a novel biotinylated probe specific for hyaluronate: its diagnostic value in diffuse malignant...

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238 The leukocyte count and risk of lung cancer Phillips AN, Neaton JD, Cook DG. Grimm RH, Shaper AG. Academic Departmenf of G&to-Urinary Medicine, MRC UK Cenrres for Coor- dinoring Epidemiological Research on AIDS and HIV, University College and Middlesex School of Medicine. James Pringle House. 73- 75 Charlotte Sweet, London WIN 8AA. Cancer 1992;69:680-4. The association between leukocyte count and subsequent risk of lung cancer was evaluated in three large cohorts from the United States and Britain. A total of 309 lung cancer events occurred among 28,181 men whose cases were followed-up for 7 to 12 years. In all three cohorts, there was a marked increase in risk of lung cancer with increasing leukocyte count, after adjustment for age and the number of cigarettes smoked per day. The adjusted relative odds in the three cohorts, for a 2OOO/pl difference in leukocyte count, were 1.58 (P = O.OoOl), 1.29 (P = 0.003) and 1.20 (p = 0.02). These relative odds persisted when current smokers were considered alone, when serum markers of cigarette smoking exposure were adjusted for, and when men with lung cancer events during the fist 5 years of follow-up were excluded. The leuko- cyte count appears 10be linked to the pathogenesis of smoking- related lung cancer. M&static bronchioloalveolar carcinoma and metastatic aden- ocarcinoma of the lung: Comparison of clinical manifestations, chemotherapeutic responses, and prognosis Feldman ER, Eagau RT. Schaid DJ. Division of Medical Oncology, Mayo Clinic, Rochesler, MN 55905. Mayo Clin Proc 1992;61:27-32. Between 1975 and 1985.25 patients with metastatic bronchioloalveolar carcinoma and 223 patients with metastatic adenccarcinomaof the lung received experimental cisplatin-based chemotherapy at the Mayo Clinic. Thechemotherapeutic response rates were 32% and 33%, respectively. The median times to progression of disease were identical (3 months in both groups). The median survival times were 4 months and 6 months. respectively. Metastatic bronchioloalveolarcarcinoma is an aggressive disease that is associated with a poor prognosis, similar to metastatic adenocarcinoma of the lung. Factor IX(i)-antithrombin (IX(i)AT) and thrombin-antithrombin (TAT) complexes in lung cancer patients Kemkes-Matthes B. Bleyl H. ZenlrumfurlnnereMedirin, Klinikrtrasse 36. W-6300 Giessen. Ann Hematol 1992;64:35-9. Coagulation activation frequently occurs in cancer patients, resulting in tbrombcembolic complications and/or intravascular coagulation activation. The mechanisms leading to these alterations still are poorly understocd. One explanation for the coagulation activation in malig- nant diseases is the presence of a direct factor X-activating cancer procoagulant. Coagulation activation in lung cancer patients develops at earlier stages than factor X activation; we demonstrated increased factor IX(i)AT complexes in addition to elevated TAT complexes. The increases of factor IX(i)AT complexes were not dependent upon the stageofthedisease.lncontrast,TATcomplexeswere higher inpatients suffering from advanced pulmonary non-small cell carcinoma than in patients with limited disease. In conclusion, coagulation activation in pulmonary cancer patients occurs at earlier steps in the coagulation cascade than factor X activation. While this activation is not dependent upon the stage of the disease, the observation that TAT complexes showed higher elevations in patients with advanced than in those with limited pulmonary non-small cell carcinoma could be an indication of a cancer procoagulant that directly activates factor X. The value of sputum cytology MacDougall B, Weinerman B. Deparrment of Medicine, St. Boniface General Hospital. 