Surg Today DOI 10.1007/s00595-014-1029-7
ORIGINAL ARTICLE
Intraoperative fine-needle aspiration biopsy (FNA) for lung cancer: diagnostic value and risk of pleural dissemination Takahisa Matsuoka • Makoto Sonobe Hiroshi Date
•
Received: 16 December 2013 / Accepted: 7 May 2014 Ó Springer Japan 2014
Abstract Purpose Intraoperative fine-needle aspiration biopsy (FNA) is one of the most important diagnostic tools for undiagnosed lung nodules suspected of being lung cancer; however, the sensitivity and safety of FNA, including the risk of intrapleural dissemination of cancer cells, have not been established. Methods Between 2006 and 2008, 324 patients underwent lung resection for cancers located in the lung periphery. Intraoperative FNA for definite diagnosis was performed immediately after thoracotomy in 147 (45.4 %) of these patients, but not in the other 177. Results A diagnosis of lung cancer was obtained by the intraoperative FNA in 124 (84.4 %) of the 147 patients. During a median follow-up of 55 months, pleural dissemination or malignant effusion ipsilateral to the operated side as the first recurrent site occurred in 11 (7.4%) of the 147 patients who underwent the needle biopsy and 10 (5.6 %) of the 177 patients who did not. This difference was not significant (P = 0.5046). Conclusion Intraoperative FNA was safe and useful for the diagnosis of peripheral lung cancer and did not increase the risk of pleural dissemination in this series.
T. Matsuoka (&) Department of Thoracic Surgery, National Hospital Organization Himeji Medical Center, 68 Honmachi, Himeji City, Hyogo 670-8520, Japan e-mail: [email protected] T. Matsuoka M. Sonobe H. Date Department of Thoracic Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
Keywords
Lung cancer Intraoperative FNA VATS
Introduction Lung cancer can be diagnosed preoperatively by transbronchial biopsy (TBB) using fiberoptic bronchoscopy, computed tomography-guided lung biopsy (CTGLB), partial resection of the lung, or intraoperative fine-needle aspiration biopsy (FNA). However, TBB is not indicated for peripheral lung cancer and although CTGLB is useful, it has been associated with several complications. According to previous reports, pneumothorax and intrapulmonary hemorrhage occurred in 23 to 55 and 4 % of patients, respectively [1–3]. Rare cases of air embolism causing fatal brain or cardiac infarction have also been documented [4–7] and there are several reports of cancer cell implantation along the biopsy route [8–12]. Using a stapling device for partial resection of the lung is expensive and there are locations where it is difficult or impossible. Intraoperative FNA (INB) can minimize the time until surgery for peripheral lung cancer by avoiding further examinations and although it is the simplest and most direct method for diagnosing lung tumors, few articles have been published on the relationship between INB and pleural dissemination. Reports have been published on the risk of dissemination by needle lung biopsy through investigations of the cancer recurrence pattern or prognosis [8, 13–19], but the true incidence of tumor seeding along the needle may be underestimated because not all cases are diagnosed. Therefore, it is necessary to wait several years to clinically identify dissemination after the procedure. The aim of this study was to elucidate the sensitivity and safety of INB, including the risk of intrapleural dissemination of cancer cells.
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Surg Today Table 1 Clinicopathological characteristics of 147 patients who underwent intraoperative needle lung biopsy and 177 patients who did not Biopsy n = 147 Age
65.5
Non-biopsy n = 177 65.9
P 0.88
Sex Male
80
121
Female
67
56
0.01
I
114
127
II
19
25
0.25
III
14
25
Stage I vs others
IV
0
0
115
114
20
45
Large cell carcinoma
2
5
Small cell carcinoma
3
1
Adenosquamous carcinoma
1
3
0.007
Pleomorphic carcinoma
2
3
Ad. vs others
LCNEC
3
4
Pathological stage
Histology Adenocarcinoma Squamous cell carcinoma
Others Tumor size (mm)
1
2
26.6
28.7
Pathological pleural involvement pl0 112 pl1
20
Intraoperative FNA (INB) technique
0.38
117 31
0.051 pl0 vs others
pl2
4
17
pl3
11
12
Pathological T classification T1
91
106
T2
43
52
0.73
T3
9
12
T1 vs others
T4
4
7
The indication for INB was an undiagnosed peripheral mass in the outer one-third of the lung parenchyma. After thoracotomy, the tumor was detected by ocular inspection during VATS or on palpation. INB was performed using a 23-gauge needle attached to a syringe through the pulmonary mesenchyme. This process was repeated several times to obtain an adequate number of specimens for cytological evaluation. When the specimens were diagnosed as lung cancer, segmentectomy or lobectomy was performed sequentially. If the specimens were not diagnosed as lung cancer, wedge resection or segmentectomy of the lung, including the tumor, was performed. When the point of INB bled, the bleeding was stopped by applying pressure or electrocoagulation. We did not perform intraoperative pleural lavage cytology routinely. Video-assisted thoracic surgery (VATS) technique
Materials and methods Patients Between January, 2006 and December, 2008, 366 patients with primary lung cancer underwent curative lung resection at Kyoto University Hospital. The subjects of this retrospective study were 324 of these patients, who had peripheral lung cancer; namely, lung cancer located in the outer one-third of the lung parenchyma. The remaining 42 patients, whose lung cancers were located centrally, were
123
excluded because most of their tumors had been diagnosed using bronchoscopy and some of these tumors were located near major blood vessels. Moreover, even if INB was performed, the risk of pleural dissemination was low because the tumor was deep. This study protocol was approved by our Institutional Review Board, and written informed consent for intraoperative FNA and resection of lung cancer was obtained from all patients before surgery. Intraoperative needle lung biopsy for definite diagnosis was performed immediately after thoracotomy in 147 (45.4 %) patients and was not needed in the other 177 patients because a preoperative diagnosis of lung cancer had been confirmed. None of these 177 patients had undergone preoperative transthoracic needle biopsy such as CTGLB. Table 1 lists the clinical characteristics of the patients.
