Intraoperative pleural lavage cytology is an independent prognostic indicator for staging non-small cell lung cancer

OBJECTIVES: For patients undergoing lung resection for cancer, macroscopic evidence of metastasis is clearly associated with adverse prognosis. However, less is known about the significance of tumor cells detected by using tests such as pleural lavage cytology. To ascertain the frequency and quantify the effect of this finding on survival, we performed a prospective study of intraoperative pleural lavage cytology. METHODS: Pleural lavage cytology consisted of cytologic analysis of 100 mL of saline irrigated over the lung surface immediately after thoracotomy. Patients were excluded if they had an existing effusion, extreme adhesions, or lateral chest wall invasion or if resection was not performed. Survival was calculated by means of Kaplan-Meier analysis and compared by using log-rank tests. Cox regression was used to ascertain independent predictors of prognosis. RESULTS: From 1995 through 2003, we performed pleural lavage cytology on 292 patients undergoing thoracotomy for lung cancer. The mean age was 64 (SD, 10) years, and 196 (67%) patients were men. Of 292 samples, 13 (4.5%) showed evidence of malignant cells. The median time to follow-up was 15 months (interquartile range, 1-40 months), with a median survival of 49 months for patients with negative pleural lavage cytology results and 13 months for patients with positive pleural lavage cytology results (P =.002). Univariate prognostic predictors were positive pleural lavage cytology status (P =.03), stage (P =.03), adenocarcinoma (P =.06), and parietal pleural involvement (P =.01). In the final multivariate model only positive pleural lavage cytology status (P =.006) and stage (P =.03) remained significant. CONCLUSIONS: Intraoperative pleural lavage cytology is a simple addition to intrathoracic staging and an independent predictor of prognosis. Positive results potentially affect survival by upstaging patients to stage IIIB or greater.     

Prognostic value of visceral pleural invasion in resected non-small cell lung cancer diagnosed by using a jet stream of saline solution

OBJECTIVE: Visceral pleural invasion caused by non-small cell lung cancer is a factor in the poor prognosis of patients with that disease. We investigated the relationship between the diagnosis of visceral pleural invasion by using a jet stream of saline solution, which was previously reported as a new cytologic method to more accurately detect the presence of visceral pleural invasion, and prognosis. METHODS: From January 1992 through December 1998, 143 consecutive patients with peripheral non-small cell lung cancer that appeared to reach the visceral pleura underwent a surgical resection at the Department of Thoracic Oncology, National Kyushu Cancer Center. The surface of the visceral pleura in patients undergoing lung cancer resection was irrigated with a jet stream of saline solution. The diagnosis of visceral pleural invasion was determined by means of either a pathologic examination or by means of a jet stream of saline solution. In addition, a cytologic examination of the pleural lavage fluid obtained immediately after a thoracotomy was evaluated. RESULTS: Forty-nine (34%) resected tumors were identified as having visceral pleural invasion. The diagnosis of visceral pleural invasion in 31, 6, and 12 patients was determined by using a jet stream of saline solution alone, pathologic examination alone, or both, respectively. The visceral pleural invasion and positive findings of intrapleural lavage cytology were linked. Although there was no significant difference between the incidence of distant metastases in the patients with visceral pleural invasion and those without visceral pleural invasion, the incidence of local recurrence, especially regarding carcinomatous pleuritis (malignant pleural effusion, pleural dissemination, or both), in the patients with visceral pleural invasion was significantly higher than in those without visceral pleural invasion. The recurrence-free survival of patients with visceral pleural invasion was significantly shorter than that of patients without visceral pleural invasion (P =.004), even patients with stage I disease (P =.02). There was also a significant difference between the patients with or without visceral pleural invasion in the overall survival (P =.02). Visceral pleural invasion was independently associated with a poor recurrence-free survival on the basis of multivariate analyses (P =.03), as were sex (P =.03), age (P = 002), and the stage of the disease (P <.0001). CONCLUSIONS: This study confirmed that the jet stream of saline solution method in addition to ordinary pathologic examination was useful for detecting visceral pleural invasion, which is considered to be one of the causes of local recurrence, especially in carcinomatous pleuritis.     

