17p13 (p53 locus), 5q21 (APC locus) and 9p21 (p16 locus) allelic deletions are frequently found in oral exfoliative cytology cells from smoker patients with non-small-cell lung cancer.

Molecular cytogenetic and LOH analyses of non-small cell lung cancer (NSCLC) have shown frequent allelic deletions in a variety of chromosomes where tumour suppressor genes are located. Allelic loss at 9p21 (p16 locus), 17p13 (p53) and 5q21(APC) has been frequently described in NSCLC and has also been described in premalignant epithelial lesions of the bronchus and normal bronchial cells. These findings suggest that a tissue field of somatic genetic alterations precedes the histopathological phenotypic changes of carcinoma. Similar changes have been described in oral and laryngeal epithelial tumours associated with smoke exposure. We previously reported frequent LOH at 5q21, 9p21 and TP53 in tumor cells and peritumoral normal bronchial cells from surgically resected NSCLC. We now analyze 96 cases of normal oral exfoliative cytology in which normal epithelial cells were obtained: 43 cases from smoker patients with NSCLC diagnosis, 33 smoker patients with no evidence of malignancy and 20 non-smoker patients with no evidence of tumour. All groups had a similar age and sex distribution. PCR amplification was performed utilising the specific markers D5S346, D9S157 and TP53. In normal oral mucosae cells from patients with NSCLC, we found that 21% of the informative cases showed LOH at any of the three analyzed loci distributed as follows: 14.3% of the informative cases showed LOH at 5q21, 7.7% at 9p21 and 22.2% at TP53. Within the smoker risk group only one case (4% of the informative cases) showed LOH at TP53, while no LOH was found at 5q21 or 9p21. No LOH was found in non-smokers. In conclusion, our results show that a significant number of patients with NSCLC have LOH at TP53, 5q21 and 9p21 in normal oral mucosae, while LOH at these loci is unusual in similar cells obtained from patients with no evidence of malignancy. Our study demonstrates that LOH studies can detect smoker patients with a mutated genotype in normal epithelial cells. Further prospective studies may confirm whether LOH studies can detect patients with a higher risk of NSCLC.

How to express tumor markers in bronchoalveolar lavage.

INTRODUCTION: Bronchoalveolar lavage (BAL) is a fundamental technique in the diagnosis of different respiratory diseases including lung cancer. Tumor marker values can be determined in the BAL fluid, but controversy still exists about how to express the results. OBJECTIVE: The aim of this study was to determine the best method of expressing tumor markers in BAL, either referring to total proteins or volume of fluid recovered. PATIENTS AND METHODS: A prospective, randomized, non-blind study was carried out. Seventy-six patients (72 men and 4 women) diagnosed with lung cancer and 17 subjects without respiratory disease were included. BAL was performed in all patients and the fluid retrieved was divided into two fractions: a bronchiolar fraction (F0) and an alveolar fraction (F1). Five tumor markers: cytokeratin fragment 19 (CYFRA 21-1), squamous cell carcinoma antigen (SCC), tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and neuron-specific enolase (NSE) as well as total protein were measured in both fractions. The concentrations were expressed in relation to the volume of BAL fluid recovered (ng or mU/mL) and in milligrams of total protein of lavage fluid (ng or mU/mg TP). The SPSS 11.01 software was used for statistical analysis. Mann-Whitney U test and ROC curves were developed when significant differences were found. RESULTS: We found significant differences in the CYFRA 21-1 values in the two BAL fractions and in both ways of expressing its concentration; in SCC in F1 expressed in ng/mg TP; in TPA in F0 expressed in mU/mg TP; in TPS in both fractions expressed in mU/mg TP, and in NSE in both fractions in ng/mg TP. The markers that best differentiated tumors from controls (ROC curves) were CYFRA 21-1 in F0 and NSE in both fractions in ng/mg TP. CONCLUSIONS: Our study demonstrates that the concentrations of tumor markers in BAL expressed in relation to total protein were more effective than if expressed in mL of BAL fluid collected.

