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Abstract
Rationale: Technological advances have improved the ability of bronchoscopists to access peripheral pulmonary lesions for tissue sampling. Radial probe endobronchial ultrasound (EBUS) provides real-time feedback to guide biopsies of peripheral lesions, thereby potentially improving diagnostic yield over conventional bronchoscopy.
Objectives: We assessed the overall diagnostic yield of peripheral bronchoscopy using radial probe EBUS for peripheral pulmonary lesions, as well as factors that might influence the diagnostic yield, such as radial ultrasound view, lesion size, and ability to locate the peripheral lesion.
Methods: We conducted a retrospective review of peripheral bronchoscopy cases in which radial probe EBUS was utilized to diagnose peripheral pulmonary lesions at a tertiary care university hospital.
Measurements and Main Results: Our study cohort comprised 496 patients who underwent bronchoscopies between January 2008 and December 2012 for the diagnosis of peripheral pulmonary lesions. Radial probe EBUS was used alone for diagnostic purposes in 467 patients. A diagnosis was made on that basis in 321 (69%) of 467 patients. A diagnosis was obtained for 83 of 144 (58%) of nodules 1–2 cm in diameter, 99 of 137 (72%) of nodules 2.1–3 cm, 54 of 70 (77%) of nodules 3.1–4 cm, 41 of 47 (87%) of nodules 4.1–5 cm, and 35 of 40 (88%) of nodules larger than 5.1 cm. Of all 467 nodules, 446 (96%) were successfully identified using radial probe EBUS. When the radial probe position was within the target lesion, the diagnostic yield was 84% compared with 48% when the probe was positioned adjacent to the lesion.
Conclusions: Radial probe EBUS can be used to guide biopsy during peripheral bronchoscopy. This technique provides real-time ultrasound-based confirmation of target lesion localization prior to biopsy. Using radial probe EBUS, the vast majority of peripheral pulmonary nodules can be identified. Radial EBUS probe position relative to the target lesion significantly affects the diagnostic yield.
The diagnosis of peripheral pulmonary nodules remains a significant challenge for the clinician. With the detection of peripheral nodules rising, and lung cancer screening for high-risk patients possibly forthcoming, there is a need for improved techniques to sample pulmonary nodules. Computed tomography (CT)-guided transthoracic needle aspiration is an available, accepted technique for percutaneous biopsy of peripheral nodules, but it carries a significant risk for pneumothorax. Conventional bronchoscopy has a diagnostic yield of less than 20% for peripheral nodules less than 2 cm in diameter (1). Recently, advanced bronchoscopic techniques, including electromagnetic navigation, virtual bronchoscopy, and radial probe endobronchial ultrasound (EBUS), have improved diagnostic yields for peripheral bronchoscopy (2–5).
Radial probe EBUS predates the existing convex probe EBUS bronchoscope currently used for transbronchial needle aspiration (TBNA) of mediastinal and hilar abnormalities. The radial miniprobe is 1.4 mm in diameter and provides a circumferential radial ultrasound image when passed through the working channel of a flexible bronchoscope into the lung periphery (6). The characteristic “snowstorm” appearance represents tissue displacing normal lung when the probe is either within or adjacent to the peripheral lesion and can be used to guide sampling.
The technique using radial probe EBUS has evolved since its implementation for peripheral nodules. Initial reports described use of the radial probe to identify lesions in which the probe was removed and biopsy instruments were passed through the bronchoscope into the same segmental bronchus, either with or without fluoroscopic assistance (7). The guided sheath technique followed this method, using a guide sheath as an extension of the flexible bronchoscope, acting as a conduit for biopsy instruments into the vicinity of a pulmonary nodule (8). Radial probe EBUS may also be performed using a small-caliber bronchoscope with or without the guide sheath, which may allow the bronchoscopist to gain closer access to the lesion at the time of biopsy (9).
We reviewed and assessed the use of radial probe EBUS for peripheral pulmonary nodules at a tertiary care university hospital to identify factors that might influence the diagnostic yield of this technique for peripheral bronchoscopy. Some of the results of this study have been reported previously in the form of an abstract (10).
