Interact CardioVasc Thorac Surg 2009;9:265-268. doi:10.1510/icvts.2009.202010
© 2009 European Association of Cardio-Thoracic Surgery
Institutional report - Thoracic oncologic |
Clinical significance of pleural lavage cytology for non-small cell lung cancer: is surgical resection valid for patients with positive pleural lavage cytology?
Riken Kawachi*,
Yohko Nakazato,
Kazuo Masui,
Hidefumi Takei,
Yoshihiko Koshi-ishi and
Tomoyuki Goya
Division of Thoracic Surgery, Kyorin University Hospital, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-0004, Japan
Received 5 January 2009;
received in revised form 20 April 2009;
accepted 21 April 2009
*Corresponding author. Tel.: +81-3-3542-2511; fax: +81-3-3542-3815.
E-mail address: rkawachi{at}kpe.biglobe.ne.jp (R. Kawachi).
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Abstract
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The purpose of the present study was to retrospectively analyze the clinicopathological characteristics and clarify the validity of surgical resection for patients with positive pleural lavage cytology (PLC). Between 1993 and 2006, 563 patients who underwent complete surgical resection for primary non-small cell lung cancer and who were examined with regard to PLC were retrospectively analyzed. Forty-two patients (7.2%) showed positive PLC. The 5-year survival rates were 65.0% and 33.5% for patients with negative and positive PLC, respectively. The 5-year survival rates for patients with positive PLC were 57.1%, 50.8%, 40.0%, and 0% for pathological stage I, II, IIIA, and IIIB, respectively. Multivariate analysis revealed that preoperative carcinoembryonic antigen (CEA) level, PLC, vascular invasion, lymphatic permeation, and pathological stage were independent prognostic factors. The 5-year survival rate for the patients with a high CEA level and positive PLC was 0%. Intrathoracic recurrence was observed more frequently in patients with positive PLC. PLC was an independent prognostic factor. While positive PLC alone may not be a contraindication for surgical resection, patients who are complicated with a high CEA level preoperatively should receive special attention since no long-term survivors were observed.
Key Words: Lung cancer; Pleural lavage cytology; Carcinoembryonic antigen; Pleural dissemination
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1. Introduction
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The status of pleural lavage cytology (PLC) has not been included in the present TNM classification [1], although PLC has been reported to be a prognostic factor and positive PLC has been regarded as early-stage of pleural dissemination in many previous reports [2–5]. A small amount of pleural effusion exists even in the normal thorax, and the definition of abnormal has never included the amount of pleural effusion present. Where is the borderline between PLC and pleural effusion? While surgical resection is not indicated for patients with either pleural dissemination or pleural effusion, surgical resection is usually performed in patients with positive PLC. Is the difference between positive PLC and pleural effusion simply an injection of normal saline into the thorax? Thoracic clinicians need tools to determine whether or not surgical resection is required. The objective of the present study was to identify the validity of surgical resection for patients with a positive PLC status in terms of clinicopathological factors, and especially survival.
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2. Patients and methods
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2.1. Patients
From May 1993 to December 2006, 1197 patients underwent surgical resection for primary lung cancer at the Kyorin University Hospital, Tokyo, Japan. In these patients, PLC was examined immediately after thoracotomy in 597. Medical records were reviewed in all patients. Preoperative staging routinely included chest X-ray (CXR) and chest and abdominal computed tomography (CT). All patients were staged clinically and pathologically according to the International Union Against Cancer TNM classification system [1]. The histology of the tumor was described according to the World Health Organization classification [6]. The present study focused on patients with non-small cell carcinoma.
2.2. Method of PLC
Fifty milliliter of normal saline solution was poured into the thorax immediately after thoracotomy without being shot directly at the tumor. Patients with severe adhesion, definite pleural effusion of more than about 300 ml or pleural dissemination were excluded. Approximately 20 ml of lavage solution was collected after agitation for 30 s. Staining was performed using the Papanicolaou method after centrifugal separation.
2.3. Statistical analysis
Survival was calculated using the Kaplan–Meier method, and differences in survival were determined by a log-rank analysis. Multivariate analysis was performed using the Cox proportional regression model, and a stepwise regression was not performed. P-values <0.05 were considered statistically significant.
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3. Results
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3.1. Clinicopathological findings
Clinical characteristics according to the status of PLC are shown in Table 1. The incidence of positive PLC was 7.2%. Positive results were observed more frequently in patients who were female or non-smokers. Pleural invasion, vascular invasion, and pulmonary metastasis were observed more frequently in patients with positive PLC. In patients with pathological stage I, 5% had a positive PLC status.
3.2. Site of recurrence
The first site of recurrence is shown in Table 2. The incidence of intrathoracic recurrence was 11.3% in patients with negative PLC and 29.3% in the patients with positive PLC (P=0.0001). In patients with a stage I, the incidence of intrathoracic recurrence was 21.1% and 6.4% for the patients with positive and negative PLC status, respectively (P<0.0001).
3.3. Survival
The median follow-up time for patients was 65.1 months. Patients with positive PLC showed significantly worse survival (34.4%) than those with a negative PLC status (64.0%) (Fig. 1, P<0.0001). Five-year survival rates according to the pathological stage were 57.1%, 50.8%, 40.0%, and 0% for pathological stage I, II, IIIA, and IIIB, respectively, in patients with positive PLC (Fig. 2). No significant difference was observed between patients with positive PLC results and patients with stage IIIA (P=0.77). Nine patients survived longer than five years. Of these, four patients had no recurrence, and they had earlier-stage disease.
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Fig. 2. Survival curves according to the status of pleural lavage cytology according to pathological stage.
