Conventional transbronchial needle aspiration (C-TBNA) is a well-established technique for the diagnosis and staging of bronchogenic carcinoma. However, in recent years the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has established itself as a primary diagnostic and staging technique for bronchogenic carcinoma.1–3 It is also being used to diagnose sarcoidosis as well as lymphoma involving the mediastinal lymph nodes.4 Beacuse of the implementation of EBUS-TBNA, the C-TBNA is being used less frequently.
Acquiring skills to perform EBUS-TBNA remain challenging; it is estimated that it takes close to 100 procedures to be proficient at the technique.5,6 Besides, minimum number of procedures required to maintain the proficiency is estimated to be 50/year.7 This challenge is further highlighted with the fact that around the world <30% of bronchoscopists perform >100 procedures per year. It is gradually being realized that to maintain its cost-effectiveness the procedure should mainly be performed at the Centers of Excellence.8 Furthermore, the ultrasound equipment and the accessories are relatively expensive9,10; in our country, the needle of EBUS-TBNA costs close to 300 Euros that is substantially higher than the reimbursement for the entire bronchoscopy procedure.11
In contrast, learning curve for C-TBNA is short and steep12; the cost is lower and does not require any financial investment. The technique is simple, safe, and has been proven to be sensitive in establishing diagnosis of mediastinal pathologies.13 Nevertheless, with higher accuracy of EBUS-TBNA in staging of bronchogenic carcinoma, popularity of C-TBNA is diminishing. Despite its proven diagnostic utility and the opinion of some authors that believe that the C-TBNA should be consider in ensuring future competence in standard bronchoscopy,14 some of the pulmonary fellowship programs and “Centers of Excellence” have chosen to eliminate training for C-TBNA from their curriculum. This certainly raises a dilemma for the community pulmonologists, should they also abandon the practice of C-TBNA?
In this study we tried to address this issue from a different perspective as both the technologies are available and actively used at our institution. It was our team’s consensus that since the implementation of EBUS-TBNA program our diagnostic yield for C-TBNA seemed to have improved. We carried out the following exercise to substantiate our perception; if proved positive it would impact our practice.
MATERIALS AND METHODS
C-TBNA is routinely performed at our institution since 1994, on an average we perform 100 C-TBNA procedures per year. We acquired and implemented EBUS-TBNA technology at our institution during September 2009. The involved bronchoscopists were trained with EBUS via hands-on courses and preceptorship. Over 50 EBUS-TBNA were performed at our institution before commencing the study. All bronchoscopists felt confident in their skills for EBUS and C-TBNA. In patients suspected to have lung cancer, since EBUS is available, it is our common practice to perform C-TBNA first for the purpose of staging and establishing the diagnosis. If the initial bronchoscopy remains negative then we perform a repeat procedure using EBUS-TBNA.
We prospectively collected data on all C-TBNAs performed at our institution, between March 2008 and November 2011 in patients with suspected non–small cell lung cancer. The decision to perform the C-TBNAs was made on the review of a prebronchoscopy computed tomography chest revealing mediastinal involvement with lymph nodes >10 mm in diameter. We compared the diagnostic performance of C-TBNA in 2 groups of patients: before (group A) and after (group B) implementing EBUS technology in our practice.
The study was approved by the institutional review board of our University.
C-TBNA was performed using standard flexible video-bronchoscopes (Olympus Optical Co. Ltd., Japan). Staging C-TBNA was performed before performing complete airway examination or collecting any other specimen to avoid contamination of the working channel of the bronchoscope. Bronchoscopic examination of the complete airway was performed after performing the TBNA.
