Intraoperative Pleural Lavage: Is It a Valid Prognostic Factor in Lung Cancer?

doi:10.1016/j.athoracsur.2004.06.115

The Annals of Thoracic Surgery

Volume 79, Issue 1, January 2005, Pages 254-257

Presented at Fortieth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 26–28, 2004.

https://doi.org/10.1016/j.athoracsur.2004.06.115 Get rights and content

Background

In patients undergoing lung resection for non-small cell lung cancer (NSCLC), the primary TNM (tumor–regional lymph node–distant metastasis) staging system is the best prognostic factor. However, it is necessary to investigate other factors that could more accurately predict a patient's prognosis. In this study we evaluated the significance of positive intraoperative pre-resectional lavage in patients with NSCLC.

Methods

We enrolled 84 patients (79 men, 5 women) aged between 36 and 81 years (mean age, 64.8 years) undergoing a major lung resection for NSCLC, with no preoperative evidence of pleural effusions. Intraoperatively, the patients were given a pre-resectional pleural lavage with physiologic saline solution. The fluid was aspirated and sent to cytology.

Results

Pre-resectional pleural lavage was positive in 19 patients (22.6%). The lavage was positive in 7.3% in patients with early stage I disease (3/41) and 37.2% in patients with stage II/III disease. In the group of 16 patients with chest wall neoplastic involvement (T3), 9 had a positive lavage (56.2%; p = 0.05). No significant correlation was found between positive lavage and nodal status, visceral pleural involvement, or histologic findings. Patients with malignant cells in the pre-resectional lavage had a significantly shorter survival than patients with a negative lavage (p = 0.025).

Conclusions

A positive cytology finding of intraoperative pre-resectional pleural lavage could be an important prognostic factor in patients undergoing major lung resection for NSCLC. Patients with a positive lavage should be upstaged. However, larger series are needed to define accurately the role of this technique in early stage lung cancer.

Section snippets

Patients and Methods

We enrolled 84 patients (79 men, 5 women) aged from 36 to 81 years (mean age, 64.8 years) who were admitted to surgery for NSCLC between January 2000 and December 2001. Patients who had received preoperative chemotherapy or radiotherapy were excluded from the study. The research was approved by the Institutional Review Board and an informed consent was obtained from each patient enrolled in the study.

All patients received a standard preoperative evaluation that comprised a detailed history,

Results

Twelve pneumonectomies, 7 bilobectomies, and 65 lobectomies were performed. Two patients requested en bloc resection of the lung lobe and chest wall. The pathologic evaluation showed 49 squamous cell, 25 adenocarcinomas, 5 large-cell carcinomas, and 5 carcinomas of other types. The postoperative staging was Ia in 23 patients, Ib in 18, IIb in 19, and IIIa in 24 patients. None of the patients had stage IIa or IIIb disease. Patient characteristics are shown in Table 1.

Pre-resectional pleural

Comment

The significance of intraoperative pleural lavage cytology for lung cancer is still debated. The presence of malignant cells in the pleural space of patients without pleural effusion could suggest a more aggressive biologic behavior of the tumor. The cause of this presence is not completely clear; most likely it results from cell exfoliation from the primary tumor or cell diapedesis through the lymphatics, or both. Another cause may be the exfoliation of malignant cells from metastatic

References (13)

C.F. Mountain
Revisions in the international system for staging lung cancer
Chest
(1997)
J. Buhr et al.
The prognostic significance of tumor cell detection in intraoperative pleural lavage and lung tissue cultures for patients with lung cancer
J Thorac Cardiovasc Surg
(1997)
M. Okumura et al.
Intraoperative pleural lavage cytology in lung cancer patients
Ann Thorac Surg
(1991)
T. Naruke et al.
Lymph node mapping and curability at various levels of metastasis in resected lung cancer
J Thorac Cardiovasc Surg
(1978)
R.T. Eagan et al.
Pleural lavage after pulmonary resection for bronchogenic carcinoma
J Thorac Cardiovasc Surg
(1984)
C.M. Dresler et al.
Prognostic value of positive pleural lavage in patients with lung cancer resection
Ann Thorac Surg
(1999)

There are more references available in the full text version of this article.