Peripheral bronchoscopy cases utilizing radial probe EBUS for peripheral pulmonary lesions performed between January 1, 2008, and December 31, 2012, were reviewed retrospectively. Inclusion criteria consisted of cases in which radial probe EBUS was used for diagnostic purposes for peripheral pulmonary lesions. Exclusion criteria consisted of cases in which radial probe EBUS was used for nondiagnostic purposes, such as assisting with placement of fiducial markers. In addition, cases in which electromagnetic navigation or virtual bronchoscopy were used were excluded. This study was approved by the Washington University School of Medicine Institutional Review Board (#201301002).
Bronchoscopy was performed in a dedicated bronchoscopy suite by interventional pulmonology attending physicians (A.C., M.M., P.C.), interventional pulmonology fellows (P.C., A.L.) or pulmonary/critical care fellows under the supervision of an interventional pulmonologist. Procedures were performed while the patients were under moderate sedation induced by midazolam and fentanyl. Bronchoscopes of varying sizes were used during the procedures. A small-caliber, thin, 4-mm bronchoscope was used in selected cases (BF MP160F; Olympus, Tokyo, Japan) at the discretion of the bronchoscopist.
Biopsy targets were selected by reviewing available CT or positron emission tomography/CT images. When possible, multiplanar reconstruction was used to create sagittal and coronal views, which were reviewed in conjunction with standard axial images. The determination to proceed with bronchoscopy was not influenced by the presence or absence of a bronchus sign. No additional image guidance software (virtual bronchoscopy or electromagnetic navigation software) was used to assist with procedure planning.
Radial probe EBUS was performed using a 1.4-mm, 20-MHz radial EBUS miniprobe (UM S20-17S; Olympus). A guide sheath (SG200C; Olympus) was used at the bronchoscopist’s discretion. A double-hinged directional curette (CC-6DR-1; Olympus) (Figure 1) was used in combination with the guide sheath in selected cases to facilitate direction of the guide sheath when necessary. Biopsies were performed using a 21-gauge transbronchial aspiration needle, 1.8-mm forceps, or a cytology brush.
Radial EBUS views of peripheral lesions were characterized as “concentric” when the radial probe appeared within and completely surrounded by the lesion and “eccentric” when the probe was largely biased toward one side of the lesion without tissue completely surrounding the probe (Figure 2).
Figure 2. Concentric radial endobronchial ultrasound (EBUS) image of a lesion with the probe centered and surrounded by the lesion (A). Eccentric radial EBUS image of a lesion with the probe positioned at the edge of the lesion (B).
[More] [Minimize]Specimens were considered diagnostic when a cytologic, histopathologic, or microbiologic diagnosis was consistent with the clinical presentation. Patients in whom the procedures were not diagnostic were referred for surgery when appropriate or were followed by surveillance chest CT. A finding of inflammation was considered diagnostic if the biopsied lesion was found to have resolved on follow-up CT. If follow-up imaging was not available or if the lesion was unchanged or enlarged, a finding of inflammation was considered nondiagnostic.
Statistical analysis was performed using SAS version 9.2 software (SAS Institute, Cary, NC), and statistical significance was set at a P value <0.05. Diagnostic yield comparison between concentric and eccentric radial EBUS views was performed using Student’s t test.
A total of 496 cases of peripheral bronchoscopy for pulmonary nodules were screened, with only radial probe EBUS used for diagnostic purposes in 467 cases.
A diagnosis was obtained in 321 of 467 patients (69%). The following is the breakdown of nodules by size for which a diagnosis was obtained: 83 of 144 (58%) nodules 1–2 cm, 99 of 137 (72%) of nodules 2.1–3 cm, 54 of 70 (77%) of nodules 3.1–4 cm, 41 of 47 (87%) of nodules 4.1–5 cm, and 35 of 40 (88%) of nodules larger than 5.1 cm (Table 1). Of 467 total nodules, 446 (96%) were successfully identified using radial probe EBUS.