Patients underwent C-TBNA with 21-G needle under moderate sedation with midazolam or deep sedation with propofol after administration of local anesthesia. In every patient, we made C-TBNA in all stations with lymph nodes >10 mm in short axis. The total number of passes obtained from each site/station was between 2 and 4 depending upon the bronchoscopists’ preference. C-TBNA technique was performed by the same bronchoscopists before (group A) and after (group B) being trained in EBUS. All TBNA samples was obtained with a 21-G cytology needle (NA-1C-1; Olympus Medical System Corp., Japan). The technique employed for inserting the needle through the tracheobronchial wall was either “jabbing” or “hub against the wall” method.15 Aspirated specimens were blown onto a slide using the “smear technique,” and were fixed with 96% alcohol and stained with either Diff-Quick (American Scientific Products, McGawPark, IL) or quick hematoxylin and eosin in the cytopathology laboratory. Any additional material retrieved from the aspiration needle was placed in a preservation solution (CytoLyt; Cytyc Corp, Marlborough, MA). After centrifugation, the solid component or the pellets were fixed in 10% formalin, prepared by standard cell-block preparation method, embedded in paraffin, and processed using standard histology and immunohistochemistry techniques. We did not perform rapid onsite evaluation (ROSE) in any case of C-TBNA. Additional samples, such as brushings, washings, and forceps biopsy samples were also obtained depending on the locations of the primary tumor and findings of the bronchoscopy.
Evaluation of Data
Samples were considered valid or adequate whenever lymphocytes were found in the smears indicating the sample was obtained from a lymph node, or samples with positive or negative results. Positive result was the presence of neoplastic cells in the samples or the final histopathologic study after mediastinoscopy or thoracotomy. Negative findings included all cases without malignant cells—including all cases of atypia, metaplasia, or dysplasia—or a specific diagnosis different from lymph node metastases. Nondiagnostic specimens with paucity of lymphocytes were considered inadequate. As mentioned earlier, we performed EBUS-TBNA if the initial bronchoscopy remained negative.
The statistical analysis was performed using SPSS 20, with license of Salamanca University. The 2×2 contingency tables were prepared to calculate the sensitivity, specificity, and positive and negative predictive values and compared for both series of cases. The Student t and Fisher exact test were used. An α value of <0.05 was considered statistically significant (P<0.05).
A total of 147 cases were included in group A (82.3% males; median age, 63), and 67 cases in group B (85.1% males; median age, 67). Although EBUS was implemented in our center in September 2009, we did not include cases in group B until July 2010. Thus only C-TBNA cases before completing the EBUS learning period (the first 50 cases) have been included in the group A.
There was no statistical differentiation in demographics between the 2 groups. The overall prevalence of N2 disease was 28.1%, and it was similar in both groups.
The stations most frequently sampled were 7, 4R and 4L in both the groups. There was no statistically significant difference neither on the number of different stations sampled among both groups (Fig. 1) neither on the size of the lymph nodes (12.6 vs. 13.1 mm).
In group A, we obtained positive results in 25% of C-TBNA. The most frequent stations sampled in that group were 4R and 7: 75% of all C-TBNA. Higher percentages of inadequate samples were obtained from station 4L. As a whole, the rate of inadequate samples was 52% of the C-TBNA and 49.7% of the patients (Table 1).
In group B, positive results were obtained in 41% of all C-TBNA, and this was significantly higher than group A (P<0.001). The most frequent stations sampled in this group were also 4R and 7 (81% of all C-TBNA). Similar to the group A, higher percentages of inadequate samples were from station 4L; although significantly lower (86% vs. 40%) P=0.001. The total rate of inadequate samples in this group was 34.7% of C-TBNA and 31.4% of the patients (Table 2).
Overall diagnostic yield of C-TBNA was significantly higher in group B than group A (P<0.001). In group A, C-TBNA was exclusively diagnostic (other techniques such as brushings, washings, and forceps biopsy samples were negatives) in 9.5% of cases, whereas that rate was 24% in group B (P<0.0001) (Table 3). Overall test accuracy and sensitivity was higher in group B as compare to group A; 86% versus 66% and 86% versus 63%, respectively (P<0.001). Negative predictive values was also higher in group B (P<0.001) (Table 4). There was a significant difference in the number of inadequate samples between groups A and B; 49.7% versus 31.1%, respectively (P=0.00001).
After analyzing each nodal station, overall accuracy was higher in station 4R but not in region 7, where we could not see any change (Table 5).
No complications related to the TBNA were encountered, neither was there any damage to the bronchoscopes.
