respiratory investigation 53 (2015) 93 –97
Contents lists available at ScienceDirect
Respiratory Investigation journal homepage: www.elsevier.com/locate/resinv
Original article
Endobronchial ultrasound-guided transbronchial biopsy with or without a guide sheath for diagnosis of lung Cancer Daisuke Minamia, Nagio Takigawab,n, Daisuke Morichikaa, Toshio Kuboa, Kadoaki Ohashia, Akiko Satoa, Katsuyuki Hottaa, Masahiro Tabataa, Mitsune Tanimotoa, Katsuyuki Kiuraa a
Department of Respiratory Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama 700-8558, Japan Department of General Internal Medicine 4, Kawasaki Medical School, 2-1-80 Nakasange, Okayama 700-8505, Japan
b
art i cle i nfo
ab st rac t
Article history:
Background: Endobronchial ultrasound-guided transbronchial biopsy with a guide sheath
Received 5 August 2014
(EBUS-GS) is widely used for diagnosing lung cancers; however, the diagnostic yield varies
Received in revised form
widely. This study aimed to assess the efficiency of EBUS-GS.
23 October 2014
Methods: We retrospectively evaluated the results of 110 patients who underwent trans-
Accepted 25 October 2014
bronchial biopsy (TBB) for diagnosis of peripheral lung cancer. Bronchoscopy with and
Available online 13 November 2014
without EBUS-GS was performed in 60 (group A) and 50 patients (group B), respectively;
Keywords: Bronchoscopy Endobronchial ultrasound-guided transbronchial biopsy Guide sheath Lung cancer
their medical records were examined, and results from the two groups were compared by using the unpaired Student t-test. Results: The diagnostic sensitivity for lung cancer was 83.3% in group A and 68% in group B (P ¼0.066) while using at least one of the following procedures: TBB, cytological brushing, and bronchial washing. The diagnostic sensitivity for lesions Z 20 mm was 86.4% in group A and 76.7% in group B (P ¼0.263). Moreover, the diagnostic sensitivity for lesions 10–20 mm was 60% in group A and 14.2% in group B (P ¼0.0004); the diagnostic sensitivity with TBB alone was 63.3% in group A and 44% in group B (P ¼0.043). The diagnostic sensitivity with TBB alone for lesions Z20 mm was 70.2% in group A and 44.8% in group B (P ¼0.051). Moreover, the diagnostic sensitivity for lesions 10–20 mm in size was 45% in group A and 14.2% in group B with TBB alone (P ¼ 0.115). Conclusion: EBUS-GS with TBB, brushing, and bronchial washing is effective in diagnosing lung cancers sized o20 mm. & 2014 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
Abbreviations: EBUS-GS, endobronchial ultrasound-guided transbronchial biopsy with a guide sheath; TBB,
transbronchial biopsy;
CT, computed tomography n Corresponding author. Tel.: þ81 862252111; fax: þ81 862328343. E-mail addresses: [email protected] (D. Minami), [email protected] (N. Takigawa), [email protected] (D. Morichika), [email protected] (T. Kubo), [email protected] (K. Ohashi), [email protected] (A. Sato), [email protected] (K. Hotta), [email protected] (M. Tabata), [email protected] (M. Tanimoto), [email protected] (K. Kiura). http://dx.doi.org/10.1016/j.resinv.2014.10.003 2212-5345/& 2014 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
94
1.
respiratory investigation 53 (2015) 93 –97
Introduction
Bronchoscopy is commonly used as a diagnostic method for peripheral pulmonary lesions, although it may cause few complications. However, its diagnostic yield has been found to vary widely among previous studies [1,2]. Endobronchial ultrasound-guided transbronchial biopsy with a guide sheath (EBUS-GS) has been used to diagnose small peripheral pulmonary lesions [3,4]. According to a recent meta-analysis, the use of new techniques such as EBUS-GS has improved the diagnostic yield of guided bronchoscopy to 470% [5]. The guidelines of the American College of Chest Physicians have reported a diagnostic yield of 470% for transbronchial biopsy (TBB) with radial endobronchial ultrasonography [6]. In another randomized study, diagnostic histologic specimens were obtained in 71% of patients with malignant lung disease with EBUS-GS [7]. Here, we present a comparative analysis of EBUS-GS versus standard bronchoscopy for diagnosing peripheral lung cancers.
