Bronchial Squamous Metaplasia Research Articles

Abstract PL01-02: Smoking, molecular markers, and the risk of second cancers in cancer patients

Abstract Chemoprevention entails the reversal, prevention, abrogation or delay of carcinogenic progression to cancer (1). A number of successful trials have been conducted in the reversal of premalignancy in breast (2,3), prostate (4,5), and colorectal (6,7) cancer. In tobacco-related cancers, compelling evidence has suggested that ongoing tobacco smoking is able to prevent the reversal of premalignant lesions (8-10). The first such evidence was demonstrated by Lee et al. who noted that only those patients who ceased smoking saw meaningful improvement in their premalignancy in a randomized trial of 13-cis-retinoic acid in reversal of premalignancy (11). This built on the seminal work by Hong et al. who were able to show that high doses of vitamin A derivatives, specifically, 13-cis-retinoic acid, were able to reverse premalignancy in head and neck cancer (12), and perhaps more importantly, prevent or delay the development of second primary tumors while patients were on high dose 13-cis-retinoic acid (13). Unfortunately, the vast majority of patients on high dose 13-CRA or isotretinoin failed to tolerate this dose and required dose reduction or dose interruption (12,13). Subsequent randomized trials of 13-CRA in prevention of second primary tumors of the lung (14) and head and neck failed (15) to show the same promise as the higher dose, but one message was clearly consistent. Those patients who stopped smoking had considerably lower rates of second primary tumors and a trend toward a lower rate of primary lung or head and neck tumor recurrence (14, 15). Similar data emerged from the selenium trial, where the agent itself was ineffective in preventing second primary tumors of the lung, but those patients who were able to cease smoking had consistently lower rates of development of second primary tumors (16). A series of recent studies have indicated that genomic testing of patients on the 13-CRA head and neck second primary tumor prevention trial can select those patients who appear to derive the greatest benefit from chemopreventive approaches with natural compounds and their derivatives (17,18). These data suggest that patients with activation of the PI3-kinase/mTOR pathway are more likely to develop second primary cancers (18), consistent with data implicating this pathway demonstrated by Spira et al (19). Similarly, the Retinoid Head and Neck Second Primary Prevention Trial has shown data that certain patient populations on the head and neck second primary trial were more likely to benefit than others, based on genomic background, and that of their tumor (17,18). Thus, a strategy emerges whereby specific molecular markers, which are likely to predict benefit from second primary tumors, will be used to select future populations who are placed on chemopreventive approaches (20). However, one lesson must remain clear, and it must impact the future of all chemoprevention trials. Since smoking cessation, generally initiated by the patient, was the single most important factor in reducing secondary primary tumor risk, on these trials (14, 15, 21), all future such trials will require active smoking cessation efforts in these patient populations in order to achieve effective and active chemoprevention approaches. Such trials are planned and are necessary to undertake. The next generation of chemoprevention trials will involve CT screening studies, now the standard for those patients deemed at high risk for developing lung cancer (22, 23), and whether using inhibitors targeting inflammation (8-10) or metabolism (24), the inclusion of effective smoking cessation strategies in these chemopreventive trials is now a must. The overwhelming weight of the evidence therefore shows that effective development of approaches that integrate smoking cessation into biomarker-based chemoprevention of tobacco-driven cancers is no longer optional.

Abstract 1606: Antitumor effects of vitamin D in a carcinogen-induced mouse model of lung cancer