At our institution our approach is to perform C-TBNA first and consider EBUS-TBNA only if the former test remains negative. With this approach in the group A we have reported sensitivity and accuracy of C-TBNA of 63% and 66%, respectively, while dealing with bronchogenic carcinoma. The results are comparable with those in the published in the literature.16 These values do vary based on the prevalence of the disease in the community as well as with availability of ROSE.17–20 A meta-analysis on the outcomes from C-TBNA analyzing such factors showed that the performance of TBNA is highly variable, with a pooled sensitivity varying from 39% to 78% depending upon the disease prevalence of mediastinal metastasis, low (34%) versus high (81%).21 In the group B these values has arisen significantly to a sensitivity and accuracy of 86% (both of them). This increase in accuracy following implementing the practice of the EBUS could be explained by an improvement in the knowledge of the anatomy of the mediastinum and the lymph node station locations.22 This anatomic correlation helped the bronchoscopist feel more secure while performing multiple passes of C-TBNA.12,17 In addition, the rate of positive diagnoses was also higher in the group B, approximately 40%, and C-TBNA was the exclusive diagnostic method in 24% of cases. In group B, after implementing the EBUS, the number of inadequate samples also decreased considerably (86% vs. 40%). In general, the rate of inadequate sampling is statistically significantly lower in the group B, after the acquisition of skills upon implementation of the EBUS.
Thus, C-TBNA also decrease the need for other evidence necessary for staging such as EBUS-TBNA or mediastinoscopy, which means that our experience represents a saving in the cost of staging. The reduction in number of mediastinoscopies for the staging of lung cancer has already been demonstrated by other authors.19 We fully agree with Kuntz et al11 that combination of C-TBNA and EBUS-TBNA seems to be the most cost-effective means for staging of lung cancer. In fact, it has already been postulated that both techniques are not mutually exclusive but complementary, and the appropriate modality can be selected in a cost-effective manner based in a more effective way depending on the purpose (staging or diagnosis) of the procedure and individual patient lymph node characteristics.23
The stations most frequently sampled in both groups were 4R, 4L, and 7. In both scenarios, before and after implementing the EBUS, most inadequate samples were obtained from the station 4L. This has also been experienced by other authors.19 This location poses most difficulty probably due to the need for a greater degree of angle for the needle and due to the proximity of great intrathoracic vessels. The increase in the diagnostic accuracy was also maintained while studying the different stations. In the 4R region the accuracy increases from 62% to 84%, but there was no such impact in subcarinal region (73 vs. 72%). Similar observations have also been reported by other authors.24 The prevalence of N2 disease in our series (31.4% group A) was low, which could influence the results of accuracy in our initial experience, (66%) although it is unlikely to be a major determining factor as the prevalence of N2 in the second series (24.8% group B) was also lower and in this diagnostic performance higher.
In our practice of the C-TBNA, ROSE is not available but it is used while performing EBUS-TBNA. Impact of ROSE, however, on the performance of C-TBNA has not been confirmed in all studies.24,25 As we did not use ROSE on our C-TBNA specimens it certainly did not impact our diagnostic yield directly, however, it is possible that its availability during the EBUS-TBNA helped us better understand the location of the mediastinal lymph nodes and also improvise our technique for both needle aspirations.
In summary, the diagnostic yield of C-TBNA increases significantly from 64.8% to 87% after the implementation of the EBUS-TBNA. Beside, exclusivity of the C-TBNA also increases after the acquiring EBUS-TBNA skills. We strongly feel that the C-TBNA should be performed routinely as the first diagnostic test in patients with suspected lung cancer and mediastinal lymphadenopathy. Therefore, the practice of C-TBNA remains useful in a variety of indications. The C-TBNA should be performed routinely during bronchoscopy and that it should be implemented in the training program for pulmonary fellows.
The authors thank Manuel Lanchas Hernando and Mª José Rodríguez Celador for daily assistance during the procedures and to Mariam Montero for the revision of the submitted article.
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Keywords:© 2014 by Lippincott Williams & Wilkins.
C-TBNA; EBUS training; non–small cell lung cancer