[Prognostic value study of lung cancer molecular markers]. / Valor pronóstico de los marcadores moleculares en el carcinoma broncogénico.

BACKGROUND AND OBJECTIVE: The aim of this study was to determine the prognostic value of molecular markers (proteins) of different paths of lung cancer development in patients with non small cell lung carcinoma (NSCLC) in initial stages. MATERIAL AND METHOD: Observational, cohort study in patients with NSCLC that was initially treated surgically in our hospital between October 1993 and September 1997. Thirty-two proteins were selected. The study consisted of the elaboration of tissue arrays with samples from resected tumour, using a semiquantitative immunohistochemical study. A prognosis analysis was done with the expression of each protein and calculation of the overall 5-year survival rate. The Wilcoxon-Gehan and Log-Rank tests were used for statistical comparisons, with p<.05 being considered to indicate a significant result. RESULTS: One hundred and forty six patients were studied. The overall 5-year survival rate was 37.7%. From 32 proteins studied, three were statistically associated with overall 5-year survival rate. RB protein expression in resected NSCLC was a positive prognostic factor (P=.01). P27 (P=.03) and Ki67 (P=.04) expression in resected NSCLC were negative prognostic factors. There was no protein with prognostic value in epidermoid tumours. CONCLUSIONS: We found three proteins with long-term prognostic value in the long-term in the general population and five adenocarcinoma prognostic proteins in our study of resected non-small cell lung cancer (NSCLC). In the future, genetic-molecular factors should be included along with anatomical (TNM staging) and clinical factors in a multidimensional lung cancer staging.

Loss of the mitochondrial bioenergetic capacity underlies the glucose avidity of carcinomas.

The down-regulation of the catalytic subunit of the mitochondrial H+-ATP synthase (beta-F1-ATPase) is a hallmark of most human carcinomas. This characteristic of the cancer cell provides a proteomic signature of cellular bioenergetics that can predict the prognosis of colon, lung, and breast cancer patients. Here we show that the in vivo tumor glucose uptake of lung carcinomas, as assessed by positron emission tomography in 110 patients using 2-deoxy-2-[18F]fluoro-d-glucose as probe, inversely correlates with the bioenergetic signature determined by immunohistochemical analysis in tumor surgical specimens. Further, we show that inhibition of the activity of oxidative phosphorylation by incubation of cancer cells with oligomycin triggers a rapid increase in their rates of aerobic glycolysis. Moreover, we show that the cellular expression level of the beta-F1-ATPase protein of mitochondrial oxidative phosphorylation inversely correlates (P < 0.001) with the rates of aerobic glycolysis in cancer cells. The results highlight the relevance of the alteration of the bioenergetic function of mitochondria for glucose capture and consumption by aerobic glycolysis in carcinomas.

Specific pattern of LKB1 and phospho-acetyl-CoA carboxylase protein immunostaining in human normal tissues and lung carcinomas.

The LKB1 tumor suppressor gene codes for a serine/threonine protein kinase, and among its substrates is the adenosine monophosphate-dependent protein kinase, a sensor of intracellular energy levels. LKB1 is genetically inactivated in several types of tumors, especially lung adenocarcinomas. Here we used immunohistochemistry to evaluate the levels of LKB1 and the phosphorylated form of the acetyl-CoA carboxylase (ACC) protein in a variety of human adult normal tissues and in 159 lung carcinomas. The enzyme ACC becomes inactive upon phosphorylation by adenosine monophosphate-dependent protein kinase. Our analysis in normal tissues revealed strong LKB1 immunostaining in most epithelia, in the seminiferous tubules of the testis, in myocytes from skeletal muscle, and in glia cells. In contrast to the cytosolic location of LKB1 found in most tissues, glia cells carried mainly nuclear LKB1. Some epithelial cells showed apical accumulation of LKB1, supporting its role in cell polarity. Regarding phospho-ACC (p-ACC), strong immunostaining was observed in myocytes from the skeletal muscle and heart, and in Leydig cells of the testis. In lung tumors, LKB1 immunostaining was absent, moderate, and high in 20%, 61%, and 19% of the tumors, respectively, whereas p-ACC immunostaining was found to be absent/low, moderate, and high in 35%, 34%, and 31% of the tumors, respectively. High levels of LKB1 and p-ACC immunostaining predominated in lung adenocarcinomas compared with squamous cell carcinomas. Finally, high p-ACC was an independent marker for prediction of better survival in lung adenocarcinoma patients. Median overall survival was longer in patients with p-ACC-positive than those with p-ACC-negative tumors (96 versus 44 months, P = .04). In conclusion, our observations provide complete information about the pattern and levels of LKB1 and p-ACC immunostaining in normal tissues and in lung tumors, and highlight the special relevance of abnormalities of the LKB1 pathway in lung adenocarcinoma.