2.
Materials and methods
2.1.
Patients
We retrospectively reviewed patients who underwent bronchoscopic examinations at Okayama University Hospital between March 2012 and March 2014. Bronchoscopy was performed for 110 consecutive patients with peripheral lung cancer. In order to transition to EBUS-GS, the procedure was performed in 10 patients between January 2013 and March 2013, following which, the EBUS-GS procedure was performed skillfully. Since April 2013, EBUS-GS has been routinely used to diagnose peripheral lung cancers at our institution. The final diagnosis was made by using TBB, cytological brushing, and bronchial washing,
endobronchial ultrasound-guided transbronchial needle aspiration, computed tomography (CT)-guided needle biopsy, and surgical resection. Among them, EBUS-GS was used in 60 patients between April 2013 and March 2014 (group A). As a historical control, bronchoscopic examination without EBUS-GS was performed in 50 patients between March 2012 and March 2013 (group B). The longest diameters of the lesions measured by using chest CT were recorded. The study was approved by the Institutional Ethics Committee of Okayama University Hospital (Approval date: July 29, 2014; Approved #: 2095).
2.2.
Procedures
For all patients in group A, conventional flexible bronchoscopy (BF-260 or P260F Bronchovideoscope, Olympus, Tokyo, Japan) was used in combination with a radial ultrasound probe (UMS20-17S, Olympus, Tokyo, Japan) and a guide sheath kit (K-201, Olympus, Tokyo, Japan). In contrast, conventional flexible bronchoscopy (BF-260 or P260F Bronchovideoscope, Olympus, Tokyo, Japan) was used in group B. Rapid on-site evaluation was used in both groups. The number of transbronchial biopsies performed was decided according to the rapid on-site evaluation method. For instance, once adequate quantities of malignant cells were obtained for pathological diagnosis on rapid on-site evaluation, the biopsy was considered complete. In addition, if adequate tissue was not obtained after ten biopsies, the procedure was terminated. Tissue diagnoses included the cytological evaluation of touch preparation samples that were stained with the Papanicolaou stain, and the histological evaluation of formalin-fixed paraffin-embedded samples stained with hematoxylin and eosin. For pretreatment, 25 mg of hydroxyzine pamoate was intramuscularly injected; 5 ml of 2% lidocaine was sprayed into the pharynx, and 5 ml of 2% lidocaine was administered through the channel during the procedures. The bronchoscope was inserted orally during midazolam-induced conscious sedation. Patients were monitored by electrocardio-
Table 1 – Characteristics of patients, and size of target lesions. Characteristics
With EBUS-GS (group A) N ¼60
Without EBUS-GS (group B) N¼ 50
P-value
Sex Male Female
35 25
29 21
0.45 0.55
Age Median, years (range)
69 (48–93)
70 (33–83)
0.68
Size Median, mm (range)
28.9 (9–78.9)
36.5 (12.8–67.8)
0.46
Distribution, by size 420 mm 10–20 mm o10 mm
37 20 3
43 7 0
0.50 0.012n
Histological type Adenocarcinoma Squamous cell carcinoma NSCLC/NOS Small cell carcinoma
50 5 3 2
32 11 1 6
0.046n 0.133 0.31 0.15
Abbreviations: EBUS-GS, Endobronchial ultrasound-guided transbronchial biopsy with a guide sheath; NSCLC: Non-small cell carcinoma, NOS: not otherwise specified. n P o 0.05
95
respiratory investigation 53 (2015) 93 –97
Table 2 – Diagnostic sensitivity using transbronchial biopsies, cytological brushing, and bronchial washing. With EBUS-GS, diagnostic sensitivity %
Without EBUS-GS, diagnostic sensitivity %
P-value 0.066 (0.043n)
All lesions
83.3 (63.3)
68 (44)
Distribution, by size 420 mm 10–20 mm o10 mm
84.6 (70.2) 60 (45) 100 (100)
76.7 (44.8) 14.2 (14.2) 0 (0)
0.263 (0.051) 0.0004n (0.115)
Abbreviations: EBUS-GS, Endobronchial ultrasound-guided transbronchial biopsy with a guide sheath. Numbers in parenthesis indicate the diagnostic sensitivity using transbronchial biopsies alone. n Po0.05.