Role of pleural lavage cytology before resection for primary lung carcinoma

OBJECTIVE: To investigate the role of pleural lavage cytology (PLC) in resection for primary lung carcinoma. SUMMARY BACKGROUND DATA: The prognostic significance of PLC before manipulation is still controversial. METHODS: Cytology of pleural lavage immediately after thoracotomy but before any manipulation of the lung was examined in 500 consecutive patients with lung cancer with no pleural effusion who underwent pulmonary resections. Eighteen patients who already had pleural dissemination were excluded from this study. RESULTS: Eighteen of 482 patients (3.7%) had positive cytologic findings. The positivity of PLC was significantly correlated with histology, extension of tumor to pleura, and presence of lymphatic permeation or vascular involvement by tumor. Positive lavage findings were seen only in adenocarcinoma. Because 6.3% of the patients with adenocarcinoma had positive cytologic findings, it is vital to perform PLC before curative resections for lung cancer, especially adenocarcinoma. The 5-year survival rates of the patients having negative and positive lavage findings were 52.9% and 14.6%, respectively. The prognosis of the patients with positive lavage findings was as poor as that of the patients with stage IIIB disease and that of the patients with malignant effusion. CONCLUSIONS: Positive findings on PLC indicate exfoliation of cancer cells into the pleural cavity, which is an essential prognostic factor. In addition, we should regard positive cytologic findings as a subclinical malignant pleural effusion that is pathologic stage T4.     

Pleural lavage after pulmonary resection for bronchogenic carcinoma

A cytologic examination of pleural fluid was performed on a pleural lavage specimen collected at the completion of operation after pulmonary resection in 135 of 599 patients undergoing curative pulmonary resection for a non-small cell carcinoma of the lung between 1977 and 1982. The cytologic results of lavage was positive for malignant cells in 12 of the 135 patients (8.9%). The incidence of positive results was correlated with lymph node status (N2 greater than N1 greater than N0), cell type (adenocarcinoma greater than other non-small cell lung cancers), stage (III greater than II greater than I), and visceral pleural status (invaded greater than not invaded). No positive cytologic results were noted in 39 patients having a diagnostic excisional pulmonary biopsy prior to more definitive resection. The disease has recurred in nine of the 12 patients with positive cytologic results (only two in the ipsilateral pleural space), and eight have died. The prognostic role of pleural lavage cytology needs more study.     

Does pleural lavage cytology before thoracic closure predict both patient's prognosis and site of cancer recurrence after resection of esophageal cancer?

BACKGROUND: Operative manipulation occasionally exfoliates and spreads cancer cells in the surgical field, and it is a matter of concern whether the exfoliated cancer cells actually affect the patient's prognosis and sites of cancer recurrence. METHODS: In 240 patients with esophageal cancers, lavage cytology (LC) of the right pleural cavity was performed before and after esophageal resection combined with regional lymphadenectomy. The cytologic results were compared with the pathologic factors associated with cancer extension, postoperative survival, and cause of surgical failure. RESULTS: Only 3 patients (1.3%) were LC positive before resection. Of the 237 LC-negative patients, LC was also negative after resection in 215 patients (90.7%) (LC-/-), but LC became positive after resection in 22 patients (9.3%) (LC-/+). The 3-year survival rate was 0% in the LC-/+ group versus 65% in the LC-/- group, and the median survival rates were 10.9 months and 25.0 months, respectively (P <.0001). Multivariate analysis revealed that LC-/+ was an independent prognostic factor (P =.0331), along with nodal involvement and depth of cancer invasion. However, there were no significant differences in the sites of cancer recurrence between the 2 groups. Only 1 patient was found to develop the first recurrence in the pleural cavity. The LC-/+ group had a higher incidence of bulky lymph-node metastasis (P =.0009). CONCLUSIONS: Pleural LC after resection of esophageal cancer seems to be a prognostic indicator of overall recurrence, but not necessarily in the pleural cavity. Patients with a positive LC after resection may benefit most by effective systemic adjuvant chemotherapy.     

Prognostic significance of pleural lavage cytology after resection for non-small cell lung cancer.

