Interact CardioVasc Thorac Surg 2009;9:102-106. doi:10.1510/icvts.2009.206045
© 2009 European Association of Cardio-Thoracic Surgery
Institutional report - Thoracic oncologic |
Prognostic significance of pleural lavage cytology after thoracotomy and before closure of the chest in lung cancer
Yuji Taniguchia,*,
Hiroshige Nakamuraa,
Ken Miwaa,
Yoshin Adachia,
Shinji Fujiokaa,
Tomohiro Harukia and
Yasushi Horieb
a Division of Thoracic Surgery, Tottori University Hospital, 36-1 Nishi-Cho, Yonago, Tottori 683-8504, Japan
b Division of Pathology, Tottori University Hospital, Yonago, Japan
Received 23 February 2009;
received in revised form 6 April 2009;
accepted 8 April 2009
*Corresponding author. Tel.: +81-859-38-6737; fax: +81-859-38-6730.
E-mail address: kuichi{at}med.tottori-u.ac.jp (Y. Taniguchi).
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Abstract
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Some reports have described pleural lavage cytology (PLC) to be a prognostic factor for non-small cell lung cancer (NSCLC) patients. However, there have only been a few reports describing the findings both immediately after thoracotomy (PLC after thoracotomy) and before the closure of the chest (PLC before closure). From April 2002 to April 2008, both PLC after thoracotomy and PLC before closure were performed in 296 consecutive patients who underwent resections for NSCLC. PLC after thoracotomy was positive in 14 patients. The survival rate in the PLC after thoracotomy positive cases was significantly poorer than in PLC after thoracotomy negative cases (P=0.047). In contrast, there were 26 PLC before closure positive cases. The survival rate in the PLC before closure positive cases was significantly poorer than in the PLC before closure negative cases (P<0.0001). Multivariate analyses revealed that PLC after thoracotomy is not an independent prognostic factor in our study. However, PLC before closure was an independent prognostic factor based on multivariate analyses. We conclude that PLC before closure was found to be a better prognostic factor than PLC after thoracotomy for NSCLC patients.
Key Words: Pleural lavage cytology; Lung cancer; Prognostic factor
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1. Introduction
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Pleural lavage cytology (PLC) was first reported in 1958 by Spjut et al. [1]. Since then, it has been sporadically reported that PLC may be a prognostic factor for non-small cell lung cancer (NSCLC) [2]. However, many of the reports on the usefulness of PLC were done regarding samples in which PLC was performed immediately after a thoracotomy. Therefore, there were only a few reports of samples in which PLC was performed immediately before closure of the chest. Furthermore, there were extremely few reports of reviews in which a multivariate analysis of covariance was used that incorporates both PLC immediately after a thoracotomy (PLC after thoracotomy) and PLC immediately before closure of the chest (PLC before closure) [3, 4]. Considering that the pathological conditions of PLC after thoracotomy positive cases may differ from that of PLC before closure positive cases, we adopted PLC before closure in addition to PLC after thoracotomy. This study analyzed the relationship between PLC after thoracotomy/PLC before closure and clinicopathological factors.
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2. Material and methods
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From April 2002 to April 2008, PLC was performed before any manipulation or resection of the lung in 296 consecutive patients who had no macroscopic pleural effusions, dissemination, or diffuse adhesion and who underwent resections for primary NSCLC at Tottori University Hospital. Informed consent was obtained from each patient before treatment.
Immediately after a thoracotomy, the pleural cavity was carefully washed with 50 ml of warm physiologic saline solution before any manipulation of the lung. The surgeon avoided touching the pleural surface, especially close to the tumor, to obtain only desquamated cells. Approximately 20 ml of fluid was collected (PLC after thoracotomy). After we performed all the procedures for lung cancer surgery, and before closure of the chest, the pleural cavity was washed with 50 ml of warm physiologic saline solution and approximately 20 ml of fluid was also collected as well as PLC after thoracotomy (PLC before closure). After PLC before closure, the pleural cavity was routinely washed with 2000 ml of warm physiologic saline solution. The PLC fluid was centrifuged at 1500 rpm for 5 min. The sediment was stained using the Papanicolaou method. The results of cytology were then classified as either negative, borderline positive, or positive. In this study, borderline positive meant that only a few cells with possible tumor cells were regarded as positive [3]. The pathologic stages were determined according to the TNM classification of the International Staging System [5]. The p factors were classified according to the Japan Lung Cancer Society criteria [6]: p0: tumor did not invade the elastic layer of visceral pleura, p1: tumor invaded the elastic layer of visceral pleura but did not expose on the visceral pleural surface, p2: tumor exposed on the visceral pleural surface, and p3: tumor invaded the parietal pleura. Lymphatic invasion (ly) and vascular invasion (v) were classified according to the gastric cancer criteria [7]: ly0 and v0; no, ly1 and v1; minimal, ly2 and v2; moderate, and ly3 and v3; marked.
