The importance of sputum cytology in the diagnosis of lung cancer: a cost-effectiveness analysis

STUDY OBJECTIVE: To assess the potential health and cost effects of initial testing with sputum cytology to diagnose lung cancer. DESIGN: Cost-effectiveness analysis. DATA SOURCES: Surveillance Epidemiology and End Results (SEER) program; cost data from Northern California Kaiser Permanente Hospitals and Universities of Stanford and Iowa; National Center for Health Statistics; and a MEDLINE search. INTERVENTIONS: The use of sputum cytologies preceding other tests (ie, fine-needle aspiration, bronchoscopy, thoracoscopy) in patients with suspected lung cancer. MAIN OUTCOME MEASURES: Mortality associated with testing and initial surgical treatment (eg, performance of thoracoscopy to remove a local-stage, centrally located cancer), cost of testing and initial treatment, life expectancy, lifetime cost of medical care, and cost-effectiveness. RESULTS: In central lesions, sputum cytology as the first test was the dominant strategy because it both lowers medical-care costs ($2,516 per patient) and lowers the mortality risk (19 deaths in 100,000 patients) of the evaluation without adversely affecting long-term survival. In peripheral lesions, sputum cytology costs less then $25,000 per year of life saved if the pretest probability of cancer exceeds 50%. The estimated annual savings of adopting sputum cytology as the first test for diagnosing lung cancer in the United States is at least $30 million. CONCLUSIONS: Experience in regional centers indicates that sputum cytologic testing is infrequently ordered before implementing invasive diagnostic techniques, even in patients with central lung masses. The study findings suggest that sputum cytology as the first test in suspected lung cancer is likely to be cost saving without adversely affecting patient outcomes.     

Visual inspection of the uterine cervix after the application of acetic acid in the detection of cervical carcinoma and its precursors

BACKGROUND: Organized cervical cytology screening programs are not feasible in many developing countries where cervical carcinoma is an important cause of mortality among adult women. This study compared visual inspection of the cervix after application of 3-4% acetic acid (VIA, or cervicoscopy) with cytology as methods for the detection of cervical carcinoma and its precursors. METHODS: Three thousand women were examined by both VIA and cytology. Those positive on one or both of the screening tests (n = 423) or those who had clinically suspicious lesions even if the tests were negative (n = 215) were invited for colposcopy. Directed biopsies were obtained from 277 of 573 women at colposcopy. Those with moderate dysplasia or worse lesions diagnosed by histology were considered true-positives. Those with no lesions or with reactive or reparative changes at colposcopy and those for whom histology revealed no pathology, reactive or reparative changes, atypia, or mild dysplasia were considered false-positives. The detection rate of true-positive cases and the approximate specificity of the two tests were compared. RESULTS: VIA was positive in 298 women (9.8%), and cytology was positive (for atypia or worse lesions) in 307 women (10.2%). Of the 51 true-positive cases (20 cases of moderate dysplasia, 7 of severe dysplasia, 12 of carcinoma in situ, and 12 of invasive carcinoma), VIA detected 46 (90.1%) and cytology 44 (86.2%), yielding a sensitivity ratio of 1.05. VIA detected five lesions missed by cytology, and cytology detected three missed by VIA; both missed two lesions. The approximate specificities were 92.2% for VIA and 91.3% for cytology. The positive predictive value of VIA was 17.0%, and that of cytology was 17.2%. CONCLUSIONS: These results indicate that VIA and cytology had very similar performance in detecting moderate dysplasia or more severe lesions in this study. VIA merits further evaluation as a primary screening test in low-resource settings.     