Alteration of the VRK1-p53 autoregulatory loop in human lung carcinomas.

Human VRK1 (vaccinia-related kinase 1) is a novel serine-threonine kinase that regulates several transcription factors, including p53, ATF2 and c-Jun; and its loss results in defects of cell proliferation. VRK1 stabilizes p53 and the accumulated p53 downregulates VRK1 forming an autoregulatory loop. Wild-type p53, but not mutant p53, was able to downregulate VRK1 in the A549 lung carcinoma cell line. VRK1 expression has been studied in human lung carcinomas. VRK1 protein level was significantly higher in squamous cell lung carcinomas than in adenocarcinomas, and inversely correlated with p16. Tumours with p53 mutations have a positive trend with those having very high levels of VRK1 protein, particularly in squamous cell lung carcinomas. These data indicate that the VRK1-p53 autoregulatory loop was not functional in a group of lung carcinomas. The accumulation of VRK1 in tumours with mutant p53 could result in stimulation of other signalling pathways that can contribute to tumour growth and progression in addition to those resulting from loss of p53 function.

Prognostic value of KIT expression in small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is a very aggressive disease, with poor survival rates despite standard treatment with combination chemotherapy with or without radiotherapy. Further insights into the molecular biology of this malignant tumour are needed to improve the therapeutic approaches and outcome. KIT protein is expressed in SCLC, and its kinase activity has been implicated in the pathophysiology of many tumours, including SCLC. The purpose of this study was to evaluate the prevalence of KIT expression in patients with SCLC and its prognostic value. METHODS: We performed an inmunohistochemical analysis of 204 SCLC samples to determine KIT protein expression. The relationship between KIT expression and clinicopathological parameters was evaluated. Univariate and multivariate analyses were performed to define its prognostic significance. RESULTS: KIT expression was observed in 149 of 204 tumour tissues (73%). KIT expression was associated with advanced disease and with decreased incidence of bone metastases. No significant differences were observed for time to disease progression (TTP) (9.1% versus 6.2% at 3 years, p=0.6) or overall survival (OS) (10.7% versus 6.9% at 3 years, p=0.37) among patients with KIT positive versus negative tumours, respectively. Multivariate analysis showed that sex, tumour stage, albumin levels and response to therapy were the only independent predictors for survival. CONCLUSION: KIT protein is expressed in a high percentage of SCLC tumours. In our study population, however, the expression of KIT had no significant impact on survival.

Molecular context of the EGFR mutations: evidence for the activation of mTOR/S6K signaling.