OBJECTIVE: In the staging of lung cancer, pleural effusion that is malignant on cytologic examination is regarded as T4 disease, and curative resection cannot be performed. We conducted this study to determine whether cancer cells can be present in the pleural cavity with no pleural effusion, to investigate the factors contributing to that occurrence, and to evaluate its prognostic significance. METHODS: Eighty-five patients (77 males, eight females) with a median age 60.1-+/--7.9 years (31--74 years) underwent a major lung resection, due to lung cancer in our department. From January 1998 to December 1999, 30 pneumonectomies, seven bilobectomies, 46 lobectomies and two wedge-resections were performed. Chest wall resection was performed in four patients. After performing a posterolateral thoracotomy and lung resection with extended mediastinal lymph node dissection, the pleural cavity was filled with 1 l physiologic saline solution (PSS) and the fluid was shaken. The lavage fluid was suctioned off (S1). Immediately after the lavage, the pleural cavity was refilled with 3 l PSS. The surgeon washed out the pleural cavity by hand for 1 min and the fluid was suctioned off. Finally, the pleural cavity was refilled with 1 l PSS and a new lavage fluid was suctioned off (S2). A cytologic examination was carried out for each sample. RESULTS: The pathology report showed 39 adenocarcinomas, 33 squamous-cell, two adenosquamous, four large-cell, two neuroendocrine and five undifferentiated carcinomas. S1 was positive in eight patients (9.4%), while S2 was positive in four patients (4.7%). The correlation of positive pleural lavage and infiltrated lymph nodes demonstrated a statistically significant relation between presence of N2 disease and positive S2 sample (P = 0.049). No significant correlation existed between positive lavage sample (S1 or S2) and TNM stage, level of T, extent of tumor invasion, kind of operation, histological type or differentiation of the cancer (Chi square test). The mean follow-up is 11.3 +/- 6.2 months (4--22 months). There are 78 patients alive. A significance difference in survival was identified in-patients with positive S1 (P = 0.0081), and positive S2 (P = 0.0251) (Kaplan--Meier). CONCLUSION: The cytologic results of lavage were positive for malignant cells in eight of 85 patients (9.4%). The existence of cancer cells in the pleural cavity can be the result of their exfoliation or surgical manipulations. The mechanical irrigation subdivides the percentage of positive samples. Our study supports that the positive findings on pleural lavage cytology is an essential prognostic factor.     

Intraoperative pleural lavage cytology in lung cancer patients

Cytology of intraoperative pleural lavage was examined in 164 lung cancer patients who underwent pulmonary resections. None of the patients had any pleural effusion or dissemination. Cytology was performed three times: (1) at thoracotomy, (2) immediately after resection, and (3) after washing the pleural cavity with 5,000 mL of physiological saline solution just before closure of the chest wall. Twenty-three patients (14%) had more than one positive cytological finding. The frequency of positive cytological findings was significantly correlated with pathological T classification, pleural status, and pathological stage. The positive lavage group had a significantly higher recurrence rate than the negative lavage group in patients with stage I or stage II cancer. Four patients in the positive lavage group (17.4%) had recurrence in pleura or pericardium whereas only 1 patient in the negative lavage group (0.7%) had a recurrence in pericardium. The positive cytological finding of pleural lavage has more important meaning as a prognostic factor in stage I and stage II and indicates a greater possibility of recurrence in pleura or pericardium, but further examinations to evaluate the viability of detected malignant cells are required so that the positive cytological findings of pleural lavage can be regarded as subclinical pleural dissemination.     

Intraoperative lavage for cytological examination in 1,297 patients with gastric carcinoma.

BACKGROUND: This study examined the clinical value of intraoperative peritoneal lavage for cytological examination in patients with gastric cancer. Peritoneal dissemination is the most frequent mode of recurrence for this tumor. METHODS: A retrospective of lavage findings, other factors, and outcome was performed in 1,297 patients with gastric cancer who underwent intraoperative peritoneal lavage. RESULTS: The 5-year survival rate of patients with positive lavage cytology was only 2%. Patients who underwent curative resection and had negative cytology had a significantly better 5-year survival rate (P < 0.001). Even among patients with macroscopic peritoneal dissemination, the survival rate was significantly better with negative cytology, which reflected fewer free cancer cells in the peritoneal cavity. Serum concentrations of carcinoembryonic antigen and carbohydrate antigen 19-9 were significantly higher in patients with positive cytology. Multivariate analyses indicated that intraoperative cytological findings was an independent prognostic factor for survival, and was the most important factor for predicting peritoneal recurrence. CONCLUSIONS: Intraoperative peritoneal lavage cytology is important in predicting survival and peritoneal recurrence in gastric cancer.     

