Negative Predictive Value Of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Research Articles

Utility and safety of endobronchial ultrasound-guided transbronchial needle aspiration in patients with mediastinal and hilar lymphadenopathy: Western region experience.

AIMS:The aim of the study was to evaluate the clinical utility and safety of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with mediastinal and hilar lymphadenopathy and to explicitly describe the utility of this procedure in patient's outcome.METHODS:A retrospective review and analysis was conducted on 52 patients with mediastinal or hilar lymphadenopathy who underwent EBUS-TBNA from June 2012 to June 2016. All the patients were evaluated by computed tomography (CT) chest with contrast before EBUS examination. Enlarged mediastinal or hilar lymph node was defined as >1 cm short axis on the enhanced CT.RESULTS:Among the 52 patients studied, 57.7% were presented with mediastinal or hilar lymphadenopathy for diagnosis and 42.3% presented with suspected mediastinal malignancy. Paratracheal stations were the most common site for puncture in 33 lymph nodes (43%). The best diagnostic yield was obtained from subcarinal stations and the lowest yield from the hilar stations. Surgical biopsies confirmed lymphoma in six patients, tuberculosis (TB) in three, sarcoidosis in two and one had metastatic adenocarcinoma of unknown primary. The sensitivity, specificity, positive predictive value, and negative predictive value of EBUS-TBNA for diagnosis of mediastinal and hilar lymph node abnormalities were 78.6%, 100%, 100%, and 80%, respectively. The diagnostic yield of EBUS-TBNA in malignant and benign conditions was 79.0%.CONCLUSIONS:EBUS-TBNA is a safe and efficacious procedure which can be performed using conscious sedation with high yields. It can be used for the staging of malignancies as well as for the diagnosis of inflammatory and infectious conditions such as sarcoidosis and TB.

Diagnostic yield of EBUS-TBNA for lymphoma and review of the literature.

Aim:Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), which enables cytological examination of mediastinal lymph node (LN) aspiration samples, is a safe and minimally invasive method for diagnosis and staging of lung cancer and diagnosis of diseases affecting mediastinal LNs. In this study, we investigated the yield of EBUS-TBNA for diagnosis of lymphoma and reviewed the literature since the British Thoracic Society (BTS) guidelines were published.Materials and Methods:We retrospectively evaluated our database for patients who underwent EBUS between March 2011 and December 2014. One hundred eighty-nine patients with isolated mediastinal lymphadenopathy were included in the study. Patients with other causes of lymphadenopathy, such as lung cancer or extrathoracic malignancy, and those with pulmonary lesions accompanying mediastinal lymphadenopathy were excluded from the study. Patients with final diagnosed lymphoma were included in the study on the basis of a history of lymphoma or newly evaluated mediastinal lymphadenopathy. The sensitivity and negative predictive value (NPV) of EBUS-TBNA were calculated.Results:There were 13 patients with the final diagnosis of lymphoma. Eleven of them were new diagnoses and 2 patients were known chronic lymphocytic leukemia (CLL), and underwent EBUS-TBNA for determination of recurrence. Twelve EBUS-TBNA procedures were performed for suspected new cases. Three (25%) were diagnostic, 2 (16.7%) were suspicious for lymphoma and underwent further interventions for definite diagnosis, and 7 (58.3%) were false negative. All 3 patients diagnosed with EBUS-TBNA were non-Hodgkin lymphoma (NHL). None of the Hodgkin lymphoma (HL) cases could be diagnosed with EBUS-TBNA. The overall diagnostic sensitivity and NPV of EBUS-TBNA in detecting lymphoma was 65% and 96.1%, respectively. For the newly diagnosed lymphoma cases, EBUS-TBNA had a sensitivity of 61.1%.Conclusion:In conclusion, we believe that since the publication of the BTS guidelines, the value of EBUS-TBNA in the diagnosis of lymphoma still remains controversial. EBUS-TBNA can be the first diagnostic modality in diagnosis of recurrent lymphomas. However, for suspected new cases, especially for HL, the diagnostic yield of EBUS-TBNA is low and negative results do not exclude lymphoma. Further interventions such as mediastinoscopy should be performed for high-suspicion patients.