PURPOSE: Activating somatic mutations in the epidermal growth factor receptor (EGFR) gene are present in a small subset of lung adenocarcinomas. These mutations cluster in specific regions and confer sensitivity to inhibitors of the tyrosine kinase activity of EGFR. To further determine the genetic and molecular characteristics of tumors carrying EGFR gene mutations, we investigated the EGFR gene status in lung adenocarcinomas and evaluated its association with specific characteristics of the patients and tumors, such as mutations at KRAS and p53, EGFR and ErbB2 gene amplification, levels of EGFR and HER2 proteins, and levels of downstream effectors of EGFR, such as phospho-extracellular signal-regulated kinase and phospho-S6 proteins. EXPERIMENTAL DESIGN: The mutational status of EGFR was determined by direct sequencing in 86 primary lung adenocarcinomas and 12 lung cancer cell lines, and was correlated with a number of variables relating to the tumor and patient. A tissue microarray containing 37 lung tumors was constructed to determine, by fluorescence in situ hybridization analysis, the number of copies of EGFR and ErbB2 genes and, by immunohistochemistry, the levels of EGFR, HER2, phospho-ERK, and phospho-S6 proteins. RESULTS: EGFR gene mutations were identified in 13% of the primary tumors. The type and clustering of the mutations were identical to those previously reported. Amplification of the EGFR occurred in 14% of the tumors and could arise in tumors with EGFR mutations. Interestingly, mTOR activation, as measured indirectly by augmented levels of phospho-S6 protein, was more frequent in tumors with gene alterations in either EGFR or KRAS (P = 0.00005; Fisher's exact test) than in their wild-type counterparts. CONCLUSIONS: Our data agree with the accumulation of EGFR mutations in a subset of patients with lung cancer. Moreover, we report EGFR gene amplification in EGFR-mutant tumors and a positive correlation between EGFR or KRAS alterations and activation of mTOR signaling.

[Bronchogenic carcinoma 2000-2001: characteristics and overall survival]. / Carcinoma broncogénico 2000-2001: características y supervivencia global.

OBJECTIVE: To describe the clinical characteristics and survival of patients diagnosed with bronchogenic carcinoma during the years 2000 and 2001 in a tertiary level hospital. PATIENTS AND METHODS: Data were collected from our hospital's tumor registry and validated with independent sources. Of all the patients diagnosed with or treated for bronchogenic carcinoma in our hospital, only those from our health care area were selected. RESULTS: During the 2-year study period, 482 patients were diagnosed. Of those, 91% were men. The mean (SD) age was 66.6 (9.65) years. Large cell carcinomas accounted for 29.4% of cases. Of all the cases of bronchogenic carcinoma, 41.3% were diagnosed in stage IV. Thirty percent of non-small cell carcinomas were classified as stage I, compared to 6% of small cell carcinomas (P< .001). The most frequent treatment was chemotherapy (42.1%) and 20% of patients underwent surgery. The overall 5-year survival rate was 13% (95% confidence interval [CI], 10%-16%), while survival was significantly lower in patients aged 68 years or older (95% CI, 3%-15%; P< .001) and in patients with small cell carcinoma (0%, P< .01). CONCLUSIONS: Our recent experience (2000-2001) confirmed the advanced age of patients with bronchogenic carcinoma, the frequency of diagnosis in advanced stages of the disease (41% in stage IV), and the low overall 5-year survival rate (13%).

[Risk factors in bronchogenic carcinoma surgery]. / Parámetros de riesgo en la cirugía del carcinoma broncogénico.

OBJECTIVE: To analyze the factors that determine the risk of morbidity and mortality associated with lung resection in patients with bronchogenic carcinoma. PATIENTS AND METHODS: Prospective multicenter study conducted between October 1, 1993 and September 30, 1997 in the 19 hospitals that make up the Bronchogenic Carcinoma Cooperative Group. During the study period, 2994 patients with bronchogenic carcinoma underwent surgery. The morbidity and mortality data at 30 days from all centers were recorded in a single registry. RESULTS: Major resection was performed in 2491 patients, whereas 212 underwent minor resection. The resection had to be extended in 296 and exploratory thoracotomy was carried out in 291. Postoperative complications were reported in 1057 patients (35.2%). Complications directly related to surgery were the most common (22.9%), followed by respiratory (19.5%) and cardiovascular (10.7%) complications. Of the patients with complications, 654 patients (21.8%) had only 1, whereas 403 (13.4%) had more than 1. After classification of complications, 21% were found to be minor and 14.2% were major. Mortality at 30 days was 6.8% (204 patients), and strongly linked to the presentation of major complications--40.8% of those with such complications died. CONCLUSIONS: Surgical treatment of bronchogenic carcinoma in Spain is associated with high morbidity and mortality. The morbidity reported in the present study lies in the middle of the ranges found in the literature, whereas mortality lies at the high end of the range. The presence of major complications and/or multiple complications should be considered as strong risk factors.