409 Toche Avenue, Winnipeg, Man. R2H 2A6. J Gen Intern Med 1992:7:ll-3. Objective: To assess the value of cytologic examination of expecto- rated sputum in the diagnosis and management of patients with sus- pected lung cancer. Design: Retrospective chart review. Setting: Inpa- tient wards, tertiary care university hospital. Measurements and main results: The char& of 357 patients were reviewed. Two hundred eighty- eight of the 357 patients had had initial sputum cytologic examination prior to other diagnostic proxdures, of which 41 (15%) had positive cytologic results. Thirty-six of the4 I were contirmed histologically or shown to have metastatic spread by noninvasive tests. Of the 222 patients with negative or unsatisfactory sputum tests, 97 went on to bronchoscopy and 35 had needle-aspiration biopsies. In the population of patients whose chest x-rays were highly suggestive of primary or metastatic lung cancer, the positive rate for cytologic examination was 38i94 (40%). There was no false-positive test in this study. Of the 50 patients with positive cytologic results, five (10%) had diseases that were of a different cell type; two of these five (40%) had diseases that involved small-cell cancer. There was an unsatisfactory delay in obtain- ing these samples for analysis. Conclusions: Sputum cytology was found to be too insensitive and insufficiently accurate to be included in the routine workup of a patient suspected of having lung cancer. The results of the test did not influence further diagnostic procedures. This test should, therefore, be reserved for patients considered on initial assessment to be too sick for further investigations and treatment. A novel biotinylated probe specific for hyaluronate: Its diagnostic value in diffuse malignant mesothelioma Azumi N, Underhill CB, Kagan E, Sheibani K. Deparfmenr ofPofhol- ogy. Georgelow UniversitySchoolofMedicine,39OOReservoirRoad. N.W., Washington, DC20007. Am J Surg Path01 1992;16:116-21. Diffuse malignant mesotheliomas are known to secrete a large amount of hyaluronate, whereas adenocarcinomas produce predomi- nantly neutral mucins. In the present study, we assessed the diagnostic usefulness of a new, highly specific and sensitive hyaluronate binding probe to discriminate between mesotheliomas and adenocarcinomas. We studied 33 mesotheliomas and 37 adenocarcinomas in order to establish specific diagnostic criteria for using the hyaluronate binding probe. Of the adenocarcinomas, only three showed significant positive staining for hyaluronate (8%). By contrast, all the mesotheliomas exhibited positive staining for hyaluronate. Furthermore, the staining reaction was classed as moderateorgreater in 26 mesotbeliomas (79%). thus suggesting the utility of this probe in the differential diagnosis of malignant mesothelioma versus adenocarcinoma. We conclude that strong cytoplasmic or membranous staining for hyaluronate is highly predictive of malignant mesothelioma. The hyaluronate binding probe should therefore be considered an importam adjunct to be used in combination with electron microscopy and immunohistochemistry in the histologic diagnosis of diffuse malignant mesothelioma. Production of granulocyte-macrophage colony-stimulating factor in two patients with lung cancer, leukocytosis, and eosinophilia Sawyers CL, Golde DW, Quan S. Nimer SD. Division ofHemaro/ogy- Oncology, School of Medicine and Jonsson Comprehensive Cancer Center, Universily of Cal$nda. Los Angeles, CA 90024. Cancer 1992;69: 1342-6. Leukocytosis in association with malignancy has been well de- scribed. but the cause is not known. One potential explanation is production of a colony- stimulating factor by the tumor, and this has been demonstrated in vitro. The authors report hvo patients with lung cancer, leukocytosis, and eosinophilia. The pleural fluid of both pa- tients contained malignant cells and biologically active granulocyte- macrophage colony-stimulating factor (GM-CSF), as demonstrated by radioimmunoassay. enzyme-linked immunosorbent assay @LISA), and colony-forming unit-granulocyte-macrophage (CFU-GM) assay. To determine whether GM-CSF is normally detectable in pleural fluid, the authors performed assays on an additional II patients with pleural effusions of various origins but without peripheral blood leukocytosis and eosinophilia; only 1 patient had a detectable level of GM-CSF (i.e.. = 0.1 ng/ml). Because GM-CSF usually is not present in pleural fluid,

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238

The leukocyte count and risk of lung cancer Phillips AN, Neaton JD, Cook DG. Grimm RH, Shaper AG. Academic Departmenf of G&to-Urinary Medicine, MRC UK Cenrres for Coor- dinoring Epidemiological Research on AIDS and HIV, University College and Middlesex School of Medicine. James Pringle House. 73- 75 Charlotte Sweet, London WIN 8AA. Cancer 1992;69:680-4.