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3.4. Multivariate analysis
Independent prognostic factors that were examined by multivariate analysis are shown in Table 3. Of these, the prognostic factors obtained preoperatively and before resection were the preoperative carcinoembryonic antigen (CEA) level and PLC status, and the 5-year survival rate in patients with these factors was 0% (CEA level >10 ng/ml) (Fig. 3).
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Fig. 3. Survival curves according to the status of pleural lavage cytology in patients with a high carcinoembryonic antigen level.
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4. Comment
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The present study investigated whether or not surgical resection should be performed or not for patients with positive PLC. Previous reports have examined whether PLC is an independent factor both immediately after thoracotomy and after resection for non-small cell lung cancer [2–5]. The 5-year survival rate was 34.3% for the patients with positive PLC, and the survival curve was similar to that for patients with pathological stage IIIA disease. Kondo et al. reported that patients with positive PLC showed survival equal to that in patients with stage IIIB or IV [2]. Lim et al. reported the same results and that positive PLC disease should be upstaged to stage IIIB or more [3]. However, we think that an immediate upstage to IIIB/IV is not appropriate for positive PLC status according to our results. Surgical indications for positive PLC could be marginal or negative with regard to overall survival itself, but survival was better and indication for surgery was still valid when limited to stage I or II disease. In the present study, multivariate analysis showed that PLC was a poor prognostic factor, but there were some long-term survivors and the survival rate was not so poor in early-stage disease. Therefore, a positive PLC status might not be a contraindication for immediate surgical resection.
Preoperative CEA, PLC, vascular invasion, lymphatic permeation, and pathological stage were prognostic factors as revealed by a multivariate analysis in the present study. Of these, the CEA level and PLC could be used as decision-making factors because they were examined before resection. The CEA level has been reported to be a good index that reflects the degree of disease progression [7–9]. The preoperative CEA level can predict latent lymph node metastases which cannot be detected by radiological imaging such as CT. In the present study, the four-year survival rate was 0% for patients with a high CEA level (>10 ng/ml) and positive PLC status, and surgical resection could not be indicated for such patients. Therefore, exploratory thoracotomy should be recommended without surgical resection if the patients have some serious complications.
Other findings of the present study included a frequent incidence of intrathoracic recurrence. Even in patients with clinical stage I, a positive PLC status was associated with a higher incidence of intrathoracic recurrence, and survival was significantly worse. According to this result, a positive PLC status may indicate a pre-stage of pleural dissemination or carcinomatous pleuritis, however, the survival rate was not so poor in stage I patients, and, therefore, surgery should still be indicated for stage I or II.
Several problems should be emphasized regarding PLC. First, the procedure used for PLC is different in every report. For example, the volume of normal saline solution is different; while only 25 ml is used in one report [4], 1000 ml is used in another [5]. Second, cytology was performed either immediately after thoracotomy or after surgical resection. Third, staining has included Papanicoleau stain, CEA stain, and other methods. Fourth, there is no clear definition of pleural effusion, and the border between pleural effusion and PLC has not yet been defined. How should we interpret a very small amount of pleural effusion? Should normal saline solution be used or should a small amount of effusion be collected? Thus, procedures and definition must first be clarified for inclusion in the TNM classification.
In conclusion, the present study revealed the clinicopathological characteristics of the PLC status, and demonstrated that PLC is an independent prognostic factor. A positive PLC status by itself should not be a contraindication for surgical resection, and patients with a high CEA level preoperatively should receive special attention because they could have very advanced lung cancer.
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References
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- International Union Against Cancer, Lung tumours. In Sobin LH, Wittekind CH, TNM Classification of Malignant Tumours, 6th ed. New York: Wiley-Liss; 2002.
- 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]
- Lim E, Ali A, Theodorou P, Nicholson AG, Ladas G, Goldstraw P. Intraoperative pleural lavage cytology is an independent prognostic indicator for staging non-small cell lung cancer. J Thorac Cardiovasc Surg 2004;127:1113–1118.[Abstract/Free Full Text]
- Riquet M, Badoual C, Le Pimpec Barthes F, Lhote FM, Souilamas R, Hubsch JP, Danel C. Visceral pleura invasion and pleural lavage tumor cytology by lung cancer: a prospective appraisal. Ann Thorac Surg 2003;75:353–355.[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]
- Travis WD, Colby TV, Corrin B, Shimosato Y, Brambilla E. Histological typing of lung and pleural tumors, World Health Organization International Histological Classification of Tumors. Berlin: Springer; 1999.
- Inoue M, Takakuwa T, Minami M, Shiono H, Utsumi T, Kadota Y, Nasu T, Aozasa K, Okumura M. Clinicopathologic factors influencing postoperative prognosis in patients with small-sized adenocarcinoma of the lung. J Thorac Cardiovasc Surg 2008;135:830–836.[Abstract/Free Full Text]
- Matsuguma H, Nakahara R, Igarashi S, Ishikawa Y, Suzuki H, Miyazawa N, Honjo S, Yokoi K. Pathologic stage I non-small cell lung cancer with high levels of preoperative serum carcinoembryonic antigen: clinicopathologic characteristics and prognosis. J Thorac Cardiovasc Surg 2008;135:44–49.[Abstract/Free Full Text]
- Okada M, Nishio W, Sakamoto T, Uchino K, Yuki T, Nakagawa A, Tsubota N. Prognostic significance of perioperative serum carcinoembryonic antigen in non-small cell lung cancer: analysis of 1,000 consecutive resections for clinical stage I disease. Ann Thorac Surg 2004;78:216–221.[Abstract/Free Full Text]
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Abstract
1. Introduction