Comparisons between the two groups were performed by the  2-test. Survival was calculated by the Kaplan–Meier method, and differences in survival were determined by means of the log-rank analysis. Multivariate analyses were performed using the Cox proportional hazards model. A P<0.05 was considered to be significant. All statistical analyses were performed using the StatView 5.0J statistical software program (SAS Institute, Inc, Cary, NC).
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3. Results
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The clinical and pathologic characteristics of the patients are summarized in Table 1. Clinical and pathologic characteristics of PLC after thoracotomy and PLC before closure are summarized in Table 2. There were 14 PLC positive patients (4.7%) identified by PLC after thoracotomy and 26 (8.8%) identified by PLC before closure.
There was a significant association between pathologic T stage and PLC after thoracotomy (P=0.028). However, there was no significant association observed between the pathologic T stage and PLC before closure. There was no significant association between the pathologic N stage and PLC after thoracotomy. However, a significant association was observed between the pathologic N stage and PLC before closure (P<0.0001). There was significant association between p factor and PLC after thoracotomy (P<0.0001). There was a significant association between p factor and PLC before closure, also (P=0.002). There was also a significant association between lymphatic invasion and PLC after thoracotomy (P=0.002). In addition, there was significant association between lymphatic invasion and PLC before closure (P<0.0001). There was no significant association between vascular invasion and PLC after thoracotomy. However, there was significant association between the pathologic N stage and PLC before closure (P<0.0001).
The distributions of the PLC group regarding the recurrence patterns are shown in Table 3. There was a significant association between the PLC group and the recurrence rate (P<0.0001). However, there was no significant association between the PLC group and the recurrence patterns. In PLC after thoracotomy, the 5-year survival rate was 45% for positive patients and 72% for negative patients (Fig. 1). The survival rate was significantly poorer in the PLC after thoracotomy positive patients than in the PLC after thoracotomy negative patients (P=0.047). In PLC before closure, the 5-year survival rate was 32% for positive patients and 76% for negative patients (Fig. 2). The survival rate was also significantly poorer in the PLC before closure positive patients than in the PLC before closure negative patients (P<0.0001). In the stage I PLC after thoracotomy patients, the 5-year survival rate was 67% for positive patients and 82% for negative patients (Fig. 3). The survival rate was significantly poorer in the PLC after thoracotomy positive patients than in the PLC after thoracotomy stage I patients (P=0.004). In the PLC before closure stage I patients, the 5-year survival rate was 33% for positive patients and 86% for negative patients (Fig. 4). The survival rate was also significantly poorer in the PLC before closure positive patients than in the PLC before closure negative stage I patients (P<0.0001). The significantly prognostic factors based on a univariate analysis were pathologic stage (P<0.0001), lymphatic invasion (P<0.0001), vascular invasion (P<0.0001), PLC after thoracotomy (P=0.047), and PLC before closure (P<0.0001). Gender was marginally a significantly prognostic factor based on a univariate analysis (P=0.064). The above six factors were analyzed by a multivariable Cox analysis. PLC before closure was found to be a significantly independent prognostic factor (P=0.001), as were lymphatic invasion (P=0.031) and pathologic stage (P=0.041) according to a multivariate analysis. However, PLC after thoracotomy was not found to be a significantly independent prognostic factor, as were gender and vascular invasion according to a multivariate analysis (Table 4).
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Fig. 1. Survival curves of the patients according to the pleural lavage cytology (PLC) findings after thoracotomy.
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Fig. 2. Survival curves of the patients according to the pleural lavage cytology (PLC) findings before closure.
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Fig. 3. Survival curves of pathologic stage I patients according to the pleural lavage cytology (PLC) findings after thoracotomy.