[Diagnostic accuracy of semiquantitative analysis of positron emission tomography in radiologically indeterminate lung lesions]. / Exactitud diagnóstica del análisis semicuantitativo de la tomografía por emisión de positrones en lesiones pulmonares radiológicamente indeterminadas.

OBJECTIVE: The objective of this work was to assess the Standardized Uptake Value (SUV) in the differential diagnosis of radiologically indeterminate lung lesions by means of ROC curves. MATERIAL AND METHOD: Forty seven patients were studied by Positron Emission Tomography with 18-fluorine-2-desoxy-D-glucose (FDG PET) analyzing the value of maximum SUV. The patients were classified into three groups. Group 1 = patients without previous neoplasia (WPN) + patients with previous neoplasia (PN). Group 2 = WPN. Group 3 = PN. RESULTS: The ROC curves showed a high diagnostic accuracy in the three groups, with area under the curve (AUC) values of 0.96, 0.98 and 0.91 respectively. The typical error was 0.03, 0.02 and 0.08. The maximum SUV cutoffs with the best diagnostic accuracy for the three groups were: 2.6; 3 and 2.4, with an accuracy (A) of 93.6%, 97% and 92.3%, respectively. Analyzing all the patients globally (group 1), we obtained one false positive result in a patient with hamartoma (max SUV = 2.8) and two false negative results in one patient with lung metastases from malignant fibrohistiocytoma (max SUV = 0.7) and in another patient with lung metastases from unknown origin adenocarcinoma (max SUV = 1.9). CONCLUSIONS: FDG PET permits differentiation with a very high diagnostic accuracy of benign and malignant lung lesions using the maximum SUV. The differences observed between the different groups are due to the different disease prevalence, obtaining a lower negative predictive value of max SUV in patients with previous neoplasia.

Defective natural killer and phagocytic activities in chronic obstructive pulmonary disease are restored by glycophosphopeptical (inmunoferón).

We have investigated both modifications in natural (innate) immunity caused by chronic obstructive pulmonary disease (COPD) and the effects of a glycophosphopeptical immunomodulator (Inmunoferón) treatment on COPD-associated immunoalterations. In a double-blinded clinical trial, 60 patients with COPD received glycophosphopeptical or placebo during 90 consecutive days at oral doses of 3 g/d. Fifty-six sex- and age-matched healthy control subjects were included as a reference group for immunologic parameters. Peripheral blood natural killer (PBNK) cell cytotoxic activity and phagocytic activity of peripheral monocytes/macrophages (Mo/Ma) and polymorphonuclear (PMN) cells were assessed at baseline and then again at the end of treatments. We found both PBNK activity and phagocytic activity to be significantly decreased in patients with COPD compared with levels in healthy volunteers. The treatment with glycophosphopeptical provoked significant stimulatory effects on PBNK cytotoxic activity. This stimulation was not mediated by an increase in CD3(-)CD56(+) NK cells. Further, glycophosphopeptical significantly increased the percentage of monocytes and PMNs that phagocytize Escherichia coli in vitro, as well as increased phagocytic indices. We conclude that peripheral blood cells of patients with COPD show clear defects in natural immunity that are partially rescued by glycophosphopeptical.

An evaluation of tissue polypeptide antigen (TPA) in the two bronchoalveolar lavage fractions of lung cancer patients.

BACKGROUND: It has been proven that cytokeratins (CKs) are useful tumor markers for the follow-up, treatment monitoring and prognosis evaluation of lung cancer and among these, tissue polypeptide antigen (TPA) plays an important role. Nevertheless, only a small number of studies have been reported about their diagnostic capacity. Bronchoalveolar lavage (BAL) can be divided into two fractions: bronchiolar (BF) and alveolar (AF). For the above reasons, our aims were (1) to analyze the diagnostic usefulness of TPA in the BAL of lung cancer patients and (2) to observe if, in lung cancer patients, TPA levels in the two BAL fractions are different. This should mean that the study of tumor markers in the BAL should be carried out in both fractions to increase their diagnostic capacity. METHODS: We studied 289 BALs divided into two phases. In phase I, TPA was analyzed in the BAL of six groups of subjects (healthy persons, chronic bronchitis, asthma, respiratory infections, diffuse interstitial pulmonary diseases and lung cancer). In phase II, TPA was studied in both BAL fractions of a group of patients with lung cancer. RESULTS: We observed that TPA levels were significantly higher in the BAL of patients with bronchogenic neoplasias. In these patients, TPA was increased in the BF of the lavage in relation to the AF. In smoker patients with pulmonary carcinomas, TPA was higher in the AF of the BAL than in the lavage of non-smokers. This did not occur in the BF. We found no relation between the TPA concentrations and cancer histology. CONCLUSIONS: We believe that TPA is a useful tumor marker with diagnostic capacity and this capacity is increased when it is studied in the two BAL fractions. Smoking habit may play a role in the secretion of tumor markers by the tumor cells.