Fig. 1 – A computed tomography image showing a 9-mm 9-mm nodular lesion in segment S1þ2 (A), with linear and fine nodules in the middle, lingular, and left S6 areas (B), which are characteristic of Mycobacterium avium. An endobronchial ultrasonography scan demonstrating an adjacent echo (C).
graphy, pulse oximetry, and blood pressure measurements without the presence of an anesthesiologist.
2.3.
Statistical analyses
Statistical analysis was performed by using Microsoft Office Excel 2007 (Microsoft Japan Corporation, Tokyo, Japan). Comparisons between two groups were made by using the unpaired Student t-test. Relationships between categorical variables were assessed by using the chi-square test. P-values o0.05 were considered statistically significant.
3.
Results
Characteristics of patients and size of target lesion are shown in Table 1. The median size of the lesions in group A was smaller than that in group B, although the difference was not statistically significant (28.9 mm vs. 36.5 mm; P ¼ 0.46). More number of patients in group A had 10–20-mm nodules compared with the patients in group B (n¼ 20 vs. n¼ 7; P¼ 0.012). Furthermore, the incidence of adenocarcinoma was higher in group A than in group B (n¼ 50 vs. n¼ 32; P¼ 0.046). For the 60 patients in group A, the definitive
96
respiratory investigation 53 (2015) 93 –97
diagnoses in 50, 7, and 3 patients were made by using bronchoscopy, surgical resection, and CT-guided needle biopsy, respectively. Similarly, for the 50 patients in group B, the definitive diagnoses in 34, 9, and 7 patients were made by using bronchoscopy, surgical resection, and CT-guided needle biopsy, respectively. The diagnostic sensitivity for lung cancer was higher in group A than in group B, while using at least one of the following procedures: TBB, and cytological brushing and bronchial washing (83.3% vs. 68%; P¼ 0.066). In particular, the diagnostic sensitivity for lesions sized 10–20 mm was significantly greater in group A than in group B (60% vs. 14.2%; P ¼0.0004). For lesions Z20 mm, the diagnostic sensitivity tended to be higher in group A than in group B (86.4% vs. 76.7%; P¼ 0.263). Moreover, the diagnostic sensitivity with TBB alone was greater in group A than in group B (63.3% vs. 44%; P¼ 0.043). For lesions sized Z20 mm and 10–20 mm, the diagnostic sensitivity tended to be higher in group A than in group B (Table 2). The diagnostic sensitivity by using TBB, brushing, and bronchial washing was 90%, 87.5%, and 0%, respectively, when internal echo, adjacent echo, and invisible echo patterns were observed by using EBUS. The diagnostic sensitivity by using TBB alone was 75%, 50%, and 0%, respectively. An adenocarcinoma was cytologically and histologically confirmed in all the 3 patients with nodules o10 mm in group A. A representative case is shown in Fig. 1; a 70-year-old woman with Mycobacterium avium had a 9-mm 9-mm nodular lesion in segment S1þ2 of the left lung. EBUS scanning demonstrated an adjacent echo pattern, while histopathological examination revealed the presence of an adenocarcinoma. Regarding complications, in group A, 2 patients developed pneumothorax, and 1 developed pneumonia; the 2 patients with pneumothorax did not require chest tube drainage. The patient with pneumonia underwent antibiotic therapy for two weeks; in this case, EBUS-GS was used to obtain the biopsy specimen as often as 10 times, which revealed the presence of squamous cell carcinoma. Because the patient had progressive symptoms of cough, sputum, and fever up to 38 1C at 7 days after bronchoscopy, he was hospitalized. CT revealed an enlarged consolidation, and a cavitary lesion with neveau formation in the left upper lobe. Conversely, there were no severe complications in the group B.