| Yield | Nodule Size | ||||
|---|---|---|---|---|---|
| 1–2 cm | 2.1–3 cm | 3.1–4 cm | 4.1–5 cm | >5 cm | |
| Total (%) | 144 (31) | 137 (29) | 70 (15) | 47 (10) | 40 (9) |
| Diagnostic (%) | 83 (58) | 99 (72) | 54 (77) | 41 (87) | 35 (88) |
Non–small cell lung cancer was the most common diagnosis overall [194 of 321 (60%)], followed by small cell carcinoma and lymphoma, among malignant diagnoses. Other malignant diagnoses included metastasis from other sites (esophageal, rectal, thyroid, breast, colon), spindle-cell carcinoma, melanoma, amyloidoma, leiomyosarcoma, myeloid sarcoma, basaloid carcinoma, and uterine sarcoma. Inflammation was most common among nonmalignant diagnoses [(64 of 321 (20%)] and included abscess (4), organizing pneumonia (12), pneumonitis (2), Aspergillus (1), and Mycobacterium avium complex (1). Other nonmalignant diagnoses included granuloma and hamartoma (Table 2). The remaining cases of inflammation were confirmed radiographically by a decrease in size or resolution of the targeted lesion visualized by follow-up chest CT within 3 months. Patients without radiographic follow-up or who became lost to follow-up were classified as nondiagnostic. Cases of inflammation that were followed up by additional biopsy using percutaneous approaches or surgery that yielded a diagnosis of malignancy were also classified as nondiagnostic.
| Diagnoses | Number (%) |
|---|---|
| Malignant | |
| Non–small cell lung cancer | 196 (61) |
| Small cell lung cancer | 6 (2) |
| Lymphoma | 3 (1) |
| Other cancer | 21 (7) |
| Nonmalignant | |
| Inflammation | 64 (20) |
| Granuloma | 29 (9) |
| Hamartoma | 2 (1) |
A concentric view of pulmonary lesions was obtained in 63% of cases (295 of 467). The diagnostic yield when a concentric view was obtained was 84% of cases (248 of 295). An eccentric view was obtained in 31% of cases (147 of 467). The diagnostic yield when an eccentric view was obtained was 48% of cases (71 of 147). Concentric views were obtained in 45% of cases in which pulmonary nodules were 1–2 cm in size versus 66% of cases in which nodules were 2.1–3 cm in size.
A guide sheath was used in 283 of 467 cases (60%) and a directional curette was used in 99 of 283 of these cases (35%). Concentric ultrasound views were obtained in 67% of guide sheath cases (190 of 283), and the overall diagnostic yield using a guide sheath was 72% (203 of 283). A 4-mm outer diameter bronchoscope was used in 23 of 467 of cases (5%), with a yield of 70% (16 of 23). Concentric views were obtained in 16 of 23 patients (70%) using this technique.
In diagnostic cases in which both forceps and transbronchial aspiration needles were used, transbronchial lung biopsy using forceps had a diagnostic yield of 77%, compared to 80% using TBNA. This yield did not appear to be influenced by the radial ultrasound view (concentric versus eccentric).
Pneumothorax occurred in 13 of 467 patients (2.8%) and required chest tube drainage in 54% of these patients (7). Bleeding greater than 300 ml occurred in two patients (340 ml and 350 ml) and required no additional intervention aside from local suctioning. Four patients had bleeding of 100–300 ml during bronchoscopy, also requiring no additional intervention.
Peripheral pulmonary lesions continue to present challenges to practicing physicians. The main challenges include getting to the target lesion and knowing reliably where to take biopsies. Radial probe EBUS addresses the latter challenge by providing real-time procedural feedback regarding the location of the target lesion relative to the probe prior to biopsy.
The overall diagnostic yield in this study of 69% for all lesions combined is consistent with data reported in previous publications (11, 12). The diagnostic yield of 58% for all lesions less than 2 cm is higher than that reported by Eberhardt and colleagues, who reported that the diagnostic yield for nodules of this size was 46% (13).
Thirty-three percent of nodules (33 of 100) in the Eberhardt study (13) could not be visualized using radial probe EBUS, compared with 4% of nodules (21 of 467) in our present study. The majority of nodules in this study [31% (144 of 467)] were 1–2 cm in size, and, aside from coronal and sagittal reconstruction of CT scans using conventional imaging software, no additional image-based software was used. This suggests that the vast majority of pulmonary nodules can be found without using additional image-guided techniques and ultimately utilizing radial probe EBUS to confirm lesion location prior to biopsy.