We used the VATS technique to resect lung cancers. Our standard technique involves three incisions, with the camera port inserted in the anterior axillary line through the sixth or seventh intercostal space, a second 2-cm incision made in the posterior axillary line through the sixth or seventh intercostal space, and a 4- to 5-cm working port placed in the fourth or fifth intercostal space anteriorly. Fortunately, there was no case of conversion to open thoracotomy in this series. Assessment of recurrence and pleural dissemination Follow-up examinations were symptom-oriented, but all patients received medical check-ups and chest X-rays at least twice a year and whole-body computed tomography
Surg Today
(CT) scans were done at least once a year. Pleural recurrence was defined as the development of a pleural lesion or malignant effusion, or both, in the hemithorax of the operated side at first relapse. Malignant pleural effusion was diagnosed cytologically, and pleural dissemination was diagnosed when multiple enhanced pleural lesions were observed on chest CT.
Table 3 Diagnostic rate according to tumor diameter
Statistical analyses
There were 12 cases of preoperative c-stage 2 or 3 cancer in the biopsy group. The ratio of p-stage 2 or 3 patients in the biopsy and non-biopsy group was 33 (22.4 %) of 147 patients and 50 (28.2 %) of 177 patients, respectively. The difference between the two groups was not significant (Fisher’s exact test; P = 0.25). In the nonbiopsy group, most cases were diagnosed by TBB, but several were diagnosed by either mediastinoscopy or Endobronchial Ultrasound Bronchoscopy (EBUS). Lung cancer was diagnosed by INB in 76 of the 84 patients with a tumor larger than 20 mm in diameter (sensitivity, 90.5 %) and only 48 of the 63 patients with a tumor smaller than 20 mm in diameter (sensitivity, 76.2 %; Table 3). The difference between the two groups based on the tumor size was significant (Fisher’s exact test; P = 0.0224). The minimal size of tumor diagnosed was 9 mm and the most frequent cell type of undiagnosed tumors smaller than 20 mm was adenocarcinoma, as observed in 17 (73.9 %) of 23 cases, including GroundGlass-Opacity (GGO) lesions. Because most of the GGO lesions were subpleural, they were palpable and four of the six were diagnosed. Eleven (7.5 %) of the 147 patients who underwent INLB and 10 (5.6 %) of the 177 patients who did not, were found to have pleural dissemination or malignant effusion ipsilateral to the operated side as the first site of recurrence during the respective 58 and 53 months of follow-up. This difference between the groups was not significant (Fisher’s exact test; P = 0.5046; Table 4). On the other hand, pathological PL0 or PL1 disease was diagnosed in 8 of 11 patients in the biopsy group and 4 of 10 patients in the other group. This difference between the groups was not significant (Fisher’s exact test; P = 0.1984). Recurrence, including pleural dissemination, developed in 34 (23.1 %) of the 147 patients who underwent INB and 53 (29.9 %) of the 177 patients who did not. Pleural dissemination or malignant effusion was found in 11 (32.4 %) of the 34 INB patients and 10 (18.9 %) of the 53 non-INB patients. These differences between the groups were not significant (Fisher’s exact test; P = 0.2004). The relapse-free survival period was 55.6 months and 51.2 months in the biopsy group and non-biopsy group, respectively, with relapsefree survival rates of 92 % (104/113) and 88.7 % (110/ 124), respectively. This difference between the groups was not significant (Fisher’s exact test; P = 0.8509).
