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First published online on June 15, 2007
Chest, doi:10.1378/chest.07-0637
doi:10.1378/chest.07-0637
(Chest. 2007; 132:603-608)
© 2007 American College of Chest Physicians
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Factors Related to Diagnostic Yield of Transbronchial Biopsy Using Endobronchial Ultrasonography With a Guide Sheath in Small Peripheral Pulmonary Lesions*

Noriyuki Yamada, MD; Koichi Yamazaki, MD, PhD; Noriaki Kurimoto, MD, PhD, FCCP; Hajime Asahina, MD, PhD; Eiki Kikuchi, MD, PhD; Naofumi Shinagawa, MD, PhD; Satoshi Oizumi, MD, PhD and Masaharu Nishimura, MD, PhD

* From the First Department of Medicine (Drs. Yamada, Yamazaki, Asahina, Kikuchi, Shinagawa, Oizumi, and Nishimura), Hokkaido University School of Medicine, Sapporo, Japan; and the Department of Surgery (Dr. Kurimoto), Division of Chest Surgery, St. Marianna University School of Medicine, Kawasaki, Japan.

Correspondence to: Koichi Yamazaki, MD, PhD, First Department of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kitaku, Sapporo 060-8638, Japan; e-mail: kyamazak{at}med.hokudai.ac.jp

Abstract

Study objectives: To evaluate factors predicting the diagnostic yield of transbronchial biopsy (TBB) using endobronchial ultrasonography with a guide sheath (EBUS-GS) in small peripheral pulmonary lesions (PPLs) ≤ 30 mm in mean diameter.

Design: Retrospective analysis.

Patients and methods: One hundred fifty-five consecutive patients with 158 small PPLs underwent TBB using EBUS-GS.

Results: A definitive diagnosis was established by TBB using EBUS-GS in 106 PPLs (67%). The diagnostic yield of PPLs ≤ 15 mm in mean diameter (40%) was significantly lower than that of PPLs > 15 mm and ≤ 30 mm in mean diameter (76%; p < 0.001). PPLs in which the probe was positioned within the PPL on the endobronchial ultrasonography (EBUS) image had a higher diagnostic yield (83%) than PPLs in which the probe was positioned adjacent to the PPL (61%) or outside the PPL (4%; p < 0.001). There were no significant differences in diagnostic yield for underlying disease, location, CT scan bronchus sign, operator, or type of EBUS probe. In the multivariate analysis, only the position of the probe (within or adjacent to the PPL when judged against outside the PPL) was determined to be a significant factor predicting diagnostic yield. On the other hand, a pathologic diagnosis was established with the first, second, third, fourth, and fifth biopsy specimens in 65%, 80%, 87%, 91%, and 97% of PPLs, respectively.

Conclusions: The position of the probe (ie, within or adjacent to the PPL) is a significant factor in predicting the diagnostic yield of TBB using EBUS-GS for small PPLs; the optimum number of biopsy specimens is at least five.

Key Words: endobronchial ultrasonography with a guide sheath • peripheral pulmonary lesions • transbronchial biopsy

Various procedures have been developed to diagnose peripheral pulmonary lesions (PPLs). The transbronchial biopsy (TBB) procedure, which uses a bronchoscope under fluoroscopic guidance, has been performed since the 1970s, with 36 to 86% diagnostic accuracy.12345 Diagnostic accuracy is influenced by lesion size; Schreiber and McCrory1 have reported in a systematic review that the diagnostic accuracy of lesions < 20 mm in mean diameter was 33%. Other studies2345 have found the diagnostic accuracy of benign lesions to be 35 to 50%, which is lower than that of malignant lesions.

These days, small-caliber, radial-type ultrasound probes can be used for the clinical application of ultrasonography to tracheal-bronchial lesions, and PPLs. Endobronchial ultrasonography (EBUS) has been used for imaging guidance in the TBB of PPLs.67 Furthermore, Kurimoto et al,8 Kikuchi et al,9 and our preliminary study have shown the feasibility and effectiveness of TBB using EBUS with a guide sheath (EBUS-GS), and several reports1011 have since demonstrated the safety and efficacy of TBB using EBUS-GS. Nevertheless, the diagnostic yield of TBB using EBUS-GS in PPLs ranges from 58 to 77%,891011 which is not even close to 100%. Accordingly, we have attempted to determine by multivariate analysis the characteristics of PPLs that cannot be reached by forceps or a bronchial brush by TBB using EBUS-GS. Moreover, as the guide sheath is left in the lesion in performing the EBUS-GS technique, multiple biopsy specimens can be obtained repeatedly and easily. Therefore, it is important to determine the optimum number of biopsy specimens required to increase the diagnostic yield. In the present study, we evaluated factors predicting the diagnostic yield of TBB using EBUS-GS in small PPLs, and evaluated the number of biopsy specimens required for successful TBB using EBUS-GS, by analyzing the cumulative diagnostic yield of successive biopsy specimens.

