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O-048 Screening for lung cancer with low-dose helical CT — Results ofbase line screening and repeated screening
Oral Sessions f Early detection~Prevention acquired specimens Both 60rag and 20mg INS316 indu~on significantly improved sensitivity (186% and 164%. p 0006 and 0003. respecOveiy) Sensitivity from normal saline induction (12.7%) was net significantly greater than from spontaneous specimens (p=0.144); however, the difference in sensltlv~ between INS316 and normal saline4nduced specimens did not roach statistical s~gnifK:ance Ibr either the high or low dose of INS316 Co= 0.190 and 0.679. respectively). For peripherally located tumors, the sensWvtty for the high and low doses of INS316 (14.4% and 15.9%. respectively) approached a statistically significant difference compared to that of normal saline (6.5%. p 0 104 and 0 060. respectively) INS316 was generally well tolerated as a sputum induc~on agent Mild-to-moderate. transient dyspnea, wheezing, and cough were reported in 1 ,5% of subjects and were reported more frequently in INS3164nduced subjects than normal saline4nduced subjects FEVi and oxyhemoglobin saturation were mildly decreased in a dose
IO-~
Screening for lung cancer with low-dose helical CT - Results of base line screening and repeated scrosnlng-
M. Kaneko I , H. Ohmatsu 2, M. Ohata 3, T. Nal~agawa 4, S. Niitsuma ~, K. Yoshikawa 6, T. Tanaka 7, ]. Tsudlda ~. M. Kusumeto I . R. Kakinuma ~ ~Nat/onal Canoar Center Hosplta/, Tokyo, Japan, 2Na#ona/ Cancer Center Hospita/ East, Japan 3Ohata Hospita/, Japan, 4Hitachi Hea/lh Care Confer' Japan, 5Niigata Mad~ca~Association for Labor Heallh, Japan, ~Shimana Environment & Health Pul,X/c CorporatJon, Japan, ZKanagawa Health S e r ~ Assoctetion, Japan Bali(ground: In Japan. lung cancer is the leading cause of cancer death and adenecercinoma, which oocurred from periphery, is increasing remarkably In order to reduce the number of lung cancer death, oady detecton of small periphery nodules is necessary. A screening by fluororeontgonography is done for eady dete~on of lung cancer, and its effect was proved by a case centTast study in Japan However. the effect of screening is lower than the other cancer screenings, and a new method to let improvement of screening precision was groped for. With that purpose, several instA,,t]ons have introduced low dose helical scan CT for lung cancer screening. We e0(amined how precision of a lung cancer screening vaned by introducing low dose helical scan CT. Methods: We gathered the data every each year in 6 institutons which have introduced CT already for the screertng of lung cancer more than six years We accumulated the data and analyzed the aging variation of detection rate of lung cancer, rate of stage IA and operation rate of bertge lesions We collected the repeated screening cases w'cich were not able to detect in stage IA and revie.~red the reasons of them Results: The e~aminee of lung cancer by low dose CT until the end of 2003 in a 6 institution was 41.219 cases in baseline screening (male 32.793. lemale 8426) and 56.651 examinations in repeated screening (male 47.281. female 9370). In baseline screening 170 lung cancers were detected and the ratio for 100.000 was 412 and ratio of stage IA was 78%. A lot of benign nodules were rasected in the fret year. but decrease afterwards. In repeated screening 127 lung cancers were detected, and the ratio for 100.000 was 224 and ratio of stage IA was ?'9% In spite of repeated screening, there were 20 cases of lung cancers that were detected without in stage IA The reasons of without stage IA. were the rabid growing in 9 cases, miss diagnosis in 7 cases and patient's delay in 4 oases Conclusion: In order to raise the precision of CT screening, improvement of diagnostic accuracy and regular check-up are necessary [O-~
Affyrnetdx gone expression profiles In premallgnant bronchial mucoEa
D Men-/ok1,2 M Suglta 2, F Hirsch 2, R Kelth ~,2, Y Miller1,2, C Coldren 2, R Lapadat2, S Wffta 2, M Geraci 2, W Franklin 2 1Denver Veteran's Affairs Mad~ca~ Center, Denver, Colorado, USA, 2University of Co~or'ado Health Sctenoas Center, Denver, USA
Background: Dysplastlc change in airway epithelium is associated with increased nsk for the subsequent development of lung cancer especially in these demonstrating severe atypia. Early detection and elimination of these lesions would greatly reduce the incidence of lung cancer in at nsk populations. Despite the potentially significant implications for the early detection of dysplasia, to date no global gone expression analyses have been performed on tissue derived from these lesions. We have employed gone expression microarray analysis in an effort to identify molecular markers of bronchial dysplasia Methods: CentTal airway lesions were identified in high-risk smokers by fluorescence brenchoscopy Acqacont biopsies were collected at abnormal
