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LUNG CANCER DIAGNOSIS

LUNG CANCER DIAGNOSIS. Patients apply to the doctor /hospital in advanced stage, 70-90 % stage III/ IV 5- year survival < 15 %, in Stage IA 90 % Early diagnosis (in preclinic stage and preinvasive lesions) and prevention is important

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LUNG CANCER DIAGNOSIS

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  1. LUNG CANCER DIAGNOSIS • Patients apply to the doctor /hospital in advanced stage, 70-90 % stage III/ IV • 5- year survival < 15 %, in Stage IA 90 % • Early diagnosis (in preclinic stage and preinvasive lesions) and prevention is important • molecular markers in sputum, and serum • Spiral CT, LD-CT (low dose CT) • Non-invasive diagnostic interventions heve increased

  2. 7% Stage II 31% Stage III 24% Stage I 38% Stage IV NON-SMALL CELL LUNG CANCERStages at the initial diagnosis Fry WA, et al. Cancer. 1996;77:1949-1995.

  3. 5 years survival % *Naruke T Ann Thorac Surg 2001, Mountain CF, Chest 1997

  4. c/p T N M L.Molins et al, Lung Cancer 2005; 49(2): p 375

  5. New Developments in the diagnosis • Early diagnosis screeninig studies DDS-CT Molecular markers New Autoflorescence bronchoskopy • Diagnostic interventions in peripheral lesions • non-invasive developments (superdimention bronchoskopy) PET-CT • incentral, near bronchial lesions bronşa komşu lezyonlarda (mass, LAP) EBUS / EUS ,virtual bronchoscopy PET-CT

  6. Early Diagnosis AIM • 3-4 years from normal epithelium to severe dysplasia, from severe dysplasia to CİS approximately 6 months, to invasive cancer 2-10 years • Detection of preinvasive lesions • early preclinical stage • To improve prognosis • To decrease mortality

  7. LUNG CANCER DIAGNOSIS - Spiral CT, LD-SCT • High sensitivity, • Diminished radiation dose (low dose CT) • High contrast difference between the aerated lung tissue and the nodule, • Size is important ! • İn lesions sized <5mm only 3 %, • 10mm> 50 % malign, • İn endobronchial lesions sensitivity is low Kim YH, J Thorac Imaging, 2002 Diederich S, Lung Cancer, 2004

  8. Pulmonary Nodules • CT > Chest X-ray 0.03-0.12/0.43-2.7 % • Non-Calcificated nodules frequency: 6-74% • Malignant lessions 0.4-2.7 % • Diagnostic algoritm: CT/ PET diameter> 10 mm and > non-calcificated nodules or nodules >7mm and rapidly progression ->malignant ? byopsi, • PET sen.% 69 spe % 91 PPV %91 NPV % 71 • invazive procedures are decreased % 20-30 Bastarrika G et al.Am J Respir Crit Care Med 2005 , Swensen SJ et al. Radiology 2005 Jett JR et al. Am J Res Crit Care Med 2006

  9. Spiral CT screening

  10. Spiral CT screening (nodules and pre-cancers)

  11. SCREENING IN LUNG CANCER DDS-CT • New York study has started. • The cost of the study is high and the effect on the mortality is expected to be a 20% decrease • It will be completed in 2009 • Early for routine recommendation

  12. Early Diagnosis New Aproaches • Gase analysis in exhaled breath 71 % sen. 92 % spes. Machada RF et al. Am J Respir Crit Care 2005: 171: 1286-91 • DNA analysis in exhaled breath Carpagnano GE et al. 2005: 172: 738-44 • Antibodies against to tumor antigenous 90 % sen. 95 % spes. Zhong L et al. Am J Res Crit Care 2005: 172: 1308-114

  13. Molecular changes in lung cancer Atipic alveolarhyperplasia Premalign adenom Common genetic changes • Loss of cell cyclus control • Loss of apoptosis • Loss of contact inhibition • Metastasis • Angiogenesis • Autocrine growth(+) Carsinogen Normal epithel Cancer Metaplasia in the epithelium Carcinoma in situ Dysplasia

  14. Mechanism of lung cancer grown Erken Intermediate Geç Normal epithel Invazivecarsinom Hiperplasia Displasia CIS 3p LOH/small telomeric deletions 3p LOH/contiguous deletions ~80% Microsatellite alterations ~50% 9p21LOH ~70% Telomerasedysregulation Telomerase upregulation ~80% mycoverexpression ~60% 8p21-23LOH ~80% Neoangiogenesis ~40% Loss of Fhit immunostaining ~40% p53 LOH p53 mutations ~70% Aneuploidy ~80% Methylation ~100% 5q21 APC-MCC LOH ~30% K-ras mutation ~20% LOH, loss of heterozygosity Hirsch et al 2001