Accuracy of helical computed tomography and [18F] fluorodeoxyglucose positron emission tomography for identifying lymph node mediastinal metastases in potentially resectable non-small-cell lung cancer.

PURPOSE: Computed tomography (CT) and [18F] Fluorodeoxyglucose positron emission tomography (FDG-PET) are considered suitable methods for the noninvasive staging of the mediastinum. Our study was intended to estimate the efficacy of contrast-enhanced helical CT (hCT) and FDG-PET, alone and combined, in the diagnosis of lymph node mediastinal metastases. METHODS: This study was a prospective and blind comparison of the efficacy of hCT and FDG-PET with two alternative reference standards, mediastinoscopy, and mediastinoscopy plus thoracotomy plus a 6-month follow-up to diagnose lymph node mediastinal metastases in 132 consecutive patients with potentially resectable non-small-cell lung cancer (NSCLC). The metastatic disease was assessed histopathologically. Further clinical information was obtained postoperatively after a median follow-up of 42 months. RESULTS: The prevalence of cN2,3 is 0.28. For hCT the sensitivity and specificity are 0.86 (95% CI, 0.70 to 0.93) and 0.67 (95% CI, 0.56 to 0.75), for PET 0.94 (95% CI, 0.81 to 0.98) and 0.59 (95% CI, 0.49 to 0.68), and for hCT and PET combined in-parallel 0.97 (95% CI, 0.84 to 0.99) and 0.44 (95% CI, 0.34 to 0.53), which translate into a negative predicted probability of 0.98 (95% CI, 0.88 to 1.00). The crude diagnostic odds ratio of PET in the total sample studied is 13.1, in the subgroup hCT+ 11.04 (3.0 to 40 0.1), and in the hCT- 3.5 (0.5 to 21.5). Similar results were obtained for hCT stratified by PET. CONCLUSION: hCT and PET perform similarly in the mediastinal staging of NSCLC, both tests are conditionally dependent and provide complementary information, and their diagnostic value mainly resides on the negative results.

Hospital volume: operative morbidity, mortality and survival in thoracotomy for lung cancer. A Spanish multicenter study of 2994 cases.

INTRODUCTION: It has been hypothesized that medical procedures performed in high-volume units carry less risk and achieve a better outcome. OBJECTIVE: To determine the relationship between the number of interventions and the operative morbidity, mortality and long-term survival in the surgery of bronchogenic carcinoma (BC). PATIENTS AND METHOD: Prospective, multicenter Spanish study was conducted in 19 departments of thoracic surgery on 2994 patients operated on consecutively with the aim of curing BC. The thoracic surgery departments have been classified into three groups, according to the number of interventions performed per year: I (1-43 cases/year; centers=7; n=565; 18.9%), II (44-54 cases/year; centers=6; n=1044; 34.9%) and III (55 or more cases/year; centers=6; n=1385; 46.3%). RESULTS: When the three groups were compared, the frequency of complete surgery was found to be 84% for group I, 76% for group II and 83% for group III (p=0.001, for comparisons between groups I/II and II/III). The pathological stages were identical in the three groups. The overall morbidity and the mortality in all patients or above the age of 75 or in pneumonectomies were not different among the groups. When considering all the patients with prognostic information (n=2758), no differences were found regarding the 5-year survival among the groups. When only patients in postoperative stage I-II and complete resection were evaluated, excluding operative mortality (n=1128), 5-year survival was 0.58 for group I, 0.57 for group II and 0.50 for group III (p=0.06 between groups II and III; p=0.08 between groups I and III). CONCLUSIONS: No significant differences that do not favor the hypothesis that there is increased surgical risk and worse survival in centers having a lower volume were found in this Spanish multicenter study.

