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Mr. B born 1942 tg,sutedja@vumc.nl. History (1). 54-yrs old >40 pack years - slight hemoptysis Feb. 2000: Severe dysplasia with brush cytology suspicious for cancer cells left upper lobe region Referral for bronchoscopic evaluation. Please vote: dysplasia → cancer.
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Mr. B born 1942 tg,sutedja@vumc.nl
History (1) • 54-yrs old >40 pack years - slight hemoptysis • Feb. 2000: Severe dysplasia with brush cytology suspicious for cancer cells left upper lobe region • Referral for bronchoscopic evaluation
Please vote: dysplasia → cancer 1. Progression of all lesions 2. Only high grade dysplasia progressive 3. Unpredicatable non-stepwise histological changes 4. Not an important finding
90,000 cells’limit <0.6 mm ???????????! 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% Breuer et al. SD CIS = 32%& Venmans et alCIS SCC 100%
Clonal Darwinism of carcinogenesis • Field of heterogeneous clones, “some”potentially malignant with, each has its own time clock • Non-stepwise histological changes (metaplasia may also become squamous cell cancer!) • No accurate prediction for malignant development based on the initial WHO histological classification Natural course of preneoplastic lesions Clinical Cancer Research 2005; 11: 537
History (2) • Autofluorescence bronchoscopy: upper division bronchus (UDB between LB2-3) abnormal • Histology: severe dysplasia • Cytology revision by a panel: not suspicious! • July 2000: Repeat AFB squamous metaplasia
History (3) • May 2001 repeat AFB normal respiratory epithelium UDB • June 2002 repeat AFB squamous metaplasia, RB7 mild dysplasia • July 2002: HRCT no abnormalities
History (4) • Feb 2003: Repeat AFB squamous metaplasia; RB7 normal • Jan 2004: Repeat AFB squamous metaplasia HRCT: no abnormalities • Aug 2004: repeat AFB UDB suspicious; distal margin invisible at least severe dysplasia; brush cytology suspicious for malignant cells
VOTE:What to do 1. Follow up AFB and HRCT 2. Intraluminal treatment e.g. PDT, electrocautery, cryotherapy 3. Surgical resection 4. Stereotactic body radiotherapy
Occult cancer: HRCT + AFB + FDG-PET Acc(ss)essible superficial intraluminal N0 with visible borders
Clinical decision and treatment • Distal microinvasion cannot be ruled out→ Surgery. Pre-treated with argon plasma • Radical lobectomy and SND left upper lobe • Resected specimen: squamous metaplastic field and mild dysplasia, no residual CIS or microinvasive squamous cancer, N0 stage!
Follow-up: feb 2007 • AFB stump suspicious + RB3 • RB7 abnormal • AFB “false negatives” (Helfritszh et al genetic abnormalities – impact?)
VOTE: CIS and AAH 1. Always surgical treatment 2. Treat bronchoscopically & SBRT 3. Wait and see until microinvasive SCC or GGO become partially solid
Early squamous: not a threat? • 38 patients primarily resectable, intraluminally treated first having HRCT & FDG-PET scan occult cancer lesions • 16 dead and 22 alive; med surv 20 months; Lung cancer death 5/16 = 31%; 4 metachronous occult cases due to previous tumor • Remaining 11 deaths: COPD, AMI, pancreatic ca, esoph.ca. CFA, sepsis etc
Early intervention: con vs. pro? They will die from co-morbidities no significant benefit from early intervention Succesful early intervention allow more to suffer/die from co-morbidities Clonal aggressive lesions incurable = CT screening interval cancer!