$19
sites, one formalin-r=ed for conventional light microscopic eo(amination and the other flash frozen for RNA extraction and oligonuoleotide microarray analysis Frozen biopsies were also sectioned to directly assess biopsy adequacy and histologic grade of the bronchial mucosa to be analyzed by microarray. RNA was extracted from the remaining frozen tissue for analysis. Affymetnx HGU 133 plus 2.0 microarray profles from dysplastic biopsies were compared with profiles of normal mucosa from never smoker volunteers. A total of 7 lesmns were assessed. 4 high grade dysplasias from high risk smokers and 3 sample sets from never smokers. Initially. data from the four dysplastic biopsies was compared with that from the three normal biopsies using ANOVA assuming equal vadances, a p-value cutoff of 0 05% and the multiple testing corre~on Benjamin/ and Hochberg false discovery rate
Subtree A
Subtree B $
rtnSh B llllllllllllllllllllllllllllll
o j _1 lllllllllllllllllllBIIIIIIII AS I lllllllllllllllllIlIIIIII M I IIIIIIIIIIIIIIIBIIIIIIIII PL I 1111111111111111111111111111 E #,' 'IIIIIIIIIIIIIIIIIIIIIIIIIIII z --IIIIIIIIIIIIiiiiiiiiiiiiiiiii Genes
Table: Gone dusters overe~pressed in dysplastic bronctial epithelium Subb'eo A
Subtroe B
Karat n 6A Karat n 6A
BCL2-related ovarian killer Ca~noembryonic antgen4-eiated cell adhesion molecule 9 CD109 antigen (Gov platelet alloantlgens) cytochmme P4,50. family 3. subfamily A. polypaptlde ,5 ep~helial membrane protein 1
Seiellin Small proline-dch protein 1A (SPRRIA) Small proline nch protein IB (cornifin) Small proline nch protein 2B Small proline-dch protein 3 Small proline-dch protein 3
GPI anchored metastasis associated protein homolog Heparin-blnding growth factor binding protein Homo sapiens cDNA: FLJ21198 fis. clone COL00220 Homo sapiens, done IMAGE: 4622062. mRNA Human tumor anbgen ([_6) mRNA. complete cds. Hypothetical gone supported by BC028978 Hypothetical protein FLJ32110 Hypothetical protein MGC35033 Keratin 32 0n/stone deecetylase inducible) Keratin 6B Potassium channel, subfamily K. member f Sedne (or cysteine) proteinase inhibitor. clade B (evalbumin). member 2 Sister~3f mammalian grainyhoad Transmembrane 4 suparfamily member I UDP~-acetyl-{~43galactosamine: polypaptlde N-acetylgalact osami ny~ans ferasa ,5 (Gal NA~ TS)
Results 163 genes were Jdentfied as overexpressed at sJgnJfica'lt levels in dysplasia as compared to normal Further filtering of the ANOVA list allowed us to focus on genes that showed high cifferental eo(pression (,5 to 3000
IO-~
Screening for lung cancer with low-dose helical CT - Results of base line screening and repeated scrosnlng-
M. Kaneko I , H. Ohmatsu 2, M. Ohata 3, T. Nal~agawa 4, S. Niitsuma ~, K. Yoshikawa 6, T. Tanaka 7, ]. Tsudlda ~. M. Kusumeto I . R. Kakinuma ~ ~Nat/onal Canoar Center Hosplta/, Tokyo, Japan, 2Na#ona/ Cancer Center Hospita/ East, Japan 3Ohata Hospita/, Japan, 4Hitachi Hea/lh Care Confer' Japan, 5Niigata Mad~ca~Association for Labor Heallh, Japan, ~Shimana Environment & Health Pul,X/c CorporatJon, Japan, ZKanagawa Health S e r ~ Assoctetion, Japan Bali(ground: In Japan. lung cancer is the leading cause of cancer death and adenecercinoma, which oocurred from periphery, is increasing remarkably In order to reduce the number of lung cancer death, oady detecton of small periphery nodules is necessary. A screening by fluororeontgonography is done for eady dete~on of lung cancer, and its effect was proved by a case centTast study in Japan However. the effect of screening is lower than the other cancer screenings, and a new method to let improvement of screening precision was groped for. With that purpose, several instA,,t]ons have introduced low dose helical scan CT for lung cancer screening. We e0(amined how precision of a lung cancer screening vaned by introducing low dose helical scan CT. Methods: We gathered the data every each year in 6 institutons which have introduced CT already for the screertng of lung cancer more than six years We accumulated the data and analyzed the aging variation of detection rate of lung cancer, rate of stage IA and operation rate of bertge lesions We collected the repeated screening cases w'cich were not able to detect in stage IA and revie.