Negative Predictive Value of Granulomas on EBUS-TBNA in Suspected Extrathoracic Malignancy

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established diagnostic tool for lung cancer, sarcoidosis, and suspected metastatic extrathoracic malignancy. EBUS-TBNA carries a high diagnostic yield, but its negative predictive value (NPV) requires further clarification. We reviewed EBUS-TBNA at our cancer center from 2008 to 2015. We identified negative diagnostic samples for adenopathy suspected to represent metastatic disease from extrathoracic malignancy. We reviewed 529 EBUS-TBNAs. Ninety patients underwent EBUS-TBNA sampling of the hilum and/or mediastinum (121 nodes, 14 masses) for suspected extrathoracic malignancy. Thirty-seven patients had negative samples (lymph node, granulomas or non-diagnostic specimens). The overall NPV was 98%. Granulomas (11 patients, 25 nodes) seen on histology had a 100% NPV, including those that were FDG-PET (fluorodeoxyglucose positron emission tomography) avid (n=14 nodes). Negative EBUS-TBNA in patients with extrathoracic malignancy and suspected secondary hilar or mediastinal metastases can infer a high NPV especially if granulomas are seen on histology. Larger prospective investigations are needed to confirm the high NPV of EBUS-TBNA with granulomas in extrathoracic malignancies.

The utility of EBUS-TBNA in mediastinal or hilar lymph node evaluation in extrapulmonary malignancy

The aim of this study was to determine the diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of mediastinal and hilar lymph nodes (LNs) in patients with known extrapulmonary malignancy. Between March 2011 and August 2013, 378 EBUS-TBNA procedures were performed. Sixty-three (16.6%) of these were performed on known extrapulmonary malignancy patients. There were 28 male and 35 female patients, with median ages of 65 years (min-max: 53-87) and 57 years (min-max: 39-76), respectively. From the 63 cases, 138 lymph nodes (LNs) were sampled with EBUS-TBNA (median: 2 LNs/patient; min-max: 1-4). Results of EBUS-TBNA revealed malignancy in 18 (28.5%) and nonmalignancy in 45 (71.5%). In the nonmalignant group, there were false negatives in 5 (7.9%), anthracosis in 13 (20.6%), reactive adenitis in 16 (25.3%), sarcoidosis in 7 (11.1%), and tuberculosis in 2 (3.1%), and 2 were not evaluated (lost to follow-up) (3.1%). The diagnostic sensitivity, accuracy, and negative predictive value of EBUS-TBNA per patient were 78.2%, 91.8%, and 88.3%, respectively. EBUS-TBNA is a safe, minimally invasive, and effective method and can be considered as the initial test for the histopathological diagnosis of mediastinal and hilar lymphadenopathy in patients with extrapulmonary malignancy.

Endobronchial ultrasound-guided transbronchial needle aspiration for systematic nodal staging of lung cancer in patients with N0 disease by computed tomography and integrated positron emission tomography-computed tomography.

Data regarding the sensitivity of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for staging of lung cancer in patients with radiographic N0 disease is scant and inconsistent. With increasing use of nonoperative ablative therapies, studies focusing on the performance characteristics of EBUS-TBNA in this population are important. To evaluate the sensitivity and negative predictive value (NPV) of EBUS-TBNA in patients with non-small cell lung cancer and radiographic N0 disease both by computed tomography (CT) and positron emission tomography (PET)-CT. This was a retrospective review of EBUS-TBNA performed for lung cancer staging at two major academic centers from 2009 to 2014. Patients with radiographic N0 disease (lymph nodes [LN]≤1 cm in the short axis and maximum standardized uptake value≤2.5 by PET-CT) were included. Primary outcome was sensitivity and NPV of EBUS-TBNA. Two hundred twenty patients with radiographic N0 disease underwent EBUS-TBNA, and 734 LN were sampled (median 3, range 1-6). Median LN diameter was 0.72 cm. One hundred patients (45.5%) underwent surgery, and 120 patients (54.5%) had nonsurgical therapy. N status was up-staged in 49 patients (22.3%): 18 by EBUS-TBNA (N1=11, N2=6, N3=1), 27 by surgery (N1 intralobar=16, N1 extralobar=3, N2=8 [5 LN in stations 4 and 7, and 3 LN in stations 5-6), and 4 by imaging follow-up (N1=2, N2=2). Overall false-negative rate of EBUS was 14.1% (sensitivity, 36.7%; specificity, 100%; and NPV, 84.7%). False-negative rate was 27 and 3.3% in surgical and nonsurgical populations, respectively. Excluding patients with occult disease "outside" the reach of EBUS, the overall false-negative rate of EBUS-TBNA was 5.5% (sensitivity, 60%; specificity, 100%; and NPV, 93.4%). This is the largest report of EBUS-TBNA in patients with N0 disease by "integrated" PET-CT. The majority of false-negative EBUS results were in LN stations outside its reach. In our study, both sensitivity and NPV of EBUS-TBNA were lower than early reports despite more extensive LN sampling. Given the high false-negative rate of imaging modalities, EBUS-TBNA may still play an important role in patients with radiographic N0 disease, particularly when nonsurgical ablative therapies are planned. Prospective studies are needed to corroborate our findings in the nonsurgical population.