Materials and Methods

Patients
The medical records of 155 consecutive patients with 158 small PPLs (≤ 30 mm in mean diameter) who underwent TBB using EBUS-GS between August 2003 and March 2006 at Hokkaido University Hospital were retrospectively reviewed. In the same period, no patients with small PPLs underwent conventional TBB. PPLs were defined as lesions that were surrounded by pulmonary parenchyma and were endoscopically invisible (ie, no evidence of endobronchial lesion, extrinsic compression, submucosal tumor, narrowing, inflammation, or bleeding of the bronchus). All chest CT scans were reviewed, and the mean diameters of the PPLs was recorded. Because this study was a retrospective analysis, we did not submit any documents related with this study to the internal review board at our institute. However, all patients then gave written informed consent to undergo the procedures described below.

TBB Using EBUS-GS
TBB using EBUS-GS was performed as described previously.89 A 20-MHz mechanical radial-type probe (XUM-S20–17R; Olympus; Tokyo, Japan) with an external diameter of 1.4 mm (ie, 1.4-mm probe) was used most often, and a 20-MHz mechanical radial-type probe (UM-S20–20R; Olympus) with an external diameter of 1.7 mm (ie, 1.7-mm probe) was used for PPLs assumed to be easily reached before bronchoscopy. The probe was connected to an endoscopic ultrasound system (EU-M30S; Olympus). A flexible fiberoptic bronchoscope with a 2.0-mm diameter working channel (BF-P-260F; Olympus) and a guide sheath with an external diameter of 1.9 mm (XB01–836-12; Olympus) were used for the 1.4-mm probe, and a flexible fiberoptic bronchoscope with a ≥ 2.8-mm diameter working channel (BF-1T-30 and BF-1T260; Olympus) and a guide sheath with an external diameter of 2.7 mm (XB01–836-13; Olympus) were used for the 1.7-mm probe. After the bronchoscope was inserted under local anesthesia as deeply as possible into the target bronchus under direct vision, an EBUS probe was inserted into the guide sheath, and the guide sheath-covered probe was then inserted through the bronchoscope working channel into the bronchi leading to the area suspected of containing the PPL. EBUS imaging and radiograph fluoroscopy were used to confirm that the probe and guide sheath had reached the PPL. If an EBUS image of the PPL could not be obtained, the probe was removed from the guide sheath and a double-hinged curette was inserted into the guide sheath; the appropriate bronchus was selected by manipulating the curette under fluoroscopic guidance. Once the bronchus was determined, the curette was removed from the guide sheath and again the probe was inserted into the guide sheath to obtain an EBUS image of the PPL. After locating the PPL on the EBUS image, the probe was removed from the guide sheath, and the guide sheath was left in the PPL. Biopsy forceps and bronchial brushes were introduced via the guide sheath, and pathologic and cytologic specimens were obtained under fluoroscopic guidance. Biopsy specimens were numbered sequentially and reported separately. Bronchoscopy procedures were performed by eight pulmonary fellows, each with > 4 years of training and experience in bronchoscopy.

When evaluating the position of the probe against the PPL on the EBUS image, the positions of the probe were divided into the following three patterns as previously reported810: (1) within (the probe was located in the bronchus inside the PPL); (2) adjacent to (the probe was located in the bronchus adjacent to the PPL); and (3) outside (the probe was located in the bronchus outside the PPL) [Fig 1 ].


Figure 1
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  		Figure 1.. When evaluating the position of the probe against the PPLs on EBUS images, the position of the probe was divided into three patterns, as previously reported. Left: within the PPL; the probe was located in the bronchus inside the PPL. Middle: adjacent to; the probe was located in the bronchus adjacent to the PPL. Right: outside; the probe was located in the bronchus outside the PPL.

 
If a definitive diagnosis was not obtained by EBUS-GS, the patient underwent other procedures (eg, video-assisted thoracoscopy or percutaneous needle biopsy) or clinical and radiologic follow-up to confirm the diagnosis of the PPL. We also reviewed images of 59 PPLs from 58 patients who had undergone high-resolution CT scanning and determined whether the PPLs contained the CT scan bronchus sign12131415 (ie, the finding on a high-resolution CT scan of a bronchus leading directly to a PPL).