Comparison of pregnancy outcome after intracytoplasmic sperm injection and in-vitro fertilization

BACKGROUND: The prognosis of patients with lung cancer is better when the diagnosis is made early; the disease is localized, and radical surgery is possible. Screening for lung cancer with mass radiography or sputum cytology should contribute to a more favorable prognosis. Large-scale screening studies have improved the survival rates for lung cancer but have yielded no reduction in mortality rates. METHODS: The histologic types, stages, treatments, and survival rates were studied in 93 men who were found to have lung cancer in a single chest radiograph screening of more than 33,000 men who smoked and were 50 to 69 years old ("screened cases"), and in 239 men of the same age range whose lung cancer was detected through ordinary health care system ("other cases") during the screening period. RESULTS: The distribution of the histology was similar in the two groups, but screening detected more instances of early-stage disease that were resectable more often than in the other group (37 vs 19%). The 5-year survival rate for men in the screened cases was 19%, and that of men in the other cases was 10% (relative risk, 0.65; 95% confidence interval [CI], 0.50 to 0.84). The survival rate of men in the screened cases remained significantly higher than that of men in the other cases even after adjustments for age, smoking status, histology, stage of the disease, and resectability of the disease (relative risk, 0.74; 95% CI, 0.55 to 1.00). CONCLUSIONS: According to this study, chest radiograph screening might improve the prognosis of lung cancer. Our results are, however, subject to many factors that were only partially controlled for, and they should be interpreted cautiously.     

Growth and development of twins compared with singletons at ages one and four years

To assess the relationship of smoking and coffee, tea, and alcohol intake to the risk of cancer of the exocrine pancreas, analyses were performed using data from a prospective cohort study of 33,976 postmenopausal Iowa women who responded to a mailed questionnaire in 1986 and were followed through 1994 for cancer incidence and total mortality. At baseline, information on cigarette smoking, consumption of tea, coffee, and alcoholic beverages, and other dietary and lifestyle factors was obtained. Age-adjusted relative risks of pancreatic cancer (n = 66 cases) showed a dose-response association with smoking. Those with fewer than 20 pack-years and those with 20 or more pack-years of smoking exposure were 1.14 (95% confidence interval, 0.53-2.45) and 1.92 (95% confidence interval, 1.12-2.30) times more likely, respectively, to develop pancreatic cancer than were nonsmokers. Current smokers were twice as likely as were nonsmokers to develop pancreatic cancer. Relative risks of pancreatic cancer increased with the amount of alcohol consumed (Ptrend = 0.11) after adjustment for age, smoking status, and pack-years of smoking. Relative risks of pancreatic cancer according to alcoholic beverage intake were as strong among never-smokers as they were in the total cohort. After the data were adjusted for age, smoking status, and pack-years of smoking, there was a statistically significant 2-fold (95% confidence interval, 1.08-4.30) elevated risk of pancreatic cancer for those who drank > 17.5 cups of coffee per week, compared to those who consumed < 7 cups/week; among never-smokers, the relative risks across coffee intake categories were still positive but were attenuated somewhat (P trend = 0.17). Tea intake was not related to cancer incidence. In summary, these findings provide evidence of an association of both alcoholic beverage and coffee consumption with pancreatic cancer incidence that is independent of age and cigarette smoking.     

Lung cancer and chronic obstructive pulmonary disease

Spirometry can predict lung health and monitor disease and response to therapy. This noninvasive test can and should be done regularly by primary care providers. It can identify patients at risk for lung cancer as well as heart attack and stroke. Patients with abnormal spirometric findings can be warned that airflow obstruction has begun, which may provide the motivation to quit smoking. Abnormal spirometry measurements correlate with all-cause mortality. Approaches to early diagnosis of lung cancer continue to expand. For example, use of the new fluorescent bronchoscope can increase diagnostic accuracy in lung cancer by highlighting lesions that are malignant or likely to be malignant. For now, however, identification of airflow obstruction with spirometry and follow-up with sputum cytology provide the widest benefit.     

