Positive Pleural Lavage Cytology Research Articles

Intraoperative rapid diagnosis of pleural lavage cytology in non-small cell lung cancer.

Positive pleural lavage cytology (PLC +) is a poor prognostic factor for non-small cell lung cancer (NSCLC). However, data on the impact of intraoperative rapid diagnosis of PLC (rPLC) are lacking. Therefore, we evaluated the efficacy of rPLC before resection during surgery. A total of 1,838 patients who underwent rPLC for NSCLC between September 2002 and December 2014 were studied retrospectively. We assessed the clinicopathological factors between rPLC findings and the impact on survival of patients with curative resection. The rPLC + status was observed in 96 (5.3%) among 1,838 patients. The rPLC + group had more unsuspected N2 (30%) than the rPLC- group (p < 0.001). The 5-year overall survival (OS) of patients who underwent lobectomy or more extensive resection with rPLC + , negative rPLC (rPLC-), and microscopic pleural dissemination (PD) and/or malignant pleural effusion (PE) were 67.3, 81.3, and 11.0%, respectively. In the rPLC + group, the prognosis of patients with pN2 was equal to that of pN0-1 (5-year OS: 77.9% vs. 63.4%, p = 0.263). Undetectable dissemination in the first evaluation immediately after starting surgery was found in 9% of rPLC + patients by additional evaluation of the thoracic cavity. Patients with rPLC + have more favorable survival than those with microscopic PD/PE after surgery. Curative resection should be performed in patients with rPLC + , even if N2 is detected during surgery. However, the rPLC + group often has N2 upstaging; therefore, systematic nodal dissection should be performed in rPLC + patients for exact staging. rPLC may contribute to preventing oversight PD by re-evaluation during surgery.

Commemorating the Silver Anniversary of the International Association for the Study of Lung Cancer International Workshop on Intrathoracic Staging

Commemorating the Silver Anniversary of the International Association for the Study of Lung Cancer International Workshop on Intrathoracic Staging

Status of pleural lavage cytology in cases of pulmonary metastasis: a single-institution retrospective study.

In primary lung cancer surgery, intraoperative pleural lavage cytology (PLC) has been identified as a prognostic marker. However, there have been no reports on PLC for pulmonary metastasectomies. Therefore, the impact of PLC status for patients undergoing pulmonary metastasectomy remains unknown. We aimed to know the incidence and prognostic impact of positive PLC findings in pulmonary metastasectomies. We retrospectively reviewed patients undergoing pulmonary metastasectomies between January 2013 and December 2018. One hundred and eighty-nine PLC procedures in 159 patients undergoing pulmonary metastasectomy were analyzed. Follow-up information was available in 107 patients who underwent 132 procedure, and they were investigated for pleural recurrence-free probability (PRFP) and overall survival (OS) after pulmonary metastasectomy. The type of primary lesion was colorectal cancer (101/189, 53%), urothelial/kidney cancer (17/189, 9%), skeletal/soft tissue tumor (18/189, 10%), hepatobiliary/pancreatic cancer (19/189, 10%), uterine/ovarian cancer (14/189, 7%), otorhinolaryngological cancer (11/189, 6%), and other minor lesions (9/189, 5%). Nine PLC-positive metastasectomies were revealed (9/189, 4.8%). They consisted of six metastasectomies from pancreatic cancer, two from osteosarcoma, and one from tongue cancer. Significant predictors for PLC status was type of primary tumor (P < 0.001). PRFP and OS rate of PLC-positive group were significantly lower than PLC-negative (P < 0.001, respectively). PLC-positive results were rarely seen in pulmonary metastasectomies. PLC status was associated with the incidence of ipsilateral pleural recurrence and survival after metastasectomy. Cytologic examination of PLC should be considered in patients undergoing pulmonary metastasectomy.