Cited by (39)

Prognostic value of intraoperative pleural lavage cytology for non-small cell lung cancer: The influence of positive pleural lavage cytology results on T classification
2014, Journal of Thoracic and Cardiovascular Surgery
Although positive pleural lavage cytology (PLC) has been demonstrated to be closely associated with a poor prognosis for patients with lung cancer, it has not been incorporated into the TNM staging system of the Union for International Cancer Control. The aim of our study was to retrospectively examine the clinical significance of PLC status and illustrate the recommendations of the International Pleural Lavage Cytology Collaborators (IPLCC) in a large national database.
The Japanese Joint Committee of Lung Cancer Registry database included 11,073 patients with non–small cell lung cancer who underwent resections in 2004. We extracted the clinicopathologic data for 4171 patients (37.3%) who underwent PLC. These patients were staged according to the seventh edition of the Union for International Cancer Control TNM classification and by recommendations of the IPLCC, in which T was singly upgraded up to a maximum of T4 for those who were PLC-positive. Prognoses based on these 2 systems were compared.
A total of 217 patients (5.2%) were PLC-positive, which was significantly associated with a higher incidence of adenocarcinoma and advanced disease. The 5-year survival for patients with positive and negative PLC results were 44.5% and 72.8%, respectively, and this difference in survival was statistically significant (P < .001). Multivariate analysis showed that positive PLC status was an independent factor for a poor prognosis (hazard ratio, 1.57; P < .001). Significant differences in survival were also found between patients with positive and negative PLC results in the same T categories and stages, including T2a, T3, stage IB, and stage IIIA. The IPLCC recommendations adjusted the prognostic differences in all T categories and stages. The significant difference in survival disappeared between the 2 groups in all T categories and stages.
Our results indicate that a T category upgrade is prognostically adequate for patients who are PLC-positive.
Pleural lavage cytology: Where do we standα
2014, Lung Cancer
Although a malignant pleural effusion is considered a manifestation of an advanced stage disease not amenable to curative resection in patients with non-small cell lung cancer, the same is not true in the case of the presence of malignant cells in the pleural cavity without an accompanying effusion, discovered incidentally during the operation with pleural lavage cytology (PLC). PLC is a diagnostic technique used to detect tumor cells and translate this finding to a prognostic index. Various reports have attempted to utilize the results of PLC and draw inferences regarding the origins of malignant cells in the pleural cavity, the association of these results with various disease characteristics and, most importantly, their impact on disease recurrence and survival. However, due to non-consistent techniques and protocols used to acquire the samples for cytological evaluation and assess their significance, results are inhomogeneous. Nevertheless, the entrance of malignant cells in the pleural cavity follows the rules posed by the natural disease process when discovered before pulmonary resection takes place, while surgical manipulations certainly play an important role in the case malignant cells are checked over after pulmonary resection. In addition, although the prognostic significance of a positive PLC result is indisputable and significantly decreases long-term survival in the majority of studies, this factor has not yet been incorporated into the TNM staging system. Lastly, some authors have advocated the use of some form of adjuvant treatment for those patients found with positive PLC results, based on the assumption that a curative resection followed by multiple pleural washings will not remove the entirety of the population of malignant cells present in the pleural space.
HTERT gene amplification and clinical significance in pleural effusions of patients with lung cancer
2012, Clinical Lung Cancer
Citation Excerpt :
qPCR is an ultrasensitive and highly accurate technique for measuring nucleic acid levels; therefore, an earlier diagnosis of malignant pleural effusions may be achieved by using qPCR to detect hTERT gene amplification in a few occult cancer cells. Vicidomini et al35 evaluated the significance of positive intraoperative pre-resectional lavage specimens in patients with non–small-cell lung cancer (NSCLC), who showed no preoperative evidence of pleural effusions and confirmed that, compared with patients with negative cytology results, those with positive results always showed poor survival and prognoses. Therefore, pleural micrometastases may be regarded as an unfavorable prognostic factor in NSCLC.
Human telomerase reverse transcriptase (hTERT) gene amplification was detected in pleural effusions of patients with lung cancer (n = 69) and in patients with benign lung disease (n = 46) when using a quantitative polymerase chain reaction (qPCR) technique.
hTERT gene relative copy numbers were significantly higher in effusions from patients with malignant, adenocarcinoma and small-cell lung cancer than in effusions from patients with benign lung disease (P < .01). By using a threshold value of 1.39, hTERT gene amplification was significantly more frequent in malignant effusions compared with benign effusions and more likely to be positive for malignant effusions, compared with cytology (P < .01). The diagnostic performance of qPCR of hTERT gene amplification was significantly higher than that of cytology, in terms of sensitivity (91.3% vs. 56.5%), negative predictive value (87.8% vs. 60.5%), and accuracy (92.2% vs. 73.9%).