have been either benign or malignant upon final diagnosis; therefore, we specifically selected patients with peripheral lung cancer. Another limitation might be the increased diagnostic sensitivity because of retrospective investigation and insufficient observation periods. There has been a paradigm shift in the recent understanding of treatment options for non-small cell lung cancers, after the identification of epidermal growth factor receptor mutations [13,14] and echinoderm microtubule associated protein like 4 - anaplastic lymphoma kinase gene translocation [15]. Although the samples obtained by using EBUS-GS are usually small, we should devise a procedure to obtain sufficient histological material for screening genetic mutations and facilitating targeted oncological therapy. In a nationwide postal survey conducted by the Japan Society for Respiratory Endoscopy, Asano et al. showed that respiratory endoscopy was performed safely [16], and the complication rate after forceps biopsy of solitary peripheral pulmonary lesions was only 1.79% (hemorrhage: 0.73%, pneumothorax: 0.63%). Kurimoto et al. reported that only moderate bleeding (1%), and no death, pneumothorax, or other clinically significant morbidities were associated with EBUS-GS procedures [3]. In another report, only one complication of pneumothorax was observed, which did not require chest tube draining, and no accounts of major bleeding, pneumonia, or air embolism were noted in 40 patients [17]. In this study, in group A, 2 patients experienced pneumothorax, and 1 patient developed pneumonia. For small pulmonary nodules, a minimum of five biopsies should be performed in order to achieve the optimum diagnostic yield with TBB using EBUS-GS [11]. Thus, care should be taken to avoid the complications observed during this study.
5.
Conclusions
TBB, brushing and bronchial washing with EBUS-GS demonstrated a higher diagnostic sensitivity than the procedures without EBUS-GS for the diagnosis of peripheral lung cancer; the procedures were especially effective for the diagnosis of lesions o20 mm in size.
Conflicts of interest 4.
Discussion
Among currently available bronchoscopic procedures, EBUSGS is the most effective method to collect samples from peripheral lung lesions [8]; its high diagnostic sensitivity precludes the use of additional invasive procedures such as surgical and CT-guided needle biopsies. In addition, EBUS-GS has been reported to have a high diagnostic yield (58–79%) for small nodules (o20 mm) [9–12]; the results presented in Table 2 are in agreement with these studies. The diagnostic sensitivity with TBB, brushing, and bronchial washing was higher than with TBB alone, and the approach with TBB, brushing, and bronchial washing may further improve the diagnostic accuracy for peripheral lung cancers. A limitation of this study was the exclusion of patients with inflammatory (non-specific) or indeterminate nodules. Such nodules might
The authors have no conflicts of interest to declare.
Acknowledgments We thank Drs. Tomoki Tamura, Hiroe Kayatani, Hiroko Gotoda, and Kichiro Ninomiya for performing the bronchoscopies, and for the helpful discussions; we would also like to thank the cytoscreener, Mr. Hirofumi Inoue.
r e f e r e n c e s
[1] Mori K, Yanase N, Kaneko M, et al. Diagnosis of peripheral lung cancer in cases of tumors 2 cm or less in size. Chest 1989;95:304–8.
respiratory investigation 53 (2015) 93 –97
[2] Chechani V. Bronchoscopic diagnosis of solitary pulmonary nodules and lung masses in the absence of endobronchial abnormality. Chest 1996;109:620–5. [3] Kurimoto N, Murayama M, Yoshioka S, et al. Analysis of the internal structure of peripheral pulmonary lesions using endobronchial ultrasonography. Chest 2002;122:1887–94. [4] Herth FJ, Ernst A, Becker HD. Endobronchial ultrasoundguided transbronchial lung biopsy in solitary pulmonary nodules and peripheral lesions. Eur Respir J 2002;20:972–4. [5] Wang Memoli JS, Nietert PJ, Silvestri GA. Meta-analysis of guided bronchoscopy for the evaluation of the pulmonary nodule. Chest 2012;142:385–93. [6] Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis of lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143:e142S–65S. [7] Oki M, Saka H, Kitagawa C, et al. Endobronchial ultrasoundguided transbronchial biopsy using novel thin bronchoscope for diagnosis of peripheral pulmonary lesions. J Thorac Oncol 2009;4:1274–7. [8] Huang CT, Ho CC, Tsai YJ, et al. Factors influencing visibility and diagnostic yield of transbronchial biopsy using endobronchial ultrasound in peripheral pulmonary lesions. Respirology 2009;14:859–64. [9] 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;126:959–65.
