Endobronchial Ultrasonography in Bronchoscopic Occult Pulmonary Lesions

Endobronchial Ultrasonography in Bronchoscopic Occult Pulmonary Lesions

ORIGINAL ARTICLE Endobronchial Ultrasonography in Bronchoscopic Occult Pulmonary Lesions Christophe A. Dooms, MD,* Eric K. Verbeken, MD, PhD,† Heinri...

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ORIGINAL ARTICLE

Endobronchial Ultrasonography in Bronchoscopic Occult Pulmonary Lesions Christophe A. Dooms, MD,* Eric K. Verbeken, MD, PhD,† Heinrich D. Becker, MD, FCCP,‡ Maurits G. Demedts, MD, PhD,* and Johan F. Vansteenkiste, MD, PhD*

Introduction: The diagnostic yield of flexible bronchoscopy for peripheral pulmonary lesions is variable and often limited. Endobronchial ultrasonography (EBUS) has been reported to help localize a bronchoscopic occult pulmonary lesion and thereby improve the diagnostic yield of transbronchial biopsy (TBB). Methods: We evaluated the yield of EBUS-guided TBB in 50 consecutive patients with a bronchoscopic occult pulmonary lesion. Results: The mean diameter of the lesions was 36.6 mm (SD ⫽ 19.7 mm). We could visualize 74% of the bronchoscopic occult lesions with EBUS, and in these patients, a histologic diagnosis on TBB was obtained in 84%. However, the diagnostic yield was very poor for lesions ⬍20 mm. Conclusion: EBUS-guided TBB is effective for localizing and diagnosing bronchoscopic occult pulmonary masses ⱖ20 mm, but its yield remains unsatisfactory for lesions ⬍20 mm. Key Words: Bronchoscopy, Endobronchial ultrasonography, Pulmonary lesion, Transbronchial biopsy. (J Thorac Oncol. 2007;2: 121–124)

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lexible bronchoscopy has a variable and often poor diagnostic yield for pulmonary lesions in cases of a normal endobronchial examination on bronchoscopy. The sensitivity of bronchoscopy for detecting malignancy in a solitary pulmonary nodule depends on the size of the nodule, the proximity to the bronchial tree, and the prevalence of cancer in the study population. For nodules that are 20 to 30 mm in diameter, the sensitivity is 40% to 60%.1 The diagnostic yield is mostly achieved with the auxiliary use of radiographic fluoroscopic guidance, but lesions ⬍20 mm in diameter remain difficult to detect, with a diagnostic yield of ⬍30%. In *Department of Pulmonology (Respiratory Oncology Unit) and Leuven Lung Cancer Group, Catholic University, Leuven, Belgium; †Department of Pathology, Catholic University Leuven, Leuven, Belgium; ‡Department of Interdisciplinary Endoscopy, Thoraxklinik, Heidelberg, Germany. Christophe A. Dooms was supported by Heinrich D. Becker with the European Respiratory Society fellowship (no. 427). Address for correspondence: Christophe A. Dooms, MD, Respiratory Oncology Unit (Department of Pulmonology), University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. E-mail: christophe.dooms@ kuleuven.be Copyright © 2007 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/07/0202-0121

the absence of radiographic fluoroscopic guidance, it can often be difficult to identify the correct distance and bronchial access to a peripheral pulmonary lesion ⬎20 mm. Endobronchial ultrasonography (EBUS) using a miniprobe has been reported to be useful in confirming the accurate bronchial route and obtaining a histologic diagnosis of peripheral pulmonary lesions.2,3 In this study, the diagnostic efficacy of EBUS-guided transbronchial biopsy (TBB), in the absence of radiographic fluoroscopic guidance, was evaluated in a series of consecutive patients with a pulmonary mass and normal bronchoscopic inspection.

