preoperative evaluation.

How to learn and to perform endoscopic ultrasound and endobronchial ultrasound for lung cancer staging: A structured guide and review

The learning of transesophageal ultrasound guided fine needle aspiration (FNA) (endoscopic ultrasound-FNA), and endobronchial ultrasound guided transbronchial needle aspiration (endosonography) should be based on the following steps: Acquiring theoretical knowledge, training on simulators, and supervised performance on patients. Each step should be completed by passing a validated exam before proceeding to the next step. This approach will assure basic competency on all levels, and testing also facilitates learning and improves retention. Competence in endosonography can be based on a systematic an easy principle consisting of 2 times six anatomical landmarks.

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.

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.

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.

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 operators 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.

Diagnostic accuracy and safety of semirigid thoracoscopy in exudative pleural effusions in Denmark.

Background:To assess the diagnostic accuracy and the safety of medical thoracoscopy (MT) performed with the semirigid thoracoscope. Methods:We retrospectively evaluated patients who underwent MT with semirigid thoracoscope under local anesthesia for unexplained exudative pleural effusion from March 1, 2009 to September 1, 2013 in Denmark. Results:Sixty-nine patients were retrospectively studied. In 13 patients it was not possible to perform the scheduled MT, in 9 cases due to an insufficient pneumothorax, in 3 due to an insufficient pleural effusion, and in 1 due to a purulent pleuritis. In 56 patients in whom MT was completed, the procedure was diagnostic in 44 cases: malignancy was reported in 26 patients and a benign diagnosis in 18. In the remaining 12 patients a definite diagnosis was not reached, and further testing was required.In an “intention-to-treat analysis” (69 patients in total), the diagnostic accuracy of MT was 63%, the sensitivity for malignancy was 59% [95% confidence interval (CI)=43%-73%], the specificity was 100% (95% CI=86%-100%), and the negative likelihood ratio was 0.41 (95% CI=0.29-0.58). Considering the 56 patients in whom it was possible to complete the procedure, the diagnostic accuracy was 78%, the sensitivity for malignancy was 74% (95% CI=54%-87%), the specificity was 100% (95% CI=83.75%-100%), and the negative likelihood ratio was 0.27 (95% CI=0.15%-0.45%). No mortality was reported. Conclusions:MT performed under local anesthesia with a semirigid scope is a simple and safe procedure with an acceptable sensitivity for malignancy.

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.