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[10] Kikuchi E, Yamazaki K, Sukoh N, et al. Endobronchial ultrasonography with guide-sheath for peripheral pulmonary lesions. Eur Respir J 2004;24:533–7. [11] Yamada N, Yamazaki K, Kurimoto N, et al. Factors related to diagnostic yield of transbronchial biopsy using endobronchial ultrasonography with a guide sheath in small peripheral pulmonary lesions. Chest 2007;132:603–8. [12] Yoshikawa M, Sukoh N, Yamazaki K, et al. Diagnostic value of endobronchial ultrasonography with a guide sheath for peripheral pulmonary lesions without X-ray fluoroscopy. Chest 2007;131:1788–93. [13] Paez JG, Ja¨nne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497–500. [14] Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129–39. [15] Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4–ALK fusion gene in nonsmall-cell lung cancer. Nature 2007;448:561–6. [16] Asano F, Aoe M, Ohsaki Y, et al. Deaths and complications associated with respiratory endoscopy: a survey by the Japan Society for Respiratory Endoscopy in 2010. Respirology 2012;17:478–85. [17] Izumo T, Sasada S, Chavez C, et al. The diagnostic utility of endobronchial ultrasonography with a guide sheath and tomosynthesis images for ground glass opacity pulmonary lesions. J Thorac Dis 2013;5:745–50.
Contents lists available at ScienceDirect
Respiratory Investigation journal homepage: www.elsevier.com/locate/resinv
Original article
Endobronchial ultrasound-guided transbronchial biopsy with or without a guide sheath for diagnosis of lung Cancer Daisuke Minamia, Nagio Takigawab,n, Daisuke Morichikaa, Toshio Kuboa, Kadoaki Ohashia, Akiko Satoa, Katsuyuki Hottaa, Masahiro Tabataa, Mitsune Tanimotoa, Katsuyuki Kiuraa a
Department of Respiratory Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Okayama 700-8558, Japan Department of General Internal Medicine 4, Kawasaki Medical School, 2-1-80 Nakasange, Okayama 700-8505, Japan
b
art i cle i nfo
ab st rac t
Article history:
Background: Endobronchial ultrasound-guided transbronchial biopsy with a guide sheath
Received 5 August 2014
(EBUS-GS) is widely used for diagnosing lung cancers; however, the diagnostic yield varies
Received in revised form
widely. This study aimed to assess the efficiency of EBUS-GS.
23 October 2014
Methods: We retrospectively evaluated the results of 110 patients who underwent trans-
Accepted 25 October 2014
bronchial biopsy (TBB) for diagnosis of peripheral lung cancer. Bronchoscopy with and
Available online 13 November 2014
without EBUS-GS was performed in 60 (group A) and 50 patients (group B), respectively;
Keywords: Bronchoscopy Endobronchial ultrasound-guided transbronchial biopsy Guide sheath Lung cancer
their medical records were examined, and results from the two groups were compared by using the unpaired Student t-test. Results: The diagnostic sensitivity for lung cancer was 83.3% in group A and 68% in group B (P ¼0.066) while using at least one of the following procedures: TBB, cytological brushing, and bronchial washing. The diagnostic sensitivity for lesions Z 20 mm was 86.4% in group A and 76.7% in group B (P ¼0.263). Moreover, the diagnostic sensitivity for lesions 10–20 mm was 60% in group A and 14.2% in group B (P ¼0.0004); the diagnostic sensitivity with TBB alone was 63.3% in group A and 44% in group B (P ¼0.043). The diagnostic sensitivity with TBB alone for lesions Z20 mm was 70.2% in group A and 44.8% in group B (P ¼0.051). Moreover, the diagnostic sensitivity for lesions 10–20 mm in size was 45% in group A and 14.2% in group B with TBB alone (P ¼ 0.115). Conclusion: EBUS-GS with TBB, brushing, and bronchial washing is effective in diagnosing lung cancers sized o20 mm. & 2014 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
Abbreviations: EBUS-GS, endobronchial ultrasound-guided transbronchial biopsy with a guide sheath; TBB,
transbronchial biopsy;
CT, computed tomography n Corresponding author. Tel.: þ81 862252111; fax: þ81 862328343. E-mail addresses: [email protected] (D. Minami), [email protected] (N. Takigawa), [email protected] (D. Morichika), [email protected] (T. Kubo), [email protected] (K. Ohashi), [email protected] (A. Sato), [email protected] (K. Hotta), [email protected] (M. Tabata), [email protected] (M. Tanimoto), [email protected] (K. Kiura). http://dx.doi.org/10.1016/j.resinv.2014.10.003 2212-5345/& 2014 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
94
1.