Endoscopic screening for dysplasia and mucosal aneuploidy in adolescents and young adults with childhood onset colitis

OBJECTIVES: In adults, the premalignant nature of ulcerative colitis (UC) has long been accepted. Currently there is increasing concern that Crohn's disease (CD) may be equally premalignant. As a consequence, most adults with long-standing UC and many with chronic CD are enrolled in ongoing endoscopic cancer surveillance programs. In contrast, the risk of colonic cancer in adolescents and young adults with either form of colitis is less well recognized, and the need for dysplasia and cancer screening in this population has not been systematically evaluated. We therefore report the prospective results of colonoscopic cancer screening in such a young population. METHODS: Thirty-five adolescents and young adults with long-standing colitis (18 UC, 17 CD; 21 +/- 3 yr old, 11 +/- 3 yr colitis duration) underwent colonoscopic cancer screening. All had multiple biopsies for flow cytometry and light microscopy. RESULTS: Seven subjects had aneuploidy (3/18 UC, 4/17 CD). Of these seven, only two had dysplasia [one high grade (UC), one low grade (CD)]. One additional subject had indefinite dysplasia with normal flow cytometry. The remaining 27 subjects had both normal flow cytometry and light microscopy. Five of the seven aneuploid subjects underwent surgery within 1 yr of screening. Four, including both subjects with dysplasia, had no evidence of colon cancer at surgery. However, a 24-yr-old female with a 14-yr history of UC and no evidence of dysplasia or cancer at screening had a Dukes C adenocarcinoma. CONCLUSIONS: Adolescents and young adults with childhood onset UC or CD are at risk for aneuploidy, dysplasia, and colon cancer. Aneuploidy can be evident 10 yr after the onset of colitis and in patients as young as 16 yr of age. Therefore, the risk for colon cancer in patients with childhood onset colitis must be based on the duration of the illness, not on their chronological age. Incorporation of flow cytometry into an endoscopic screening protocol appears to enhance the ability to identify individuals at highest risk for colon cancer.     

Premalignant lesions of the vocal cords. A retrospective study of 62 cases treated with CO2 laser

A series of 62 patients treated by (repeated) CO2 laser excision and/or vaporization for premalignant lesions of the vocal cords was analysed retrospectively. Of the 54 patients available for follow-up (ranging from 1 to 15 years), five patients (9%) developed an invasive glottic carcinoma and needed radiotherapy. Only two patients (4%) needed extensive surgery (total laryngectomy). One patient (2%) died of a recurrent carcinoma despite radiotherapy and laryngectomy, and six patients (11%) died of a metachronic lung carcinoma. The therapeutic results of (repeated) laser therapy were comparable to those in other reports regarding radiotherapy or stripping. The subjective functional results were satisfactory and tended to improve along with refinement of laser surgery techniques. Follow-up of patients who once had a premalignant laryngeal lesion is mandatory ad vitam, regardless of the grade of the lesion. For the screening of lung cancer, there is still no consensus on a standard-of-care. The classical chest X-ray remains the most accessible and comfortable screening procedure.     

Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance

BACKGROUND: Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and vitamin A. PURPOSE: We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. METHODS: A total of 29,133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests. RESULTS: No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (> or = 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24). CONCLUSIONS: Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke. beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake. IMPLICATIONS: While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation.     

Glutathione S-transferase mu1 and N-acetyltransferase 2 genetic polymorphisms and exposure to tobacco smoke in nonsmoking and smoking lung cancer patients and population controls

We conducted a case-control study to assess the risk of lung cancer in relation to genetic polymorphisms of the detoxifying enzymes glutathione-S-transferase mu1 (GSTM1) and N-acetyl transferase 2 (NAT2), focusing on never-smokers, women, and older people. The study base consisted of persons > or =30 years of age in Stockholm County from 1992 to 1995. We recruited never-smoking lung cancer cases and a sex- and age-matched sample of ever-smoking cases at the three county hospitals mainly responsible for diagnosing and treating lung cancer. A total of 185 cases (25.4% men; 47.6% never-smokers) and 164 frequency-matched population controls (28.7% men; 48.2% never-smokers) supplied blood for genotyping. Detailed information was collected by interview on active and passive smoking, occupations, residences, and diet. The overall odds ratio (OR) for lung cancer associated with the GSTM1 null (GSTM1-) versus GSTM1+ genotype was 0.8 [95% confidence interval (CI), 0.5-1.2], with an OR close to unity among smokers, and lower ORs suggested among never-smokers. For NAT2 slow versus rapid acetylator genotypes, the OR was 1.0 (95% CI, 0.6-1.5) overall, which broke down into an increased risk for slow acetylators among never-smokers but an increased risk for rapid acetylators among smokers. Among never-smokers, a gene interaction was suggested, with combined slow acetylator and GSTM1+ genotype conferring particularly high risk (OR = 3.1; 95% CI, 1.1-8.6), but no clear pattern emerged among smokers. A detailed analysis among smokers showed no interaction between pack-years of smoking and the GSTM1 genotype but suggested a steeper increase in risk with increasing pack-years of smoking exposure for rapid than for slow acetylators. Our results do not support a major role for the GSTM1 genetic polymorphism as a risk factor for lung cancer among smokers or nonsmokers. There was, however, some suggestion that the slow acetylator genotype may confer an increased risk among never-smokers and that the rapid acetylator genotype interacts with pack-year dose to produce a steeper risk gradient among smokers.     