Detecting hTERT gene amplification by qPCR appears suitable for distinguishing carcinoma cells from reactive mesothelial cells in pleural effusions. hTERT gene amplification was more sensitive than cytology and may be useful for diagnosing pleural micrometastases.
Impact of positive pleural lavage cytology on survival in patients having lung resection for non-small-cell lung cancer: An international individual patient data meta-analysis
2010, Journal of Thoracic and Cardiovascular Surgery
Citation Excerpt :
There was no funding associated with this project. From 345 abstracts, we identified 31 publications1-3,5-32 from 22 centers/research groups that performed PLC during surgery for non–small-cell lung cancer. All lead authors from the identified centers or research groups were contacted by E-mail or telephone or in person.
Pleural lavage cytology is the microscopic study of cells obtained from saline instilled into and retrieved from the chest during surgery for non–small-cell lung cancer. The aims of this study were to collate multi-institutional individual patient data for meta-analysis to determine independence as a prognostic marker and to characterize the impact of positive results on stage-adjusted survival.
We identified 31 publications from 22 centers/research groups that performed pleural lavage cytology during surgery for non–small-cell lung cancer and invited submission of individual patient data. Actuarial survival was calculated using Kaplan-Meier methods, and comparisons were performed using the log-rank test. Cox proportional hazards regression was used to ascertain the covariates associated with survival.
By January 1, 2008, submissions were received internationally from 11 centers with individual data from 8763 patients. In total, 511 (5.8%) patients had a positive pleural lavage cytology result, and this was shown to be an independent predictor of adverse survival associated with a hazard ratio of 1.465 (1.290–1.665; P < .001) compared with a reference hazard ratio of 1 for a negative result. On statistical modeling, the best adjustment for patients with a positive pleural lavage cytology result was a single increase in the T category assigned to the case, up to a maximum of T4. Correction for differences in survival were obtained in stages IB (P = .315) and IIB (P = .453), with a degree of correction in stage IIIA (P = .07).
Pleural lavage cytology should be considered in all patients with non–small-cell lung cancer suitable for resection. A positive result is an independent predictor of adverse survival, and the impact on survival suggests that it may be appropriate to upstage patients by 1 T category.
The impact on survival of positive intraoperative pleural lavage cytology in patients with non-small-cell lung cancer
2010, Journal of Thoracic and Cardiovascular Surgery
The aim of this study was to analyze intraoperative pleural lavage cytology results in patients with non–small-cell lung cancer and quantify the impact on survival and recurrence.
From August 1992 through November 2006, pleural lavage cytology results before and after lung resection were both available in 2178 patients with non–small-cell lung cancer. We assessed the pre–pleural lavage cytology impact on survival, comparing with 9 factors available before lung resection by multivariate analyses. We also compared the impact with that of pleural dissemination or malignant pleural effusion. For post–pleural lavage cytology, we analyzed its survival impact in relation with 15 clinicopathologic factors, including those available after resection, by multivariate analyses.
Pre–pleural lavage cytology proved to be a strong independent prognostic factor, but the 5-year survival rate was 37% in 65 patients without dissemination but with a positive pre–pleural lavage cytology, which was significantly higher than 12% in 86 patients with dissemination. When factors available after resection were combined, post–pleural lavage cytology showed a stronger survival impact than pre–pleural lavage cytology. Post–pleural lavage cytology was also a strong predictor of recurrence. The positive post–pleural lavage cytology group had a marginally, but not significantly, better survival compared with the malignant pleural effusion group. Almost all patients with positive post–pleural lavage cytology relapsed within 5 years.
Pre–pleural lavage cytology is of less use in clinical practice. Post–pleural lavage cytology was a very strong independent prognostic factor, and almost all patients with positive post–pleural lavage cytology relapsed within 5 years. We propose that positive post–pleural lavage cytology disease should be classified to pathologic T4 and managed similarly to dissemination.
Pleural disease
2009, Revue des Maladies Respiratoires Actualites

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Original articleGeneral thoracicIntraoperative Pleural Lavage: Is It a Valid Prognostic Factor in Lung Cancer?

Background

Methods

Results

Conclusions

Section snippets

Patients and Methods

Results

Comment

Chest

J Thorac Cardiovasc Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Ann Thorac Surg

Original article
General thoracic
Intraoperative Pleural Lavage: Is It a Valid Prognostic Factor in Lung Cancer?