Complication rate of endosonography (endobronchial and endoscopic ultrasound): a systematic review.

BACKGROUND: Endosonography [endoscopic ultrasound (EUS)-guided fine needle aspiration and endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration] is increasingly used for lung cancer staging and the assessment of sarcoidosis. Serious adverse events (SAE) have been reported in case reports, but the true incidence of complications is yet unknown. OBJECTIVES: To assess the rate of SAE related to endosonography and to investigate associated risk factors. MATERIALS AND METHODS: PubMed, EMBASE and Cochrane libraries were searched for eligible references up to April 2012 and these included studies reporting on linear EUS or EBUS for the analysis of mediastinal/hilar nodal or central intrapulmonary lesions. Case series describing complications were excluded. Reported complications were classified into SAE or minor adverse events (AE). RESULTS: 190 studies met the inclusion criteria. Information on follow-up was missing in half of the studies. In 16,181 patients, 23 SAE (0.14%) and 35 AE (0.22%) were reported. No mortality was observed. SAE were more frequent in patients investigated with EUS (0.30%) than in those investigated with EBUS (0.05%). Infectious SAE were most prevalent (0.07%) and predominantly occurred in patients with cystic lesions and sarcoidosis. In lung cancer patients, complications were rare. DISCUSSION: Endosonography for intrathoracic nodal assessment seems safe for lung cancer patients and mortality has not been reported. For cystic lesions and sarcoidosis, there may be a small, but nonnegligible risk of infectious complications. The true incidence of SAE might be higher as accurate documentation of complications is missing in most studies.

Reliable and valid assessment of competence in endoscopic ultrasonography and fine-needle aspiration for mediastinal staging of non-small cell lung cancer.

BACKGROUND AND STUDY AIMS: Fine-needle aspiration (FNA) guided by endoscopic ultrasonography (EUS) is important in mediastinal staging of non-small cell lung cancer (NSCLC). Training standards and implementation strategies of this technique are currently under discussion. The aim of this study was to explore the reliability and validity of a newly developed EUS Assessment Tool (EUSAT) designed to measure competence in EUS - FNA for mediastinal staging of NSCLC. PATIENTS AND METHODS: A total of 30 patients with proven or suspected NSCLC underwent EUS - FNA for mediastinal staging by three trainees and three experienced physicians. Their performances were assessed prospectively by three experts in EUS under direct observation and again 2 months later in a blinded fashion using digital video-recordings. Based on the assessments, intra-rater reliability, inter-rater reliability, and construct validity were explored. RESULTS: The intra-rater reliability was good (Cronbach's α = 0.80), but comparison of results based on direct observations and blinded video-recordings indicated a significant bias favoring consultants (P = 0.022). Inter-rater reliability was very good (Cronbach's α = 0.93). However, one rater assessing five procedures or two raters each assessing four procedures were necessary to secure a generalizability coefficient of 0.80. The assessment tool demonstrated construct validity by discriminating between trainees and experienced physicians (P = 0.034). CONCLUSIONS: Competency in mediastinal staging of NSCLC using EUS and EUS - FNA can be assessed in a reliable and valid way using the EUSAT assessment tool. Measuring and defining competency and training requirements could improve EUS quality and benefit patient care.

Transesophageal endoscopic ultrasound-guided fine-needle aspiration for the mediastinal staging of extrathoracic tumors: a new perspective.

BACKGROUND: Several extrathoracic tumors metastasize to the mediastinum. Mediastinoscopy is the standard method to obtain tissue proof of mediastinal spread, but drawbacks are its invasiveness, requirement for general anesthesia and costs. Transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is indicated in lung cancer staging guidelines as a minimally invasive alternative for surgical staging. The diagnostic values in patients with suspected mediastinal metastases and various (previous) extrathoracic malignancies were assessed. PATIENTS AND METHODS: Consecutive patients with suspected mediastinal metastases (on computed tomography or positron emission tomography) and an (previous) extrathoracic malignancy underwent EUS-FNA. RESULTS: Seventy-five patients with current (n = 14) or previously diagnosed (n = 61) extrathoracic malignancies were evaluated. EUS-FNA detected mediastinal malignancies in 43 patients (57%) [metastases of extrathoracic tumors, n = 36 (48%); second malignancy (lung cancer), n = 7 (9%)]. Mediastinal metastases were found at subsequent surgical staging in seven patients or during follow-up (one patient). In seven patients, an alternative diagnosis was established. Sensitivity, specificity, accuracy and negative predictive value of EUS-FNA for mediastinal staging were 86%, 100%, 91% and 72%, respectively. CONCLUSION: EUS-FNA is a minimally invasive mediastinal staging method for patients with extrathoracic malignancies to confirm nodal metastatic spread and therefore may qualify as an alternative for surgical staging.