Impact of Positive Pleural Lavage Cytology for Each Stage of Non-Small Cell Lung Cancer Patients

Positive preresection pleural lavage cytology (PLC+) is a poor prognostic factor in non-small cell lung cancer (NSCLC). This study evaluated the prognostic value of PLC+ for the different pathologic stages (p-stages) of NSCLC. A retrospective analysis was conducted of all 1293 staged patients who underwent curative resection in the Shizuoka Cancer Center Hospital, Shizuoka, Japan, for NSCLC to evaluate the impact of PLC+ on survival, specifically in patients with p-stage I NSCLC. The survival rate between patients with and without PLC+ was compared using the Kaplan-Meier method with the log-rank test for comparison. PLC+ was identified in 50 of the 1293 patients (3.9%) and was correlated with lymph node metastasis (P < .001), a pathologic tumor size larger than 3 cm (P= .033), the presence of pleural invasion (P < .001), and adenocarcinoma (P= .038). In patients with PLC+, the 5-year disease-free survival (DFS) was 31.1%, compared with 75.7% for patients with a negative PLC (PLC-) (P < .001). On multivariate analysis, the PLC+ status was an independent prognostic factor of DFS (hazard ratio 1.70; P= .013). Among the 818 patients with p-stage I NSCLC, PLC+ was identified in 22, with a 5-year DFS of 40.4%. The prognosis in patients with p-stage I NSCLC with PLC+ was equal to that in patients with p-stage IIIA NSCLC with PLC- (5-year DFS, 40.4% and 39.0%). PLC is an independent prognostic factor in early-stage NSCLC. Therefore, it may be appropriate to up-stage an NSCLC diagnosis in the presence of PLC+, especially for patients with p stage I.

Latest Progress of Intraoperative Pleural Lavage Cytology in Lung Cancer Surgery

非小细胞肺癌（non-small cell lung cancer, NSCLC）根治术中胸腔冲洗液细胞学检查是一种常用的检测肿瘤进展并评估患者预后的诊断技术。长期以来大量研究者致力于阐明术中胸腔冲洗液细胞学检查结果与肺癌患者术后生存及肿瘤复发转移的关系。由于不同研究间存在明显异质性，其结论也各有不同。但能肯定的是，胸腔冲洗液肿瘤细胞检查阳性已被证实为手术患者的不良预后因素之一。本文尝试从临床意义、影响因素及可能发生机制等角度就近年来术中胸膜腔冲洗的研究进展作一综述。

Relevance of Intraoperative Pleural Lavage Cytology and Histologic Subtype in Lung Adenocarcinoma

The association between pleural lavage cytology (PLC) and histologic subtype remains unknown. In this study, we evaluated the effect of a micropapillary pattern (MPP) in lung adenocarcinomas on results of PLC. We retrospectively reviewed 600 consecutive patients with surgically resected pulmonary adenocarcinomas and investigated the relationship between PLC status and clinicopathologic factors, including a histologically identified MPP component. PLC was positive in 25 patients (4.2%). Positive PLC was significantly associated with MPP (p=0.0001), lymph node metastasis (p= 0.01), and pleural invasion (p < 0.0001) according to multivariate analysis. Furthermore, the presence of MPP reinforced the effect of some established predictive factors, such as large tumor size, lymph node metastasis, pleural invasion, and lymphovascular invasion, on positive PLC. Two factors-MPP and positive PLC-were associated with a higher incidence of occult N2 lymph node metastases. The prognosis of adenocarcinomas in patients with MPP or positive PLC was significantly worse than that of patients without these features. Furthermore, the survival of MPP and positive PLC group (MPP+ PLC+) was significantly worse than that of MPP and negative PLC group (MPP+ PLC-, p= 0.03). The presence of MPP in lung adenocarcinoma can be an independent predictor of positive PLC. These two factors have complementary and synergistic roles as prognostic factors. Detailed preoperative or intraoperative examination of histologic subtype and PLC findings may provide important information for prediction of tumor progression and decisions regarding the surgical procedure.

P3.16-051 Implications of Preoperative Serum Tumor Levels on Pathological Characteristics in Patients with Lung Adenocarcinoma