Abstract Lung cancer accounts for the majority of cancer mortality in both men and women. It is critical to better understand the biology of lung cancer development as no preventive agents and few effective treatment options exist for lung cancer. Epidemiological studies indicate that low serum levels of 25(OH)D3 are associated with increased risk and poor prognosis of lung cancer. Calcitriol, the active metabolite of vitamin D, induces cell cycle arrest, apoptosis and differentiation in preclinical and clinical studies, has limited toxicity, and hence, is an attractive agent for chemoprevention. To investigate the preventive effects of vitamin D on lung squamous cell carcinoma (SCC), pre-clinical studies were conducted using a carcinogen-induced (CI) mouse model of lung SCC which uses N-nitroso-tris-chloroethylurea (NTCU) applied topically to the back of a SWR/J mouse twice weekly. Following ∼15 weeks of NTCU treatment, mice begin to develop bronchial epithelial hyperplasia and in time, progress through metaplasia, carcinoma in situ, and ultimately form lung SCC by approximately 35 to 40 weeks. We conducted a preliminary study investigating the effects of vitamin D on cancer progression in the CI model where animals received NTCU (80 mM/week). 12 week old female mice were randomized into one of three treatment groups: 1) vitamin D deficient diet (DD) (0IU D3 in the diet), 2) sufficient diet (SD) (2000IU/day D3 in the diet) and 3) SD with weekly intraperitoneal (IP) injections of calcitriol (80 ug/kg) (SD+D). Animals treated with NTCU on a DD, SD and SD+D had average serum 25(OH)D3 levels of 15, 70 and 75 nmol/L, respectively (normal range in mice is 70- 90 nmol/L). Preliminary histological evaluation at 12 weeks revealed bronchial epithelial hyperplasia in both the SD and SD+D groups. There were more advanced changes including hyperplasia, metaplasia and dysplasia in the DD mice. The histological evaluation of the DD mice at 24 weeks revealed even more advanced disease, in that most mice had developed lung SCC. The histological evaluation of the SD and SD+D groups at 24 weeks indicated the presence of bronchial epithelial hyperplasia, squamous metaplasia and dysplasia in all mice with some low level of carcinoma in situ. This study indicates that mice deficient in vitamin D develop disease at a more rapid rate suggesting that vitamin D status may play an important role in progression of lung SCC. Supported by NCCAM F31 AT006487 & R01-CA-067267. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1606. doi:1538-7445.AM2012-1606

CT detected indeterminate pulmonary nodules in a chemoprevention trial of fluticasone

In animal models of lung carcinogenesis, inhaled corticosteroids appear to reduce the number of new lung tumors. In a trial of budesonide in smokers with bronchial dysplasia, the proportion of indeterminate CT detected pulmonary nodules that resolved was larger in the treatment group. We performed a secondary analysis of CT data of subjects at risk of lung cancer enrolled in a chemoprevention trial of fluticasone. Subjects with bronchial squamous metaplasia or dysplasia had a baseline chest CT scan. They were randomized to fluticasone or a placebo. After 6 months a repeat CT was performed and the change in number and size of nodules was evaluated. Two hundred and one subjects were screened. Of the 108 volunteers included in the study, 74 were male, mean age was 53 years and mean number of pack years 48. Baseline: 35 subjects had 91 nodules in total, 62% <4mm. In the fluticasone arm more subjects had a decrease and fewer had an increase in number of nodules, however this trend did not reach statistical significance. In this preliminary study there was a tendency of nodules to resolve, however, studies with CT detected nodules as inclusion criterion are needed.

Expression of histo-blood group antigens in bronchial squamous metaplasia

The aim of the present study was to evaluate the expression of blood group antigens in squamous bronchial metaplasia in order to determine whether this factor could identify patients at risk of lung cancer. In total, 100 bronchial biopsies were included in the present study. The cases were classified according to the World Health Organization grading system. Immunohistochemical stains for histo-blood groups A and B, and reactivity tests to p53 and the cellular proliferation index were performed. A total of 56 (56%) patients belonged to blood group A. Among them, six (10.7%) patients who did not express antigen in squamous metaplasia, showed carcinoma at the moment of the biopsy (n = 3) or developed synchronous lung carcinoma (n = 3). A total of nine (9%) patients belonged to blood group B. Loss of antigenic expression was observed in five cases. All of them developed synchronous lung carcinoma. The patients with low- and high-grade dysplasia developed lung cancer in 71 and 100% of the cases, respectively. In conclusion, the findings of the present study suggest that the loss of histo-blood antigens expression is an event in the carcinogenesis of bronchial mucosa and it is usually associated with high-grade lesions and hyperproliferative activity.