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of sarcoidosis.

BACKGROUND AND STUDY AIMS: Transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of mediastinal lymph nodes is increasingly used to detect noncaseating granulomas in patients with suspected sarcoidosis. The optimal needle size and tissue processing method for detecting noncaseating granulomas are debated. We assessed the value of cell-block analysis when added to conventional cytological evaluation of EUS aspirates obtained by 22-gauge needles in patients with stage I and II sarcoidosis. PATIENTS AND METHODS: Data from 101 consecutive patients (55 % of whom had previously had a nondiagnostic bronchoscopy) with suspected pulmonary sarcoidosis (stage I and II), who underwent EUS-FNA of mediastinal lymph nodes with 22-gauge needles were retrospectively analyzed. RESULTS: The sensitivity of EUS in detecting granulomas was 87 % (cytology and cell-block analysis together) (stage I, 92 %; stage II, 77 %). In 33 % of cytology negative patients (n = 6), granulomas were present in the cell block. The optimal yield for granuloma detection was reached with four needle passes. One patient developed mediastinitis after EUS-FNA. CONCLUSIONS: Cell-block analysis added to conventional cytological evaluation of 22-gauge EUS aspirates, results in a high yield in detecting granulomas in patients with suspected sarcoidosis and reduces the false-negative rate substantially. EUS has a considerably higher yield in stage I compared with stage II sarcoidosis. For an optimal yield, four needle passes are required.

The expanding role of endobronchial ultrasound in patients with centrally located intrapulmonary tumors.

OBJECTIVES: Tissue acquisition of lung tumors is crucial for diagnostic and treatment purposes. In patients with centrally located lung tumors without endobronchial abnormalities the yield of conventional bronchoscopy is poor. Objective of this study was to assess diagnostic yield of EBUS-TBNA in patients with lung tumors, located near or adjacent to the major airways. METHODS: International multicenter retrospective analysis (2013-2018) of linear EBUS databases in Bologna, Italy and Amsterdam, The Netherlands. Patients with a centrally-located lung tumor without endobronchial abnormalities who underwent lung tumor search with linear EBUS were included. Diagnostic yield, feasibility of EBUS guided tumor sampling, complication rate, adequacy of the aspirates for mutational analysis, and assessment of mediastinal/vascular invasion (T4) were evaluated. RESULTS AND CONCLUSION: Real-time EBUS-TBNA diagnostic yield to sample centrally located intrapulmonary tumor was 83% (136/163) and it was independent of tumor location (paratracheal, mainstem, lobar, segmental bronchus). The feasibility to sample the lung tumor was 89% (145/163). In 4 cases the tumor was not found with EBUS. In the other 14 cases, tumor sampling was not performed due to: loss of the echo window after needle insertion [n = 3], interposition of a large vessel [n = 7], switch to radial EBUS [n = 1], switch and sampling through EUS or EUS-B [n = 3]. No major complications occurred. Mutational analysis was successful in 54/63 (86%) of samples. Using surgery as reference standard, EBUS proved more reliable than CT (24/24, 100% versus 22/24, 91.7%, respectively) in the assessment of mediastinal/vascular tumor invasion (T4 status). IN CONCLUSION: Lung tumors presenting without endobronchial abnormalities and located adjacent to the major airways can be safely sampled by EBUS-TBNA resulting in high diagnostic yield irrespective of tumor location. Successful molecular profiling and reliable assessment of mediastinal/vascular invasion (T4) in patients with advanced disease provide additional value to EBUS procedures in the setting of centrally-located lung lesions.

Emerging understanding of the mechanism of action of Bronchial Thermoplasty in asthma.

Bronchial Thermoplasty (BT) is an endoscopic treatment for moderate-to-severe asthma patients who are uncontrolled despite optimal medical therapy. Effectiveness of BT has been demonstrated in several randomized clinical trials. However, the asthma phenotype that benefits most of this treatment is unclear, partly because the mechanism of action is incompletely understood. BT was designed to reduce the amount of airway smooth muscle (ASM), but additional direct and indirect effects on airway pathophysiology are expected. This review will provide an overview of the different components of airway pathophysiology including remodeling, with the ASM as the key player. Current concepts in the understanding of BT clinical effectiveness with a focus on its impact on airway remodeling will be reviewed.

Towards a minimally invasive staging strategy in NSCLC: analysis of PET positive mediastinal lesions by EUS-FNA.