Data are presented as mean ± SD. Student’s t test was used for continuous variables, and Fisher’s exact test was used for categorical variables. All tests were two-sided and a value of P \ 0.05 was considered significant. Statistical analyses were conducted using the Stat View 5.0 software program (SAS Institute, Cary, NC).
Results The patients’ clinicopathological characteristics are shown in Table 1. There were no significant differences in age, pathological stage, tumor size, pathological PL-factor, and pathological T classification (Fisher’s exact test) between the patients who underwent INB and those who did not. However, there were significant differences in gender and histology (Fisher’s exact test; P = 0.01 and 0.007, respectively). There were no adverse effects associated with INB, including massive hemorrhage, intrapulmonary or intrabronchial hemorrhage or air embolism. Lung cancer was diagnosed intraoperatively based on cytological examination of specimens from the INB in 124 (84.4 %) of the 147 patients who underwent INB. The sensitivity did not differ according to the tumor histology (Table 2). In the biopsy group, 24 patients underwent wedge resection or segmentectomy and 123 underwent lobectomy. In the non-biopsy group, 60 patients underwent wedge resection or segmentectomy and 117 underwent lobectomy.
Table 2 Concurrence of intraoperative needle lung biopsy results with the final pathological results (n = 124) (%) Adenocarcinoma (Ad)
84/93
90
Squamous cell carcinoma (Sq)
15/15
100
Small cell carcinoma
3/3
100
LCNEC
1/2
50
Carcinoid
1/1
100
łNSCLC 10 ? Ad 5, Sq 2, Pleo 1, LCNEC 1, Ad-Sq 1 LCNEC Large cell neuroendocrine carcinoma, Pleo Pleomorphic carcinoma, Ad-Sq Adenosquamous carcinoma
Size (mm)
No.
(%)
0–20
48/63
76.2
21–30
33/36
91.2
P = 0.0224
31–50
36/40
90.0
0–20 vs others
51–
7/8
87.5
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Surg Today Table 4 Incidence of pleural dissemination or malignant effusion in patients who underwent intraoperative needle lung biopsy vs. those who did not No. Biopsy
11/147 (7.5 %)
Non-biopsy
10/177 (5.6 %)
P = 0.5046
Discussion Histological confirmation is crucial for the management of lung nodules suspected to be lung cancer and INB is one of the most important diagnostic tools for this purpose. However, it is important to understand the sensitivity and comorbidities associated with this procedure. In this series, the sensitivity of INB was 84.4 %. As the sensitivity of CTGLB was reported to be 90–95.9 % [20, 21], its sensitivity seems to be higher than that of INB, probably because a larger specimen can be obtained using a 20-gauge core biopsy needle, and because CTGLB is performed under real-time CT observation. There have also been several reports of intraoperative FNA of pulmonary neoplasms during open thoracotomy [22–25]. The sensitivity of FNA has been reported to range from 95 to 100 %, although without documentation of the exact tumor diameters. Moreover, the tumor can be detected more easily and fixed by hand than during VATS. In relation to the tumor diameter, the sensitivity was 90.5 % for tumors [20 mm and 76.2 % for tumors \20 mm (p = 0.0224), which stands to reason because it is more difficult to hit a smaller nodule, and it is hard to gauge the circumference of the tumor punctured, especially if it is adenocarcinoma, because the cells often have low dysplasia. It seems that the sensitivity did not change even if the size of the needle did, because the movement was limited in VATS, and some bias was created by the surgeons’ personal preferences in performing certain maneuvers. Preoperative marking may be needed to improve the rate of diagnosis for smaller tumors. There were no adverse effects associated with INB, such as pulmonary hemorrhage or air embolism, in the present study, although several substantial complications associated with CTGLB have been reported. For example, pneumothorax and intrapulmonary hemorrhage occurred in 23 to 55 and 4 % of cases, respectively [1–3]. There were also several case reports of air emboli [4–7], however, there are no reports of air emboli induced by INB under VATS. In our study, INB was not associated with pleural dissemination or malignant effusion ipsilateral to the operated side as a first recurrent site. Matsuguma et al. [26] reported