  15. SPUTUM CYTOLOGY NEW TECHNOLOGY • Stage I Saccomanno cytology sen % 14 spe % 99 Saccomanno G,Cancer 1974 • Semi-automated sputum cytometry sen % 75 spe % 98 Marek U, ERJ 2001 • High –resolution image cytometry sen % 45 spe % 90 Adeno % 60 % 90 Palcic B ,Cytometry 2002 • Automated quantitative image cytometry (AQC) with sputum, CT ve FFOB 3.3 % Tm + McWilliams A , AJ Res Crit Care Med 2003

  16. MOLEKULAR MARKERS ONCOGENS • sVEGF : I,II,IIIA < 119 pg/ml > IIIB, IV p=0.03, s-VEGF and s-EGFR high in distant metastases p<0.05, no relation with stage C.Camps Lung Cancer 2005 • VEGF-CveD : lymph node+pleura metastasis A. Kaya Chest 2003, H.Ishii Lung Cancer 2005 • High sCyfra- 21-1 sLDH, sTPA : Stage III-IV A.Turna Chest 2003, Buccheri G,Chest 2000 M.Szturmowicz ERS Congress 2004 • sOsteopontin (OPN): Extracellularmatrixprotein Lymph node metastasis p<0.001, advanced stage III-IV p<0.05 Y.Gao, Lung Cancer 2005 • sTNF-Alfa: 308 G/A type in lung cancer development and progression Chuen-Ming Shih, Lung Cancer 2006

  17. MOLECULAR BIOLOGY OF LUNG CANCER • DNA based analysis Determining tumor related DNA in sputum, RT-PCR technique, • DNA methilation abnormalities p16 methilation clinical diagnosis 3 years ago and/or O6 metilguanin DNA metiltransferaz, RARbeta2, H-cadherin, RASSF1A • FISH (Fluorescence in situ hybridisation) analysis: Determining cancer risk and early diagnosis: c-myc, EGFR, 5p15, CEP 6 low sensitivity % 41, high spesifity % 94, with atipical sputum cytology sensitivity %83, spesifity % 80 • K-ras , p53 mutations: K-ras Frequently adeno carsinom before clinical diagnosis (1-46 months) Deppermann KM, Lung Cancer, 2004; 45: 39-42. Palmisano WA et al, Cancer Res, 2000; 60: 5954-8. Hirsch FR et al, Lung Cancer, 2003; 41: 586. Varella-Garcia M et al, Proc AACR, Clin Res 2003; 44: 297.

  18. Sputum examination + Radiology X-ray / spiral CT - Repeat after a year - + Fluorescence bronchoskopy FOB - Repeat sputum - + CIS, tm...tdv, profilaksi Fluorescence endoscopy + tdv Early Diagnosis (High risk case)

  19. LUNG CANCER DIAGNOSIS - AFB • Autofluorescence bronchoskopy (AFB) FOB (WLB)is inadequate in the detection of early lung cancer and premalignant changes in the bronchial epithelium, sensitivity 9 %, with AFB 56 % • Canada sudy CİS % 1.6,moderate/severe displasia 19 %, Europe: 3.9 % • Diagnosis is better with automatic quantitative image cytometry Spektrometry / spektrofluorometry • Optic coherence tomography (OCT) / OCT bronchoscopy Khanavkar B. J Bronchol, 2000; 7: 60-6. Lam S et al, Cancer, 2000; 89: 2468-73. Kusunoki Y et al, Chest 2000; 118: 1776-82.

  20. AFB (LIFE) • CIS/ in moderate and severe dysplasies • WLB % 8.8 • WLB+LIFE % 55.9 • In invasive cancers • WLB % 65 • WLB+LIFE % 95 Lam S, Chest 1998 • Sensitivity in dysplasies • WLB % 56 • LIFE % 83 Ikeda N, Diagn Ther Endosc 1999

  21. Bronchoskopy White light LIFE

  22. AFB - LIFE • SAFE1000 • Sensitivity for cancer/dysplasia 90 % • D-Light AB • İn moderate and severe dysplasies 67 % • BVS • sensitivity 72 % specificity 53 % Chhajed P, Eur Respır J 2005 Kakihana M, Diagn Ther Endosc 1999 Ernst A, J Bronchol 2005

  23. AFB + WLB (VE) • In the detection of dysplasia and intraepithelial lesions, sensitivity is better, bronchi can be examined in detail, • İnstead of FOB ,Videoendoscopy (VE) (SAFE 3000) • CİS+ dysplasia sensitivity: WLB % 65, SAFE % 90 N. Ikeda, Lung Cancer 2006

  24. Xillix- LIFE (WLB+AFB)

  25. BVS ABIn dysplasies • sensitivity • WLB 53 %, LIFE 96 %, BVS AB 80 % • specificity • WLB 50 %, LIFE 36 %, BVS AB 83.3 % Chiyo M, Lung Cancer 2005