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Fig. 4. Survival curves of pathologic stage I patients according to the pleural lavage cytology (PLC) findings before closure.
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4. Discussion
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According to the previous reports, the positive rate for PLC after thoracotomy and PLC before closure was 2.7–22.6% [3, 4, 8–14] and 3.7–13.5% [3, 4, 9, 15], respectively. In this study, the positive rates for PLC after thoracotomy and PLC before closure were 4.7% and 8.8%, respectively. These figures generally appear to be reasonable. The uppermost problem in performing PLC is considered to be the amount of lavage fluid. The amount of lavage fluid varies from 50 ml [8, 10] to 1000 ml [14] among studies. It cannot be ruled out that, when the amount of lavage fluid is small, there is a risk of reducing the PLC sensitivity. On the other hand, when the amount of lavage fluid is large, particularly in PLC after thoracotomy, the pleural surface near a tumor is saturated with the lavage fluid. Due to the action of washing, cancer cells may possibly become deposited in the pleural cavity. In that case, it would result in detecting a positive that is not the original purpose of the PLC after thoracotomy of ‘detecting a potential malignant effusion’. As for the timing of performing pleural lavage, for PLC after thoracotomy, it is thought that a consensus has generally been gained that it should be immediately done after a thoracotomy. However, the timing for performing PLC before closure varies among researchers. Dresler et al. [9] performed PLC before closure before pleural lavage, which is routinely done before closure of the chest. On the other hand, Higashiyama et al. [3] performed PLC before closure after pleural lavage, which is routinely done before closure of the chest. It has been reported that PLC is useful as a prognostic factor after NSCLC [2]. In addition, this examination does not require any special techniques, so it will most likely be performed at even more facilities in the future. Accordingly, we believe that it is necessary to review the timing of performing PLC, the amount of lavage fluid, etc., in order to standardize the same.
In this study, a significant correlation was found between PLC after thoracotomy and T factor, p factor, ly factor, and particularly p factor and ly factor. As stated above, it is inferred that the main mechanism for PLC after thoracotomy being positive is that, in addition to cancer cells that have directly infiltrated the visceral pleura, those that are present in the lymphatic vessels directly in the subpleural space of the visceral pleura have also dispersed into the pleural cavity. Kondo et al. [8] considered this mechanism in a similar way. On the other hand, a significant correlation was found between PLC before closure and N factor, p factor, ly factor, v factor, and particularly N factor, ly factor, and v factor. As stated above, it can be inferred that the main mechanism for PLC before closure being positive is not the same as the mechanism for PLC after thoracotomy being positive. Regarding one of the mechanisms for PLC before closure being positive, it is believed that cancer cells that are present in the micro-vessels, such as the lymphatic vessels directly in the subpleural space of the visceral pleura and those that connect the lymph nodes, may have been deposited during surgical procedure, such as lung resection and lymph node dissection.
Regarding the prognosis, PLC, particularly PLC before closure, served as an independent prognostic factor according to multivariate analyses. Furthermore, compared to PLC after thoracotomy, PLC before closure showed a good correlation with the prognosis. These results conform to those from Enatsu et al. [4]. This basis suggests, as described above, that the mechanism for PLC after thoracotomy being positive is different from the mechanism for PLC before closure being positive. In addition, further examination is required in order to elucidate whether a poor prognosis is due to the procedure of spreading cancer cells within the pleural cavity or whether the pathological condition of lung cancer, that renders cancer cells diffuse within the pleural cavity, serves as an indicator of a poor prognosis. Regarding treatment for PLC positive patients, including PLC before closure, according to the fact that no significant difference was observed between PLC negative patients and the recurrence patterns, and the report that local therapy alone is unable to achieve an extended survival period [10], we believe that systemic therapy is desirable. For PLC before closure positive patients in particular, even in stage I cases, the 5-year survival rate was only 33%. Furthermore, for the PLC after thoracotomy positive stage I cases, only six positive patients were observed. However, similar to other reports [8, 9, 11, 13, 14], a statistically significant difference was observed. Accordingly, in line with the findings of Satoh et al. [13], we believe that it is desirable to administer postoperative systemic adjuvant therapy to PLC positive stage I cases.