The association between leukocyte count and subsequent risk of lung cancer was evaluated in three large cohorts from the United States and Britain. A total of 309 lung cancer events occurred among 28,181 men whose cases were followed-up for 7 to 12 years. In all three cohorts, there was a marked increase in risk of lung cancer with increasing leukocyte count, after adjustment for age and the number of cigarettes smoked per day. The adjusted relative odds in the three cohorts, for a 2OOO/pl difference in leukocyte count, were 1.58 (P = O.OoOl), 1.29 (P = 0.003) and 1.20 (p = 0.02). These relative odds persisted when current smokers were considered alone, when serum markers of cigarette smoking exposure were adjusted for, and when men with lung cancer events during the fist 5 years of follow-up were excluded. The leuko- cyte count appears 10 be linked to the pathogenesis of smoking- related lung cancer.

M&static bronchioloalveolar carcinoma and metastatic aden- ocarcinoma of the lung: Comparison of clinical manifestations, chemotherapeutic responses, and prognosis Feldman ER, Eagau RT. Schaid DJ. Division of Medical Oncology, Mayo Clinic, Rochesler, MN 55905. Mayo Clin Proc 1992;61:27-32.

Between 1975 and 1985.25 patients with metastatic bronchioloalveolar carcinoma and 223 patients with metastatic adenccarcinomaof the lung received experimental cisplatin-based chemotherapy at the Mayo Clinic. Thechemotherapeutic response rates were 32% and 33%, respectively. The median times to progression of disease were identical (3 months in both groups). The median survival times were 4 months and 6 months. respectively. Metastatic bronchioloalveolarcarcinoma is an aggressive disease that is associated with a poor prognosis, similar to metastatic adenocarcinoma of the lung.

Factor IX(i)-antithrombin (IX(i)AT) and thrombin-antithrombin (TAT) complexes in lung cancer patients Kemkes-Matthes B. Bleyl H. ZenlrumfurlnnereMedirin, Klinikrtrasse 36. W-6300 Giessen. Ann Hematol 1992;64:35-9.

Coagulation activation frequently occurs in cancer patients, resulting in tbrombcembolic complications and/or intravascular coagulation activation. The mechanisms leading to these alterations still are poorly understocd. One explanation for the coagulation activation in malig- nant diseases is the presence of a direct factor X-activating cancer procoagulant. Coagulation activation in lung cancer patients develops at earlier stages than factor X activation; we demonstrated increased factor IX(i)AT complexes in addition to elevated TAT complexes. The increases of factor IX(i)AT complexes were not dependent upon the stageofthedisease.lncontrast,TATcomplexeswere higher inpatients suffering from advanced pulmonary non-small cell carcinoma than in patients with limited disease. In conclusion, coagulation activation in pulmonary cancer patients occurs at earlier steps in the coagulation cascade than factor X activation. While this activation is not dependent upon the stage of the disease, the observation that TAT complexes showed higher elevations in patients with advanced than in those with limited pulmonary non-small cell carcinoma could be an indication of a cancer procoagulant that directly activates factor X.

The value of sputum cytology MacDougall B, Weinerman B. Deparrment of Medicine, St. Boniface General Hospital. 409 Toche Avenue, Winnipeg, Man. R2H 2A6. J Gen Intern Med 1992:7:ll-3.