The Jewish physician in the post Columbus era: the 15th century Spanish inquisition and expulsion revisited in 20th century Germany and Austria

Lung cancer is the cancer with the largest mortality in Belgium. Nowadays, the most potent risk factor for lung cancer, tobacco smoking, is increasing, principally in teenagers. It is therefore necessary to intervene more efficiently in the natural history of the disease. This aim can be achieve by the early detection and the local treatment of small size lung cancer and in situ carcinoma. Interestingly, pulmonary preneoplastic lung lesions have been identified and characterized in the central airways as well as in the peripheral lung parenchyma. These preneoplastic lesions can evolve to invasive cancer or regress after tobacco smoking cessation or chemoprevention treatment. A new autofluorescence based endoscopy technique is described, that allows to detect preneoplastic pulmonary lesions and radio-occult lung cancer. These small sized lesions can be cured with endoscopic local treatment such as photodynamic therapy.     

Preliminary results of fine needle aspiration biopsy histology in upper gastrointestinal submucosal tumors

To elucidate the characteristics of lung cancer complicated by pneumoconiosis, we compared the clinical features of complicated and uncomplicated lung cancer cases. The average age at onset was higher for patients with pneumoconiosis than for those without. Because pneumoconiosis presents various respiratory symptoms, subjective symptoms were less important than objective symptoms in detecting lung cancer complicated by pneumoconiosis. Although fiberoptic bronchoscopy was the predominant diagnostic method, it could not be used with the pneumoconiosis patients. Diagnoses of lung cancer complicated by pneumoconiosis were made more after by percutaneous needle aspiration cytology. Squamous cell carcinoma is the most frequent form of cancer in patients with pneumoconiosis, which suggests that the inhalation of carcinogens may play a role in the pathogenesis of lung cancer. With respect to the smoking index (SI), histological specimens indicated that the incidence of squamous cell carcinoma in patients with pneumoconiosis was significantly higher in heavy smokers (SI > or = 600) than in light smokers (SI < 600) or nonsmokers. It is suspected that smoking affects carcinogenesis of pneumoconiosis. No differences in the distribution of lung cancer (right-left, hilar-peripheral) distinguished the 2 groups. Many of the patients with peripheral-type lung cancer and pneumoconiosis had tumors in the lower lung lobes. These findings underline the importance of encouraging pneumoconiosis patients to avoid lung cancer by not smoking, and to have lung cancer detected in its early stages by undergoing regular medical exams.     

Three cases of pulmonary embolism incorrectly diagnosed as lung cancer

Pulmonary embolism is commonly misdiagnosed as lung cancer, since sputum cytological tests often show atypical or malignant cells. We report three operated cases of pulmonary embolism incorrectly diagnosed as lung cancer. The first patient is a 39-year-old male with chest pain an bloody sputum. Chest x-ray revealed abnormal shadows and subsequent sputum cytological tests identified malignant cells. The second patient is a 63-year-old male with the same diagnostic pattern as the first case. The third patient is a 72-year-old male whose routine chest x-ray showed an abnormal shadow; malignant cells were identified by cytological tests on transbronchial fiberscope brushings. These three patients were histopathologically diagnosed as suffering pulmonary embolism by wedge resection under thoracotomy. When a patient has chest pain or bloody sputum with showing temporarily malignant cells on cytology, the possibility of pulmonary embolism should be taken into consideration.     