PATIENTS AND METHODS From January 1 to May 31, 2005, we prospectively studied the use of EBUS-guided TBBs in patients referred to the endoscopy unit with a pulmonary nodule or solid mass. During this period, EBUS was added in 50 consecutive patients having normal endoluminal findings on routine diagnostic bronchoscopy. A pulmonary nodule or solid mass was defined as a lesion surrounded by pulmonary parenchyma on computed tomography (CT). Spiral chest CT was reviewed before the procedure, and the largest diameter of the lesion was measured on the soft-tissue windows. Patients with a spiral CT showing a pulmonary infiltrate (with the presence of an air bronchogram in the lesion and thus a high likelihood of a benign infectious lesion) or a subpleural lesion lying entirely within 10 mm from the pleura (as an EBUS miniprobe performs only radial scanning at 10 mm from its distal tip) were excluded from this study. After informed consent, bronchoscopy using local anesthesia was performed with a flexible bronchoscope (BF-1T160; Olympus). All patients received oxygen 2 liters/min via a nasal cannula, and blood oxygenation was monitored with continuous pulse oximetry. Fluoroscopy was not used during the procedure because it is not available in our endoscopy unit. The EBUS system (processor EU-M20 and driving unit MH-240; Olympus), equipped with a 20-MHz mechanical radial miniprobe (UM-BS20-26R; Olympus) with a balloon sheath (MAJ-643R; Olympus), has been used by one staff member of the respiratory endoscopy unit. After localization of the lesion, the bronchoscope was kept in place at the nearest visible subsegmental carina, and the miniprobe was removed while measuring the distance to the lesion. We did not use a catheter sheath because it renders the procedure

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technically less comfortable and limits the size of the biopsy forceps used. Thereafter, a biopsy forceps (FB-20C-1; Olympus) was introduced into the subsegmental bronchus for a distance as measured before, and four or more biopsy specimens were taken and fixed in Bouin’s solution for histologic analysis. No biopsy specimens were taken in those patients in whom EBUS did not image the lesion. At the end of the procedure, wedged bronchial lavage was performed in all patients in the suspected subsegmental bronchus using 50 ml of saline. This material was stored in Cytorich Red solution for cytologic analysis.

RESULTS A total of 50 patients (34 males and 16 females) with an average age of 69 years were examined. The mean diameter of the lesions on CT was 36.6 ⫾ 19.7 mm (range, 8 –90 mm). The location of the lesions was variously distributed: 14 in the right upper lobe, five in the right middle lobe, eight in the right lower lobe, 15 in the left upper lobe, and eight in the left lower lobe. In 34 patients, a pathologic (histology ⫹ cytology) diagnosis could be established: primary lung cancer in 28 patients (adenocarcinoma, n ⫽ 7; squamous cell carcinoma, n ⫽ 5; large cell carcinoma, n ⫽ 13; and small cell lung carcinoma, n ⫽ 3). A benign lesion could be documented in six patients (bronchiolitis obliterans in two patients and posttransplantation lymphoma, mucor mycosis infection, anthracosilicosis that proved to be stable at follow-up, and Mycobacterium tuberculosis infection in one patient each) (Table 1). The bronchoscopic occult lesion could be visualized with EBUS in 37 of 50 patients (74%), and a histologic diagnosis could be established in 31 of these 37 (84%). In 16 patients, no diagnosis was obtained during bronchoscopy (Table 1). These undiagnosed lesions were homogeneously spread: 34% (10 of 34 lesions) in the upper lobe segments, 29% (six of 21 lesions) in the lower/middle lobe segments. In 13 patients, the lesion could not be found with EBUS, although access was considered feasible based on the CT scan, leading to 11 nondiagnostic bronchoscopies, as additional cytologic examination of the lavage fluid was diagnostic in two of these (non-small cell lung cancer and Mycobacterium tuberculosis one each). A bronchoscopic diagnosis was also lacking in five patients in whom the lesion was visible on EBUS. In two of these, with visualization on a

TABLE 1. Description of the Pathologic Result in Relation to EBUS Characteristics

EBUS visible (n ⫽ 37) Histology diagnosis No diagnosis Cytology diagnosis EBUS invisible (n ⫽ 13) No diagnosis Cytology diagnosis

All

<20 mm

>20 mm

31 5 1

1 1 0

30 4 1

11 2

8 1

3 1

EBUS, endobronchial ultrasonography.

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TABLE 2.