Although preoperative serum tumor marker levels, such as carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC) are often evaluated in non-small cell lung cancer patients, the implication of these levels are still unknown. This study examined the predictive effect of preoperative tumor marker levels on pathological characteristics of lung adenocarcinoma. We retrospectively reviewed patients with lung adenocarcinoma who underwent macroscopic complete resection. The pathological metastasis and/or involvement was defined that positive pleural effusion or lavage cytology, pleural involvement, pulmonary metastasis, lymph node metastasis, and/or lymphovascular involvement were identified on pathological examination. To identify predictors for the pathological metastasis and/or involvement, tumor markers (CEA, SCC, Sialyl Lewisx-1 [SLX], cytokeratin-19 fragments [CYFRA], neuron-specific enolase [NSE], and pro-gastrin-releasing peptide [ProGRP]), and demographic and clinical factors were analyzed by a univariate analysis and multivariate logistic regression analysis. For the significant tumor markers, optimal cutoff points were determined with a receiver operating characteristic analysis. Of the 263 eligible patients, 138 were male and 125 were female. The median age was 70 years. The median preoperative CEA, SCC, SLX, CYFRA, NSE, and ProGRP levels were 3.7 ng/ml, 0.8 ng/ml, 28 U/ml, 1.8 ng/ml, 8.4 ng/ml, and 46.9 pg/ml, respectively. According to the 7th edition of the TNM classification, 186 patients (71%) had c-stage IA disease, 48 (18%) had c-stage IB disease, 26 (10%) had c-stage II disease, and 3 (1%) had c-stage III disease. Positive pleural effusion, positive pleural lavage cytology, pleural involvement, pulmonary metastasis, lymph node metastasis, lymphatic permeation, and vascular invasion were identified in 3 (1%), 4 (2%), 48 (18%), 9 (3%), 28 (11%), 20 (8%), and 35 patients (13%), respectively, and in total, 83 patients (32%) developed the pathological metastasis and/or involvement. The univariate analysis identified CEA, smoking index, size, solid size, and c-stage as significant predictors. A multivariate analysis revealed CEA (OR: 1.113, p=0.005) and solid size (OR: 1.052, p<0.001) as significant predictors. The optimal cutoff point was determined as 6.0 ng/ml for the preoperative CEA, and 35 of the 63 patients (56%) with ≥6.0 ng/ml of CEA developed the pathological metastasis and/or involvement whereas 48 of the 200 patients (24%) with <6.0 ng/ml of CEA developed pathological metastasis and/or involvement. Our results suggested the predictive effect of the high preoperative CEA level on pathological metastasis and involvement in patients with lung adenocarcinoma, and thus, we may consider preoperative CEA to decide surgical procedure for these patients, such as the extent of pulmonary resection and lymphadenectomy.

The Significance of SCC and CEA mRNA in the Pleural Cavity After Lymphadenectomy in Esophageal Cancer Patients who Underwent Preoperative Treatment.

This report focuses on the surgical manipulation and spread of cancer cells. Our previous study suggested an association between a poor prognosis and positive pleural lavage cytology after resection of esophageal cancer without preoperative treatment. However, little is known regarding the clinical significance of the lavage procedure in esophageal cancer patients who undergo preoperative treatment. A cohort of 94 patients with squamous cell carcinoma of the esophagus who underwent esophagectomy with radical lymph node dissection was prospectively analyzed for free cancer cells in the pleural cavity after mediastinal lymphadenectomy. Reverse transcription-polymerase chain reaction was performed to detect free cancer cells in the pleural lavage fluid by measuring squamous cell carcinoma-related antigen (SCC) and carcinoembryonic antigen (CEA). Forty-two patients (44.7%) were positive for SCC after thoracic lymphadenectomy, and 15 patients (15.9%) were positive for CEA. SCC positivity was significantly associated with venous invasion (p=0.037) and with the clinical response to preoperative treatment (p=0.001). Furthermore, SCC positivity was associated with poor prognosis compared with negative SCC (p=0.026). Multivariate analysis revealed that SCC positivity was an independent prognostic factor. Regarding recurrence patterns, SCC positivity tended to be associated with hematogenous recurrence (p=0.063). Conversely, positive CEA was not associated with any clinicopathological finding, treatment response, prognosis, or recurrence pattern. Tumor spillage during the evaluated surgical manipulation was assessed in esophageal cancer patients who underwent preoperative treatment. Tumor spillage as evaluated by SCC mRNA was associated with a poor prognosis.

Assessing the prognostic impact of the International Association for the Study of Lung Cancer proposed definitions of complete, uncertain, and incomplete resection in non-small cell lung cancer surgery