SEL1L expression in non–small cell lung cancer

SEL1L gene product plays a role in cell transformation and tumor progression in human breast, pancreas, esophageal, and prostate cancer. SEL1L expression was evaluated in a series of 76 surgically resected non-small cell lung carcinomas to investigate its clinical significance. SEL1L is scarcely detectable in normal lung, whereas in the initial stages of cell transformation, it becomes consistently expressed with evident staining in bronchial squamous metaplasia and in associated dysplastic changes. SEL1L immunoreactivity can be detected both in the cytoplasm and less commonly in the nuclei; the subcellular location correlates with tumor histotype, with cytoplasmic immunoreactivity being most prevalent in squamous cell carcinomas (P = .0005) and nuclear immunoreactivity being associated with adenocarcinomas (P = .02). Nuclear import and export signals are present in the SEL1L coding sequence, justifying the different subcellular location of the protein. SEL1L immunoreactivity was inversely correlated with tumor grade (P = .05); when considering only the adenocarcinomas, a stronger association was found (P = .006). SEL1L messenger RNA and protein evaluation in lung cancer cell lines confirmed the expression of the gene and the dual subcellular location of the protein in lung tumors. The data here reported suggest that, in non-small cell lung carcinoma, SEL1L may be an indicator of cell transformation, thus having important biologic and clinical implications.

Frequent loss of E-cadherin and/or catenins in intrabronchial lesions during carcinogenesis of the bronchial epithelium

Inactivation of the cadherin-mediated cell-cell adhesion system is believed to play a role in the initial steps of cancer invasion and metastasis. Expression of E-cadherin and its intracytoplasmic binding molecules (alpha-catenin, beta-catenin, and plakoglobin) was examined immunohistochemically in 84 cases of intrabronchial precancerous lesions (bronchial squamous metaplasia (BSM) without atypia, BSM with atypia, dysplasia), and 21 cases of carcinoma in situ, and 4 cases of microinvasion to the bronchial wall, and 32 cases of stage I well differentiated squamous cell carcinoma (squamous cell carcinoma) to investigate the association between expression of E-cadherin and/or catenins and cancer progression. Reduced expression of E-cadherin and/or catenins was closely correlated with an atypical grade of dysplasia in the basal layer (p<0.05). In particular, downregulation of E-cadherin and/or catenins was associated with an atypical grade of BSM with atypia in intrabronchial lesions (p<0.01). We conclude that downregulation of alpha-catenin and/or beta-catenin, which may reflect dysfunction of the cadherin-mediated cell-cell adhesion system, is an important marker for atypical grade during carcinogenesis of the bronchial epithelium.

Survivin gene expression in early-stage non-small cell lung cancer.

Survivin is an inhibitor of apoptosis protein, overexpressed in most human malignancies and implicated in mitosis regulation and preservation of cell viability. In order to investigate the prevalence and clinical significance of survivin in early-stage non-small cell lung carcinoma (NSCLC), survivin mRNA levels and protein expression were evaluated, using quantitative real-time RT-PCR and immunohistochemistry, respectively, in a series of 83 patients with stage I (IA and IB) surgically resected NSCLC. Detectable survivin mRNA levels could be demonstrated in all non-neoplastic lung tissue samples and in the tumours analysed. Survivin mRNA levels were elevated in 80 carcinomas (96%) compared to normal lung (p = 0.008). Among all tumours, survivin transcripts were present at a higher level in squamous cell carcinomas (p = 0.0022). Cytoplasmic and nuclear immunoreactivity was found in 70% and 80% of tumours, respectively and both were present in 54%. Cytoplasmic immunoreactivity correlated with tumour stage (p = 0.019). Survivin expression levels did not correlate with patient survival. In one specimen, cytoplasmic and focal nuclear immunostaining was observed in dysplastic bronchial squamous metaplasia. These results document that survivin overexpression is almost always present in early-stage NSCLC, suggesting that this protein may play a role in lung tumourigenesis. This ubiquitous expression makes survivin an appealing new target for novel therapies in lung cancer. In addition, this study also documents that survivin overexpression could be exploited for diagnostic purposes and that quantitative real-time RT-PCR can be a useful tool for evaluating survivin activation in NSCLC.

Dietary vitamin A and prevalence of bronchial metaplasia in asbestos-exposed workers