Diagnostic Yield in Relation to Lesion Size

No. of patients EBUS-V, no. (%) EBUS-TBB, no. (%) Pathologic diagnosis, n (%)

All Lesions

Lesions <20 mm

Lesions >20 mm

50 37/50 (74) 31/37 (84) 34/50 (68)

11 2/11 (18) 1/2 (50) 2/11 (18)

39 35/39 (90) 30/35 (86) 32/39 (82)

EBUS-V, visible on endobronchial ultrasonography; EBUS-TBB, positive endobronchial ultrasonography when visible on endobronchial ultrasonography.

tangential EBUS image, the diagnosis ultimately proved to be non-small cell lung cancer (B2r, 37mm) and metastasis of a colorectal carcinoma (B3r, 11 mm) in one each. Three patients, with visualization on circular EBUS, ultimately proved to have a lymphoma (B5l, 43 mm) and two had an unknown but stable lesion at follow-up (B1l, 23 mm and B1r, 40 mm). Moderate bleeding requiring only bronchoscopic hemostasis was noted in one patient. No significant adverse effects (pneumothorax, respiratory distress, or urgent surgery) occurred. An overall pathologic diagnostic yield of 68% was obtained (Table 2). For lesions ⬍20 mm in the greatest diameter, the pathologic diagnostic yield decreased to 18%, whereas 82% was reached for lesions ⱖ20 mm. In the overall group, the average diameter of the diagnosed lesions (41 mm; range, 15–90) was significantly higher than the average diameter of the undiagnosed lesions (27 mm; range, 8 – 87, p ⫽ 0.013). However, when considering only lesions ⱖ20 mm, there was no difference between the average diameter of the diagnosed lesions (42 mm; range, 20 –90) and the average diameter of the undiagnosed lesions (43 mm; range, 23– 87, p ⫽ 0.977). Because size does not discriminate between diagnosed and undiagnosed lesions for the subgroup ⱖ20 mm, we hypothesized that other factors did, such as a tangential visualization (e.g., hematogenous metastasis) or an inaccessible target bronchus (e.g., occlusion of the bronchus leading toward the lesion).

DISCUSSION EBUS can guide TBB by revealing the optimal bronchial access and measure the distance to a pulmonary lesion. The reflection of adjacent zones of normal aerated lung tissue generally defines a peripheral lesion as a clear hypoechoic texture on EBUS (Figure 1). Most of the published studies (Table 3) used radiographic fluoroscopy, with radiation exposure for both the patient and medical staff.4 – 6 Only Herth et al.3 reported on the feasibility of EBUS-guided TBB without the use of fluoroscopy in lesions ⬎20 mm. In the present study, the use of EBUS led to visualization of 90% of the bronchoscopic occult lesions ⱖ20 mm and to a pathologic diagnostic yield of 82% (Table 2). This result is in line with the study by Herth et al., including only peripheral pulmonary lesions ⬎20 mm and reporting a diagnostic yield of 87% for EBUS-guided TBB without the need for radiographic equipment or radiation exposure (Table 3). For lesions ⬍20 mm, our yield of EBUS-guided detection and pathologic diagnosis decreased to 18%. In contrast, Japa-

Copyright © 2007 by the International Association for the Study of Lung Cancer

Journal of Thoracic Oncology • Volume 2, Number 2, February 2007

Endobronchial Ultrasonography-Guided Biopsy

FIGURE 1. An 81-year-old man presented with a persistent cough. Chest computed tomography revealed a solitary pulmonary lesion of 29 mm in largest diameter in segment B4 of the right lung (A, B). The endobronchial ultrasonography miniprobe within (C ) and adjacent to (D) the lesion visualized a hypoechoic nodule surrounded by a strong reflected interface. Large cell lung carcinoma was diagnosed on transbronchial biopsy. TABLE 3. Literature Results of EBUS-Guided Diagnosis of Peripheral Lesions Study Herth et al.3 Shirakawa et al.4 Kurimoto et al.5 Kikuchi et al.6 This study

Probe

FS

No.

UM-3/4R US20-20R UM-3/4R US20-20R ⫹GS UM-S20-20R ⫹GS XUM-S20-17R ⫹GS UM-BS20-26R

Y/N

50

Nodule/mass

Y

50

Nodule/infiltrate

150 24 50

Nodule/infiltrate Nodule Nodule/mass

Y/N Y N

Lesion

Mean (range) 33.1 (20–60) na na 18.4 (8–27.5) 36.6 (8–90)

No. of TBBs

EBUS-V

EBUS-TBB

PD

4.3

92%

87%

80%

na

78%

na

na

1 3.5 ⱖ4

93% 79% 74%

72% 58% 84%

77% 58% 68%

GS, use of guide sheath; FS, use of fluoroscopy; Y, yes; N, no; No. of TBBs, mean number of transbronchial biopsies performed; EBUS-V, visible on endobronchial ultrasonography; EBUS-TBB, positive transbronchial biopsy specimens when visible on endobronchial ultrasonography; PD, overall pathologic diagnosis; na, not available.