[Bronchioloalveolar carcinoma in Spain: a rare and different form of lung cancer]. / Carcinoma bronquioloalveolar en España. Un cáncer de pulmón infrecuente y diferente.

OBJECTIVE: To describe a series of cases of bronchioloalveolar carcinoma (BAC) treated surgically between 1993 and 1997 in the 19 hospitals that make up the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pulmonology and Thoracic Surgery (GCCB-S). PATIENTS AND METHODS: From a total of 2,944 cases of non-small cell lung cancer (NSCLC), 82 (3%) were BAC. The clinical characteristics and prognosis of patients with BAC were compared with those of the remaining 2,862 patients with NSCLC. RESULTS: The percentage of men was lower for BAC than for other types of NSCLC (64.6% compared with 93.5%; P< .001) and BAC was associated with less comorbidity (50% vs 62%; P< .05), particularly in terms of chronic obstructive pulmonary disease (33% vs 47.2%; P< .05). Other characteristics showing significant differences were the higher frequency of BAC as a chance finding and the lower likelihood of weight loss or reduced performance status at the time of diagnosis. Classification as stage cI was significantly more common in patients with BAC (87% vs 75%; P.001), and this difference between groups was more pronounced for stage pI (68.5% vs 47%; P< .01). Only taking into account patients classified as stage pI with complete resection of NSCLC and following exclusion of operative mortality, patients with BAC presented an overall 5-year survival of 65% (95% confidence interval [CI], 51%-79%), compared with a significantly lower survival of 53% (95% CI, 50%-56%; P< .05) in patients with other forms of NSCLC. CONCLUSIONS: In Spain, among cases of lung cancer treated by surgery, BAC is very rare (3%) and displays clinical characteristics that are different from other forms of NSCLC. Controlling for the most basic prognostic factors (stage pI and complete resection), survival is significantly higher for BAC.

Survival of 2,991 patients with surgical lung cancer: the denominator effect in survival.

OBJECTIVE: To evaluate the current staging system of lung cancer, taking into account different selection criteria for the studied population. POPULATION: A total of 2,991 consecutive patients with surgical lung cancer were prospectively compiled from 19 Spanish hospitals (Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery) between 1993 and 1997. METHODS: The Kaplan-Meier method was used to calculate survival at 5 years (S5) for each pathologic stage, and the log-rank test was used for comparison purposes. These studies were performed in the total group (population 1, n = 2,972); excluding operative mortality and small cell lung cancer cases (population 2, n = 2,697); excluding cases with induction therapy (population 3, n = 2,542); excluding cases with exploratory thoracotomy (population 4, n = 2,304); and, lastly, excluding cases with incomplete resection (population 5, n = 2082) [70% of the initial population]. RESULTS: The global S5 was similar in populations 1, 2, and 3: 34% (95% confidence interval [CI] 32 to 36%), 37% (95% CI, 35 to 39%), and 38% (95% CI, 35 to 39%), but different from that of populations 4 and 5: 40% (95% CI, 39 to 43%) and 43% (41 to 45%), respectively. For pathologic stage I, pathologic stage II, and pathologic state IIIA (pIIIA), S5 was similar in the five reported populations. In pathologic stage IIIB (pIIIB), there were differences in S5 between populations 1, 2, and 3 (13 to 15%; 95% CI, 10 to 19%) and populations 4 and 5 (26 to 29%; 95% CI, 19 to 38%). In population 4, there was no significant prognostic difference between two specific stage groups, that is between pathologic stage IB (pIB) and pathologic state IIA (pIIA) [p = 0.70] and between pIIIA and pIIIB (p = 0.79); the pathologic T3N2M0 combination has a S5 (13%) lower than that for pIIIB (26%). CONCLUSION: The definition of the population that constitutes the denominator for the analysis of survival in surgical lung cancer is important in pIIIB. The inclusion or exclusion of cases without resection is the most important factor for the selection of such population. This study detected that there are no prognostic differences between pIB and pIIA, and between pIIIA and pIIIB.