The purpose of this investigation was to examine the association between dietary intake of vitamin A in the form of retinol and provitamin A carotenoids and the prevalence of bronchial squamous metaplasia in a sample of asbestos workers from an industrial clinic. Bronchial biopsies were obtained from 49 asbestos workers. Pulmonary function testing was done and in-person interviews were conducted to estimate dietary intake of retinol and provitamin A carotenoids, tobacco exposure, and asbestos exposure. Results indicated that workers with metaplasia reported consuming a significantly lower intake of total vitamin A [2000 retinol equivalents (RE)/d] than did subjects without metaplasia (2710 RE/d, P = 0.02). Logistic regression analyses showed that higher intakes of retinol [odds ratio (OR): 0.31; 95% CI: 0.04, 2.44], provitamin A carotenoids (OR: 0.31; 95% CI: 0.03, 2.84), and total vitamin A (OR: 0.29; 95% CI: 0.03, 2.49) were associated with a nonsignificant reduction in the OR for metaplasia (highest quartile compared with lowest quartile, adjusted ORs). Current smoking (OR: 5.25; 95% CI: 0.50, 55.1) and former smoking (OR: 2.95; 95% CI: 0.31, 28.1) were associated with a nonsignificant increase in the OR for bronchial metaplasia compared with never smoking. Greater airway obstruction [decreased forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)] was associated with an increased OR for metaplasia (OR: 2.86; 95% CI: 1.09, 7.69). These results suggest that a higher (ie, above the median) intake of vitamin A from foods decreases the risk of bronchial metaplasia in workers occupationally exposed to asbestos.

Moving promising research findings to the clinic: Methodological issues in the design and conduct of clinical trials of retinoids

International Journal of CancerVolume 70, Issue 4 p. 467-469 Special ReportFree Access Moving promising research findings to the clinic: Methodological issues in the design and conduct of clinical trials of retinoids Andrew Arnold, Corresponding Author Andrew Arnold Department of Medical Oncology, Ontario Cancer Treatment and Research Foundation, Hamilton Regional Cancer Centre and McMaster University, Hamilton, CanadaDepartment of Medical Oncology, Hamilton Regional Cancer Centre, 699 Concession Street, Hamilton, Ontario L8V 5C2, Canada, Fax (905) 575-6316Search for more papers by this author Andrew Arnold, Corresponding Author Andrew Arnold Department of Medical Oncology, Ontario Cancer Treatment and Research Foundation, Hamilton Regional Cancer Centre and McMaster University, Hamilton, CanadaDepartment of Medical Oncology, Hamilton Regional Cancer Centre, 699 Concession Street, Hamilton, Ontario L8V 5C2, Canada, Fax (905) 575-6316Search for more papers by this author First published: 06 December 1998 https://doi.org/10.1002/(SICI)1097-0215(19970207)70:4<467::AID-IJC15>3.0.CO;2-CCitations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References Arnold, A. M., Browman, G. P., Levine, M. N., D'Souza, T., Johnstone, B., Skingley, P., Turner-Smith, L., Cayco, R., Booker, L., Newhouse, M. and Hryniuk, W. M., The effect of the synthetic retinoid etretinate on sputum cytology-results from a randomized trial. Brit. J. Cancer, 65, 737– 743 (1992). Arnold, A., Kowaleski, B., Tozer, R. and Hirte, H., The arotinoids: early clinical experience and discussion of future development. Leukemia, 11, 1817– 1824 (1994). Eisenhauer, E. A., Lippman, S. M., Kavanagh, J. J., Paredes-Espinoza, M., Arnold, A., Hong, W. K., Massimini, G., Schleuniger, U., Bollag, W., Holdener, E. and Krakoff, I., Combination 13-cis-retinoic acid and interferon α2a in the therapy of solid tumours. Leukemia, 10, 1622– 1625 (1994). Eliason, J. F., Kaufmann, F., Tanaka, T. and Tsukaguchi, T., Anti-proliferative effects of the arotinoid Ro 40–8757 on human cancer cell lines in vitro. Brit. J. Cancer, 67, 1293– 1298 (1993). Goodman, G. E., Metch, B. J. and Omenn, G. S., The effect of long-term beta-carotene and vitamin A administration on serum concentrations of alpha-tocopherol. Cancer Epidemiol. Biomarkers Prev., 3, 429– 432 (1994). Hennekens, C., Buring, J., Manson, J., Stampfer, M., Rosner, B., Cook, N., Belanger, C., LaMotte, R., Gaziano, J., Ridker, P., Willett, W. and Peto, R., Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. New Engl. J. Med., 334, 1145– 1149 (1996). Kelly, K., Evaluation of k-ras mutations in sputum samples by single stranded conformation polymorphism [Abstract]. Lung Cancer, 11 (Suppl.), 225 (1994). Lee, J. S., Lippman, S. M., Benner, S. E., Lee, J. J., Ro, J. Y., Leukeman, J. M., Morice, R. C., Peters, E. J., Pang, A. C., Fritsche, H. A. and Hong, W. K., Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia. J. clin. Oncol., 12, 937– 945 (1994). Mathé, G., Gouveia, J. and Hercend, T., Correlation between precancerous bronchial metaplasia and cigarette consumption, and preliminary results of retinoid treatment. Cancer Detect. Prevent., 5, 461– 466 (1982). Omenn, G., Goodman, G., Thornquist, M., Balmes, J., Cullen, M., Glass, A., Keogh, J., Meyskens, F., Valanis, B., Williams, J., Barnhart, S. and Hammar, S., Effects of a combination of beta-carotene and vitamin A on lung cancer and cardiovascular disease. New Engl. J. Med., 334, 1150– 1155 (1996). Omenn, G. S., Goodman, G., Thornquist, M., Grizzle, J., Rosenstock, L., Barnhart, S., Balmes, J., Cherniack, M. G., Cullen, M. R. and Glass, A., The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers. Cancer Res., 54 (Suppl.), 2038s– 2043s (1994). Citing Literature Volume70, Issue47 February 1997Pages 467-469 ReferencesRelatedInformation