respiratory investigation 53 (2015) 93 –97
Introduction
Bronchoscopy is commonly used as a diagnostic method for peripheral pulmonary lesions, although it may cause few complications. However, its diagnostic yield has been found to vary widely among previous studies [1,2]. Endobronchial ultrasound-guided transbronchial biopsy with a guide sheath (EBUS-GS) has been used to diagnose small peripheral pulmonary lesions [3,4]. According to a recent meta-analysis, the use of new techniques such as EBUS-GS has improved the diagnostic yield of guided bronchoscopy to 470% [5]. The guidelines of the American College of Chest Physicians have reported a diagnostic yield of 470% for transbronchial biopsy (TBB) with radial endobronchial ultrasonography [6]. In another randomized study, diagnostic histologic specimens were obtained in 71% of patients with malignant lung disease with EBUS-GS [7]. Here, we present a comparative analysis of EBUS-GS versus standard bronchoscopy for diagnosing peripheral lung cancers.
2.
Materials and methods
2.1.
Patients
We retrospectively reviewed patients who underwent bronchoscopic examinations at Okayama University Hospital between March 2012 and March 2014. Bronchoscopy was performed for 110 consecutive patients with peripheral lung cancer. In order to transition to EBUS-GS, the procedure was performed in 10 patients between January 2013 and March 2013, following which, the EBUS-GS procedure was performed skillfully. Since April 2013, EBUS-GS has been routinely used to diagnose peripheral lung cancers at our institution. The final diagnosis was made by using TBB, cytological brushing, and bronchial washing,
endobronchial ultrasound-guided transbronchial needle aspiration, computed tomography (CT)-guided needle biopsy, and surgical resection. Among them, EBUS-GS was used in 60 patients between April 2013 and March 2014 (group A). As a historical control, bronchoscopic examination without EBUS-GS was performed in 50 patients between March 2012 and March 2013 (group B). The longest diameters of the lesions measured by using chest CT were recorded. The study was approved by the Institutional Ethics Committee of Okayama University Hospital (Approval date: July 29, 2014; Approved #: 2095).
2.2.
Procedures
For all patients in group A, conventional flexible bronchoscopy (BF-260 or P260F Bronchovideoscope, Olympus, Tokyo, Japan) was used in combination with a radial ultrasound probe (UMS20-17S, Olympus, Tokyo, Japan) and a guide sheath kit (K-201, Olympus, Tokyo, Japan). In contrast, conventional flexible bronchoscopy (BF-260 or P260F Bronchovideoscope, Olympus, Tokyo, Japan) was used in group B. Rapid on-site evaluation was used in both groups. The number of transbronchial biopsies performed was decided according to the rapid on-site evaluation method. For instance, once adequate quantities of malignant cells were obtained for pathological diagnosis on rapid on-site evaluation, the biopsy was considered complete. In addition, if adequate tissue was not obtained after ten biopsies, the procedure was terminated. Tissue diagnoses included the cytological evaluation of touch preparation samples that were stained with the Papanicolaou stain, and the histological evaluation of formalin-fixed paraffin-embedded samples stained with hematoxylin and eosin. For pretreatment, 25 mg of hydroxyzine pamoate was intramuscularly injected; 5 ml of 2% lidocaine was sprayed into the pharynx, and 5 ml of 2% lidocaine was administered through the channel during the procedures. The bronchoscope was inserted orally during midazolam-induced conscious sedation. Patients were monitored by electrocardio-
Table 1 – Characteristics of patients, and size of target lesions. Characteristics
With EBUS-GS (group A) N ¼60
Without EBUS-GS (group B) N¼ 50
P-value
Sex Male Female
35 25
29 21
0.45 0.55
Age Median, years (range)
69 (48–93)
70 (33–83)
0.68
Size Median, mm (range)
28.9 (9–78.9)
36.5 (12.8–67.8)
0.46
Distribution, by size 420 mm 10–20 mm o10 mm
37 20 3
43 7 0
0.50 0.012n
Histological type Adenocarcinoma Squamous cell carcinoma NSCLC/NOS Small cell carcinoma
50 5 3 2
32 11 1 6
0.046n 0.133 0.31 0.15
Abbreviations: EBUS-GS, Endobronchial ultrasound-guided transbronchial biopsy with a guide sheath; NSCLC: Non-small cell carcinoma, NOS: not otherwise specified. n P o 0.05
95
respiratory investigation 53 (2015) 93 –97
