A prerequisite to the developement of an efficient cell and/or gene therapy for lung cancer is a precise characterization of the inflammatory cell populations spontaneously present in the tumor stroma associated with this cancer. This study was designed to define the cytotoxic potential and the relationship with stroma development of tumor infiltrating lymphocytes (TIL) and tumor associated macrophages (TAM). Tumor samples from 48 patients undergoing surgery for non-small cell lung cancer (NSCLC) were analyzed, by immunohistochemistry and in situ hybridization, with a panel of antibodies and probes specific for cell proteins linked to cytotoxicity, cytokines, and growth factors, and the replication status of TIL and TAM was evaluated by in vivo 5-bromodeoxyuridine incorporation. It was shown that, in NSCLC: (1) tumor stroma inflammatory cells are mainly TIL (approximately 2/3) (among them, 80 % are T-cells) and TAM (approximately 1/3), with almost no natural killer (NK) cells, and a few dentritic cells; (2) TAM and TIL are poorly replicating, but mainly recruited to the tumor stroma; (3) more than half TAM show an antibody-dependent cytotoxic potential, and one third of T-cells are TIA-1 positive CD8 activated cytotoxic lymphocytes; (4) cancer cells from only a few tumor express HLA class I and II antigens; (5) TAM production of cytotoxic cytokines [interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha)] and of transforming growth factor-beta1 (TGF-beta1) is low, in contrast to their strong release of platelet-derived growth factor (PDGF). We concluded that, in NSCLC, TIL cytotoxicity is likely to be low because of a poor class I MHC expression by tumor cells, and TAM low production of cytotoxic cytokines is a major limit to their possible cytotoxic activity. In contrast, TAM may favor tumor progression by contributing to tumor stroma formation and angiogenesis through their release of PDGF, in conjunction with TGF-beta1 production by tumor cells.

Lung cancer, with a high incidence and a 14% survival rate at 5 years is the leading cause of death in France. Because of past and present smoking habits in the French population and the lack of real expectations for significant therapeutic progress within a short or mid-term delay, the only reasonable way to try to limit the predictable hecatomb in the next 2 decades is to reduce exposure to the main risk factors (tobacco smoke, asbestos.), implement an early and effective (radiographic and/or endoscopic) screening system, and/or determine an active chemoprevention scheme. The principle of chemoprevention is based on the fundamental concept that since lung cancer develops through several stages, subjects exposed to risk factors could be given a compound or compounds counteracting the deleterious effect of carcinogenic substances on DNA and/or blocking the subsequent cascade of molecular events. Two families of products have been considered as potential chemoprevention agents: antioxidants (selenium, beta-caroten, vitamin E, and N-acetyl-cystein) and vitamin A and its analogs. Unfortunately, despite promising experimental data, large-scale clinical trials have not evidenced any protective effect of these compounds that have even been observed to produce opposing effects. To date, no chemopreventive substance can be reasonable proposed for subjects at risk. Due to the lack of proof of the efficacy of the different screening systems proposed, the only preventive action with proven efficacy is to limit exposure to risk factors. All health care givers must actively participate in the fight against active and passive smoking.

Although cutaneous disorders preceding Wegener's granulomatosis are common, they usually are not isolated clinical features. We describe the case of a patient who presented Wegener's granulomatosis-related cutaneous disorders ten years before diagnosis, suggesting a protracted form of the disease.At first visit in 1987 a 44-year-old woman presented leg skin nodules since six months. Following biopsy clinical findings showed non-specific inflammation. Due to lung nodular lesions tuberculosis was diagnosed in 1993. Though bacteriology did not confirm diagnosis, treatment was successful. After relapse in 1996, thoracotomy was performed and anatomic pathology findings uncovered Wegener's granulomatosis. The patient's history showed many flares of skin nodules since 1986. This is only in 1997 that cutaneous pathologic findings showed the existence of Wegener's granulomatosis.The time to diagnosis after the occurrence of the first clinical signs is usually shorter than that observed. Superficial, protracted forms of the disease have been described. As in the present case, they raise diagnostic issues regarding the lack of specificity of anatomic pathology findings. This also suggests that Wegener's granulomatosis and infections might be related.