Initial experience with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) from a tuberculosis endemic population.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a widely accepted minimally invasive procedure for the evaluation of mediastinal lymphadenopathy. Most of the published literature on EBUS-TBNA is focused on the diagnostic and staging aspects of lung cancer. Literature on the utility of this modality from developing countries and settings with a high prevalence of tuberculosis (TB) is limited. We herein describe our preliminary experience over 1 year on the utility of EBUS-TBNA from a tertiary care teaching center in North India. The primary objective was to evaluate the utility of convex probe EBUS-TBNA as a modality for diagnosis in patients with mediastinal lymphadenopathy presenting to our center. EBUS-TBNA was performed under local anesthesia and conscious sedation in the bronchoscopy laboratory. Rapid on-site evaluation was available for most of the procedures. Patients were discharged the same day from the hospital. A total of 102 patients with mean age of 42.1±14.2 years underwent EBUS-TBNA for a clinical indication of enlarged mediastinal lymph nodes, between September 2012 and September 2013.There were 63 males (61.8%) and 39 females (38.2%). EBUS-TBNA was performed for staging lung cancer in 5 patients.A total of 216 lymph node stations were sampled in 102 patients. Rapid on-site evaluation was performed in 95 patients (93.1%). Adequate/representative samples could be obtained in 98 of 102 patients (96.1%). Overall, EBUS-TBNA was diagnostic in 76 patients (74.5%). EBUS-TBNA was diagnostic in 80.9%, 84.8%, and 75% of patients with sarcoidosis, TB, and lung cancer, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value of EBUS-TBNA were 81.7%, 100%, 100%, and 22.73%, respectively. EBUS-TBNA is a safe and efficacious procedure for obtaining tissue diagnosis in patients with mediastinal lymph node enlargement. The yield of EBUS-TBNA in diagnosis of mediastinal lymph node enlargement due to TB is especially high.

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Differentiating N0 Versus N1 Lung Cancer

The aim of this study was to assess the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for differentiating cN0 versus cN1 non-small cell lung cancer. A retrospective review of EBUS-TBNA results in patients with potentially resectable clinical N0 or N1 non-small cell lung cancer based on computed tomography and positron emission tomography was performed. Systematic mediastinal and hilar lymph node sampling was performed by EBUS-TBNA. Lymph nodes larger than 5 mm in short axis or suspicious nodes were targeted. In the absence of N2 or N3 disease, patients underwent resection with lymph node dissection. A total of 981 patients underwent EBUS-TBNA during the study period, of which 163 patients met the study criteria. There were 94 cN0 and 69 cN1 patients. A total of 453 lymph nodes (338 mediastinal and 115 N1 lymph nodes, average 2.8 nodes/patient) were sampled. Endobronchial ultrasound upstaged 9 (5.5%) patients to N2 disease, but was falsely negative in the mediastinum in 7 (4.3%) patients. In cN0 patients, EBUS confirmed N0 in 87 (53.4%) and upstaged in 7 (4.3%, N1 in 1, N2 in 6). In cN1 patients, EBUS confirmed N1 in 19 (11.7%), downstaged in 47 (28.8%), and upstaged in 3 (1.8%). The sensitivity, specificity, diagnostic accuracy, and negative predictive value of EBUS-TBNA to accurately differentiate between N0 and N1 disease was 76.2%, 100%, 96.6%, and 96.2%, respectively. The accuracy of mediastinal staging was 95.7%. Endobronchial ultrasound-guided transbronchial needle aspiration can accurately access the hilar and interlobar lymph nodes in patients with potentially resectable lung cancer. Accurate assessment of cN0 versus cN1 by EBUS-TBNA may be used to guide induction therapy before surgery.

Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of intrathoracic lymph node metastases from extrathoracic malignancies.

Intrathoracic lymph node enlargement is a common finding in patients with extrathoracic malignancies. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a technique that is commonly used for lung cancer diagnosis and staging but that has not been widely investigated for the diagnosis of enlarged mediastinal and lobar lymph nodes in patients with extrathoracic malignancies. We conducted a retrospective study of 117 patients with extrathoracic malignancies who underwent EBUS-TBNA for diagnosis of intrathoracic lymph node enlargement from October 2005 to December 2009 and compared the EBUS-TBNA findings with the final diagnoses. EBUS-TBNA diagnosed mediastinal metastases in 51 of the 117 (43.6 %) cases and gave an alternate diagnosis or ruled out the presence of malignancy in 35 (56.4 %). Fourteen of these 35 patients underwent further surgical investigation, while the remaining 21 had clinical and radiological follow-up for 18 months. No false negatives were found in the surgery group. In the follow-up group, 13 patients had stable or regressive lymphadenopathy, and eight developed clinicoradiological progression and were assumed to have been false negatives by EBUS-TBNA. The sensitivity and negative predictive value of EBUS-TBNA were 86.4 and 75 %, respectively. Immunohistochemical staining (IHC) was performed in 80.4 % of the samples obtained by EBUS-TBNA. In samples obtained from ten patients with metastatic breast cancer, estrogen receptor expression was successfully assessed in eight patients and progesterone receptor and human epidermal growth factor receptor 2 in four. EBUS-TBNA is an accurate procedure for the diagnosis of thoracic lymph node metastases in patients with extrathoracic malignancies and should be an initial diagnostic tool in these patients. Furthermore, EBUS-TBNA can obtain high-quality specimens from metastatic lymph nodes for use in molecular analyses.

Endobronchial Ultrasound–guided Transbronchial Needle Aspiration Prevents Mediastinoscopies in the Diagnosis of Isolated Mediastinal Lymphadenopathy

Patients with isolated mediastinal lymphadenopathy (IML) are a common presentation to physicians, and mediastinoscopy is traditionally considered the "gold standard" investigation when a pathological diagnosis is required. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is established as an alternative to mediastinoscopy in patients with lung cancer. To determine the efficacy and health care costs of EBUS-TBNA as an alternative initial investigation to mediastinoscopy in patients with isolated IML. Prospective multicenter single-arm clinical trial of 77 consecutive patients with IML from 5 centers between April 2009 and March 2011. All patients underwent EBUS-TBNA. If EBUS-TBNA did not provide a diagnosis, then participants underwent mediastinoscopy. EBUS-TBNA prevented 87% of mediastinoscopies (95% confidence interval [CI], 77-94%; P < 0.001) but failed to provide a diagnosis in 10 patients (13%), all of whom underwent mediastinoscopy. The sensitivity and negative predictive value of EBUS-TBNA in patients with IML were 92% (95% CI, 83-95%) and 40% (95% CI, 12-74%), respectively. One patient developed a lower respiratory tract infection after EBUS-TBNA, requiring inpatient admission. The cost of the EBUS-TBNA procedure per patient was £1,382 ($2,190). The mean cost of the EBUS-TBNA strategy was £1,892 ($2,998) per patient, whereas a strategy of mediastinoscopy alone was significantly more costly at £3,228 ($5,115) per patient (P < 0.001). The EBUS-TBNA strategy is less costly than mediastinoscopy if the cost per EBUS-TBNA procedure is less than £2,718 ($4,307) per patient. EBUS-TBNA is a safe, highly sensitive, and cost-saving initial investigation in patients with IML. Clinical trial registered with ClinicalTrials.gov (NCT00932854).