Genesis of squamous cell lung carcinoma: Sequential changes of proliferation, DNA ploidy, and p53 expression: Hirano T, Franzen B, Kato H, Ebihara Y, Auer G. Division of Tumor Pathology, Department of Pathology, Karolinska Hospital and Institute, 17176 Stockholm. Am J Pathol 1994;144:296–302

Squamous cell lung carcinomas (SCCs) represent a highly malignant group of tumors, and effective treatment is greatly dependent upon early diagnosis. However, objective diagnosis of atypia is difficult and useful markers need to be defined. In this study, genomic instability, cell proliferation, and cellular accumulation of mutant p53, as reflected by DNA aneuploidy, proliferating cell nuclear antigen, and p53 immunoreactivity, respectively, were evaluated in bronchial squamous metaplasia without atypia (n = 4), bronchial squamous metaplasia with low-grade atypia (n = 12), bronchial squamous metaplasia with high-grade atypia (n = 15), early-stage SCC (n = 15), and advanced-stage SCC (n = 33). Our results suggest that hyperproliferation is an early event followed by DNA aneuploidy, which in turn precedes p53 immunoreactivity in the genesis of SCC. We conclude that routine assessment of proliferating cell nuclear antigen, DNA ploidy, and p53 may be valuable for the early diagnosis of SCC.

Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia

Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia

Chemoprevention Effects on Bronchial Squamous Metaplasia by Folate and Vitamin in Heavy Smokers

The purpose of this study was to observe the effects of folate and vitamin B12 on bronchial squamous metaplasia with cellular atypia, known to be a precancerous change, in heavy smokers. Cases of squamous metaplasia were recognized on sputum cytologic study. The location of bronchial lesions was identified by bronchofiberoscopy in all cases. The grade of cellular atypia was evaluated on the basis of histologic specimens. Thirty-eight patients with squamous metaplasia, including 21 patients receiving folate and vitamin B12 and 17 patients without any medication, were investigated prospectively for 1 year. Consecutive bronchofiberoscopic examinations were performed in each patient in 3 to 4 months after the first examination in order to evaluate the lesions. Grades of cellular atypia were examined by histologic specimens using a scoring system from 0 to 3. There was no significant difference in mean scores at entry in the medication group (1.7) and control group (1.4). The medication group showed significant decrease in mean scores (0.4) while the control group had no change in mean scores (1.2) at termination. Plasma levels in the medication group were significantly increased at termination of the study while those of the control group showed a slight decrease. The results show that the cellular atypia squamous metaplasia in heavy smokers can be reduced by administration of folate and vitamin B12.