Prognostic value of chronic obstructive pulmonary disease in 2994 cases of lung cancer.

OBJECTIVE: Given the frequent association between chronic obstructive pulmonary disease (COPD) and lung cancer (LC), the objective of this paper is to analyse the prognosis of this comorbidity. METHODS: Multicenter prospective study compiling 2994 consecutive cases of surgically treated LC (1993-1997), the population with non-small cell lung cancer and complete resection was selected for the prognostic study of COPD. COPD is defined when the FEV1/FVC is <0.7 (n=1370; 46%). Overall and conditional survivals (survival likelihood when alive at 2, 3 or 5 years after treatment) as well as the degree of severity (FEV1% percentiles) were calculated to establish prognosis. RESULTS: Although the overall survival is similar whether or not COPD is present (Log-rank: 0.34), the conditional survival analysis is different in every stage at 60 months (Log-rank: 0.02) and different in stage pI at 24-36 months (Log-rank: 0.04). In LC (stage pI) with COPD, the presence of a worst pulmonary function (last FEV1% percentile vs first FEV1% percentile) is a bad prognostic factor (Log-rank: 0.002). CONCLUSIONS: The analysis of conditional survival at 24 months shows that COPD can be considered as a prognostic factor and that there is a clear relationship between the severity of the condition (FEV1%) and survival.

Interferon gamma levels in pleural fluid for the diagnosis of tuberculosis.

PURPOSE: To assess the utility of interferon gamma levels, including identification of the best cutoff for the diagnosis of tuberculosis. METHODS: We prospectively studied consecutive patients in a tertiary care, university-affiliated hospital who had pleural effusions. Interferon gamma levels were measured blindly by radioimmunoassay. The diagnosis of tuberculosis was established using prespecified standard criteria. RESULTS: Of the 595 patients with pleural effusions, 82 patients (14%) had tuberculosis. The area under the receiver operating characteristic (ROC) curve for elevated interferon gamma levels in the diagnosis of tuberculosis was 0.99 (95% confidence interval [CI]: 0.97 to 1.00). A cutoff of 3.7 IU/mL yielded a sensitivity of 0.98 (95% CI: 0.91 to 1.00) and a specificity of 0.98 (95% CI: 0.96 to 0.99). The areas under the ROC curves, and the test's sensitivity and specificity, were similar among patients of different ages and by percentage of lymphocytes in the pleural fluid. In 5 of the 28 patients with hematologic malignancies, interferon gamma levels were slightly above the cutoff; no patient with vasculitis or granulomatous diseases had levels higher than 3.7 IU/mL. The 14 immunocompromised patients and the 3 transplantation patients with tuberculosis had interferon gamma levels greater than the cutoff. CONCLUSION: Elevated pleural interferon gamma levels (>3.7 IU/mL) are very valuable in diagnosing pleural tuberculosis. Patients with pleural effusion due to hematologic neoplasms occasionally have levels slightly above the cutoff.

Clinical implications of appearance of pleural fluid at thoracentesis.