Increased epidermal growth factor receptor expression in metaplastic bronchial epithelium

Epidermal growth factor receptor (EGFr) is expressed in human bronchial epithelial cells, and non-small cell lung cancers express increased EGFr. Squamous metaplasia of the bronchial epithelium occurs in chronic smokers and is considered an early premalignant change. In this study, EGFr expression was examined in biopsies of histologically normal and metaplastic bronchial tissues obtained from 69 smokers who were enrolled in a randomized placebo-controlled chemoprevention trial. This trial tested the effects of 6 months of treatment with 13-cis retinoic acid (13cRA) on bronchial metaplasia. EGFr expression was examined as a marker of bronchial metaplasia and response to 13cRA treatment. In bronchial biopsies obtained from patients in this study, EGFr expression was higher in metaplastic biopsies than in normal biopsies (P = 0.02). Smoking cessation during treatment correlated with reduced metaplasia (P < 0.001) and EGFr expression (P = 0.02), but multivariate analysis suggested that this effect of smoking cessation on EGFr expression was dependent upon reversal of bronchial metaplasia. 13cRA treatment did not alter EGFr expression (P = 0.23). Baseline EGFr expression levels in metaplastic biopsies did not predict metaplasia reversal. This study demonstrated that increased EGFr expression is a biomarker of bronchial metaplasia, but it did not support the hypothesis that EGFr is a biomarker of retinoid response in lung cancer chemoprevention trials.     

Detection of K-ras point mutations in sputum from patients with adenocarcinoma of the lung by point-EXACCT

PURPOSE: Kirsten ras (K-ras) point mutations are found in 30% to 56% of pulmonary adenocarcinomas by means of highly sensitive techniques. Recently, the Point-EXACCT (point mutation detection using exonuclease amplification coupled capture technique) method was described, which detected one cell with a mutation in 15,000 normal cells. The aim of this study was to examine whether K-ras point mutations could be found with this rapid method in the sputum of patients with adenocarcinoma of the lung. PATIENTS AND METHODS: DNA from paraffin-embedded adenocarcinoma and corresponding sputum samples were analyzed for mutations of the K-ras gene. Twenty-eight biopsy specimens and 54 sputum samples of 22 patients were used for amplification and K-ras codon 12 point mutation detection. RESULTS: In 11 of 22 patients (50%), a mutation in K-ras codon 12 was shown in the tumor sample. In five of 11 patients (45%) with a K-ras mutation in the tumor, the same type of mutation was identified in at least one sputum sample. A mutation could not be detected in any of the sputum samples from patients with a K-ras-negative tumor. Time between K-ras point mutation detection in sputum and clinical diagnosis of lung cancer varied from 1 month to almost 4 years. In two of the five patients with K-ras-positive sputum specimens, malignant cells were found with cytologic examination. CONCLUSION: Point-EXACCT is suitable for the detection of K-ras point mutations in sputum samples of patients with adenocarcinoma of the lung. This approach may be an important adjunct to cytology in the early diagnosis of lung cancer.     

Immunoglobulin-complexed aspartate aminotransferase

We reviewed our experience with 9,726 cases of fine-needle aspiration cytology of the breast that were done from January 1983 to February 1992. During our review, we found that 214 aspirates had been submitted from pregnant and lactating women for the investigation of breast mass(es). Despite a variable clinical presentation and spectrum of cytologic findings, we considered the application of aspiration cytology in these women as useful as in the nonpregnant-nonlactating women for management decision. A team approach between the clinician and cytopathologist was always maintained; with this approach, the false-positive or -negative diagnoses were reduced to almost nil. In all cases in which the cytodiagnosis of carcinoma of breast was made, the findings corresponded with subsequent cell blocks from the aspirate and tissue examination. Benign lesions were diagnosed cytologically with minimal difficulty, and all aspirates that were less than optimal for cytodiagnosis were repeated to minimize the chance of missing an abnormality. All the benign lesions were followed throughout pregnancy, postpartum, and thereafter; if the mass persisted, the aspiration was repeated. With this protocol of follow-up, the need for a customary liberal surgical biopsy was reduced to a minimum.     