Statistical Analysis
Data were analyzed using Pearson {chi}2 test. Multivariate analysis was used to identify the factors affecting diagnostic yield. All variables reaching a significant level of 5% in univariate analysis were tested in a logistic regression analysis. Statistical software (SPSS, version 11.0.1; SPSS; Chicago, IL) was used for all analyses. Statistical significance was established at the p < 0.05 level, and all analyses were two-sided.

Results

The mean (± SD) diameter of the PPLs was 20.8 ± 6.1 mm (range, 9.5 to 30 mm). Of the 158 PPLs examined, 120 (76%) were examined with the 1.4-mm probe and 38 (34%) were examined with the 1.7-mm probe. A total of 134 PPLs (85%) were detected by EBUS. A definitive diagnosis was established in 106 PPLs (67%) by TBB using EBUS-GS (Table 1 ). Pathologic diagnosis and cytologic diagnosis were performed in 85 of 128 PPLs (66%) and 83 of 133 PPLs (62%), respectively.


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  		Table 1.. Established Diagnosis in All 158 Lesions

 
Table 2 shows the features associated with the diagnostic yield of TBB using EBUS-GS. The diagnostic yields of PPLs ≤ 15 mm in mean diameter, PPLs > 15 mm and ≤ 20 mm, PPLs > 20 mm and ≤ 25 mm, and PPLs > 25 and ≤ 30 mm were 40% (16 of 40 PPLs), 74% (25 of 34 PPLs), 72% (26 of 36 PPLs), and 81% (39 of 48 PPLs), respectively. The diagnostic yield of PPLs ≤ 15 mm in mean diameter was significantly lower than that of the PPLs > 15 and ≤ 30 mm in mean diameter (p < 0.001). The position of the probe had a significant effect on the diagnostic yield. PPLs in which the probe position was within the PPL on the EBUS image had a higher diagnostic yield (80 of 96 PPLs; 83%), compared to PPLs in which the probe was positioned adjacent to the PPL (22 of 36 PPLs; 61%) or PPLs in which the probe was positioned outside the PPL (1 of 23 PPLs; 4%; p < 0.001). There were no significant differences in diagnostic yields for underlying disease, location of the PPLs, CT scan bronchus sign, an operator who had performed > 11 examinations, and type of EBUS probe.


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  		Table 2.. Features Associated With Diagnostic Yield of TBB Using EBUS-GS

 
In the univariate analysis, size (ie, PPL < 15 mm in mean diameter), the position of the probe (ie, within or adjacent to the PPL), and the position of the probe (ie, within the PPL) were identified as significant factors in predicting diagnostic yield. In the multivariate analysis, only the position of the probe (within or adjacent to the PPL when judged against outside the PPL) was determined to be a significant factor predicting diagnostic yield. The "within-the-PPL" position of the probe was not a significant factor when judged against being adjacent to the PPL, but tended toward predicting diagnostic yield (p = 0.064) [Table 3 ].


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  		Table 3.. Logistic Regression Analysis of Factors on Diagnostic Yield of TBB Using EBUS-GS*

 
In TBB using EBUS-GS, 128 of the 158 PPLs yielded 632 biopsy specimens (mean number of specimens, 4.9 ± 2.0 per PPL; range, 1 to 14 per PPL; median, 5 per PPL), and 85 of these 128 PPLs (66%) were pathologically diagnosed. The cumulative diagnostic yield with the number of sequential biopsy specimens from the PPLs pathologically diagnosed by TBB using EBUS-GS is displayed in Figure 2 . A diagnosis was established with the first, second, third, fourth, and fifth biopsy specimens for 65%, 80%, 87%, 91%, and 97% of PPLs, respectively. The cumulative diagnostic yield after the fifth biopsy specimen almost reached a plateau. For features including malignant/benign, size, position of the probe, and probe type, ≥ 95% of the cumulative diagnostic yield was reached by the fifth biopsy specimen (Table 4 ).


Figure 2
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  		Figure 2.. Cumulative diagnostic yield along with the number of sequential biopsy specimens from the PPLs pathologically diagnosed by TBB using EBUS-GS.