ObjectiveThe aim of this study was to assess the prognostic impact of the definitions of complete, uncertain, and incomplete resection in non-small cell lung cancer (NSCLC) surgery, as proposed by the International Association for the Study of Lung Cancer (IASLC). Patients and methodsSingle institution retrospective study of consecutive patients undergoing surgery for NSCLC between 1998 and 2007. Complete resection was defined by absence of gross and microscopic residual disease; systematic nodal dissection; no extracapsular extension in distal lymph nodes; and negativity of the highest mediastinal node removed. An uncertain resection was defined by free resection margins, but one of the following applied: lymph node evaluation less rigorous than systematic nodal dissection; positivity of the highest mediastinal node removed; presence of carcinoma in situ at the bronchial margin; positive pleural lavage cytology. A resection was defined incomplete by presence of residual disease; extracapsular extension in distal lymph nodes; positive cytology of pleural or pericardial effusions. Follow-up was complete and all patients were followed up until death or for a minimum period of 5 years. Overall survival (OS) was analyzed using Kaplan-Meier method, log rank test, and Cox proportional hazards model. ResultsA total of 1277 patients were identified. One thousand and three patients (78.5%) underwent complete resection, 185 (14.5%) underwent uncertain resection, and 89 (7.0%) underwent incomplete resection. Both uncertain and incomplete resection were associated with significantly worse OS when compared with complete resection (hazard ratio: 1.69 and 3.18, respectively; both p=0.0001). Median OS and 5-year survival rate were 80.1, 39.9, 17.3 months and 58.8%, 37.3%, 15.7% in patients undergoing complete, uncertain, and incomplete resection, respectively. ConclusionThe present analysis suggests that in patients undergoing surgery for NSCLC, the IASLC definitions of complete, uncertain, and incomplete resection are associated with statistically significant differences in survival.

Characteristics and timing of recurrence during postoperative surveillance after curative resection for lung adenocarcinoma

To establish the most effective methods of postoperative surveillance to detect early recurrence of lung adenocarcinoma. The subjects of this retrospective study were 485 patients with p-stage I-III lung adenocarcinoma, who underwent postoperative surveillance. We examined the sites and detection modes of recurrence and calculated the recurrence-free probabilities. Patients with stage I disease were divided into low- and high-risk recurrence groups using a risk score calculated by assigning points proportional to risk factor regression coefficients. Of the 112 patients with recurrence, 86 had intrathoracic recurrence. Routine computed tomography (CT) revealed recurrence in 60 patients. The recurrence-free probability curves showed that 95% of recurrences were identified within the first 4years after resection in patients with stage II/III disease. In patients with stage I disease, the predictors of recurrence included male sex, positive pleural lavage cytology, moderate-to-poor differentiation, and visceral pleural invasion. Postoperative recurrences were detected throughout the follow-up period in the high-risk group. Routine chest CT plays an important role in the postoperative surveillance of lung adenocarcinoma. We recommend intensive follow-up during the early post-resection period for patients with advanced stage disease and long-term follow-up for high-risk patients with stage I disease.

P1.08-002 The Prognostic Significance of Pleural Lavage Cytology before and after Lung Resection

The status of intraoperative pleural lavage cytology (PLC) has been reported to be a predictive factor of recurrence in resected non-small cell lung cancer (NSCLC). However, prognostic significance of PLC remains unclear and it has not been included in the TNM classification. Furthermore, the appropriate timing to perform PLC, before lung resection (pre-PLC) or after lung resection (post-PLC), is not evident. Of 627 consecutive patients with NSCLC who underwent complete resection (segmentectomy or more) in Tottori University Hospital from January 2004 to December 2013, 615 patients who were performed both pre-PLC and post-PLC were enrolled in present study. Patients were divided into four groups, negative pre-PLC / negative post-PLC (Group A), positive pre-PLC / negative post-PLC (Group B), negative pre-PLC / positive post-PLC (Group C), and positive pre-PLC / positive post-PLC (Group D). Then differences in recurrence free survival (RFS) and disease specific survival (DSS) among each groups were analyzed by log-rank test. Moreover, PLC status as a prognostic factor for RFS and DSS were analyzed using univariate and multivariate Cox regression models. There were 573 patients in Group A, 11 in Group B, 14 in Group C, and 17 in Group D, respectively. Survival analysis revealed significant differences in not only RFS but also DSS between Group A and Group B (log-rank test, p<0.001), Group A and Group C (p<0.001), Group A and Group D (p<0.001), respectively. However, there was no significant differences among Group B, C, and D (p=0.861). Multivariate analysis identified advanced age (75≤), male sex, larger tumor size (3cm<), lymph node metastasis, lymphatic invasion, and positive PLC status (Hazard Ratio: 3.735, 95% confidence interval: 2.312 to 6.063, p<0.001) as statistically independent prognostic factors for DSS. In conclusion, positivity of both pre-PLC and post-PLC were significant worse prognostic factor for DSS of patients with completely resected NSCLC. Therefore, surgeons should consider performing PLC both before and after lung resection to estimate patients’ prognosis correctly. Moreover, further accumulation of knowledge about PLC is needed to reflect PLC status in the TNM classification.