  26. AFI system

  27. endoschopic visual with WLB, AFB and AFI systems ( A: squamous cell Ca B: squamous displasia, C:bronchitis)

  28. Thorax CT Histological diagnosis PeripheralCentral FOB FOB BAL Biopsy TBİA Lavage TBB TBNA Brushing Brushing TTNA VATS Thoracotomy Stage Operability (MRG, E-USG, PET) (TNM, bronchoskopic, mediastinoscopy) (Organ screening– brain, bone, liver, adrenal) History (age, gender, occupation, smoking status, symptoms, history) Physical examination Chest x-ray / Lateral x-ray Laboratory, Hemogram Sedim, Urine analysis Biochemistry, PFT, ECG Sputum cytology 

  29. Peripheral tumour Central tumour FOB % 60 FOB % 96 TTNA % 40 Sputum cytology %45 Balgam sitolojisi % 70 TBB,brushing,TBNA Bronş lavajı % 25 %50 TBB,brushing,TBNA % 96.4 VATS TTNA % 4 Thoracotomy Thoracotomy Yüksekol İ et al. Tüberküloz ve Toraks Dergisi, 2003; 51(3): 258-64

  30. Biopsy , lavage , brushing • Forceps biopsy • Rate of diagnosis in endobronchial masses 55-85 % • sensitivity 74 % • İn submucosal and peribronchal infiltrations 55 % • Addition of bronchial lavage and brushing 90 % • If number of biopsies is one 65 % • 5 or more 95 -100 % • Brushing • sensitivity 59 % • Lavage • 48 % Popovich J 1982, Shure D 1983, Schreiber G 2003

  31. Bronchial washing and BAL • Diagnosis with lavage + biopsy + brushing *in central tumours 90 % *in peripheral tumours 20-50 % • In peripheral tumours with indirect tumour findings *Diagnostic yield of BAL is 40-50 % *with TBB and brushing 75 %

  32. TBB • In submucosal tumours 55 % • In peripheral lesions 30-50 % • with BAL and brushing 75 % • In peripheral tumours • > 2 cm. 62 % • < 2 cm 33 % • Fluoroscopy / CT guided 90 % • EBUS sensitivity 87-92 %, specifity 100%

  33. TBNA In mediastinal staging sensitivity 76 % specifity 96 % High rate of diagnosis in SCLC In central tumours 89 %

  34. TTNA • 2cm> 95 %, <2cm 91 % diagnostic • Sensitivity TTNA > FOB • Peripheral lesions • sen. 90 %, spes. 97 % • False positivity < 5 % • False negativity 25 % • With Fluoroscopy, USG and CT guided effective result • In cases with a high complication;SUPERDIMENTION !!

  35. Super Dimension/ Bronchus System=SDBS Electromagnetic Navigation System =EMNS • Before the process: 3-D CT • Section thickness: 2.5 mm • Section interval: 1.5 mm • Section number: 160 • DICOM formated recording to CD. Roadmap forming. • Electromagnetic area in bronchoscopy table =thickness 1cm and size 47x56cm • 1 mm diametered 8 mm length sensor probe+ 360 degree rotatable locatable guide/LG • Ekstended working channel LG • Computer ve monitor • Maximum 2.8 mm diametered FOB

  36. SDBS • Diagnosis of peripheral lung lession

  37. SDBS • Diagnosis of Peripheral Nodules <2cm…. • Bronchoscopic Approach • Fluoroscopic guidance • Poor visualization of lesions under 2 cm • No adequate side view imaging • No direct pathway imaging • Steering of tools to lesion is difficult 27% to 54% success rate

  38. SDBS • Diagnosis of Peripheral Nodules <2cm…. • Bronchoscopic Approach • CT Fluoroscopy • Real time • Radiation • Time slot • Performed in CT room

  39. LG Tip Catheter as Extended Working Channel (EWC) Locatable Guide • Locatable Guide (LG) together with dedicated catheter (Extended Working Channel - EWC) is inserted into bronchoscope • Upon reaching target EWC is fixed • LG is retracted • Tools are inserted via EWC to lesion EWC Tool EWC

  40. SPN / MASS - PET • Sensitivity in pulmonary nodules is 97 % (83-100) • In lesions sized <1 cm , sensitivity 50 % • Low metabolic activity in carsinoid tumors and BAC Gould MK 2001, Kapucu LO 1998, Wilkinson MD 2003, Brudin LH 1994, Croft DR 2002, Bakheer SM 2000.

  41. PET - CT

  42. PET Example: Soliter pulmonary is seen in left upper lobe (black arrow). Strongly 18-FDG uptake in PET-FDG analysis (white arrow).

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