~red the reasons of them Results: The e~aminee of lung cancer by low dose CT until the end of 2003 in a 6 institution was 41.219 cases in baseline screening (male 32.793. lemale 8426) and 56.651 examinations in repeated screening (male 47.281. female 9370). In baseline screening 170 lung cancers were detected and the ratio for 100.000 was 412 and ratio of stage IA was 78%. A lot of benign nodules were rasected in the fret year. but decrease afterwards. In repeated screening 127 lung cancers were detected, and the ratio for 100.000 was 224 and ratio of stage IA was ?'9% In spite of repeated screening, there were 20 cases of lung cancers that were detected without in stage IA The reasons of without stage IA. were the rabid growing in 9 cases, miss diagnosis in 7 cases and patient's delay in 4 oases Conclusion: In order to raise the precision of CT screening, improvement of diagnostic accuracy and regular check-up are necessary [O-~
Affyrnetdx gone expression profiles In premallgnant bronchial mucoEa
D Men-/ok1,2 M Suglta 2, F Hirsch 2, R Kelth ~,2, Y Miller1,2, C Coldren 2, R Lapadat2, S Wffta 2, M Geraci 2, W Franklin 2 1Denver Veteran's Affairs Mad~ca~ Center, Denver, Colorado, USA, 2University of Co~or'ado Health Sctenoas Center, Denver, USA
Background: Dysplastlc change in airway epithelium is associated with increased nsk for the subsequent development of lung cancer especially in these demonstrating severe atypia. Early detection and elimination of these lesions would greatly reduce the incidence of lung cancer in at nsk populations. Despite the potentially significant implications for the early detection of dysplasia, to date no global gone expression analyses have been performed on tissue derived from these lesions. We have employed gone expression microarray analysis in an effort to identify molecular markers of bronchial dysplasia Methods: CentTal airway lesions were identified in high-risk smokers by fluorescence brenchoscopy Acqacont biopsies were collected at abnormal
$19
sites, one formalin-r=ed for conventional light microscopic eo(amination and the other flash frozen for RNA extraction and oligonuoleotide microarray analysis Frozen biopsies were also sectioned to directly assess biopsy adequacy and histologic grade of the bronchial mucosa to be analyzed by microarray. RNA was extracted from the remaining frozen tissue for analysis. Affymetnx HGU 133 plus 2.0 microarray profles from dysplastic biopsies were compared with profiles of normal mucosa from never smoker volunteers. A total of 7 lesmns were assessed. 4 high grade dysplasias from high risk smokers and 3 sample sets from never smokers. Initially. data from the four dysplastic biopsies was compared with that from the three normal biopsies using ANOVA assuming equal vadances, a p-value cutoff of 0 05% and the multiple testing corre~on Benjamin/ and Hochberg false discovery rate
Subtree A
Subtree B $
rtnSh B llllllllllllllllllllllllllllll
o j _1 lllllllllllllllllllBIIIIIIII AS I lllllllllllllllllIlIIIIII M I IIIIIIIIIIIIIIIBIIIIIIIII PL I 1111111111111111111111111111 E #,' 'IIIIIIIIIIIIIIIIIIIIIIIIIIII z --IIIIIIIIIIIIiiiiiiiiiiiiiiiii Genes
Table: Gone dusters overe~pressed in dysplastic bronctial epithelium Subb'eo A
Subtroe B
Karat n 6A Karat n 6A
BCL2-related ovarian killer Ca~noembryonic antgen4-eiated cell adhesion molecule 9 CD109 antigen (Gov platelet alloantlgens) cytochmme P4,50. family 3. subfamily A. polypaptlde ,5 ep~helial membrane protein 1
Seiellin Small proline-dch protein 1A (SPRRIA) Small proline nch protein IB (cornifin) Small proline nch protein 2B Small proline-dch protein 3 Small proline-dch protein 3
GPI anchored metastasis associated protein homolog Heparin-blnding growth factor binding protein Homo sapiens cDNA: FLJ21198 fis. clone COL00220 Homo sapiens, done IMAGE: 4622062. mRNA Human tumor anbgen ([_6) mRNA. complete cds. Hypothetical gone supported by BC028978 Hypothetical protein FLJ32110 Hypothetical protein MGC35033 Keratin 32 0n/stone deecetylase inducible) Keratin 6B Potassium channel, subfamily K. member f Sedne (or cysteine) proteinase inhibitor. clade B (evalbumin). member 2 Sister~3f mammalian grainyhoad Transmembrane 4 suparfamily member I UDP~-acetyl-{~43galactosamine: polypaptlde N-acetylgalact osami ny~ans ferasa ,5 (Gal NA~ TS)
Results 163 genes were Jdentfied as overexpressed at sJgnJfica'lt levels in dysplasia as compared to normal Further filtering of the ANOVA list allowed us to focus on genes that showed high cifferental eo(pression (,5 to 3000