Table 2 – Diagnostic sensitivity using transbronchial biopsies, cytological brushing, and bronchial washing. With EBUS-GS, diagnostic sensitivity %
Without EBUS-GS, diagnostic sensitivity %
P-value 0.066 (0.043n)
All lesions
83.3 (63.3)
68 (44)
Distribution, by size 420 mm 10–20 mm o10 mm
84.6 (70.2) 60 (45) 100 (100)
76.7 (44.8) 14.2 (14.2) 0 (0)
0.263 (0.051) 0.0004n (0.115)
Abbreviations: EBUS-GS, Endobronchial ultrasound-guided transbronchial biopsy with a guide sheath. Numbers in parenthesis indicate the diagnostic sensitivity using transbronchial biopsies alone. n Po0.05.
Fig. 1 – A computed tomography image showing a 9-mm 9-mm nodular lesion in segment S1þ2 (A), with linear and fine nodules in the middle, lingular, and left S6 areas (B), which are characteristic of Mycobacterium avium. An endobronchial ultrasonography scan demonstrating an adjacent echo (C).
graphy, pulse oximetry, and blood pressure measurements without the presence of an anesthesiologist.
2.3.
Statistical analyses
Statistical analysis was performed by using Microsoft Office Excel 2007 (Microsoft Japan Corporation, Tokyo, Japan). Comparisons between two groups were made by using the unpaired Student t-test. Relationships between categorical variables were assessed by using the chi-square test. P-values o0.05 were considered statistically significant.
3.
Results
Characteristics of patients and size of target lesion are shown in Table 1. The median size of the lesions in group A was smaller than that in group B, although the difference was not statistically significant (28.9 mm vs. 36.5 mm; P ¼ 0.46). More number of patients in group A had 10–20-mm nodules compared with the patients in group B (n¼ 20 vs. n¼ 7; P¼ 0.012). Furthermore, the incidence of adenocarcinoma was higher in group A than in group B (n¼ 50 vs. n¼ 32; P¼ 0.046). For the 60 patients in group A, the definitive
96
respiratory investigation 53 (2015) 93 –97
diagnoses in 50, 7, and 3 patients were made by using bronchoscopy, surgical resection, and CT-guided needle biopsy, respectively. Similarly, for the 50 patients in group B, the definitive diagnoses in 34, 9, and 7 patients were made by using bronchoscopy, surgical resection, and CT-guided needle biopsy, respectively. The diagnostic sensitivity for lung cancer was higher in group A than in group B, while using at least one of the following procedures: TBB, and cytological brushing and bronchial washing (83.3% vs. 68%; P¼ 0.066). In particular, the diagnostic sensitivity for lesions sized 10–20 mm was significantly greater in group A than in group B (60% vs. 14.2%; P ¼0.0004). For lesions Z20 mm, the diagnostic sensitivity tended to be higher in group A than in group B (86.4% vs. 76.7%; P¼ 0.263). Moreover, the diagnostic sensitivity with TBB alone was greater in group A than in group B (63.3% vs. 44%; P¼ 0.043). For lesions sized Z20 mm and 10–20 mm, the diagnostic sensitivity tended to be higher in group A than in group B (Table 2). The diagnostic sensitivity by using TBB, brushing, and bronchial washing was 90%, 87.5%, and 0%, respectively, when internal echo, adjacent echo, and invisible echo patterns were observed by using EBUS. The diagnostic sensitivity by using TBB alone was 75%, 50%, and 0%, respectively. An adenocarcinoma was cytologically and histologically confirmed in all the 3 patients with nodules o10 mm in group A. A representative case is shown in Fig. 1; a 70-year-old woman with Mycobacterium avium had a 9-mm 9-mm nodular lesion in segment S1þ2 of the left lung. EBUS scanning demonstrated an adjacent echo pattern, while histopathological examination revealed the presence of an adenocarcinoma. Regarding complications, in group A, 2 patients developed pneumothorax, and 1 developed pneumonia; the 2 patients with pneumothorax did not require chest tube drainage. The patient with pneumonia underwent antibiotic therapy for two weeks; in this case, EBUS-GS was used to obtain the biopsy specimen as often as 10 times, which revealed the presence of squamous cell carcinoma. Because the patient had progressive symptoms of cough, sputum, and fever up to 38 1C at 7 days after bronchoscopy, he was hospitalized. CT revealed an enlarged consolidation, and a cavitary lesion with neveau formation in the left upper lobe. Conversely, there were no severe complications in the group B.