Prognostic impact of pleural lavage cytology in patients with primary lung cancer

ObjectivesPositive pleural lavage cytology (PLC) has been reported to have a negative prognostic impact in patients with surgically resected non-small cell lung cancer (NSCLC). However, positive PLC does not upgrade the stage according to the 7th edition of TNM classification for lung cancer. The objectives of this study were to evaluate the prognostic impact of positive PLC in patients with NSCLC and to clarify its contribution to TNM classification. Materials and methodsSeven hundred fifty-four patients who underwent surgical resection of NSCLC from January 2007 through December 2013 were retrospectively studied. PLC was performed using 50ml of saline immediately after thoracotomy. ResultsThirty-eight of the 754 patients were positive for PLC (5.1%). The overall survival (OS) of patients with positive PLC was significantly shorter than that of those with negative PLC (P=0.007, log-rank test). In multivariate analyses of OS, positive PLC was a significant independent prognostic factor (hazard ratio=2.21, 95% confidence interval: 1.21–4.04, P=0.009). The OS of patients with positive PLC was significantly shorter than that of those with negative PLC and pT1 (P<0.0001) or negative PLC and pT2 (P<0.0001) and almost overlapped with that of those with negative PLC and pT3 disease (P=0.601). ConclusionPositive PLC is an independent prognostic factor in patients with resected NSCLC. Based on our analyses, we propose that patients with positive PLC be staged as pT3.

Predictive Value of Preoperative Serum Tumor Marker Levels for Pathological Characteristics of Resected Lung Adenocarcinoma

SESSION TITLE: Lung Cancer I SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM PURPOSE: The aim of this study was to investigate the association between preoperative serum tumor marker levels and pathological characteristics of resected lung adenocarcinoma. METHODS: We retrospectively reviewed patients with lung adenocarcinoma who had undergone macroscopic complete resection from 2013 to 2015. Patients with multiple lung cancer other than adenocarcinoma, previous treatment history of lung cancer, or active other malignancies were excluded. Preoperative serum tumor marker levels (CEA, SCC, SLX, CYFRA, ProGRP, and NSE) and preoperative clinical factors (age, sex, smoking index, and tumor size) were analyzed with univariate analysis (Fisher’s exact test or the chi-square test) and multivariate logistic regression analysis to identify predictors for the pathological involvement (positive pleural effusion or lavage cytology, pleural involvement, pulmonary metastasis, lymph node involvement, lymphovascular involvement, and/or upstaging) or the poor prognostic subtypes (solid or micropapillary predominant adenocarcinoma). For the significant factors, optimal cutoff points were determined with a receiver operating characteristic (ROC) analysis. RESULTS: Of a total of consecutive 183 patients, 100 were male and 83 were female, and the median age was 70 years. On pathologic diagnosis, 4 (2%) patients had positive pleural effusion or lavage cytology, 36 (20%) had pleural involvement, 6 (3%) had pulmonary metastasis, 20 (11%) had lymph node involvement, 39 (21%) had lymphovascular involvement, and 43 (23%) showed upstaging. In total, 72 patients (39%) had the pathological involvement. In the subtypes of adenocarcinoma, 17 (9%) patients had solid or micropapillary predominant adenocarcinoma, 129 (71%) had invasive adenocarcinoma other than these 2 subtypes, and 37 (20%) had AIS or MIA. Both univariate and multivariate analysis identified CEA and tumor size for the pathological involvement and smoking index and SLX for the poor prognostic subtypes as significant predictors. Of patients with CEA ≥5.3 ng/ml or SLX ≥34 U/ml which were determined by the ROC analysis, 33 of 57 (58%) and 9 of 39 (23%) patients had the pathological involvement or the poor prognostic subtypes, respectively. CONCLUSIONS: Preoperative higher CEA and SLX may predict pathological characteristics of lung adenocarcinoma, such as presence of pathological involvement and poor prognostic subtypes. CLINICAL IMPLICATIONS: Preoperative serum tumor marker levels should be considered for deciding surgical treatment strategy of lung adenocarcinoma. DISCLOSURE: The following authors have nothing to disclose: Terumoto Koike, Akihiko Kitahara, Seijiro Sato, Takehisa Hashimoto, Shin-ichi Toyabe, Masanori Tsuchida No Product/Research Disclosure Information

Prognostic Value of Pleural Lavage Cytology in Patients with Lung Cancer Resection: An Updated Meta-Analysis.