nese groups have reported diagnostic yields of 53% and 72%, respectively, for lesions ⬍20 mm using EBUS-guided TBB with a catheter sheath and under radiographic fluoroscopy.5,6 More recently, one of these Japanese groups performed EBUS-guided TBB using virtual bronchoscopic navigation and detected 67% of lesions ⬍20 mm on EBUS, resulting in a diagnostic yield of 44%.7 A higher diagnostic yield of 63% has been reported for CT-guided TBB, but this method is less desirable because of excessive radiation exposure from CT and lengthy occupation of the CT room.8 CT-guided percutaneous transthoracic fine-needle aspiration biopsy may be considered in very small, easily accessible peripheral lesions. Its sensitivity for detecting malignancy in lesions ⬍20 mm in diameter has been reported to be ⬎60%.9,10 Electromagnetic navigation in bronchoscopy is a novel method of assessing the localization of peripheral pulmonary lesions and may be of further help to improve the diagnostic yield of bronchoscopy in very small peripheral pulmonary nodules.11,12 In summary, in the daily experience of clinicians, EBUS-guided TBB is effective for detecting and diagnosing

peripheral pulmonary nodules or masses ⱖ20 mm, but its yield remains unsatisfactory for lesions ⬍20 mm. Based on these findings, increased use of the technique, both in standard pulmonary practice and in prospective multicenter studies, is warranted. The advantage of using an EBUS miniprobe in the detection and diagnosis of bronchoscopic occult pulmonary lesions ⱖ20 mm is that use of radiographic fluoroscopy can be abandoned. Careful positioning and measurement of the distance to the lesion remain essential. Studies with new navigation techniques such as virtual bronchoscopy and electromagnetic navigation may improve the diagnostic yield of lesions ⬍20 mm, but EBUS will be useful as well in these cases to confirm accurate insertion into the lesion. REFERENCES 1. Swensen S, Jett J, Payne W, et al. An integrated approach to evaluation of the solitary pulmonary nodule. Mayo Clin Proc 1990;65:173–186. 2. Hu¨rter T, Hanrath P. Endobronchial sonography: feasibility and preliminary results. Thorax 1992;47:565–567. 3. Herth F, Ernst A, Becker H. Endobronchial ultrasound-guided transbron-

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4. 5. 6. 7.

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chial lung biopsy in solitary pulmonary nodules and peripheral lesions. Eur Respir J 2002;20:972–974. Shirakawa T, Imamura F, Hamamoto J, et al. Usefulness of endobronchial ultrasonography for transbronchial lung biopsies of peripheral lung lesions. Respiration 2004;71:260–268. Kurimoto N, Miyazawa T, Okimasa S, et al. Endobronchial ultrasonography using a guide sheath increases the ability to diagnose peripheral pulmonary lesions endoscopically. Chest 2004;126:959–965. Kikuchi E, Yamazaki K, Sukoh N, et al. Endobronchial ultrasonography with guide-sheath for peripheral pulmonary lesions. Eur Respir J 2004; 24:533–537. Asahina H, Yamazaki K, Onodera Y, et al. Transbronchial biopsy using endobronchial ultrasonography with a guide sheath and virtual bronchoscopic navigation. Chest 2005;128:1761–1765.

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8. Tsushima K, Sone S, Hanaoka T, et al. Comparison of bronchoscopic diagnosis for peripheral pulmonary nodule under fluoroscopic guidance with CT guidance. Respir Med 2006;100:737–745. 9. Berquist T, Bailey P, Cortese D, et al. Transthoracic needle biopsy: accuracy and complications in relation to location and type of lesion. Mayo Clin Proc 1980;55:475–481. 10. Ohno Y, Hatabu H, Takenaka D, et al. CT-guided transthoracic needle aspiration biopsy of small (⬍ or ⫽ 20mm) solitary pulmonary nodules. AJR Am J Roentgenol 2003;180:1665–1669. 11. Hautmann H, Schneider A, Pinkau T, et al. Electromagnetic catheter navigation during bronchoscopy. Chest 2005;128:382–387. 12. Schwarz Y, Greif J, Becker HD, et al. Real-time electromagnetic navigation bronchoscopy to peripheral lung lesions using overlaid CT images: the first human study. Chest 2006;129:988–994.

Copyright © 2007 by the International Association for the Study of Lung Cancer