Cancer of the lung is ranked number one among men and seventh among women in our country.1 Its incidence has been reported to be 14.2/100,000 population.2 Similar to all other developing countries, causes such as working in risk-bearing industries, unrestricted smoking in the community, and unrestrained accessibility to tobacco products in the market despite regulations have continued to contribute to the increasing incidence of lung cancer in our country.3 Even in 2011, the 5-year survival from lung cancer was around 15%.4 Interestingly, the majority of patients with lung cancer present with unresectable disease and frequently undergo futile major surgical procedures.5 Studies from our country show that between 52% and 88% of patients have unresectable disease at the time of diagnosis.6,7
Tuberculosis (TB) is also quite prevalent in our country and is often included in the differential diagnosis in these patients because of its nonspecific presentation.
The proper diagnosis and staging of lung cancer is mandatory for the optimal management of these patients. Along with this, it is also essential to avoid unnecessary mediastinoscopy and thoracotomy in this group.
In recent years, positron emission tomography has been found to be a useful noninvasive staging tool for lung cancer patients; however, its utility remains limited because of its cost, access (availability), and false-positive and false-negative results.8
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has gained widespread popularity as a diagnostic and a staging tool for patients with lung cancer. Unfortunately, its use also remains limited because of its cost and the training and skills required, especially in the developing countries.9,10
Conventional transbronchial needle aspiration (C-TBNA) has been proven to be a safe, minimally invasive, and cost-effective technique in establishing the diagnosis of mediastinal pathologies.11–13 Despite its established advantages, it still remains underutilized and underemphasized in fellowship training programs.14 We believe that the C-TBNA procedure is simple enough that it could be learned outside the interventional pulmonology fellowship program through secondary measures.15 Bronchoscopists in the community can easily learn this technique for the diagnosis and the staging of lung cancer.
We present our preliminary experience with C-TBNA in the management of patients who presented to our institution with a suspected diagnosis of lung cancer.
PATIENTS AND METHODS
Our institution provides primary and tertiary care to the community it serves. There are a total of 15 physicians (consultants and fellows) in the pulmonary diseases department. We collectively perform approximately 50 conventional diagnostic bronchoscopies per month in our department. We currently do not offer any therapeutic or advanced diagnostic endobronchial procedure. We recently started performing C-TBNA in December 2009 after a review of the published literature,16–20 viewing of video tapes (ConMed Corporation, Mentor, OH, 2005, WANG Transbronchial Aspiration Needle, A Procedural Overview of Transbronchial Needle Aspiration), participation in a hands-on training course organized by an international society, and then through practice on an inanimate model for TBNA (BARD Corporation, Boston, MA and “Zavala Lung Model”). Since then, the procedure has been performed using Wang’s technique on consecutive patients presenting with mediastinal lymphadenopathy on chest computed tomography and suspected of having lung cancer.21 Our study was performed in a prospective open-label manner. Patients for whom the procedure was indicated for either diagnostic or staging purposes were included in the study. Patients in whom bronchoscopy was contraindicated were excluded from the study. Chest computed tomography was reviewed by the pulmonologist and by the radiologist independently to estimate the size and identify the location of “abnormal” lymph nodes (LN).22 Nodes were considered abnormal/enlarged if their diameter in the short axis was >10 mm.
Smooth Shot Needles (Olympus, Japan) of 21- and/or 19-gauge were used at the discretion of the bronchoscopist. 19-guage needle was mainly chosen if a benign diagnosis was included in the differential. After its insertion, the 19-gauge needed was moved back and forth by 2 to 3 mm through the tracheobronchial wall to obtain a core specimen for histologic examination; in contrast, when the 21-gauge needle was inserted to its fullest length, the catheter was agitated while applying suction at the proximal end using a 50 mL syringe to obtain loose cells for cytologic examination. Tissue specimens were prepared according to published guidelines.21
C-TBNA was performed at all N2 and N3 locations (if present) for staging and at the N1 location to establish a diagnosis of suspected lung cancer. Cytologic studies were carried out without using rapid on-site cytology examination.23 If LN from more than 1 location were sampled, calculations were carried out using the one with the largest size. A “leak test” is routinely performed after every TBNA procedure at our institution to rule out any damage to the bronchoscope.24
C-TBNA results were categorized into (1) malignant; (2) nonmalignant; and (3) nondiagnostic groups. The diagnosis of malignancy was established on the basis of cytology and/or histology findings. When tissue representative of a benign diagnosis such as sarcoidosis was present, the results were considered representative for nonmalignant or benign LN. Both malignant and benign diagnoses were considered “true positive” if they matched the clinical suspicion; otherwise, further diagnostic steps were adopted to rule out “false positives.” The results were labeled as “nondiagnostic” if no material was obtained (dry tap) or if the material was nonrepresentative of the above groups. In cases where the C-TBNA was either nondiagnostic or showed only normal lymphocytes, the final diagnosis was established by any of the following: mediastinoscopy, transthoracic needle aspiration, peripheral lymph node, and/or endobronchial biopsy. Aspirates with normal lymphocytes were considered “true negative” if no definite diagnosis was established by any of the above methods.