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pleural recurrence or needle track implantation in 9.1 % (6/ 66) of their patients who underwent CTGLB, and 7.4 % (2/ 27) of those who underwent INB, and concluded that needle biopsy, especially that using a cutting-type biopsy needle, could cause pleural recurrence, in addition to needle track implantation. However, pleural recurrence is one of the major patterns of lung cancer relapse. Therefore, their data do not conclusively demonstrate that needle aspiration of lung cancer itself increases the incidence of pleural dissemination. Inoue et al. [27] conducted a study focusing on patients with subpleural lesions (SPLs) and reported that there was no pleural relapse in patients with nonsubpleural lesions (NSPLs) after CTGLB, and that NSPL lung cancer is a good indication for CTGLB. They suggested that an intentional approach through the pulmonary mesenchyme for a SPL might reduce the risk of the implantation of cancer cells. This approach is easy in INB, even for SPLs. Our method of INB is performed similarly through the lung parenchyma to reach the tumor. Sawabata et al. [28] reported that cancer cells were detected in 60 % of all cells in pulmonary surface lavage cytology samples after puncture with a 22-gauge needle, but that these seeding cancer cells could not always generate pleural dissemination. As we used a 23-gauge needle for cytological diagnosis in this study, the risk of extrapulmonary seeding might have been lower. This study has some limitations, which should be considered when interpreting the results. First, all of the patients had lung cancer; therefore, accuracy could not be determined because there are no data INB for benign peripheral lung nodules. Second, there may have been bias among the operators’ maneuvers, including the number of times the lesion was punctured, but this was not taken into account and we could not propose a way to increase the sensitivity based on our findings. In conclusion, we investigated the sensitivity and risk of pleural dissemination after INB based on the outcomes of our lung cancer patients who underwent this diagnostic procedure. We found that INB had a sensitivity of 84.4 %, and it did not increase the risk of pleural dissemination. Thus, we conclude that INB is a safe and useful method for diagnosing peripheral lung cancer. Conflict of interest Takahisa Matsuoka and his co-authors have no conflicts of interest.
References 1. 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;229:475–81.
Surg Today 2. Chakrabarti B, Earis JE, Pandey R, Jones Y, Slaven K, Amin S, et al. Risk assessment of pneumothorax and pulmonary haemorrhage complicating percutaneous co-axial cutting needle lung biopsy. Respir Med. 2009;103:449–55. 3. Yeow KM, Su IH, Pan KT, Tsay PK, Lui KW, Cheung YC, et al. Risk factors of pneumothorax and bleeding:multivariate analysis of 660 CT-guided coaxial cutting needle lung biopsies. Chest. 2004;126:748–54. 4. Ishikawa Y, Matsuguma H, Nakahara R, Ui A, Suzuki H, Yokoi K. Arterial air embolism:a rare but life-threatening complication of percutaneous needle biopsy of the lung. Ann Thorac Surg. 2009;87:1622. 5. Hiraki T, Fujiwara H, Sakurai J, Iguchi T, Gobara H, Tajiri N, et al. Nonfatal systemic air embolism complicating percutaneous CT-guided transthoracic needle biopsy:four cases from a single institution. Chest. 2007;132:684–90. 6. Lattin G Jr, O’Brien W Sr, McCrary B, Kearney P, Gover D. Massive systemic air embolism treated with hyperbaric oxygen therapy following CT-guided transthoracic needle biopsy of a pulmonary nodule. J Vasc Interv Radiol. 2006;17:1355–8. 7. Mansour A, AbdelRaouf S, Qandeel M, Swaidan M. Acute coronary artery air embolism following CT-guided lung biopsy. Cardiovasc Intervent Radiol. 2005;28(1):131–4. 8. Kara M, Alver G, Sak SD, Kavukcu S. Implantation metastasis caused by fine needle aspiration biopsy following curative resection of stage IB nonsmall cell lung cancer. Eur J Cardiothor Surg. 2001;20:868–70. 9. Kim JH, Kim YT, Lim HK, Kim YH, Sung SW. Management for chest wall implantation on non-small cell lung cancer after fineneedle aspiration biopsy. Eur J Cardiothorac Surg. 2003;23:8. 10. Voravud N, Shin DM, Dekmezian RH, Dimery I, Lee JS, Hong WK. Implantation metastasis of carcinoma after percutaneous fine-needle aspiration biopsy. Chest. 1992;102:313–5. 11. Redwood N, Beggs D, Morgan WE. Disssemination of tumour cells from fine needle biopsy. Thorax. 1989;44:826–7. 12. Seyfer AE, Walsh DS, Graeber GM, Muno IN, Eliasson AH. Chest wall implantation of lung cancer after thin-needle aspiration biopsy. Ann Thorac Surg. 1989;48:284–6. 13. Berger RL, Dargan EL, Huang BL. Dissemination of cancer cells by needle biopsy of the lung. J Thor Cardiovasc Surg. 1972;63: 430–2. 14. Freise G, Larios R, Takeno Y. Cell dissemination and implantation of neoplasms through biopsy and excision of malignant tumors. Dis Chest. 1967;52:485–9. 15. Christensen ES. Iatrogenic dissemination of tumor cells:dissemination of tumor cells along the needle track after percutaneous, transthoracic lung biopsy. Danish Med Bull. 1978;25:82–7.