STUDY OBJECTIVE: To asses the value of endoscopic ultrasound guided fine needle aspiration (EUS-FNA) in the nodal staging of patients with (suspected) non-small cell lung cancer (NSCLC) and a (18)FDG positron emission tomography (PET) scan suspect for N2/N3 mediastinal lymph node (MLN) metastases. BACKGROUND: Due to the imperfect specificity of positron emission tomography, PET positive MLN should be biopsied in order to confirm or rule out metastasis. Currently, invasive surgical diagnostic techniques such as mediastinoscopy/-tomy are standard procedures to obtain MLN tissue. The minimally invasive technique of EUS-FNA has a high diagnostic accuracy (90-94%) for the analysis of MLN in patients with enlarged MLN on computed tomography of the chest (CT). DESIGN AND PATIENTS: Thirty-six patients with proven n=26 or suspected n=10 non-small cell lung cancer and a PET scan suspect for N2/N3 lymph node metastases underwent EUS-FNA. When EUS-FNA did not confirm metastasis and the PET lesion was within reach of mediastinoscopy, a mediastinoscopy was performed. EUS-FNA negative patients with PET lesions beyond the reach of mediastinoscopy or those with a negative mediastinoscopy were referred for surgical resection of the tumour and MLN sampling or dissection. RESULTS: EUS-FNA confirmed N2/N3 disease in 25 of the 36 patients (69%) and was highly suspicious in one. In the remaining 10 patients, one PET positive and one PET negative N2 metastasis was detected at thoracotomy. The PPV, NPV, sensitivity, specificity and accuracy of EUS-FNA in analysing PET positive MLN were 100%, 80%, 93%, 100% and 94%, respectively. No complications of EUS-FNA were recorded. CONCLUSIONS AND SIGNIFICANCE: EUS-FNA yields minimally invasive confirmation of MLN metastases in 69% of the patients with potential mediastinal involvement at FDG PET. The combination of PET and EUS-FNA might qualify as a minimally invasive staging strategy for NSCLC.

Clinical effectiveness and cost-effectiveness of endobronchial and endoscopic ultrasound relative to surgical staging in potentially resectable lung cancer: results from the ASTER randomised controlled trial.

OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of endosonography (followed by surgical staging if endosonography was negative), compared with standard surgical staging alone, in patients with non-small cell lung cancer (NSCLC) who are otherwise candidates for surgery with curative intent. DESIGN: A prospective, international, open-label, randomised controlled study, with a trial-based economic analysis. SETTING: Four centres: Ghent University Hospital, Belgium; Leuven University Hospitals, Belgium; Leiden University Medical Centre, the Netherlands; and Papworth Hospital, UK. INCLUSION CRITERIA: known/suspected NSCLC, with suspected mediastinal lymph node involvement; otherwise eligible for surgery with curative intent; clinically fit for endosonography and surgery; and no evidence of metastatic disease. EXCLUSION CRITERIA: previous lung cancer treatment; concurrent malignancy; uncorrected coagulopathy; and not suitable for surgical staging. INTERVENTIONS: Study patients were randomised to either surgical staging alone (n = 118) or endosonography followed by surgical staging if endosonography was negative (n = 123). Endosonography diagnostic strategy used endoscopic ultrasound-guided fine-needle aspiration combined with endobronchial ultrasound-guided transbronchial needle aspiration, followed by surgical staging if these tests were negative. Patients with no evidence of mediastinal metastases or tumour invasion were referred for surgery with curative intent. If evidence of malignancy was found, patients were referred for chemoradiotherapy. MAIN OUTCOME MEASURES: The main clinical outcomes were sensitivity (positive diagnostic test/nodal involvement during any diagnostic test or thoracotomy) and negative predictive value (NPV) of each diagnostic strategy for the detection of N2/N3 metastases, unnecessary thoracotomy and complication rates. The primary economic outcome was cost-utility of the endosonography strategy compared with surgical staging alone, up to 6 months after randomisation, from a UK NHS perspective. RESULTS: Clinical and resource-use data were available for all 241 patients, and complete utilities were available for 144. Sensitivity for detecting N2/N3 metastases was 79% [41/52; 95% confidence interval (CI) 66% to 88%] for the surgical arm compared with 94% (62/66; 95% CI 85% to 98%) for the endosonography strategy (p = 0.02). Corresponding NPVs were 86% (66/77; 95% CI 76% to 92%) and 93% (57/61; 95% CI 84% to 97%; p = 0.26). There were 21/118 (18%) unnecessary thoracotomies in the surgical arm compared with 9/123 (7%) in the endosonography arm (p = 0.02). Complications occurred in 7/118 (6%) in the surgical arm and 6/123 (5%) in the endosonography arm (p = 0.78): one pneumothorax related to endosonography and 12 complications related to surgical staging. Patients in the endosonography arm had greater EQ-5D (European Quality of Life-5 Dimensions) utility at the end of staging (0.117; 95% CI 0.042 to 0.192; p = 0.003). There were no other significant differences in utility. The main difference in resource use was the number of thoracotomies: 66% patients in the surgical arm compared with 53% in the endosonography arm. Resource use was similar between the groups in all other items. The 6-month cost of the endosonography strategy was £9713 (95% CI £7209 to £13,307) per patient versus £10,459 (£7732 to £13,890) for the surgical arm, mean difference £746 (95% CI -£756 to £2494). The mean difference in quality-adjusted life-year was 0.015 (95% CI -0.023 to 0.052) in favour of endosonography, so this strategy was cheaper and more effective. CONCLUSIONS: Endosonography (followed by surgical staging if negative) had higher sensitivity and NPVs, resulted in fewer unnecessary thoracotomies and better quality of life during staging, and was slightly more effective and less expensive than surgical staging alone. Future work could investigate the need for confirmatory mediastinoscopy following negative endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), the diagnostic accuracy of EUS-FNA or EBUS-TBNA separately and the delivery of both EUS-FNA or EBUS-TBNA by suitably trained chest physicians. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 97311620. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 18. See the HTA programme website for further project information.