Diagnostic yield, sensitivity, specificity, positive predicted value (PPV), negative predicted value (NPV), and diagnostic efficacy were defined as follows:
Diagnostic yield: number of true positives (TP)/total number of procedures.
Sensitivity: TP/TP+number of false negatives (FN).
Specificity: number of true negatives (TN)/TN+number of false positives (FP).
Diagnostic efficacy (accuracy): TP+TN/total patients×100
where TP indicates abnormal LN correctly diagnosed as abnormal (malignant and benign); FP, normal LN incorrectly identified as abnormal; TN, normal LN correctly identified as normal; FN, abnormal LN incorrectly identified as normal.
All of the above values were expressed as the median and range for continuous variables.
The impact of the size and location of the lymph node on the diagnostic yield of C-TBNA was analyzed using the χ2 test. All statistical tests were 2-sided and P<0.05 was considered statistically significant. All data were analyzed using a statistical software package (SPSS, version 11.5 for windows; SPSS Inc; Chicago, IL).
The study was approved by our Institutional review board and all patients signed a detailed informed consent to participate in the study.
Fifty-four patients (M:F=38:16), mean age of 56.9±11.8 (27 to 78) years, underwent C-TBNA using either 21 or19 g (or both) Smooth Shot Olympus needles for mediastinal lymphadenopathy. Thirty-three patients had LNs >20 mm (mean: 33.8±9.7 mm) and the rest had LNs between 10 and 20 mm in size (mean: 17.8±1.9 mm). The mean diameter for all LNs was 27.5±1.09 mm. The locations of the target LNs were as follows: 19 right paratracheal, 21 subcarinal, and 14 hilar. All patients were suspected to have lung cancer; however, other conditions as a part of the differential diagnoses included lymphoma, 1; metastatic cancer, 1; TB, 8; and sarcoidosis, 12. All TBNAs were performed for staging and for diagnosis in suspected lung cancer patients. The final diagnoses were as follows: lung cancer in 26 (Fig. 1), sarcoidosis in 9 (Figs. 2, 3), reactive LNs in 15, metastatic cancer in 2 (pancreatic and rectal cancer), TB in 1, and lymphoma in 1. The final diagnosis was established by C-TBNA in 27 patients (diagnostic yield 50%), by mediastinoscopy in 19 patients, by transthoracic needle aspiration in 5 patients, by peripheral LN biopsies in 2 patients, and by endobronchial biopsy in 1 patient. The exclusive diagnostic yield of TBNA was 42.5% (n: 23). In 2 patients, the diagnosis was made by TBNA+endobronchial biopsy, whereas the diagnosis was established by TBNA+brushing and TBNA + bronchial washings in one for each. Thus, because of the use of TBNA, further diagnostic testing including mediastinoscopy was not required in >40% (23) of our patients, including in 73% of patients (19/27) with lung cancer. Bronchial washing had a diagnostic yield of 1.9%, whereas brushing had a yield of 18.5% (n: 10). Satisfactory C-TBNA specimens were obtained from all aspirates except one (dry tap).
C-TBNA revealed a definitive diagnosis in 27 patients (20, lung cancer; 2, metastatic cancers; 5, sarcoidosis); 16 aspirates revealed normal lymphocytes, whereas 10 specimens had limited cellularity and a specific diagnosis could not be established.