ObjectivePleural lavage cytology (PLC) is considered as a possible tool for assessing prognosis of lung cancer patients. We aimed to comprehensively review the prognosis value of PLC in patients undergoing surgical resection.MethodsWe searched 4 electronic databases for relevant studies comparing positive PLC and negative PLC. The primary outcomes included survival rate and recurrence rate at maximum follow-up.ResultsThe meta-analysis included 28 studies, with a total of 20,714 patients. For the overall survival rate of all stages, the results demonstrated that positive pre-resection, post-resection and pooled PLC were associated with unfavorable survival: hazard ratio (HR) 2.89 (95% confidence interval [CI] 2.48–3.37), 2.70 (1.90–3.83), and 2.89 (2.52–3.31), respectively. For the stage I survival rate, the combined results also suggested that positive pre-resection, post-resection and pooled PLC were associated with unfavorable survival: HR 3.29 (95% CI 2.55–4.25), 4.85 (2.31–10.20), and 3.16 (2.53–3.94), respectively. Furthermore, a meta-analysis of 14 studies included 14,279 patients showed that positive pre-resection, post-resection and pooled PLC were associated with an increased risk of overall recurrence: risk ratio (RR) 2.45 (95% CI 1.91–3.15), 2.37 (1.11–5.09), and 2.37 (95% CI 2.00–2.80), respectively. Positive PLC was also associated with a high pleural recurrence (RR 4.77; 95% CI 3.13–7.26) or distant recurrence (RR 2.33; 95% CI 1.65–3.29).ConclusionsBoth positive pre- resection and post-resection PLC are associated with not only higher tumor recurrence but also unfavorable survival outcomes in patients with lung cancer resection. This technique can therefore act as a strong prognostic factor for tumor recurrence and adverse survival rates.

Malignant pleural effusions because of lung cancer.

The discovery of a pleural effusion in the setting of lung cancer has diagnostic, prognostic, and therapeutic challenges, some of which are addressed in this review. Around 20% of patients with lung cancer have minimal pleural effusions, which are not amenable to a diagnostic thoracentesis. These patients have a poorer overall survival (∼7.5 months) than those without effusions (∼12-18 months), although slightly better than those with proven malignant fluids (∼5.5 months). Tumor genotype techniques are feasible on pleural fluid specimens and clinically helpful in identifying patients who may benefit from targeted therapies. If limited pleural involvement is detected during lung cancer surgery despite the presurgical imaging studies, macroscopic complete resection of the lung tumor is still a treatment option. Cytological examination for cancer cells in pleural cavity washings at the time of thoracotomy (pleural lavage cytology) is recommended to uncover pleural dissemination. Patients with non-small cell lung cancer with visceral pleural invasion might be considered candidates for postsurgical adjuvant therapy. Some predictors of adverse survival in patients with lung cancer include the presence of a minimal pleural effusion, positive pleural lavage cytology, visceral pleural invasion on pathologic examination, and unexpected pleural involvement during surgery.

Efficacy of adjuvant chemotherapy for lung adenocarcinoma patients with positive pleural lavage cytology findings.

Positive pleural lavage cytology (PLC) findings are considered to be predictive of a poor prognosis in patients with non-small-cell lung cancer (NSCLC). We investigated the clinical benefit of adjuvant chemotherapy for lung adenocarcinoma patients with positive PLC findings. We retrospectively reviewed the medical records of lung adenocarcinoma patients who underwent tumour resection and had positive PLC findings between January 2000 and December 2009. Fifty-three patients (4.8%) of 1114 patients with lung adenocarcinoma had positive PLC findings. The median follow-up period was 33.6 months. Adjuvant chemotherapy was administered to 24 patients (adjuvant chemotherapy group); 7, 8 and 9 patients had pathological Stage I, II and III, respectively . The surgery-alone group comprised 29 patients; 12, 8 and 9 patients had pathological Stage I, II and III, respectively. The 5-year recurrence-free survival (RFS) rates were 34.6 and 15.7% (P < 0.01) in adjuvant chemotherapy and surgery-alone groups, respectively. The rate of distant recurrence was significantly reduced in the adjuvant chemotherapy group (25.0 and 58.6%; P = 0.01). Even for Stage I cases, adjuvant chemotherapy tended to improve the 5-year RFS rate compared with surgery alone (60.1 and 29%; P = 0.11). Multivariate analysis for RFS revealed that adjuvant chemotherapy [hazard ratio (HR), 0.45; P = 0.03], tumour size >30 mm (HR, 2.23; P = 0.02) and lymph node metastasis (HR, 2.67; P < 0.01) were significant independent prognostic factors for recurrence. Adjuvant chemotherapy for lung adenocarcinoma patients with positive PLC findings significantly improved recurrence-free survival.