The utility of endobronchial ultrasound-guided transbronchial needle aspiration in mediastinal or hilar lymph node evaluation in extrathoracic malignancy: Benign or malignant?

OBJECTIVE:Newly arising enlarged or hypermetabolic mediastinal/hilar lymph nodes (LNs) in patients with previously diagnosed extrathoracic malignancies raise suspicion of metastasis. Relatively high proportion of these LNs is due to a benign condition. We aimed to determine frequency of malignant LNs and role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for clarification of the origin of suspicious LNs in these patients.METHODS:Consecutive patients with a known extrathoracic malignancy and suspected hilar/mediastinal LN were included in this prospective study. Computed tomography (CT) of thorax and positron emission tomography-CT of all patients were taken. LNs with short axis >1 cm at CT of thorax and SUV ≥ 2.5 were accepted suspicious for malignancy. All patients underwent EBUS-TBNA for pathological verification of LNs. Patients with benign diagnosis either underwent invasive procedures or were followed up. The results were evaluated for frequency of malignant hilar/mediastinal LNs and sensitivity, specificity, and diagnostic values of EBUS-TBNA.RESULTS:A total of 48 cases with a mean age of 57.4±11.6 were included. All cases had the diagnosis of an extrathoracic malignancy. 78 LNs were aspirated with EBUS-TBNA in 48 cases (1.62 LNs/patient). The mean short axis of aspirated LNs was 1.51±0.63. Results of EBUS-TBNA revealed malignancy in 15 cases (31.2%), tuberculosis in six cases (12.5%), sarcoidosis in four cases (8.3%), and reactive adenitis in 23 cases (48%). The sensitivity, specificity, and negative predictive value of EBUS-TBNA for malignancy were 83.3%, 100%, and 90.9%, respectively. When both benign and malignant diseases were considered, sensitivity, specificity, negative predictive value, and diagnostic accuracy of EBUS-TBNA were 89.2%, 100%, 86.9%, and 93.7%, respectively.CONCLUSIONS:The ratio of benign LNs in patients with extrathoracic malignancies is relatively high. EBUS-TBNA is a safe, minimally invasive, and effective method for clarification of intrathoracic LNs.

Application of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Following Integrated PET/CT in Mediastinal Staging of Potentially Operable Non-small Cell Lung Cancer

The role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) following integrated PET/CT scanning in mediastinal staging of non-small cell lung cancer (NSCLC) has not been assessed. We prospectively evaluated the diagnostic values of PET/CT scanning and EBUS-TBNA for mediastinal staging in 117 patients with potentially operable NSCLC with accessible mediastinal lymph nodes (diameter range, 5 to 20 mm) by EBUS-TBNA. Subgroup analysis according to histologic type was performed. Of 30 cases of mediastinal metastasis, 27 were confirmed by EBUS-TBNA and 3 were confirmed by surgery. EBUS-TBNA results confirmed all cases with true-positive PET/CT scan findings and six of nine cases with false-negative PET/CT scan findings. The sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy of EBUS-TBNA in the detection of mediastinal metastasis were 90.0%, 100%, 100%, 96.7%, and 97.4%, respectively. For PET/CT scans, the values were 70.0%, 59.8%, 37.5%, 85.2%, and 62.4%, respectively (p = 0.052; p < 0.001; p < 0.001; p = 0.011; p < 0.001, respectively). In adenocarcinoma (n = 55), EBUS-TBNA detected four of six cases with false-negative PET/CT scan findings, and the NPV was higher for EBUS-TBNA than for PET/CT scans (94.6% vs 77.8%, respectively; p = 0.044). In squamous cell carcinoma (n = 53), the NPV of EBUS-TBNA and PET/CT scans were similarly high (97.9% vs 96.3%, respectively; p = 0.689). EBUS-TBNA was an effective invasive method following PET/CT scanning in the mediastinal staging of potentially operable NSCLC. In mediastinal PET/CT scan-positive cases, EBUS-TBNA was an excellent tool for detecting mediastinal metastasis. Even in mediastinal PET/CT scan-negative cases, EBUS-TBNA can be useful for confirming mediastinal metastases, especially in adenocarcinoma.