Tumour cell frequency in pleural lavage in cases with stage I epidermoid lung cancer with no visceral pleural involvement

BACKGROUND: The presence of tumour cells in the pleural lavage of lung cancer patients with no malignant pleural effusion is a negative prognosticator. In the present study we aimed to determine the lowest frequency of positive pleural lavage in lung cancer. METHODS: The study included 26 consecutive patients who underwent thoracotomy for curative resection for Stage I epidermoid lung cancer. The cases had neither visceral pleural involvement nor obstructive pneumopathy. The patients were applied pleural lavage cytology immediately after thoracotomy. RESULTS: The frequency of malignant cells in pleural lavage was 7.7% (Stage IA, n = 1, and IB, n = 1). CONCLUSION: Our series, in which we predicted the lowest probability of the presence of tumour cells in pleural lavage, had such a frequency of positive tumour cells that should'nt be neglected. The present study concluded that pleural lavage cytology before pulmonary resection should routinely be performed in 'all' lung cancers and that pleural lavage cytology may also be included in the current staging system.     

Visceral pleura invasion and pleural lavage tumor cytology by lung cancer: a prospective appraisal

BACKGROUND: Despite an early-stage diagnosis, lung cancer presenting with visceral pleura invasion (VPI) or malignant pleural lavage cytology (PLC) has a poor prognosis. The purpose of this study was to correlate VPI to malignant PLC. METHODS: One hundred forty-three consecutive patients scheduled for surgical lung resection having undergone preresectional pleural lavage cytology were reviewed. There were 121 malignant and 22 nonmalignant lesions. All cases were studied by pathology, histology, previous transthoracic puncture, VPI, and presence of pleural lymphatic involvement. RESULTS: PLC was positive (n = 13) or suspected (n = 5) for malignant cells in, respectively, 10.7% and 4.1% of patients with lung cancer. There was no positive PLC in cases of nonmalignant disease. PLC was positive only in pT2 tumors and almost always when the tumor was exposed on the pleural surface, thus possibly exfoliating within the pleural space (12/17 patients, 70.6%; p < 0.01). Positive PLC was obtained whatever the histology but did not appear related to previous transthoracic puncture or involvement of pleural lymphatics by tumor cells. CONCLUSIONS: VPI and positive PLC are linked, and the appearance of tumor cells within the pleural cavity can be explained by tumor desquamation. The role that visceral pleura involvement and parietal pleura reabsorption play in lung cancer is of paramount importance and deserves further research. A better understanding of their relationship could have major implications in the therapeutic management of non-small cell lung cancer.     

Should three slide-touch print cytology replace pleural lavage cytology for detection of pleural micrometastases in cases of bronchogenic carcinoma?

A prospective study, including 112 patients, designed to estimate the sensitivity and specificity of slide-touch and pleural lavage cytology for diagnosis of pleural micrometastases in operable non-small cell lung cancer (NSCLC). Histopathologically, excised tumors showed P0 in 22 patients (19%), P1 in 44 patients (39%), P2 in 32 patients (29%), P3 in 14 patients (13%). Cytological examination of the three slide-touch prints from visceral pleura overlying the tumor (slide 1), parietal pleura facing tumor (slide 2), parietal pleura in paravertebral gutter (slide 3) resulted in: slide 1: positive in 60% (66/112) [this included p0 (2 out of 22), p1 (22 out of 44), p2 (32 out of 32) and p3 (10 out of 14)], slide 2: positive in 13% (14/112); all of them had P3, and slide 3 positive in 8% (9/112). Total positive slides 62% (70/112). Pleural lavage: positive in 19% (22/112), all of them were detected with slide 1 and/or slide 2. During follow-up, patients with negative slides had no local or distant metastases (truly negative), six recurrences among those with positive slide 1, including four with positive lavage. Thus, slide touch print is more sensitive than lavage cytology, both of prognostic significance. Slide 1 is a highly sensitive detector of visceral pleural micrometastases; slide 2 is a more sensitive detector of parietal pleural invasion; slide 3 is the least.     