Pleural lavage cytology as an independent prognostic factor in non-small-cell lung cancer patients with stage I disease and adenocarcinoma.

We previously reported that cancer cells may be detected through pleural lavage cytology (PLC). In this study, we sought to re-examine the prognostic significance of the PLC status based on an extended dataset with an additional follow-up period. Pleural lavage following thoracotomy was cytologically examined in 1,317 consecutive patients who were diagnosed with NSCLC between 1987 and 2004 at the Thoracic Surgery Units of Kobe University Graduate School of Medicine and Hyogo Cancer Center. Among the investigated patients, 46 exhibited positive cytological findings. The prognosis of these patients was significantly worse compared to that of patients without positive PLC. Of the 844 pathological stage I patients, 18 had a positive PLC status and their prognosis was significantly worse compared to that of patients with stage I disease without positive PLC. In conclusion, positive PLC findings were associated with a poor prognosis and this finding was significant for patients with stage I disease. These results suggest the need for PLC status evaluation during staging and treatment planning in patients with NSCLC.

Prognostic value of intraoperative pleural lavage cytology for non–small cell lung cancer: The influence of positive pleural lavage cytology results on T classification

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.

Positive intraoperative pleural lavage cytology is a predictive marker of disease recurrence in stage I lung adenocarcinoma

This study aimed at analysing the relationship between the pleural lavage cytology (PLC) status and clinicopathological characteristics, including the outcome of examined patients and tumour recurrence sites in surgically resected stage I non-small-cell lung carcinoma. From April 2002 to August 2012, PLC was performed immediately after thoracotomy in 428 consecutive patients undergoing pulmonary resection for lung cancer. The relationship between clinicopathological characteristics and the PLC status was retrospectively analysed. The frequency of PLC-positive results was 4.4%, and larger tumour size, stage IB and pleural invasion were found more frequently in PLC-positive patients. Patients with a PLC-positive status had significantly worse disease-free survival (DFS) than those with a PLC-negative status (PLC positive versus PLC negative: hazard ratio [HR] = 2.79, 95% confidence interval [CI]: 1.4-5.57, P < 0.004; 5-year DFS: 46.6 vs 76.5%). With regard to the PLC status and histological type, adenocarcinoma was associated with a worse DFS in PLC-positive patients when compared with PLC-negative patients (5-year DFS: 38.1 vs 81.1%, P < 0.001). In multivariate analysis, PLC status remained significantly associated with DFS in patients with a PLC-positive status having an increased risk of recurrence, compared with PLC-negative patients (HR = 2.494, 95% CI: 1.241-5.011, P = 0.01) only in the case of adenocarcinoma. Our current study showed the clinicopathological characteristics associated with PLC status and demonstrated that PLC status was an independent predictor of increased recurrence in stage I lung adenocarcinoma.

Five-Year Survivors of Non-Small Cell Lung Cancer Patients with Positive Pleural Lavage Cytology

Background: The pleural lavage cytology (PLC) for non-small cell lung cancer (NSCLC) patients has been reported as a significant prognostic factor. The aim of this study is to clarify the clinicopathological characteristics of 5-year survivors of patients with positive PLC. Methods: Among 401 resected NSCLC patients, 30 (7.48%) patients with positive PLC were reviewed retrospectively. Results: Only 7 of 30 patients (23.3%) survived more than 5-year. There were no differences in age, gender, histology, pT status and pN status between 5-year survivors and non-survivors. On the other hand, the serum carcinoembryonic antigen (CEA) level was significantly higher in non-survivors. Among these 5-year survivors, 4 of 7 patients died of NSCLC recurrences more than 5 years after surgery. Remaining 3 patients survived without cancer recurrences. Interestingly these 3 survivors had not received any adjuvant therapies after surgery. Conclusion: None of the 5-year survivor with positive PLC had high serum CEA level. Furthermore 5-year survival did not equal to cure in NSCLC patients with positive PLC.