 

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  		Table 4.. Features Associated With Cumulative Diagnostic Yield Along With the Number of Sequential Biopsy Specimens From the PPLs Pathologically Diagnosed by TBB Using EBUS-GS*

 
Discussion

Several studies891011 have reported the efficacy and safety of TBB using EBUS-GS. However, as the diagnostic yield of TBB using EBUS-GS in PPLs still ranges from 58 to 77%,891011 the determination of the factors related to the diagnostic yield of TBB using EBUS in PPLs is important in increasing in the diagnostic yield. In general, the diagnostic yield is lower in small PPLs; in our preliminary report on TBB using EBUS-GS,9 small PPLs < 20 mm in mean diameter had a lower diagnostic yield than those ≥ 20 mm. On the other hand, Kurimoto et al8 reported a significantly higher diagnostic yield when the probe could be placed within the PPL than when the probe was adjacent to the PPL. Shirakawa et al10 also reported the importance of the position of the probe. In the present retrospective study, univariate analysis revealed that size (< 15 mm in mean diameter) and the position of the probe were significant factors in predicting diagnostic yield. However, in the multivariate analysis, only the position of the probe (within or adjacent to the PPL when judged against outside the PPL), and not size, was determined to be a significant factor predicting diagnostic yield. The position within the PPL was not a significant factor when judged against adjacent to the PPL, but was almost significant in the multivariate analysis (p = 0.064). Therefore, it is most important to advance the probe within or adjacent to the PPL on the EBUS image.

A PPL size of < 15 mm in mean diameter was a significant factor predicting diagnostic yield in the univariate analysis, but in the multivariate analysis statistical significance was not shown. In the present study, 27 of 40 PPLs ≤ 15 mm in mean diameter (68%) were detected on the EBUS image using the within or adjacent to the PPL positions, while 107 of the 118 (91%) PPLs > 15 mm and ≤ 30 mm in mean diameter were detected (p < 0.001). In PPLs ≤ 15 mm in mean diameter, the correct bronchus is sometimes difficult to select to gain a favorable EBUS image. On the other hand, correct diagnosis is made even in small PPLs that are ≤ 15 mm in mean diameter when the probe is advanced within or adjacent to the PPLs on the EBUS image.

One interesting result of the present study was the lack of statistical significance of diagnostic yield among operators with > 4 years of training and experience in bronchoscopy. TBB using EBUS-GS is performed by at least two operators. One holds and manipulates the bronchoscope in addition to manipulating the guide sheath and EBUS probe, and the other assists the main operator. Cooperation between the two operators makes for a smooth and successful examination, and, if at least one of them is experienced in TBB using EBUS-GS, high diagnostic yield and a safe examination should be attained.

The number of biopsy specimens that should be obtained is another important factor in increasing the diagnostic yield. When the probe is adjacent to the PPL, intact bronchial mucosa caught between the probe and the tumor has to be destroyed by repeated biopsy in order to obtain tumor tissue in deeper zones. In patients with benign disease, not all specimens are supportive of an accurate diagnosis. In small PPLs, the guide sheath does not always remain well positioned in the PPL; thus, several biopsy specimens are required to ensure a diagnosis. In EBUS-GS, the guide sheath is left in the PPL during examination, ensuring that several biopsies specimens from the target can be obtained. However, the relationship between diagnosis and number of biopsy specimens obtained by TBB using EBUS-GS has not been previously determined. In the present retrospective study, we determined the cumulative diagnostic yield of successive biopsy specimens. Although the absolute diagnostic yield differs among underlying disease, the size of PPLs, and the position of the probe, the stepwise increment in cumulative diagnostic yield is similar, and the fifth biopsy specimen provided ≥ 95% of the diagnostic yield among these features. While some limitation would exist because of retrospective analysis, we recommend that at least five biopsy specimens be obtained by TBB using EBUS-GS.

A strategy also needs to be developed to raise the diagnostic yield of TBB using EBUS-GS. As the position of the probe is a significant predictor of diagnostic yield, operators should try to obtain a favorable EBUS image. However, the correct bronchi for access to the PPLs cannot always be found in the limited examination time. This problem may be overcome by navigation with virtual bronchoscopy (VB). VB navigation has been reported1617 to be useful for CT scan-guided TBB using an ultrathin bronchoscope. Our preliminary study18 also showed the usefulness of TBB using EBUS-GS with VB navigation. However, the efficacy of VB navigation in EBUS-GS requires more investigation in a randomized trial.