肺癌胸腔冲洗液细胞学研究

目的　探讨无胸水肺癌病人胸腔游离癌细胞的存在及相关病理因素 ,及肺癌胸腔冲洗液细胞学 (PLC)研究的临床意义。方法　 1998 7～ 1999 2治疗无胸水、无远处转移的原发性肺癌 5 8例。每个病例均收集开胸后 (A液 )、关胸前 (B液 )胸腔冲洗液 ;其中 47例收集JSS法所获液体 (C液 )。所得液体经处理后涂片病理检验。数据行 χ2 统计。结果　A液阳性 6例 (10 34 % ) ,同肿瘤N分期、TNM分期有关。B液阳性 2例 (3 45 % )。C液阳性 8例 (17 12 % ) ,阳性病例均为P1或P2 期。结论　无胸水肺癌病人胸膜腔中可存在癌细胞 ,应重视。A液检测可列为常规检查。对于A液阳性或肿瘤累及脏层胸膜病例 ,应行胸腔内局部处理。     

Pleural lavage cytology in esophageal cancer without pleural effusions: clinicopathologic analysis.

OBJECTIVE: The literature of pleural lavage cytology (PLC) is focused on lung cancer. We conducted this pilot study to determine the incidence of malignant pleural cytologies in patients without pleural effusions who undergo curative resection for esophageal cancer, and to evaluate the clinicopathologic significance of positive cytology. METHODS: Forty-eight patients underwent esophagectomy for thoracic esophageal cancer in our unit from January 1998 to January 1999. After thoracotomy, pleural lavage was performed before any intrathoracic manipulation and cytologically evaluated. RESULTS: There was one patient with stage I, 27 patients with stage II, and 20 patients with stage III cancer of the thoracic esophagus. The mean age was 55 years (range 41-77 years). Fifteen cases (31.3%) were found to have positive lymph nodes (N1). Squamous cell carcinoma was the dominant histopathologic type (91.7%). Positive lavage cytology in the whole group was found in 18.8% (9/48). There was no significant correlation to gender, age, clinical symptoms, histology, T or N status, TNM stage, or tumor location. CONCLUSIONS: The incidence of positive pleural lavage cytology in esophageal cancer is disconcertingly high. Positive cytology might suggest a more aggressive tumor biology. Future studies on its relation to survival and occult lymphatic metastasis are warranted.     

Does the intraoperative peritoneal lavage cytology add prognostic information in patients with potentially curative gastric resection?

Peritoneal recurrence is the foremost pattern of failure after potentially curative resection for gastric cancer. Our aim was to evaluate the prognostic value of intraperitoneal free cancer cells (IFCCs) in peritoneal lavage of patients who underwent potentially curative resection for gastric carcinoma. Two hundred twenty patients with gastric cancer stage I, II, or III were prospectively evaluated with peritoneal lavage and cytologic examination. Aspirated fluid from the abdominal cavity was centrifuged and subjected to Papanicolaou staining. The mean age was 60.9 years (range, 21–89 years), and 63.6% were men. IFCCs were detected in 6.8% of the patients; suspicious in 2.7%, and negative in 84.5%. No judgment could be given in 5.9% of the cases. Invasion of the gastric serosa (pT3) was observed in all positive cytology patients. Patients with IFCCs had a mean survival time of 10.5 months, while those with negative IFCC had a mean survival time of 61 months (P = 0.00001). There was no correlation between the presence of IFCCs and tumor size, histology, pN, or tumor site. Our conclusions are that (1) positive cytology indicates a poor prognosis in patients who underwent potentially curative gastric resection and (2) peritoneal lavage cytology improves staging in assessing these patients and may alter their therapeutic approach.     

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

BACKGROUND: The prognosis of patients with resected non-small cell lung cancer without carcinomatous pleuritis whose intrapleural cancer cells were detected by means of a cytologic examination of pleural lavage fluid obtained immediately after a thoracotomy has been reported to be poor. METHODS: The Japan Clinical Oncology Group conducted a phase III trial for a 3-year period starting from October 1994 to determine whether intraoperative intrapleural hypotonic cisplatin treatment could effectively control pleural disease and thereby prolong the survival of these patients. The patients were randomized to receive either intraoperative intrapleural hypotonic cisplatin treatment or no treatment before closure of the open thorax. The intraoperative intrapleural hypotonic cisplatin treatment consisted of exposing the entire thorax to cisplatin (50 microg/mL) in distilled water for 15 minutes. RESULTS: Because of the slow registration pace, the study was prematurely terminated in January 1998. During the 41-month period from the start of the registration, 49 patients were entered into the study, and all were eligible. Twenty-five and 24 patients were randomly assigned to the treatment and control groups, respectively. No statistically significant difference in the overall survival and disease-free survival between the 2 groups was observed. However, the appearance of carcinomatous pleuritis was suppressed by the hypotonic cisplatin treatment (42% of the control group vs 8% of the treatment group, P =.008). CONCLUSIONS: Although the randomized trial was prematurely terminated, the intraoperative intrapleural hypotonic cisplatin treatment was found to effectively suppress the appearance of carcinomatous pleuritis in resected patients who demonstrated a positive pleural lavage cytology finding.     