[Cytologic and biochemical component in 203 bronchoalveolar lavages. Reference values]. / El componente citológico y bioquímico en 203 lavados broncoalveolares. Valores de referencia.

The bronchoalveolar lavage (BAL) is considered a basic technique as a diagnostic aid in Pneumology. However, one of the main problems faced by the clinician is the lack of standardization of the technique. This has been resolved through the drafting of international standards. The other problem is the lack of what might be called a "reference" BAL. In order to establish a reference BAL, we analyzed 203 BAL divided in two groups: a control group and a pathologic group, make up by extrinsic asthma, intrinsic asthma, pulmonary infections, diffuse interstitial pneumopathies, bronchopulmonary tumors and chronic bronchitis. We have studied both the cytologic and the biochemical component of the BAL. Among the biochemical markers, we have considered; carcinoembrionary antigen (CEA), tissular polypeptidic antigen (TPA), neuronal specific enolase (NSE), ferritin (FER), calcitonin (CT), ACTH, histamin (HIS) and prostaglandin (PGE2). In order to establish the reference values, we have used the modified Baye's theorema. The BAL that we obtained was the following: volume 20 ml, cells 35 x 10(5) cells/ml, macrophages 77%, lymphocytes 22%, neutrophils 4%, eosinophils 2%, CEA 14 ng/mg, TPA 84 U/g PT, NSE 5 ng/mg PT, FER 42 ng/mg PT, CT 15 pg/mg PT, ACTH 51 pg/mg PT, HIS 1.22 ng/mg PT, PGE2 35 pg/mg PT.

Carcinoembryonic antigen in the diagnosis of lung-cancer using bronchoalveolar lavage - a comparative-study with healthy-subjects, chronic-bronchitis, respiratory-infections and interstitial pulmonary-diseases.

The use of serum CEA values in the prognosis and in monitoring the course of lung cancer is well accepted. However, the main problem presented by using serum CEA determinations for diagnosis is the lack of sensitivity. In this study, sensitivity was increased by determining CEA using bronchoalveolar lavage (BAL) of the affected lung. We studied CEA in the BAL of healthy subjects and patients with chronic bronchitis, respiratory infections and interstitial pulmonary diseases to observe if CEA could differentiate malignancies from benign pulmonary pathologies. Five groups of patients (previously described) were studied using BAL in the affected area of the patients with lung pathologies or in the middle lobe and lingula of healthy people. CEA was analyzed in the BAL using radioimmunoanalysis according to the Behring Institute recommendations. CEA levels in BAL of lung cancer patients were higher than in the other groups. No correlation was found between CEA concentrations in BAL and tumor histology. CEA studies in BAL may be useful in the diagnosis of lung cancer and in the screening of the high risk people to develop bronchial carcinoma.

Total pulmonary torsion without vascular compromise--a case report.

A new case of pulmonary torsion is reported. Only 15 cases of this rare entity have been published in the literature, all of them either surgically treated short term or resulting in death. Small right-side pneumothorax following diagnostic transthoracic puncture seemed to be the mechanism of production. Because of the absence of acute clinical manifestations, fibroscopy, isotopic perfusion scanning, and hemodynamic and pulmonary angiographic studies were done. The lack of compromise in the pulmonary flow and venous pulmonary return explains the surprisingly good progress (ten months, at present) of the patient.