Among patients with resected non-small cell lung carcinoma, about 50% will present a tumor recurrence. Thus, it would be of major importance to be able to predict and try to prevent these relapses by an active chemotherapy and/or radiotherapy. In an attempt to answer this question, the tumors of 227 patients with a surgically resected non-small cell lung carcinoma were evaluated as follows: tumors were classified as squamous cell carcinoma (n = 132) or adenocarcinoma (n = 95), and tumor differentiation was evaluated for each type. Then, all tumors were classified in respect to their pathological TNM staging (WHO) and screened by immunohistochemistry for the detection of the expression of the following antigens: Bcl-2, A+B+H blood group antigens, c-erb-b2, p53, and Pan-Ras antigens. Furthermore, adenocarcinomas were screened for the presence of point mutations in Ki-Ras codons 1-31. Finally, the patient blood group was defined, and patient survival was analyzed using nonparametric tests and proportional hazard Cox models. Using Kaplan-Meier survival curves, disease pathological TNM staging was shown to be a strong predictive factor of survival for both squamous cell carcinoma and adenocarcinoma. Patients with squamous cell carcinoma experienced fewer relapses than those with adenocarcinoma (42% versus 63%; P = 0.0002) and had a significantly better survival. All evaluated antigens were more often present in squamous cell carcinoma than in adenocarcinoma except for Pan-Ras (three times more frequent in adenocarcinoma). In patients with squamous cell carcinoma, only tumor staging had a significant prognosis value (P = 0.01). In patients with lung adenocarcinoma, a well-differentiated tumor (P = 0.009) as well as a positive Bcl-2 staining (P = 0.009) and an A+B+H antigen tumor staining (P = 0.024) were associated with a better survival. In contrast, patients with a stage I or II disease and a p53-positive tumor staining and patients with the O blood group (P = 0.01) had a shorter survival. Interestingly, no relation with patient survival was related to c-erb-b2 and Pan-Ras staining. Finally, 12 point mutations were found out of 81 tumors (15%) evaluated for Ki-Ras codons 1-31; they involved codon 12 but also 8, 14, and 15 without any relationship to survival. In respect to lung adenocarcinoma, using Cox proportional hazard models stratified on tumor staging, the following markers were shown to be related to survival: (a) Independent markers of longer survival (ie., high histological degree of tumor differentiation and positive Bcl-2 and A+B+H blood group antigen expression by tumor cells); and (b) Independent markers of shorter survival (i.e., O blood group for all patients and p53 tumor staining in patients with stage I and II diseases). This study suggests that, in patients who undergo surgery for lung adenocarcinoma, the presence or absence of these criteria could be used to define a subset of patients who may benefit from a more specific follow-up.

Although cutaneous disorders preceding Wegener's granulomatosis are common, they usually are not isolated clinical features. We describe the case of a patient who presented Wegener's granulomatosis-related cutaneous disorders ten years before diagnosis, suggesting a protracted form of the disease.At first visit in 1987 a 44-year-old woman presented leg skin nodules since six months. Following biopsy clinical findings showed non-specific inflammation. Due to lung nodular lesions tuberculosis was diagnosed in 1993. Though bacteriology did not confirm diagnosis, treatment was successful. After relapse in 1996, thoracotomy was performed and anatomic pathology findings uncovered Wegener's granulomatosis. The patient's history showed many flares of skin nodules since 1986. This is only in 1997 that cutaneous pathologic findings showed the existence of Wegener's granulomatosis.The time to diagnosis after the occurrence of the first clinical signs is usually shorter than that observed. Superficial, protracted forms of the disease have been described. As in the present case, they raise diagnostic issues regarding the lack of specificity of anatomic pathology findings. This also suggests that Wegener's granulomatosis and infections might be related.

To the Editor: We describe a woman with Behcet's syndrome characterized by recurrent oral and genital aphthous ulcers, severe eye involvement, and the onset of arthritis at the age of 29 years. She had started smoking at the age of 17 and regularly smoked 20 cigarettes a day (total history of smoking, approximately 20 pack-years). At the age of 35, during a remission of symptoms of Behcet's syndrome, she stopped smoking without the use of nicotine-replacement therapy. Within two weeks after she had quit, several large and extremely painful buccal aphthous ulcers developed, with no genital involvement. These ulcerations were . . .