PLC, particularly PLC before closure, is regarded as a possible prognostic factor. Further examination will be necessary in order to standardize the detailed method for performing PLC, including the timing of lavage, the amount of lavage fluid, etc. At the same time, it is also necessary to promote an analysis of the pathological conditions that lead to PLC positive findings.
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References
|
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- Spjut JH, Hendrix VJ, Ramirez GA, Roper CL. Carcinoma cell in pleural cavity washing. Cancer 1958;11:1222–1225.[CrossRef][Medline]
- Li YN, Shi HZ, Liang QL, Yang HB, Huang GM. Prognostic significance of pleural lavage cytology in patients with lung cancer: a meta-analysis. Lung Cancer 2008;60:183–192.[CrossRef][Medline]
- Higashiyama M, Doi O, Kodama K, Yokouchi H, Tateishi R, Horai T, Ashimura J, Nagumo S, Naruse Y. Pleural lavage cytology immediately after thoracotomy and before closure of the thoracic cavity for lung cancer without pleural effusion and dissemination: clinicopathologic and prognostic analysis. Ann Surg Oncol 1996;4:409–415.[CrossRef]
- Enatsu S, Yoshida J, Yokose T, Nishimura M, Nishiwaki Y, Shirakusa T, Nagai K. Pleural lavage cytology before and after lung resection in non-small cell lung cancer patients. Ann Thorac Surg 2006;81:298–304.[Abstract/Free Full Text]
- Mountain CF. Revisions in the international system for staging lung cancer. Chest 1997;111:1710–1717.[CrossRef][Medline]
- The Japan Lung Cancer Society, General rule for clinical and pathological record of lung cancer (in Japanese), 6th edition. Tokyo, Japan: Kanehara; 2003.
- Japanese Gastric Cancer Association, Japanese classification of gastric carcinoma, 2nd English edition, Gastric Cancer, 1998, 1, 10–24.[Medline]
- Kondo H, Asamura H, Suemasu K, Goya T, Tsuchiya R, Naruke T, Yamagishi K, Uei Y. Prognostic significance of pleural lavage cytology immediately after thoracotomy in patients with lung cancer. J Thorac Cardiovasc Surg 1993;106:1092–1097.[Abstract]
- Dresler CM, Fratelli C, Babb J. Prognostic value of positive pleural lavage in patients with lung cancer resection. Ann Thorac Surg 1999;67:1435–1439.[Abstract/Free Full Text]
- Ichinose Y, Tsuchiya R, Koike T, Yasumitsu T, Nakamura K, Tada T, Yoshimura H, Mitsudomi T, Nakagawa K, Yokoi K, Kato H. A prematurely terminated phase III trial of intraoperative intrapleural hypotonic cisplatin treatment in patients with resected non-small cell lung cancer with positive pleural lavage cytology: the incidence of carcinomatous pleuritis after surgical intervention. J Thorac Cardiovasc Surg 2002;123:695–699.[Abstract/Free Full Text]
- Okada M, Sakamoto T, Nishio W, Uchino K, Tsuboshima K, Tsubota N. Pleural lavage cytology in non-small cell lung cancer: lessons from 1000 consecutive resections. J Thorac Cardiovasc Surg 2003;126:1911–1915.[Abstract/Free Full Text]
- Vicidomini G, Santini M, Fiorello A, Parascandolo V, Calabrò B, Pastore V. Intraoperative pleural lavage: is it a valid prognostic factor in lung cancer. Ann Thorac Surg 2005;79:254–257.[Abstract/Free Full Text]
- Satoh Y, Hoshi R, Ishikawa Y, Horai T, Okumura S, Nakagawa K. Recurrence patterns in patients with early stage non-small cell lung cancers undergoing positive pleural lavage cytology. Ann Thorac Surg 2007;83:197–203.[Abstract/Free Full Text]
- Nakagawa T, Okumura N, Kokado Y, Miyoshi K, Matsuoka T, Kameyama K. Clinical relevance of intraoperative pleural lavage cytology in non-small cell lung cancer. Ann Thorac Surg 2007;83:204–208.[Abstract/Free Full Text]
- Okumura M, Ohshima S, Kotake Y, Morino H, Kikui M, Yasumitsu T. Intraoperative pleural lavage cytology in lung cancer patients. Ann Thorac Surg 1991;51:599–604.[Abstract]
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Abstract
1. Introduction