STUDY OBJECTIVES: The aims of this study were to describe the different appearances of pleural fluid during thoracentesis and their frequency in relation to diagnosis, and to evaluate the causes and clinical implications of bloody pleural effusions. SETTING: Tertiary care, university-affiliated hospital. SUBJECTS AND METHODS: Seven hundred fifteen patients with pleural effusion were prospectively assessed from December 1991 to December 1997. INTERVENTIONS: The appearance of the fluid was assessed in a glass assay tube containing 10 mL of pleural fluid. RESULTS: The most common presentations were serous and blood tinged, with 80% of the fluids fitting into one of these categories. The most frequent cause of watery fluid was transudate, although most transudates were classified as serous effusions. There were 59 bloody and 656 nonbloody pleural fluids. The most common cause of bloody pleural effusion (BPE) was malignancy (47%). Fluid with a bloody appearance slightly increased the probability of malignancy in our series (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.01 to 2.94; p = 0.04). Nevertheless, only 11% of the neoplastic effusions were BPE. Other common causes of BPE were posttraumatic (12%) or parapneumonic (10%) pleural effusions. Tuberculosis and transudates were uncommon causes of BPE. Fluid that was bloody in appearance decreased the probability for both diseases (OR, 0.15; 95% CI, 0.04 to 0.57; p = 0.003 and OR, 0.25; 95% CI, 0.06 to 0.95; p = 0.04, respectively). CONCLUSIONS: Serous and blood tinged were the most common presentations of pleural fluid at thoracentesis. Almost half of BPEs were secondary to neoplasms, but only 11% of the neoplastic effusions were BPEs. Other common causes of BPE were parapneumonic and posttraumatic.

Staging in lung cancer: is 3 cm a prognostic threshold in pathologic stage I non-small cell lung cancer? A multicenter study of 1,020 patients.

INTRODUCTION: Since 1974, a tumor size of 3 cm in diameter has been regarded as the prognostic threshold in the staging of bronchogenic carcinoma. OBJECTIVE: To study the prognostic behavior of surgical-pathologic tumor size in non-small cell lung cancer (NSCLC) with complete resection. DESIGN: Four-year multi-institutional prospective study from 1993 to 1997. PATIENTS: Consecutive cases of NSCLC in pathologic stages IA-IB (pIA-pIB) treated surgically with complete resection in hospitals belonging to the Bronchogenic Carcinoma Co-operative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S). METHODS: The Schoenfeld procedure was used to identify different prognostic groups, considering 1 cm as the measurement unit. RESULTS: Based on the 1,020 cases evaluated, four prognostic groups were identified: 0 to 2 cm (group A; n = 147), 2.1 to 4 cm (group B; n = 448), 4.1 to 7 cm (group C; n = 336), and > 7 cm (group D; n = 89). At 5 years, survival was 0.63 (95% confidence interval [CI], 0.58 to 0.68), 0.56 (95% CI, 0.53 to 0.59), 0.49 (95% CI, 0.46 to 0.52), and 0.38 (95% CI, 0.32 to 0.44) for groups A, B, C, and D, respectively. Differences between paired groups (log-rank) were significant: 0.0074 between groups A and B, 0.0048 between groups B and C, and 0.0034 between groups C and D. CONCLUSIONS: In initial stages (pIA-pIB) of NSCLC, the 3-cm value was not found to behave as a prognostic threshold; in this study, four surgical-pathologic tumor size groups were identified with strong prognostic differences: from 0 to 2 cm, from 2.1 to 4 cm, from 4.1 to 7 cm, and > 7 cm.

Amylase levels in pleural effusions: a consecutive unselected series of 841 patients.

STUDY OBJECTIVES: To describe the causes and relative frequency of amylase-rich pleural effusion (ARPE), and to study the origin and histologic type of the tumors with ARPE, the strength of the association between ARPE and the result of pleural cytology, and whether pleural amylase (PA) is a prognostic factor in the survival of patients with a malignant pleural effusion. SETTING: Tertiary-care, university-affiliated hospital. PATIENTS: Eight hundred forty-one consecutive patients with pleural effusion prospectively assessed from 1991 to 1999. RESULTS: There were 66 ARPEs: 40 neoplastic, and 26 benign with tuberculosis, pancreatitis, and liver cirrhosis as the most frequent causes. Thirty-six percent of patients in our series and 61% of patients with ARPE had a neoplastic disease (odds ratio [OR], 3; p < 0.001); this association got much stronger for cases with PA levels > or = 600 IU/L (95th percentile); [OR, 10; p < 0.001]. The most frequent tumor origin was lung cancer (13 cases). Adenocarcinoma was the most frequent histologic type (18 cases). Two mesothelioma effusions were ARPEs. There was a positive association between ARPE and the finding of tumor cells in pleural fluid (OR, 2.79; p < 0.01). In the malignant group, PA levels > or = 600 IU/L identified a group of patients with quite a short median survival (p = 0.016). CONCLUSIONS: The most common cause of ARPE was neoplasm. There was a positive association between ARPE and malignancy, stronger with the highest levels (95th percentile). Lung cancer and adenocarcinoma were the most common tumor and histologic type associated with ARPE. Mesothelioma may also produce ARPE. There was an association between ARPE and the finding of tumor cells in the pleural fluid. The highest PA levels identified a group of patients with a median shorter survival.