16. Ferrucci JT, Wittenberg J, Marggolies MN, Carey RW. Malignant seeding of the tract after thin-needle aspiration biopsy. Radiology. 1979;130:345–6. 17. Yoshikawa T, Yoshida J, Nishimura M, Yokose T, Nishiwaki Y, Nagai K. Lung cancer implantation in the chest wall following percutaneous fine needle aspiration biopsy. Jpn J Clin Oncol. 2000;30:450–2. 18. Tomiyama N, Yasuhara Y, Nakajima Y, Adachi S, Arai Y, Kusumoto M, et al. CT-guided fine-needle biopsy of lung lesions:a survey of severe complication based on 9783 biopsies in Japan. Eur J Radiol. 2006;59:60–4. 19. Laspas F, Roussakis A, Efthimiadou R, Papaioannou D, Papadopoulos S, Andreou J. Percutaneous CT-guided fine-neeedle aspiration of pulmonary lesions:Results and complications in 409 patients. J Med Imaging Radiat Oncol. 2008;52:458–62. 20. Schreiber G, McCrory DC. Performance characteristics of different modalities for diagnosis of suspected lung cancer: summary of published evidence. Chest. 2003;123(Suppl):115S–28S. 21. Sano Y, Date H, Toyooka S, Oto T, Yamane M, Hiraki T, et al. Percutaneous computed tomography-guided lung biopsy and pleural dissemination. Cancer. 2009;115:5526–33. 22. McCarthy WJ, Christ ML, Fry WA. Intraoperative fine needle aspiration biopsy of thoracic lesions. Ann Thorac Surg. 1980; 30(1):24–9. 23. DeCaro LF, Pak HY, Yokota S, Teplitz RL, Benfield JR. Intraoperative cytodiagnosis of lung tumors by needle aspiration. J Thorac Cardiovasc Surg. 1983;85:404–8. 24. Terada Y, Matsunobe S, Nemoto T, Tsuda T, Shimizu Y. Feasibility of intraoperative cytodiagnosis of lung cancer. Chest. 1990;98:1156–8. 25. Capellari JO, Thompson EN, Wallenhaupt SL. Utility of intraoperative fine needle aspiration biopsy in the surgical management of patients with pulmonary masses. Acta Cytol. 1994;38: 707–10. 26. Matsuguma H, Nakahara R, Kondo T, Kamiyama Y, Mori K, Yokoi K. Risk of pleural recurrence after needle biopsy in patients with resected early stage lung cancer. Ann Thor Surg. 2005;80:2026–31. 27. Inoue M, Honda O, Tomiyama N, Minami M, Sawabata N, Kadota Y, et al. Risk of pleural recurrence after computed tomographic-guided percutaneous needle biopsy in stage I lung cancer patient. Ann Thorac Surg. 2011;91:1066–72. 28. Sawabata N, Ohta M, Maeda H. Fine-needle aspiration cytologic technique for lung cancer has a high potential of malignant cell spread through the tract. Chest. 2000;118:936–9.
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ORIGINAL ARTICLE
Intraoperative fine-needle aspiration biopsy (FNA) for lung cancer: diagnostic value and risk of pleural dissemination Takahisa Matsuoka • Makoto Sonobe Hiroshi Date
•
Received: 16 December 2013 / Accepted: 7 May 2014 Ó Springer Japan 2014
Abstract Purpose Intraoperative fine-needle aspiration biopsy (FNA) is one of the most important diagnostic tools for undiagnosed lung nodules suspected of being lung cancer; however, the sensitivity and safety of FNA, including the risk of intrapleural dissemination of cancer cells, have not been established. Methods Between 2006 and 2008, 324 patients underwent lung resection for cancers located in the lung periphery. Intraoperative FNA for definite diagnosis was performed immediately after thoracotomy in 147 (45.4 %) of these patients, but not in the other 177. Results A diagnosis of lung cancer was obtained by the intraoperative FNA in 124 (84.4 %) of the 147 patients. During a median follow-up of 55 months, pleural dissemination or malignant effusion ipsilateral to the operated side as the first recurrent site occurred in 11 (7.4%) of the 147 patients who underwent the needle biopsy and 10 (5.6 %) of the 177 patients who did not. This difference was not significant (P = 0.5046). Conclusion Intraoperative FNA was safe and useful for the diagnosis of peripheral lung cancer and did not increase the risk of pleural dissemination in this series.