In conclusion, based on our retrospective analysis, the position of the probe (within or adjacent to the PPL when judged against outside the PPL) is a significant factor predicting the diagnostic yield of TBB using EBUS-GS for small PPLs, while the optimum number of biopsy specimens is at least five. TBB using EBUS-GS is a reasonable procedure for evaluating small PPLs, although limitations remain and more investigation is necessary to raise the diagnostic yield of TBB using EBUS-GS in small PPLs.

Footnotes

Abbreviations: EBUS = endobronchial ultrasonography; EBUS-GS = endobronchial ultrasonography with guide sheath; PPL = peripheral pulmonary lesion; TBB = transbronchial biopsy; VB = virtual bronchoscopy

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Received for publication March 21, 2007. Accepted for publication April 25, 2007.

References

  1. Schreiber, G, McCrory, DC (2003) Performance characteristics of different modalities for diagnosis of suspected lung cancer: summary of published evidence. Chest 123(suppl),115s-128s[CrossRef][ISI][Medline]
  2. Baaklini, WA, Reinoso, MA, Gorin, AB, et al Diagnostic yield of fiberoptic bronchoscopy in evaluating solitary pulmonary nodules. Chest 2000;117,1049-1054[Abstract/Free Full Text]
  3. Chechani, V Bronchoscopic diagnosis of solitary pulmonary nodules and lung masses in the absence of endobronchial abnormality. Chest 1996;109,620-625[Abstract/Free Full Text]
  4. Gasparini, S, Ferretti, M, Secchi, EB, et al Integration of transbronchial and percutaneous approach in the diagnosis of peripheral pulmonary nodules or masses: experience with 1,027 consecutive cases. Chest 1995;108,131-137[Abstract/Free Full Text]
  5. Radke, JR, Conway, WA, Eyler, WR, et al Diagnostic accuracy in peripheral lung lesions: factors predicting success with flexible fiberoptic bronchoscopy. Chest 1979;76,176-179[Abstract]
  6. Herth, FJF, Ernst, A, Becker, HD, et al Endobronchial ultrasound-guided transbronchial lung biopsy in solitary pulmonary nodules and peripheral lesions. Eur Respir J 2002;20,972-974[Abstract/Free Full Text]
  7. Paone, G, Nicastri, E, Lucantoni, G, et al Endobronchial ultrasound-driven biopsy in the diagnosis of peripheral lung lesions. Chest 2005;128,3551-3557[Abstract/Free Full Text]
  8. 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[Abstract/Free Full Text]
  9. Kikuchi, E, Yamazaki, K, Sukoh, N, et al Endobronchial ultrasonography with guide-sheath for peripheral pulmonary lesions. Eur Respir J 2004;24,533-537[Abstract/Free Full Text]
  10. 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[CrossRef][ISI][Medline]
  11. Herth, FJF, Eberhardt, R, Becker, HD, et al Endobronchial ultrasound-guided transbronchial lung biopsy in fluoroscopically invisible solitary pulmonary nodules: prospective trial. Chest 2006;129,147-150[Abstract/Free Full Text]
  12. Gaeta, M, Barone, M, Russi, EG, et al Carcinomatous solitary pulmonary nodules: evaluation of the tumor-bronchi relationship with thin-section CT. Radiology 1993;187,535-539[Abstract/Free Full Text]
  13. Naidich, DP, Sussman, R, Kutcher, WL, et al Solitary pulmonary nodules CT-bronchoscopic correlation. Chest 1988;93,595-598[Abstract/Free Full Text]
  14. Gaeta, M, Pandolfo, I, Volta, S, et al Bronchus sign on CT in peripheral carcinoma of the lung: value in predicting results of transbronchial biopsy. AJR Am J Roentgenol 1991;157,1181-1185[Abstract/Free Full Text]
  15. Bilaceroglu, S, Kumcuoglu, Z, Alper, H, et al CT bronchus sign-guided bronchoscopic multiple diagnostic procedures in carcinomatous solitary pulmonary nodules and masses. Respiration 1998;65,49-55[CrossRef][ISI][Medline]
  16. Asano, F, Matsuno, Y, Matsushita, T, et al Transbronchial diagnosis of a small peripheral pulmonary lesion using an ultrathin bronchoscope with virtual bronchoscopic navigation. J Bronchol 2002;9,108-111[CrossRef]
  17. Shinagawa, N, Yamazaki, K, Onodera, Y, et al CT-guided transbronchial biopsy using an ultrathin bronchoscope with virtual bronchoscopic navigation. Chest 2004;125,1138-1143[Abstract/Free Full Text]
  18. 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[Abstract/Free Full Text]




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