have been either benign or malignant upon final diagnosis; therefore, we specifically selected patients with peripheral lung cancer. Another limitation might be the increased diagnostic sensitivity because of retrospective investigation and insufficient observation periods. There has been a paradigm shift in the recent understanding of treatment options for non-small cell lung cancers, after the identification of epidermal growth factor receptor mutations [13,14] and echinoderm microtubule associated protein like 4 - anaplastic lymphoma kinase gene translocation [15]. Although the samples obtained by using EBUS-GS are usually small, we should devise a procedure to obtain sufficient histological material for screening genetic mutations and facilitating targeted oncological therapy. In a nationwide postal survey conducted by the Japan Society for Respiratory Endoscopy, Asano et al. showed that respiratory endoscopy was performed safely [16], and the complication rate after forceps biopsy of solitary peripheral pulmonary lesions was only 1.79% (hemorrhage: 0.73%, pneumothorax: 0.63%). Kurimoto et al. reported that only moderate bleeding (1%), and no death, pneumothorax, or other clinically significant morbidities were associated with EBUS-GS procedures [3]. In another report, only one complication of pneumothorax was observed, which did not require chest tube draining, and no accounts of major bleeding, pneumonia, or air embolism were noted in 40 patients [17]. In this study, in group A, 2 patients experienced pneumothorax, and 1 patient developed pneumonia. For small pulmonary nodules, a minimum of five biopsies should be performed in order to achieve the optimum diagnostic yield with TBB using EBUS-GS [11]. Thus, care should be taken to avoid the complications observed during this study.
5.
Conclusions
TBB, brushing and bronchial washing with EBUS-GS demonstrated a higher diagnostic sensitivity than the procedures without EBUS-GS for the diagnosis of peripheral lung cancer; the procedures were especially effective for the diagnosis of lesions o20 mm in size.
Conflicts of interest 4.
Discussion
Among currently available bronchoscopic procedures, EBUSGS is the most effective method to collect samples from peripheral lung lesions [8]; its high diagnostic sensitivity precludes the use of additional invasive procedures such as surgical and CT-guided needle biopsies. In addition, EBUS-GS has been reported to have a high diagnostic yield (58–79%) for small nodules (o20 mm) [9–12]; the results presented in Table 2 are in agreement with these studies. The diagnostic sensitivity with TBB, brushing, and bronchial washing was higher than with TBB alone, and the approach with TBB, brushing, and bronchial washing may further improve the diagnostic accuracy for peripheral lung cancers. A limitation of this study was the exclusion of patients with inflammatory (non-specific) or indeterminate nodules. Such nodules might
The authors have no conflicts of interest to declare.
Acknowledgments We thank Drs. Tomoki Tamura, Hiroe Kayatani, Hiroko Gotoda, and Kichiro Ninomiya for performing the bronchoscopies, and for the helpful discussions; we would also like to thank the cytoscreener, Mr. Hirofumi Inoue.
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