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Background: Lung cancer is the leading cause of cancer deaths in the United States. A long-standing goal of cancer researchers has been to develop tests that would facilitate earlier diagnosis and treatment of lung cancer and thereby decrease mortality from this disease. Because cancer results from the accumulation of a variety of genetic events (e.g., mutations, rearrangements, and deletions) in genes controlling cell growth and differentiation, these changes might serve as diagnostically useful molecular markers. Activation of the K-ras oncogene by point mutations in codon 12, which occurs in many cases of lung adenocarcinoma, may serve as one such clinically useful molecular marker. For detection of K-ras point mutations in bronchoalveolar lavage fluid, in which small numbers of malignant cells are mixed with a population of predominantly genetically normal cells, the sensitivity of commonly used assays for ras mutations risks false-negative results. Purpose: By applying a highly sensitive assay, we investigated whether detection of K-ras codon 12 mutations in samples of bronchoalveolar lavage fluid could be clinically useful in diagnosing lung cancer. Methods: We developed a highly sensitive assay for detecting K-ras codon 12 mutations based on an enriched polymerase chain reaction (PCR) technique. This technique was applied to 87 specimens of bronchoalveolar lavage fluid specimens that were obtained from 86 patients, and associated tumor biopsy specimens obtained from 35 of these patients who underwent diagnostic bronchoscopy for clinically suspected lung cancer. Lavage fluid specimens were also obtained from nine patients undergoing nondiagnostic bronchoscopy. Statistical comparisons were performed by using the two-tailed Fisher's exact test. Results: Of 52 patients with confirmed lung cancer, samples of bronchoalveolar lavage fluid from 16 patients contained K-ras codon 12 mutations, including 14 (56%) of 25 patients with lung adenocarcinomas, one (33%) of three with bronchoalveolar carcinomas, one (20%) of five with large-cell carcinomas, and none of the 14 with squamous cell carcinomas. Mutations were detected in four additional cases in which cancer was suspected but had not been histologically confirmed. Tissue samples from 35 of the patients all yielded the identical K-ras codon 12 genotype found in the corresponding samples of bronchoalveolar lavage fluid. No mutation was found in any sample from 30 patients with diagnoses other than non-small-cell lung cancer. Thus, for those cases in which tissue was available and tested, the sensitivity and specificity of detecting K-ras mutations in bronchoalveolar lavage fluid for diagnosing K-ras mutation-positive lung cancer were both 100%. For nine patients, K-ras mutations were detected in bronchoalveolar lavage fluid obtained during otherwise nondiagnostic bronchoscopies. Conclusions: Our data demonstrate that sensitive detection of K-ras codon 12 mutations can serve as an important adjunct to cytology in the diagnosis of lung cancer. Implications: Detection of these mutations could lead to earlier cancer diagnosis and less need for invasive diagnostic procedures.

Objectives: The purpose of the study was to describe demographic and clinical characteristics of patients at the only long-term care facility for homeless men with tuberculosis in New York City, and to evaluate the outcome of a directly observed therapy program for these men. Methods: The study population included residents at the 'tuberculosis unit' for men in the New York City municipal shelter system. A cross-sectional survey described the characteristics of 76 men in the unit during November 1991. A retrospective cohort study evaluated 104 consecutive admissions to the facility from October 1, 1990, through March 30, 1991, and determined the outcome of directly observed therapy. Results: Cross-sectional survey (n=76). The median age was 43 years (range, 25 to 60 years); 67 patients (88%) had pulmonary tuberculosis. Among 58 isolates of Mycobactarium tuberculosis, eight were resistant to one drug (14%) and an additional nine were resistant to at least two drugs (16%). A history of previous treatment was associated with an odds ratio of 5.1 for having multiple drug-resistant tuberculosis (exact 95% confidence interval, 0.8 to 53.5). Retrospective cohort (n=104). Excluding 21 men whose care was transferred to other agencies or institutions, 39 (47%) of 83 subjects completed or were still receiving treatment after 12 months and 44 (53%) of 83 subjects failed to complete the program. Conclusions: As expected, previous treatment for tuberculosis among homeless men is associated with an increased risk of having multiple-drug resistance. A directly observed therapy program successfully treated less than half of the enrolled subjects. Increased efforts are needed to control the spread of tuberculosis among homeless individuals. (Arch Intern Med. 1994;154:2069-2073)