p34cdc2 expression and meiotic competence in growing goat oocytes

Proper control of environmental factors can be crucial to the identification of genes that influence susceptibility to a complex trait, especially for a trait such as lung cancer, for which the environmental factor (smoking) accounts for a significant etiologic fraction of the disease. An earlier segregation analysis of 337 Louisiana families, which incorporated direct measure of tobacco consumption, provided evidence for autosomal codominant inheritance of a major gene that influenced age at onset of lung cancer. Subsequent analyses were performed in which the families were stratified into two subsets based on birth cohort of the proband; results suggested the presence of heterogeneity that were postulated to reflect the influence of cohort trends in tobacco consumption. To evaluate this hypothesis further, we simulated a population of three-generation pedigrees in which an autosomal dominant mode of susceptibility to lung cancer was transmitted, but tobacco use varied across generations corresponding to published trends in smoking. A total of 200,000 individuals in families of various sizes, ages, and cigarette smoking habits were simulated from 1900 to 1980. From this population, 324 families (2,405 individuals) with 380 cases of lung cancer were ascertained through 328 lung cancer probands. Complex segregation analysis was performed using the REGTL program of S.A.G.E. in which pack-years of tobacco exposure were incorporated directly into the likelihood calculations. Although the no major gene, environmental, and Mendelian recessive hypotheses were rejected, both dominant and codominant transmission provided a good fit to the data. Thus in a population of simulated families with autosomal dominant susceptibility to lung cancer, intergenerational differences in tobacco consumption led to the detection of autosomal codominant transmission as an acceptable hypothesis. These results underscore the potential danger of segregation analysis of complex traits in which exposure to known environmental influences may differ across generations.     

Cytomorphometric markers for uterine cancer in intermediate cells

Precise microphotometric assessment of intermediate cells from patients with normal cervical cytology and from patients with dysplasia or carcinoma in situ shows the existence of small but consistent differences. Marker features for the presence of premalignant and malignant disease can be extracted from the cell images of "normal"-appearing intermediate cells. The marker features and their diagnostic classification potential are described.     

Cytological studies in pulmonary pathology

Cytological investigations of the bronchial secretion and sputum in particular have acquired in recent years a great practical significance in pulmonary pathology. It is recommended to use cytodiagnosis along with prophylactic X-ray examinations of the population to detect pulmonary pathology, in particular among individuals with a higher risk of developing cancer. A substantiated opinion is put forward that cytodiagnosis should precede examinations of patients with clinico-roentgenologically confirmed changes in the lungs.     

Preclinical drug development paradigms for chemopreventives

Preclinical screening studies and animal efficacy testing models currently are used by the National Cancer Institute's chemoprevention drug discovery program to assess and identify chemical agents and natural products that may have the potential to prevent human cancer. Identification of potential cancer preventing agents begins by subjecting each compound to a sequential series of short-term, in vitro prescreens of mechanistic, biochemical assays to provide quantitative data to help establish an early indication of chemopreventive efficacy and to assist in prioritizing agents for further evaluation in longer-term, in vitro transformation bioassays and whole animal models. Promising chemical agents or combinations of agents that work through different inhibitory mechanisms subsequently are tested in well-established, chemically induced, animal tumor models, which include models of the lung, bladder, mammaries, prostate, and skin. These preclinical bioassays afford a strategic framework for evaluating agents according to defined criteria, and not only provide evidence of agent efficacy, but also serve to generate valuable dose-response, toxicity, and pharmacokinetic data required prior to phase I clinical safety testing. Based on preclinical efficacy and toxicity screening studies, only the most successful agents considered to have potential as human chemopreventives progress into clinical chemoprevention trials.