Intraoperative lavage cytologic analysis of surgical margins as a predictor of local recurrence in pulmonary metastasectomy

HYPOTHESIS: Cytologic analysis of intraoperative lavage at the surgical margin during wedge or segmental resection for pulmonary metastatic lesions predicts postoperative local failure at the surgical margin of the pulmonary parenchyma. DESIGN: Prospective nonrandomized trial. SETTINGS: Institution-based study. PATIENTS: Fifty-one consecutive patients undergoing wedge or segmental resection for 87 pulmonary metastatic lesions of various primary tumor types from November 1, 1997, through January 31, 2001, were prospectively enrolled. INTERVENTIONS: An intraoperative lavage cytologic technique at the surgical margin for each pulmonary metastasis was performed as described previously. MAIN OUTCOME MEASURES: Incidence of positive cytologic findings and postoperative local recurrence at the surgical margin. RESULTS: Of the examined lesions, 10 (11%) showed positive cytologic results at the surgical margin, despite a macroscopically safe margin in the attempted resection. Of these, metastasectomy was converted to segmentectomy in 3. An additional wedge resection and evaporation using an Nd:YAG laser in the surgical margin were performed in 1 and 4 lesions, respectively. Complications precluded further treatment in 2 lesions. By July 2001, although no local recurrence at the surgical margin area was found among the lesions with negative cytologic results, recurrence at the surgical margin occurred in 2 with positive cytologic results, including 1 receiving no treatment and 1 receiving Nd:YAG laser evaporation, indicating that a significant difference in the recurrence rate according to lavage cytologic status (P<.001). CONCLUSIONS: This intraoperative lavage cytologic technique in wedge or segmental resection of pulmonary metastases of various primary tumors may be a useful predictor of local recurrence at the surgical margin. With these test results, local recurrence at the surgical margin may be controllable in patients undergoing pulmonary metastasectomy.     

Long-term survival and prognostic factors of five-year survivors with complete resection of non-small cell lung carcinoma

OBJECTIVE: We analyzed the long-term follow-up data on cancer-related death in 5-year survivors of complete resection of their non-small cell lung cancer and examined the prognostic factors having an impact on subsequent survival. METHODS: Of 848 consecutive patients with proven primary non-small cell carcinoma who underwent complete removal of the primary tumor together with hilar and mediastinal lymph nodes, 421 patients (49.6%) survived 5 years or longer after the initial surgical treatment. Of all the data analyzed, only death related to cancer was treated as death. RESULTS: The median follow-up of 5-year survivors was 84 months from the original treatment (range, 60 to 200 months). Their overall survival rate at 10 years was 91.0%. Multivariable Cox analysis demonstrated that although advanced surgical-pathological stage (P =.0001), nodal involvement (P =.0245), male gender (P =.0313), and non-squamous type of the tumor (P =.0034) were significant, independent, unfavorable prognostic determinants in all patients, none of the variables investigated significantly influenced the long-term survival of 5-year survivors. The rate of recurrence beyond 5 years was much lower compared with that within 5 years. In contrast, the rate of occurrence of new malignancies was unchanged throughout the long-term postoperative period. CONCLUSIONS: Among 5-year survivors of complete resection of non-small cell lung cancer, neither stage, nodal status, sex, nor histologic condition further affected subsequent survival, suggesting that the 5-year interval might be sufficient to declare that a patient with lung cancer has been cured.     

A biologic risk model for stage I lung cancer: immunohistochemical analysis of 408 patients with the use of ten molecular markers