Objective: To assess the value of cytologic examination of expecto- rated sputum in the diagnosis and management of patients with sus-

pected lung cancer. Design: Retrospective chart review. Setting: Inpa- tient wards, tertiary care university hospital. Measurements and main results: The char& of 357 patients were reviewed. Two hundred eighty- eight of the 357 patients had had initial sputum cytologic examination prior to other diagnostic proxdures, of which 41 (15%) had positive cytologic results. Thirty-six of the4 I were contirmed histologically or shown to have metastatic spread by noninvasive tests. Of the 222 patients with negative or unsatisfactory sputum tests, 97 went on to bronchoscopy and 35 had needle-aspiration biopsies. In the population of patients whose chest x-rays were highly suggestive of primary or metastatic lung cancer, the positive rate for cytologic examination was 38i94 (40%). There was no false-positive test in this study. Of the 50 patients with positive cytologic results, five (10%) had diseases that were of a different cell type; two of these five (40%) had diseases that involved small-cell cancer. There was an unsatisfactory delay in obtain- ing these samples for analysis. Conclusions: Sputum cytology was found to be too insensitive and insufficiently accurate to be included in the routine workup of a patient suspected of having lung cancer. The results of the test did not influence further diagnostic procedures. This test should, therefore, be reserved for patients considered on initial assessment to be too sick for further investigations and treatment.

A novel biotinylated probe specific for hyaluronate: Its diagnostic value in diffuse malignant mesothelioma Azumi N, Underhill CB, Kagan E, Sheibani K. Deparfmenr ofPofhol- ogy. Georgelow UniversitySchoolofMedicine,39OOReservoirRoad. N.W., Washington, DC20007. Am J Surg Path01 1992;16:116-21.

Diffuse malignant mesotheliomas are known to secrete a large amount of hyaluronate, whereas adenocarcinomas produce predomi- nantly neutral mucins. In the present study, we assessed the diagnostic usefulness of a new, highly specific and sensitive hyaluronate binding probe to discriminate between mesotheliomas and adenocarcinomas. We studied 33 mesotheliomas and 37 adenocarcinomas in order to establish specific diagnostic criteria for using the hyaluronate binding probe. Of the adenocarcinomas, only three showed significant positive staining for hyaluronate (8%). By contrast, all the mesotheliomas exhibited positive staining for hyaluronate. Furthermore, the staining reaction was classed as moderateorgreater in 26 mesotbeliomas (79%). thus suggesting the utility of this probe in the differential diagnosis of malignant mesothelioma versus adenocarcinoma. We conclude that strong cytoplasmic or membranous staining for hyaluronate is highly predictive of malignant mesothelioma. The hyaluronate binding probe should therefore be considered an importam adjunct to be used in combination with electron microscopy and immunohistochemistry in the histologic diagnosis of diffuse malignant mesothelioma.

Production of granulocyte-macrophage colony-stimulating factor in two patients with lung cancer, leukocytosis, and eosinophilia Sawyers CL, Golde DW, Quan S. Nimer SD. Division ofHemaro/ogy- Oncology, School of Medicine and Jonsson Comprehensive Cancer Center, Universily of Cal$nda. Los Angeles, CA 90024. Cancer 1992;69: 1342-6.

Leukocytosis in association with malignancy has been well de- scribed. but the cause is not known. One potential explanation is production of a colony- stimulating factor by the tumor, and this has been demonstrated in vitro. The authors report hvo patients with lung cancer, leukocytosis, and eosinophilia. The pleural fluid of both pa- tients contained malignant cells and biologically active granulocyte- macrophage colony-stimulating factor (GM-CSF), as demonstrated by radioimmunoassay. enzyme-linked immunosorbent assay @LISA), and colony-forming unit-granulocyte-macrophage (CFU-GM) assay. To determine whether GM-CSF is normally detectable in pleural fluid, the authors performed assays on an additional II patients with pleural effusions of various origins but without peripheral blood leukocytosis and eosinophilia; only 1 patient had a detectable level of GM-CSF (i.e.. = 0.1 ng/ml). Because GM-CSF usually is not present in pleural fluid,