T. Matsuoka (&) Department of Thoracic Surgery, National Hospital Organization Himeji Medical Center, 68 Honmachi, Himeji City, Hyogo 670-8520, Japan e-mail: [email protected] T. Matsuoka M. Sonobe H. Date Department of Thoracic Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
Keywords
Lung cancer Intraoperative FNA VATS
Introduction Lung cancer can be diagnosed preoperatively by transbronchial biopsy (TBB) using fiberoptic bronchoscopy, computed tomography-guided lung biopsy (CTGLB), partial resection of the lung, or intraoperative fine-needle aspiration biopsy (FNA). However, TBB is not indicated for peripheral lung cancer and although CTGLB is useful, it has been associated with several complications. According to previous reports, pneumothorax and intrapulmonary hemorrhage occurred in 23 to 55 and 4 % of patients, respectively [1–3]. Rare cases of air embolism causing fatal brain or cardiac infarction have also been documented [4–7] and there are several reports of cancer cell implantation along the biopsy route [8–12]. Using a stapling device for partial resection of the lung is expensive and there are locations where it is difficult or impossible. Intraoperative FNA (INB) can minimize the time until surgery for peripheral lung cancer by avoiding further examinations and although it is the simplest and most direct method for diagnosing lung tumors, few articles have been published on the relationship between INB and pleural dissemination. Reports have been published on the risk of dissemination by needle lung biopsy through investigations of the cancer recurrence pattern or prognosis [8, 13–19], but the true incidence of tumor seeding along the needle may be underestimated because not all cases are diagnosed. Therefore, it is necessary to wait several years to clinically identify dissemination after the procedure. The aim of this study was to elucidate the sensitivity and safety of INB, including the risk of intrapleural dissemination of cancer cells.
123
Surg Today Table 1 Clinicopathological characteristics of 147 patients who underwent intraoperative needle lung biopsy and 177 patients who did not Biopsy n = 147 Age
65.5
Non-biopsy n = 177 65.9
P 0.88
Sex Male
80
121
Female
67
56
0.01
I
114
127
II
19
25
0.25
III
14
25
Stage I vs others
IV
0
0
115
114
20
45
Large cell carcinoma
2
5
Small cell carcinoma
3
1
Adenosquamous carcinoma
1
3
0.007
Pleomorphic carcinoma
2
3
Ad. vs others
LCNEC
3
4
Pathological stage
Histology Adenocarcinoma Squamous cell carcinoma
Others Tumor size (mm)
1
2
26.6
28.7
Pathological pleural involvement pl0 112 pl1
20
Intraoperative FNA (INB) technique
0.38
117 31
0.051 pl0 vs others
pl2
4
17
pl3
11
12
Pathological T classification T1
91
106
T2
43
52
0.73
T3
9
12
T1 vs others
T4
4
7
The indication for INB was an undiagnosed peripheral mass in the outer one-third of the lung parenchyma. After thoracotomy, the tumor was detected by ocular inspection during VATS or on palpation. INB was performed using a 23-gauge needle attached to a syringe through the pulmonary mesenchyme. This process was repeated several times to obtain an adequate number of specimens for cytological evaluation. When the specimens were diagnosed as lung cancer, segmentectomy or lobectomy was performed sequentially. If the specimens were not diagnosed as lung cancer, wedge resection or segmentectomy of the lung, including the tumor, was performed. When the point of INB bled, the bleeding was stopped by applying pressure or electrocoagulation. We did not perform intraoperative pleural lavage cytology routinely. Video-assisted thoracic surgery (VATS) technique
Materials and methods Patients Between January, 2006 and December, 2008, 366 patients with primary lung cancer underwent curative lung resection at Kyoto University Hospital. The subjects of this retrospective study were 324 of these patients, who had peripheral lung cancer; namely, lung cancer located in the outer one-third of the lung parenchyma. The remaining 42 patients, whose lung cancers were located centrally, were
123
excluded because most of their tumors had been diagnosed using bronchoscopy and some of these tumors were located near major blood vessels. Moreover, even if INB was performed, the risk of pleural dissemination was low because the tumor was deep. This study protocol was approved by our Institutional Review Board, and written informed consent for intraoperative FNA and resection of lung cancer was obtained from all patients before surgery. Intraoperative needle lung biopsy for definite diagnosis was performed immediately after thoracotomy in 147 (45.4 %) patients and was not needed in the other 177 patients because a preoperative diagnosis of lung cancer had been confirmed. None of these 177 patients had undergone preoperative transthoracic needle biopsy such as CTGLB. Table 1 lists the clinical characteristics of the patients.