The effect of folate and vitamin B 12 for treatment of bronchial squamous metaplasia : T. Tsuchida, H. Kato, M. Saito, T. Hirano, T. Kamura, H. Shibanuma, T. Kobayashi, N. Kawate, C. Konaka. Department of Surgery, Tokyo Medical College, Tokyo, Japan

The effect of folate and vitamin B 12 for treatment of bronchial squamous metaplasia : T. Tsuchida, H. Kato, M. Saito, T. Hirano, T. Kamura, H. Shibanuma, T. Kobayashi, N. Kawate, C. Konaka. Department of Surgery, Tokyo Medical College, Tokyo, Japan

Demonstration of nucleolar organizer regions in lung carcinoma by silver staining

Nucleolar organizer regions (NORs) were investigated in lung carcinomas by silver staining. This method was applied to 111 lung carcinoma specimens, including 40 with squamous cell carcinoma (SCC), 42 with adenocarcinoma (ADENO), 8 with adenosquamous carcinoma (ADESQ), 8 with small cell carcinoma (SMCC), 6 with large cell carcinoma (LGCC), and 7 with typical carcinoid tumors (CAOID). The mean AgNOR counts of ADENO, SCC, ADESQ, SMCC, and LGCC were significantly higher than those of the normal bronchial surface and those of the glandular or alveolar epithelium. The mean AgNOR count of CAOID was significantly higher than those of the normal glandular and alveolar epithelium but not that of the surface epithelium. The mean AgNOR count of SCC was significantly higher than that of bronchial squamous metaplasia, and the count of SMCC was significantly higher than that of CAOID. Within the same cancer category, the mean number of AgNORs increased in parallel with the histological tumor grades. These results indicate that the AgNOR method is useful for differentiating lung carcinoma from its normal counterparts and for evaluating histological tumor grades in the same lineage of lung carcinoma.

Tints Omitted From Tables.

—An error occurred in the PRELIMINARY COMMUNICATION entitled "Improvement in Bronchial Squamous Metaplasia in Smokers Treated With Folate and Vitamin B₁₂: Report of a Preliminary Randomized, Double-blind Intervention Trial" published in the March 11 issue ofThe Journal(1988;259:1525-1530). The tints were omitted from the following tables:

Improvement in Bronchial Squamous Metaplasia in Smokers Treated With Folate and Vitamin B12

To test whether changes in folate and vitamin B12 nutrition modify the severity of potentially premalignant lesions identified by cytology in sputum samples of smokers, we conducted a randomized, controlled prospective intervention trial in smokers with bronchial squamous metaplasia. Seventy-three men with a history of 20 or more pack-years of cigarette smoking who had metaplasia on one or more sputum samples were stratified according to smoking level and randomly assigned to four months' treatment with either placebo or 10 mg of folate plus 500 micrograms of hydroxocobalamin. Direct cytological comparison of the two groups after four months showed significantly greater reduction of atypia in the supplemented group. This provides preliminary evidence that atypical bronchial squamous metaplasia may be reduced by supplementation with folate and vitamin B12. However, the significance of these findings is tempered by substantial spontaneous variation in sputum cytologies, the small study population, the short duration of the trial, and the supraphysiological doses of folate and B12 used. The results should not be construed as pointing to a potential way of preventing lung cancer in individuals who continue to smoke or as supporting self-medication with large doses of folate or B12 by smokers.

Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B12. Report of a preliminary randomized, double-blind intervention trial

Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B12. Report of a preliminary randomized, double-blind intervention trial

Duration of Bronchial Squamous Metaplasia Produced in Dogs by Cigarette Smoke Condensate&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;

Duration of Bronchial Squamous Metaplasia Produced in Dogs by Cigarette Smoke Condensate&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;

Significant Cytologic Findings in Non-Malignant Pulmonary Disease

In a relatively new field of study, such as pulmonary cytology, one is impressed by rapid changes in diagnostic acumen and confidence which occur during the space of a few years. During our years of investigative research in sputum cytologic studies for the detection of malignant cells, we have attempted to correlate appearances of the stained cells with any available histologic, roentgenologic and clinical findings, and we have been particularly interested in reviewing those cases in which our laboratory has made a false “positive” or false “suspicious” report of cancer. In the course of this investigation it has become apparent that cytologic appearances of the cells in a large number of non-malignant pulmonary conditions may be quite characteristic of the specific disease. Equally important, they may show close resemblance to carcinoma cells. This was found to be true for such widely different conditions as bronchial squamous metaplasia, pulmonary infarction, asthma, and lipid pneumonia. We feel that careful evaluation of these cellular alterations will serve two purposes. In the first place, since many of these pathologic states produce cells which cytologically closely resemble cancer cells, cognizance of their possible presence should assist in reducing to an absolute minimum the hazard of false positive reports. Secondly, we have found that identification of these cellular alterations can often contribute materially to a differential diagnosis in a number of non-neoplastic pulmonary diseases.