Radial probe position relative to the target lesion had the greatest impact on diagnostic yield. Cases in which a concentric view was obtained had a significantly higher diagnostic yield than those with an eccentric view (84% versus 48%, P = 0.0008). This finding is consistent with data reported in prior publications that noted significant differences in diagnostic yield when the radial EBUS probe was positioned adjacent to the lesion rather than within it (8). In the present study, when the initial view was eccentric, attempts were made to achieve a concentric view by repositioning the probe using the directional curette or by using the smaller-caliber bronchoscope to direct the probe. The ability to obtain a concentric view may have been influenced by nodule size. A concentric view was obtained more often in 2.1- to 3-cm nodules than in 1- to 2-cm nodules (66% and 45%, respectively). The directional curette was used in 35% of cases (99 of 283) in which the guide sheath was utilized to this effect. When the smaller-caliber bronchoscope was used, no guide sheath was utilized. The bronchoscope was used as the guide sheath with the potential benefit that it could be used to direct a biopsy instrument. The ability to achieve a concentric view was not statistically significantly different between techniques using the guide sheath and directional curette [190 of 283 (67%)] compared with using the smaller-caliber bronchoscope [16 of 23 (70%)].
When a concentric radial ultrasound image was obtained, the diagnostic yield of bronchoscopy was 84%, which is comparable to that of transthoracic needle aspiration using CT guidance (14, 15). Pneumothorax occurred in 13 patients (2.8%) and required chest tube drainage in 7 patients (1.5%). This complication rate compares favorably with that for transthoracic needle biopsy, for which the incidence of pneumothorax reported in the literature ranges from 8% to 64% (16).
The number of bronchoscopies performed for pulmonary nodules increased during the 5-year course of this study and the average size of targeted nodules decreased, suggesting a shift in clinical practice toward the bronchoscopic biopsy of pulmonary nodules. The overall diagnostic yield by year did not change significantly, despite the trend toward biopsying smaller nodules (Figure 3).
Figure 3. Graph illustrating the increase in radial endobronchial ultrasound bronchoscopies performed over the 5-year study period and percentage of cases performed for nodules 1–2 cm in size.
[More] [Minimize]This study has limitations. As it is a retrospective review, drawing definitive conclusions regarding specific interventions is difficult. Different techniques of radial EBUS are described in this study, representing an evolving practice pattern and style. Although we provide results of use of the radial probe with a guide sheath, without a guide sheath, and with the smaller-caliber bronchoscope and no guide sheath, we are unable to provide any randomized direct comparisons between these different techniques.
Additionally, patient selection is an important consideration. Our institution offers peripheral bronchoscopy for peripheral lesions using electromagnetic navigation as well CT-guided transthoracic needle aspiration. Triage of patients may lead to selection of specific cases amenable to bronchoscopy with radial probe EBUS based on patient and lesion characteristics. Our institutional practice has moved largely toward bronchoscopy for peripheral lesions as an initial test. Our review of records over the time course of this study indicate that fewer than 10 cases reviewed by interventional pulmonology attending physicians (A.C., M.M., P.C.) were referred initially for CT-guided needle aspiration prior to or instead of bronchoscopy. Of those cases in which bronchoscopy was performed, radial probe EBUS was utilized in 467 of 496 (94%) as the sole means of image guidance during the procedure; in the remaining cases, electromagnetic navigation was used.
In this study, we summarize observations of a clinical practice over a 5-year period and nearly 500 cases of peripheral bronchoscopy utilizing radial probe EBUS for peripheral pulmonary lesions. Radial EBUS was introduced into the practice to potentially improve the diagnostic yield of bronchoscopy for peripheral lesions, regardless of size, relative location in the periphery, or presence or absence of an air bronchus sign. Of all peripheral lesions 1 cm and larger reported in this study, 96% were identified using radial EBUS and fluoroscopy alone, suggesting that bronchoscopists can identify the vast majority of lesions by using a conventional chest CT scan as a reference. Radial probe EBUS provides real-time feedback regarding the position of the bronchus relative to the target lesion prior to biopsy. In so doing, it may help the clinician predict the likelihood of a diagnostic biopsy based on a concentric versus an eccentric ultrasound view. Improved techniques are needed to sample lesions that are adjacent to a bronchus, where present options are limited.