EUS-FNA in the preoperative staging of non-small cell lung cancer.

BACKGROUND: According to current guidelines, transesophageal ultrasound-guided fine needle aspiration (EUS-FNA) can be performed as an alternative for surgical staging to confirm mediastinal metastases in patients with non-small cell lung cancer (NSCLC). To date however, data regarding the routine use of EUS-FNA in the preoperative staging of unselected patients with NSCLC are limited. AIMS AND OBJECTIVES: (1) To evaluate the diagnostic value of EUS-FNA in consecutive, patients with NSCLC regardless of nodal size at CT. (2) To determine the impact of EUS-FNA on the prevention of surgical staging procedures. (3) To assess the accuracy of mediastinal staging by combining EUS-FNA and mediastinoscopy. (4) To investigate whether a subgroup of patients exists that can be accurately staged by EUS-FNA alone. METHODS: 152 consecutive operable patients with proven or suspected NSCLC who underwent EUS-FNA were retrospectively analyzed. In the absence of mediastinal metastases, mediastinoscopy and/or thoracotomy with lymph node dissection was performed. RESULTS: The prevalence of mediastinal metastases was 49%. Sensitivity, negative predictive value (NPV) and accuracy of EUS-FNA for N2/N3 disease were 74%, 73% and 85% respectively, whereas these values for the combined staging of EUS-FNA and mediastinoscopy were 92%, 85% and 95%. Additional surgical staging in patients staged N0 at EUS-FNA reduces the false negative EUS-findings by 55%. The NPV of EUS-FNA for left-sided tumors was 68%. EUS-FNA prevented surgical staging procedures in 60 of 152 patients (39%). No major complications occurred during EUS-FNA. CONCLUSION: Routine use of EUS-FNA in unselected patients with NSCLC reduces the need for surgical staging procedures in nearly half of patients. Additional surgical staging in patients without nodal metastases at EUS-FNA reduces the false negative EUS-FNA findings considerably regardless of the location of the primary lung tumor.

Transbronchial and transoesophageal (ultrasound-guided) needle aspirations for the analysis of mediastinal lesions.

A tissue diagnosis of mediastinal nodes is frequently needed for accurate lung cancer staging as well as the assessment of mediastinal masses. Transbronchial needle aspiration (TBNA) is a safe procedure that is performed during routine bronchoscopy. Provided mediastinal metastases are confirmed, TBNA has a high impact on patient management. Unfortunately, TBNA remains underused in current daily practice, mainly due to the lack of real-time needle visualisation. The introduction of echo-endoscopes has overcome this problem. Endobronchial ultrasound-guided TBNA (EBUS-TBNA) allows real-time controlled tissue sampling of paratracheal, subcarinal and hilar lymph nodes. Mediastinal lymph nodes located adjacent to the oesophagus can be assessed by transoesophageal ultrasound-guided fine needle aspiration (EUS-FNA). Owing to the complementary reach of EBUS-TBNA and EUS-FNA in assessing different regions of the mediastinum, recent studies suggest that complete and accurate mediastinal staging can be achieved by the combination of both procedures. It is expected that implementation of minimally invasive endoscopic methods of endobronchial ultrasound-guided transbronchial needle aspiration and transoesophageal ultrasound-guided fine needle aspiration will reduce the need for surgical staging of lung cancer significantly.