AllergyVolume 54, Issue 3 p. 296-297 Isoniazid-induced bullous skin reaction P Scheid, P Scheid *Service de Pneumologie A Hôpital de Brabois Rue du Morvan 54511 Vandœuvre-lès-Nancy Cedex France Tel. (33) 3 83 15 34 00 Fax: (33) 3 83 15 35 41Search for more papers by this authorG Kanny, Ph. Tréchot, G Kanny, Ph. Tréchot *Service de Pneumologie A Hôpital de Brabois Rue du Morvan 54511 Vandœuvre-lès-Nancy Cedex France Tel. (33) 3 83 15 34 00 Fax: (33) 3 83 15 35 41Search for more papers by this authorV Rosner, V Rosner *Service de Pneumologie A Hôpital de Brabois Rue du Morvan 54511 Vandœuvre-lès-Nancy Cedex France Tel. (33) 3 83 15 34 00 Fax: (33) 3 83 15 35 41Search for more papers by this authorO Ménard, O Ménard *Service de Pneumologie A Hôpital de Brabois Rue du Morvan 54511 Vandœuvre-lès-Nancy Cedex France Tel. (33) 3 83 15 34 00 Fax: (33) 3 83 15 35 41Search for more papers by this authorJM Vignaud, JM Vignaud *Service de Pneumologie A Hôpital de Brabois Rue du Morvan 54511 Vandœuvre-lès-Nancy Cedex France Tel. (33) 3 83 15 34 00 Fax: (33) 3 83 15 35 41Search for more papers by this authorD Anthoine, D Anthoine *Service de Pneumologie A Hôpital de Brabois Rue du Morvan 54511 Vandœuvre-lès-Nancy Cedex France Tel. (33) 3 83 15 34 00 Fax: (33) 3 83 15 35 41Search for more papers by this authorY Martinet, Y Martinet *Service de Pneumologie A Hôpital de Brabois Rue du Morvan 54511 Vandœuvre-lès-Nancy Cedex France Tel. (33) 3 83 15 34 00 Fax: (33) 3 83 15 35 41Search for more papers by this author P Scheid, P Scheid *Service de Pneumologie A Hôpital de Brabois Rue du Morvan 54511 Vandœuvre-lès-Nancy Cedex France Tel. (33) 3 83 15 34 00 Fax: (33) 3 83 15 35 41Search for more papers by this authorG Kanny, Ph. Tréchot, G Kanny, Ph. Tréchot *Service de Pneumologie A Hôpital de Brabois Rue du Morvan 54511 Vandœuvre-lès-Nancy Cedex France Tel. (33) 3 83 15 34 00 Fax: (33) 3 83 15 35 41Search for more papers by this authorV Rosner, V Rosner *Service de Pneumologie A Hôpital de Brabois Rue du Morvan 54511 Vandœuvre-lès-Nancy Cedex France Tel. (33) 3 83 15 34 00 Fax: (33) 3 83 15 35 41Search for more papers by this authorO Ménard, O Ménard *Service de Pneumologie A Hôpital de Brabois Rue du Morvan 54511 Vandœuvre-lès-Nancy Cedex France Tel. (33) 3 83 15 34 00 Fax: (33) 3 83 15 35 41Search for more papers by this authorJM Vignaud, JM Vignaud *Service de Pneumologie A Hôpital de Brabois Rue du Morvan 54511 Vandœuvre-lès-Nancy Cedex France Tel. (33) 3 83 15 34 00 Fax: (33) 3 83 15 35 41Search for more papers by this authorD Anthoine, D Anthoine *Service de Pneumologie A Hôpital de Brabois Rue du Morvan 54511 Vandœuvre-lès-Nancy Cedex France Tel. (33) 3 83 15 34 00 Fax: (33) 3 83 15 35 41Search for more papers by this authorY Martinet, Y Martinet *Service de Pneumologie A Hôpital de Brabois Rue du Morvan 54511 Vandœuvre-lès-Nancy Cedex France Tel. (33) 3 83 15 34 00 Fax: (33) 3 83 15 35 41Search for more papers by this author First published: 24 December 2001 https://doi.org/10.1034/j.1398-9995.1999.00049.xCitations: 9Read the full textAboutPDF 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.Citing Literature Volume54, Issue3March 1999Pages 296-297 RelatedInformation

Aims: We present the clinical and histopathological findings of an unusual pulmonary cystic lymphoepithelial lesion in an HIV sero-positive patient. Methods and results: The 32-year-old female patient developed two nodules in the vicinity of the right and left hila. Left upper lobectomy showed a 40-mm wide cystic lesion. The cyst wall was lined by a squamous epithelium and lymphoid tissue with a marked follicular hyperplasia and a prominent follicular cell dendritic network expressing HIV major core protein p24. Conclusions: The absence of an Epstein-Barr virus infected lymphoid population and monoclonal immunoglobulin gene rearrangement supported the benign nature of the lesion.

Radon is a natural radioactive gas, with worldwide distribution, deriving from uranium decay products, which can be inhaled, weather in mining condition (extraction and management of uranium ores) or in domestic condition (in some high risk homes or geographic areas). The main epidemiologic studies on uranium mining workers have all confirmed an excess in relative risk of primary lung cancer. Epidemiologic studies on indoor exposure suggest a role of radon in the genesis of a certain number of primary lung cancer, although these results remain controversial and need to be confirmed. An overview of the main actual problems related to this bronchial carcinogen is presented in this paper.

Radon is a natural radioactive gas, with worldwide distribution, deriving from uranium decay products, which can be inhaled, eather in mining condition (extraction and management of uranium ores) or in domestic condition (in some high risk homes or geographic areas). The main epidemiologic studies on uranium mining workers have all confirmed an excess in relative risk of primary lung cancer.