| 1 . | Baaklini WA, Reinoso MA, Gorin AB, Sharafkaneh A, Manian P. Diagnostic yield of fiberoptic bronchoscopy in evaluating solitary pulmonary nodules. Chest 2000;117:1049–1054. |
| 2 . | Gildea TR, Mazzone PJ, Karnak D, Meziane M, Mehta AC. Electromagnetic navigation diagnostic bronchoscopy: a prospective study. Am J Respir Crit Care Med 2006;174:982–989. |
| 3 . | Eberhardt R, Anantham D, Herth F, Feller-Kopman D, Ernst A. Electromagnetic navigation diagnostic bronchoscopy in peripheral lung lesions. Chest 2007;131:1800–1805. |
| 4 . | Tamiya M, Okamoto N, Sasada S, Shiroyama T, Morishita N, Suzuki H, Yoshida E, Hirashima T, Kawahara K, Kawase I. Diagnostic yield of combined bronchoscopy and endobronchial ultrasonography, under LungPoint guidance for small peripheral pulmonary lesions. Respirology 2013;18:834–839. |
| 5 . | Kikuchi E, Yamazaki K, Sukoh N, Kikuchi J, Asahina H, Imura M, Onodera Y, Kurimoto N, Kinoshita I, Nishimura M. Endobronchial ultrasonography with guide-sheath for peripheral pulmonary lesions. Eur Respir J 2004;24:533–537. |
| 6 . | Yamada N, Yamazaki K, Kurimoto N, Asahina H, Kikuchi E, Shinagawa N, Oizumi S, Nishimura M. Factors related to diagnostic yield of transbronchial biopsy using endobronchial ultrasonography with a guide sheath in small peripheral pulmonary lesions. Chest 2007;132:603–608. |
| 7 . | Yoshikawa M, Sukoh N, Yamazaki K, Kanazawa K, Fukumoto SI, Harada M, Kikuchi E, Munakata M, Nishimura M, Isobe H. Diagnostic value of endobronchial ultrasonography with a guide sheath for peripheral pulmonary lesions without X-ray fluoroscopy. Chest 2007;131:1788–1793. |
| 8 . | Kurimoto N, Miyazawa T, Okimasa S, Maeda A, Oiwa H, Miyazu Y, Murayama M. Endobronchial ultrasonography using a guide sheath increases the ability to diagnose peripheral pulmonary lesions endoscopically. Chest 2004;126:959–965. |
| 9 . | Oki M, Saka H, Kitagawa C, Kogure Y, Murata N, Adachi T, Ando M. Randomized study of endobronchial ultrasound-guided transbronchial biopsy: thin bronchoscopic method versus guide sheath method. J Thorac Oncol 2012;7:535–541. |
| 10 . | Chen A, Chenna P, Loiselle A, Mayse M, Massoni J, Misselhorn D. Radial probe endobronchial ultrasound for peripheral pulmonary lesions: five years and five hundred cases. American College of Chest Physicians annual meeting. Chicago, October 2013. |
| 11 . | Eberhardt R, Anantham D, Ernst A, Feller-Kopman D, Herth F. Multimodality bronchoscopic diagnosis of peripheral lung lesions: a randomized controlled trial. Am J Respir Crit Care Med 2007;176:36–41. |
| 12 . | Steinfort DP, Khor YH, Manser RL, Irving LB. Radial probe endobronchial ultrasound for the diagnosis of peripheral lung cancer: systematic review and meta-analysis. Eur Respir J 2011;37:902–910. |
| 13 . | Eberhardt R, Ernst A, Herth FJF. Ultrasound-guided transbronchial biopsy of solitary pulmonary nodules less than 20 mm. Eur Respir J 2009;34:1284–1287. |
| 14 . | Ng YL, Patsios D, Roberts H, Walsham A, Paul NS, Chung T, Herman S, Weisbrod G. CT-guided percutaneous fine-needle aspiration biopsy of pulmonary nodules measuring 10 mm or less. Clin Radiol 2008;63:272–277. |
| 15 . | Liao WY, Chen MZ, Chang YL, Wu HD, Yu CJ, Kuo PH, Yang PC. US-guided transthoracic cutting biopsy for peripheral thoracic lesions less than 3 cm in diameter. Radiology 2000;217:685–691. |
| 16 . | Geraghty PR, Kee ST, McFarlane G, Razavi MK, Sze DY, Dake MD. CT-guided transthoracic needle aspiration biopsy of pulmonary nodules: needle size and pneumothorax rate. Radiology 2003;229:475–481. |
Author Contributions: All authors were responsible for the study concept and design, analysis and interpretation of data, and drafting of the manuscript.
Author disclosures are available with the text of this article at www.atsjournals.org.