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of sarcoidosis.

The objective of the current study was to assess the yield of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) for the diagnosis of sarcoidosis in a large patient group. Bronchoscopy with transbronchial lung biopsy (TBLB) is nondiagnostic in 30% of patients with suspected sarcoidosis and has a risk of pneumothorax and haemoptysis. In order to obtain a diagnosis, mediastinoscopy is often performed as the next diagnostic procedure. EUS-FNA provides a nonsurgical alternative for the demonstration of noncaseating granulomas by aspirating mediastinal lymph nodes from the oesophagus. In total, 51 patients with suspected sarcoidosis stage I and II underwent EUS-FNA. Thirty-six patients (71%) previously underwent a nondiagnostic bronchoscopy. All patients were clinically followed (median 18 months) and surgical-pathological verification occurred in those patients with EUS aspirates that contained unrepresentative material. EUS-FNA demonstrated noncaseating granulomas without necrosis in 41 of 50 patients (82%) with the final diagnosis of sarcoidosis. Specific ultrasound features of clustered, well-demarcated iso-echoic lymph nodes were observed in 64% of patients with sarcoidosis. No complications occurred. Endoscopic ultrasound-guided fine-needle aspiration has a high yield in diagnosing sarcoidosis and qualifies as the next diagnostic step after a nondiagnostic bronchoscopy. The current authors expect that endoscopic ultrasound-guided fine-needle aspiration will reduce the number of mediastinoscopies for the diagnosis of sarcoidosis dramatically.

[Endoscopic ultrasound-guided fine-needle aspiration in pulmonary medicine]. / Endosonographisch gesteuerte Feinnadelpunktion in der pneumologischen Diagnostik.

Endoscopic ultrasound-guided fine-needle aspiration has significantly increased the capacity of pulmonary diagnostic procedures. Since this method was introduced, 1212 examinations have been performed at two centres of pulmonary medicine. Data on indications, procedures, findings, diagnostic yield and complications have been recorded. This paper describes the experiences thus gained regarding the possibilities and limitations of the method and assesses the current significance of the technique in pulmonary medicine according to previous studies. In primary diagnosis of mediastinal tissue alterations and in staging of malignant diseases the method offers a low-complication diagnostic measure which has a seminal impact on therapy in many cases, even though in daily practise the diagnostic accuracy of published studies is not always attained.

Mediastinitis caused by EUS-FNA of a bronchogenic cyst.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a safe and minimally invasive diagnostic technique for the analysis of mediastinal lesions. This case report describes a patient who developed a life-threatening mediastinitis after EUS-FNA of a mediastinal lesion, which (based on computed tomography of the thorax) had been suspected to be a lymph-node metastasis, but proved to be a bronchogenic cyst.

Chronic respiratory symptoms and airway responsiveness to methacholine are associated with eosinophilia in older men: the Normative Aging Study.

Identification of subsets of patients with chronic obstructive lung disease (COLD) in order to determine disease outcomes and, possibly, the effects of treatment is an area of clinical interest. At present, it remains unclear which patients with COLD are most likely to benefit from anti-inflammatory therapy. We investigated this question in a community-dwelling sample of men. In this study, the relationship of chronic respiratory symptoms, airway responsiveness to methacholine, and skin test reactivity to peripheral-blood eosinophil and neutrophil counts was examined among 894 male participants in the Normative Aging Study (mean age 60 yrs; range 41-90 yrs). The symptoms considered were asthma, persistent wheeze, dyspnoea, chronic cough and phlegm. Responsiveness to methacholine was defined as a provocative dose producing a 20% fall in forced expiratory volume in one second (PD20FEV1) of < or = 8.6 mumol, a positive skin test as a wheal diameter of > or = 5 mm after subtraction of the diameter of any wheal reaction to a glycerin control, and eosinophilia as an eosinophil count of > or = 275 cells.mm-3 in peripheral blood. Chronic symptoms (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.4-2.7), airway responsiveness (OR 1.7; CI 1.1-2.7), and the combination of symptoms and airway responsiveness (OR 3.4; CI 2.0-5.6) were positively and significantly related to peripheral-blood eosinophil counts. These relationships remained significant after adjustment for the effects of age and smoking, and after exclusion of asthmatic subjects. Symptoms and airway responsiveness combined were not significantly related to neutrophil counts.(ABSTRACT TRUNCATED AT 250 WORDS)