OBJECTIVE: The standard treatment of patients with stage I non-small cell lung cancer is resection of the primary tumor; however, the recurrence rate is 28% to 45%. This study evaluates a panel of molecular markers in a large population of patients with stage I non-small cell lung cancer to determine the prognostic value of each marker and to create a biologic risk model. METHODS: Pathologic specimens were collected from 408 consecutive patients after complete resection for stage I non-small cell lung cancer at a single institution, with follow-up of at least 5 years. A panel of 10 molecular markers was chosen for immunohistochemical analysis of the primary tumor on the basis of differing oncogenic mechanisms. Local tumor expansion requires growth regulating proteins (epidermal growth factor receptor, the protooncogene erb-b2); apoptosis proteins (p53, bcl-2); and cell cycle regulating proteins (retinoblastoma recessive oncogene, KI-67). Local tumor invasion requires angiogenesis (factor viii). The development of distant metastases involves the expression of adhesion proteins (CD-44, sialyl-Tn, blood group A). Cox proportional hazards regression analysis was used to construct an independent risk model for cancer recurrence and death. RESULTS: Multivariable analysis demonstrated significantly elevated risk for the following molecular markers: p53 (hazard ratio, 1.68; P =.004); factor viii (hazard ratio, 1.47 P =. 033); erb-b2 (hazard ratio, 1.43; P =.044); CD-44 (hazard ratio, 1. 40; P =.050); and retinoblastoma recessive oncogene (hazard ratio, 0. 747; P =.084). CONCLUSIONS: Five molecular markers were associated with the risk of recurrence and death, representing independent metastatic pathways: apoptosis (p53), angiogenesis (factor viii), growth regulation (erb-b2), adhesion (CD-44), and cell cycle regulation (retinoblastoma recessive oncogene). This study demonstrates the validity of this molecular biologic risk model in patients with stage I non- small cell lung cancer.     

Pleural lavage cytology immediately after thoracotomy in patients with completely resected non-small cell lung cancer

This study evaluated 325 patients who had undergone pleural lavage cytology (PLC) immediately after thoracotomy following a complete resection for non-small cell lung cancer (NSCLC) between 2004 and 2008. The number of patients with negative and positive findings in PLC was 309 and 13, respectively. The proportion of T1 in the PLC-positive group was significantly smaller than that of the PLC-negative group. The pathologic examinations revealed that the parietal pleural invasion was significantly more severe in the PLC-positive group than in the PLC-negative group. Pathologic lymphovascular invasion was also significantly more prominent in the PLC-positive group than in the PLC-negative group. The 5-year survival rate after surgery in the PLC-positive group and PLC-negative group was 54.7% and 79.0%, respectively. The positive finding in PLC showed a tendency of an unfavorable prognosis for NSCLC patents following complete resection. Further clinical studies will be necessary to evaluate the efficacy of adjuvant therapy for PLC-positive patients.     

The significance of intraoperative pleural effusion during surgery for bronchogenic carcinoma.

OBJECTIVES: To analyze patients submitted to thoracotomy for lung carcinoma presenting with an intraoperative pleural effusion (PE). METHODS: From 1993 to 1999, 1279 patients received thoracotomy with curative intent for primary lung carcinoma. Intraoperatively, 52 patients (4%) presented a PE >100ml which was not diagnosed preoperatively. Of these, seven patients had received preoperative transthoracic fine-needle biopsy FNB and were excluded from the analysis. In the remaining 45 patients pleural fluid cytology was undertaken. In patients with cytology-negative PE, clinico-pathologic characteristics including intratumoral vascular invasion, intratumoral perineural invasion, peritumoral lymphocytic infiltrate, visceral, parietal and mediastinal pleural involvement, pTNM and survival were analyzed and compared with our total population of lung cancer patients operated on during the same period. RESULTS: The mean amount of collected fluid was 210ml (100-450ml). Of the 45 patients with intraoperative PE, 16 (35%) received exploratory thoracotomy because of pleural carcinosis or major involvement of mediastinal structures; eight (18%) received resection of the tumor, although the cytologic examination of the pleural fluid eventually resulted positive for neoplastic cells. Median survival for the two groups was 6 and 9 months, respectively. Twenty-one patients (47%) received resection of the tumor with a cytology-negative pleural fluid. In this group, analysis of clinico-pathologic characteristics revealed that squamous cell type and mediastinal pleural involvement were significantly associated with the presence of intraoperative PE (P=0.01 and P=0.05, respectively); 3- and 5-year survivals of this group were similar to those observed in our total population of resected lung cancer patients (68 and 56% vs. 54 and 42%, P=0.27). CONCLUSIONS: The presence of a PE at thoracotomy during surgery for lung carcinoma is an infrequent occurrence. In more than 50% of the cases cytology is positive and prognosis is poor. In the remaining cases, however, cytology is negative and the PE should be considered as reactive; in these patients a curative resection can be accomplished with an anticipated chance of long-term survival.