We used the VATS technique to resect lung cancers. Our standard technique involves three incisions, with the camera port inserted in the anterior axillary line through the sixth or seventh intercostal space, a second 2-cm incision made in the posterior axillary line through the sixth or seventh intercostal space, and a 4- to 5-cm working port placed in the fourth or fifth intercostal space anteriorly. Fortunately, there was no case of conversion to open thoracotomy in this series. Assessment of recurrence and pleural dissemination Follow-up examinations were symptom-oriented, but all patients received medical check-ups and chest X-rays at least twice a year and whole-body computed tomography
Surg Today
(CT) scans were done at least once a year. Pleural recurrence was defined as the development of a pleural lesion or malignant effusion, or both, in the hemithorax of the operated side at first relapse. Malignant pleural effusion was diagnosed cytologically, and pleural dissemination was diagnosed when multiple enhanced pleural lesions were observed on chest CT.
Table 3 Diagnostic rate according to tumor diameter
Statistical analyses
There were 12 cases of preoperative c-stage 2 or 3 cancer in the biopsy group. The ratio of p-stage 2 or 3 patients in the biopsy and non-biopsy group was 33 (22.4 %) of 147 patients and 50 (28.2 %) of 177 patients, respectively. The difference between the two groups was not significant (Fisher’s exact test; P = 0.25). In the nonbiopsy group, most cases were diagnosed by TBB, but several were diagnosed by either mediastinoscopy or Endobronchial Ultrasound Bronchoscopy (EBUS). Lung cancer was diagnosed by INB in 76 of the 84 patients with a tumor larger than 20 mm in diameter (sensitivity, 90.5 %) and only 48 of the 63 patients with a tumor smaller than 20 mm in diameter (sensitivity, 76.2 %; Table 3). The difference between the two groups based on the tumor size was significant (Fisher’s exact test; P = 0.0224). The minimal size of tumor diagnosed was 9 mm and the most frequent cell type of undiagnosed tumors smaller than 20 mm was adenocarcinoma, as observed in 17 (73.9 %) of 23 cases, including GroundGlass-Opacity (GGO) lesions. Because most of the GGO lesions were subpleural, they were palpable and four of the six were diagnosed. Eleven (7.5 %) of the 147 patients who underwent INLB and 10 (5.6 %) of the 177 patients who did not, were found to have pleural dissemination or malignant effusion ipsilateral to the operated side as the first site of recurrence during the respective 58 and 53 months of follow-up. This difference between the groups was not significant (Fisher’s exact test; P = 0.5046; Table 4). On the other hand, pathological PL0 or PL1 disease was diagnosed in 8 of 11 patients in the biopsy group and 4 of 10 patients in the other group. This difference between the groups was not significant (Fisher’s exact test; P = 0.1984). Recurrence, including pleural dissemination, developed in 34 (23.1 %) of the 147 patients who underwent INB and 53 (29.9 %) of the 177 patients who did not. Pleural dissemination or malignant effusion was found in 11 (32.4 %) of the 34 INB patients and 10 (18.9 %) of the 53 non-INB patients. These differences between the groups were not significant (Fisher’s exact test; P = 0.2004). The relapse-free survival period was 55.6 months and 51.2 months in the biopsy group and non-biopsy group, respectively, with relapsefree survival rates of 92 % (104/113) and 88.7 % (110/ 124), respectively. This difference between the groups was not significant (Fisher’s exact test; P = 0.8509).
Data are presented as mean ± SD. Student’s t test was used for continuous variables, and Fisher’s exact test was used for categorical variables. All tests were two-sided and a value of P \ 0.05 was considered significant. Statistical analyses were conducted using the Stat View 5.0 software program (SAS Institute, Cary, NC).
Results The patients’ clinicopathological characteristics are shown in Table 1. There were no significant differences in age, pathological stage, tumor size, pathological PL-factor, and pathological T classification (Fisher’s exact test) between the patients who underwent INB and those who did not. However, there were significant differences in gender and histology (Fisher’s exact test; P = 0.01 and 0.007, respectively). There were no adverse effects associated with INB, including massive hemorrhage, intrapulmonary or intrabronchial hemorrhage or air embolism. Lung cancer was diagnosed intraoperatively based on cytological examination of specimens from the INB in 124 (84.4 %) of the 147 patients who underwent INB. The sensitivity did not differ according to the tumor histology (Table 2). In the biopsy group, 24 patients underwent wedge resection or segmentectomy and 123 underwent lobectomy. In the non-biopsy group, 60 patients underwent wedge resection or segmentectomy and 117 underwent lobectomy.
Table 2 Concurrence of intraoperative needle lung biopsy results with the final pathological results (n = 124) (%) Adenocarcinoma (Ad)
84/93
90
Squamous cell carcinoma (Sq)
15/15
100
Small cell carcinoma
3/3
100
LCNEC
1/2
50
Carcinoid
1/1
100
łNSCLC 10 ? Ad 5, Sq 2, Pleo 1, LCNEC 1, Ad-Sq 1 LCNEC Large cell neuroendocrine carcinoma, Pleo Pleomorphic carcinoma, Ad-Sq Adenosquamous carcinoma
Size (mm)
No.
