Resultaten van 2 jaar ervaring met fluorescentie bronchoscopie ter detectie van intraepitheliale neo

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Autofluorescence bronchoscopy (AFB) for early
detection?
tg.sutedja_at_vumc.nl
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Autofluorescence real time imaging
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Outline basic questions

• Why ? autofluorescence bronchoscopy
• What are the results so far?
• (Any?) Future

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Why find early stage?

• Stage shift finding early N0 tumors
• Minimal invasive endoscopic techniques (early
  detection, staging and treatment!) less
  morbid alternatives for resection
• Large number individuals at risk smokers, COPD,
  Cardiovascular risk, subsequent primaries!

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Find early stage lung cancer!
Exploit time window Prior to N1!
Nstatus 0 ? 1
Advanced
T1 lt1 cm lt3mm
Tis
T0
TX
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Difficult to locate early cancer!

• 200 pos. sputum cytology 175 central lesions
  proximal to segmental bronchi
• 527 bronchoscopic sessions ?45 minutes! All
  segments brushings washings
• False negatives ? delay 30 months is
  counterproductive to stage shift!

Sato et al. Lung Cancer 19982017-24
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• The (CIS) lesions varied in average depth
• from about 4 cells to a maximum of 38 cells,
• the majority being about 5 cells in depth

• Auerbach NEJM 1961263253

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A u t o f l u o r e s c e n c e
ONCO-L I F E?
Dr. S. Lam BCCA

• S. Lam BCCA

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Outline basic questions

• Why ? autofluorescence bronchoscopy
• Is AFB more sensitive?
• Any future?

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AFB-LIFE better than WLB alone!
55 391 7.1 40/3211.7/58 1.0 / 3.1 /
3.7 1.0 / 0.9 / 0.6 WLB 0.67 LIFE 1.39
n persons n biopsies n biopsies/subject ?dysplasi
a/persons rel. sens.WLB/LIFE/both rel. spec.
WLB/LIFE/both Detection ratio for ASD
Hirsch et al JNCI 2001931385
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Lung Cancer 2003 41 303
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CIS histology NOT a gold standard
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Natural history of pre-cancerous lesions
????????????????????
? ? Bota et al. 6.1 high grade CIS ? SCC
87 Moro Sibolot et al. SD/CIS ? persistent/CIS
63/2 yrs Kennedy et al. SD sputum ?
SD-malignancy 15.6 Ours SD ? CIS 32 CIS ?
SCC 100
 
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Non- stepwise dynamic fluctuations!
Natural history of each lesion?
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AFB track molecular changes
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No. suspicious AFB predicts malignancy
?1 lt5 chance 67 of the group ?2 ?50
Lung Cancer 2003 41295
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AFB detects invisible primaries!

• Prevalence of synchronous 4.3 - 9.3 Venmans
  et al, Pierard et al ,v Rens et al, Shibuya et
  al
• 10-15 additional CIS detected!

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AFB for more accurate staging
?EBUS/PET
Chest 20011201327
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AFB ? Intraluminal treatment
Lung Cancer 2003 3949 accurate staging
intraluminal electrocautery ? 97 local cure!
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AFB intergrated in early intervention
?
?
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Outline basic questions

• Why ? autofluorescence bronchoscopy
• What are the results so far?
• Any future?

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Towards micro-dynamic imaging
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Endoscope
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Resolution vs Observation Area
Size(mm)
Magnifying endoscope
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1
100 µm
?COSM
Resolution
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0.1
0.1
?COSM
EOCT
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EBUS
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Resolution vs Depth of Tomography
100
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You will never find it!
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Bio-molecular pathways e.g. EGFR
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Confocal technique
Cancer
Normal
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In-vivo confocal micro-dynamic imaging (1-3 ?m
1.8 mmØ)
Fresh biopsy sub-mucosa 25-30um below surface
(left) superimposed reflectance - fluorescence
(right), 437nm illumination. Courtesy Dr.
MacAulay BCCA
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In vivo targeting mini ? µ? ?
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Reduce morbidity mortality(?)
???
small cell behavior / gt N1
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Overdiagnosis treatment lepidic BAC
? clonal darwinism lead time
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Answers to basic questions

• Why ? stage shift, to find CIS N0
• Results ? histology? potentially malignant clonal
  dysplasia visible, more CIS detected
• Any future? ? in vivo study on natural history