We found that lymph node size had an impact on the outcome of TBNA (P=0.002) (diagnostic yield in <20 mm LNs: 23.8%, diagnostic yield in >20 mm LNs: 66.7%), whereas location did not (P=0.82) (Table 1). C-TBNA was positive in 22/34 when only a malignant diagnosis was suspected (diagnostic yield 64.7%), whereas in cases for which nonmalignant conditions were included in the differential diagnosis, it was positive in 5/20 patients (diagnostic yield 25%) and this difference was statistically significant (P=0.005) (Table 2). We did not obtain any false-positive results that did not match our clinical suspicion (false-positive). C-TBNA had a higher diagnostic yield in malignant processes (22/29) than in the nonmalignant processes (5/25) (75.9% vs. 20%, P=0.000). The sensitivity and specificity of C-TBNA was 79.4% and 100%, respectively. The PPV was 100% and the NPV was 73%. The overall accuracy of the procedure was 85.1% (Table 2). We did not have any specific difficulty in using either 21- or 19-gauge needles. There were no complications and no damage to the bronchoscope.
Smoking is highly prevalent in Turkey. It is estimated that there are in excess of 20 million tobacco users in the country and the numbers of smokers have increased by 80% in the last 20 years.25 Because of this high smoking rate, lung cancer is a major health hazard in our country. Unfortunately, most patients have unresectable disease at the time of diagnosis. Studies from our country show that between 52% and 88% of patients have unresectable disease at the time of diagnosis.6,7 Yet, many undergo either mediastinoscopy or thoracotomy.26 All of our lung cancer patients were also found to have unresectable disease at the time of presentation. C-TBNA facilitates the diagnosis of mediastinal lesions and staging of lung cancer in a minimally invasive manner.27 The yield of C-TBNA in the diagnosis and staging of lung cancer has been reported to be between 20% and 80% in the literature.17–22 In our country, most patients do not have access to a tertiary care center where a Positron emission tomography scan or EBUS is frequently used, whereas C-TBNA can be carried out in a community setting.
In our population, the sensitivity and the diagnostic yield of C-TBNA for lung cancer has been found to be between 58% to 70% and 60% to 100%, respectively.28–35 The use of C-TBNA along with conventional diagnostic procedures increases the diagnostic yield in patients with visible endobronchial lesions.36 A prospective study from our university involving 95 patients presenting with visible tumors detected during bronchoscopy showed that TBNA must be performed in patients with submucosal-peribronchial disease. Under the circumstances, it increases the diagnostic yield of flexible bronchoscopy from 69.4% to 94.4% (P=0.008).35
In our study, the sensitivity of C-TBNA for lung cancer was 80%, which agrees with the literature. A few reports published from Turkey have revealed the diagnostic yield to be between 42% and 87.5%.28,30,35 Our study shows that C-TBNA could be exclusively diagnostic in 42.5% of patients and mediastinoscopy can be avoided in 50% of patients, improving patient welfare and reducing the cost of medical care.
In the present study, similar to other studies, LN size was found to show a significantly positive correlation with C-TBNA diagnostic yield.37–39 However, we could not demonstrate any significant difference in the yield on the basis of the LN location; this could have been because of the small size of our study.37–40 The diagnostic yield of TBNA was lower in benign diseases compared with malignant diseases, consistent with the literature,3,37 despite the use of a histology needle.
Although C-TBNA is a simple technique, it remains underutilized,41,42 for which several reasons have been provided, including lack of proper training, and fear of entering the major intrathoracic vessels and damage to the bronchoscope.42
We believe that the procedure of C-TBNA is simple enough that it could be learned outside the IP fellowship program through secondary measures, and could be carried out in community practice.15 In recent years, the popularity of endobronchial (EBUS) and esophageal ultrasound has led to reduced interest in the training of C-TBNA, and the availability of instruments is also limited in the developing countries.40
There are several weaknesses in our study. First, this is a preliminary study and that we are still on a learning curve. We were also not able to establish a diagnosis when the LN were <20 mm in size and all of our lung cancer patients had unresectable disease. Yet, the latter is exactly the reason we wish to promote C-TBNA as it would prevent unnecessary mediastinoscopy and thoracotomy in our patients. Second, we had a small sample size of patients. However, our results do agree with the studies published from centers with more experience. Moreover, we did not use rapid on-site cytology examination, which has been shown to significantly impact the diagnostic yield of TBNA and reduce the number of dry taps.23
In conclusion, C-TBNA is a safe, simple, and a reliable technique. It remains underutilized due to several reasons including lack of required formal training. Our study proves that the procedure can be successfully learned without formal training and can be easily applied in the community practice.15 Even in the era of EBUS and esophageal ultrasound, acquisition of skills to perform C-TBNA is essential as availability of instruments and accessories is limited in the developing countries.43 C-TBNA benefits patients with suspected lung cancer.
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