(%)
0–20
48/63
76.2
21–30
33/36
91.2
P = 0.0224
31–50
36/40
90.0
0–20 vs others
51–
7/8
87.5
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Surg Today Table 4 Incidence of pleural dissemination or malignant effusion in patients who underwent intraoperative needle lung biopsy vs. those who did not No. Biopsy
11/147 (7.5 %)
Non-biopsy
10/177 (5.6 %)
P = 0.5046
Discussion Histological confirmation is crucial for the management of lung nodules suspected to be lung cancer and INB is one of the most important diagnostic tools for this purpose. However, it is important to understand the sensitivity and comorbidities associated with this procedure. In this series, the sensitivity of INB was 84.4 %. As the sensitivity of CTGLB was reported to be 90–95.9 % [20, 21], its sensitivity seems to be higher than that of INB, probably because a larger specimen can be obtained using a 20-gauge core biopsy needle, and because CTGLB is performed under real-time CT observation. There have also been several reports of intraoperative FNA of pulmonary neoplasms during open thoracotomy [22–25]. The sensitivity of FNA has been reported to range from 95 to 100 %, although without documentation of the exact tumor diameters. Moreover, the tumor can be detected more easily and fixed by hand than during VATS. In relation to the tumor diameter, the sensitivity was 90.5 % for tumors [20 mm and 76.2 % for tumors \20 mm (p = 0.0224), which stands to reason because it is more difficult to hit a smaller nodule, and it is hard to gauge the circumference of the tumor punctured, especially if it is adenocarcinoma, because the cells often have low dysplasia. It seems that the sensitivity did not change even if the size of the needle did, because the movement was limited in VATS, and some bias was created by the surgeons’ personal preferences in performing certain maneuvers. Preoperative marking may be needed to improve the rate of diagnosis for smaller tumors. There were no adverse effects associated with INB, such as pulmonary hemorrhage or air embolism, in the present study, although several substantial complications associated with CTGLB have been reported. For example, pneumothorax and intrapulmonary hemorrhage occurred in 23 to 55 and 4 % of cases, respectively [1–3]. There were also several case reports of air emboli [4–7], however, there are no reports of air emboli induced by INB under VATS. In our study, INB was not associated with pleural dissemination or malignant effusion ipsilateral to the operated side as a first recurrent site. Matsuguma et al. [26] reported
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pleural recurrence or needle track implantation in 9.1 % (6/ 66) of their patients who underwent CTGLB, and 7.4 % (2/ 27) of those who underwent INB, and concluded that needle biopsy, especially that using a cutting-type biopsy needle, could cause pleural recurrence, in addition to needle track implantation. However, pleural recurrence is one of the major patterns of lung cancer relapse. Therefore, their data do not conclusively demonstrate that needle aspiration of lung cancer itself increases the incidence of pleural dissemination. Inoue et al. [27] conducted a study focusing on patients with subpleural lesions (SPLs) and reported that there was no pleural relapse in patients with nonsubpleural lesions (NSPLs) after CTGLB, and that NSPL lung cancer is a good indication for CTGLB. They suggested that an intentional approach through the pulmonary mesenchyme for a SPL might reduce the risk of the implantation of cancer cells. This approach is easy in INB, even for SPLs. Our method of INB is performed similarly through the lung parenchyma to reach the tumor. Sawabata et al. [28] reported that cancer cells were detected in 60 % of all cells in pulmonary surface lavage cytology samples after puncture with a 22-gauge needle, but that these seeding cancer cells could not always generate pleural dissemination. As we used a 23-gauge needle for cytological diagnosis in this study, the risk of extrapulmonary seeding might have been lower. This study has some limitations, which should be considered when interpreting the results. First, all of the patients had lung cancer; therefore, accuracy could not be determined because there are no data INB for benign peripheral lung nodules. Second, there may have been bias among the operators’ maneuvers, including the number of times the lesion was punctured, but this was not taken into account and we could not propose a way to increase the sensitivity based on our findings. In conclusion, we investigated the sensitivity and risk of pleural dissemination after INB based on the outcomes of our lung cancer patients who underwent this diagnostic procedure. We found that INB had a sensitivity of 84.4 %, and it did not increase the risk of pleural dissemination. Thus, we conclude that INB is a safe and useful method for diagnosing peripheral lung cancer. Conflict of interest Takahisa Matsuoka and his co-authors have no conflicts of interest.
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