Comorbidity in operable lung cancer: a multicenter descriptive study on 2992 patients.

STUDY OBJECTIVES: To ascertain the frequency of diseases associated (comorbidity) with operable lung cancer (LC) globally, in relation to the presence of neoplastic clinical symptoms and age. DESIGN: Prospective; multi-institutional of 19 Spanish hospitals. PATIENTS: Two thousand nine hundred and ninety two consecutive cases of LC, treated surgically by the Bronchogenic Carcinoma Co-operative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S) between 1993 and 1997, are analysed. METHODS: At time of treatment, data on the presence or absence of different specific comorbidities in all consecutive patients operated on for LC were entered on identical forms at all hospitals of the GCCB-S. RESULTS: In 2189 patients (73%) there was one or several comorbidities (chronic obstructive pulmonary disease [COPD], systemic arterial hypertension, previous tumour, cardiac disease, peripheral vascular disease or diabetes). Fifty percent of the LC was associated to COPD; in 32% of these patients with COPD, preoperative measurement of FEV1 was 70% below the theoretical value. In comparing the cases with symptoms ascribable to LC, it was found that in asymptomatic patients the presence of a previous tumour, arterial hypertension or cardiac disease was significantly more frequent. Conversely, in symptomatic patients, COPD was significantly more frequent. The frequency of all evaluated comorbidities is significantly higher in the older age groups. CONCLUSIONS: In this multicenter study encompassing 2992 patients with operable LC, a high frequency of comorbidity has been found, COPD occurring most frequently. Certain diseases are more prevalent in asymptomatic patients, probably due to a screening bias. In older patients, there was a significant increase of all comorbidities.

Surgical lung cancer. Risk operative analysis.

STUDY OBJECTIVE: To identify those variables that are associated with operative morbidity or mortality in cases of thoracotomy in lung cancer. SETTING: Third level university hospital. PATIENTS: Consecutive patients with thoracotomy due to lung cancer operated on between 1994 and 1997 (n = 115). METHODS: Pre- and postoperative variables potentially associated with operative morbidity or mortality were retrieved prospectively as follows: demographic and clinical characteristics of the patients, cardiopulmonary function characteristics, tumour characteristics, and treatment characteristics. A bivariate analysis of all variables under evaluation was carried out in order to identify those variables associated with operative morbidity and mortality. A multivariable analysis of the selected variables was then conducted using a logistic model. RESULTS: The predicted postoperative product (predicted FEV1 x predicting diffusing capacity of carbon monoxide), the carbon monoxide diffusion coefficient (Kco) and the contralateral pulmonary perfusion are variables that relate to the overall morbidity or mortality (number of events 63, 55%) (-2 log likelihood chi2 = 22.9; R2 = 0.27). For variables associated with postoperative morbidity, the best associative model combines functional variables (diffusion, predicted FEV1), endoscopic variables (obstructed segments to be resected), clinical variables (comorbidity) and an important postoperative variable, the pathological tumoural staging (pN) (number of events 49, 43%) (-2 log likelihood chi2 = 32.9; R2 = 0.36). CONCLUSION: The numerous variables under analysis are poorly associated with morbidity or mortality after thoracotomy in lung cancer. With regard to postoperative morbidity, the best associative models combine information that is known pre- and postoperatively and which is provided by both the patient and the tumour.