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Diagnosis and Causation
The Engle Class
22nd Conference of the
Tobacco Products Liability Project
Their Day in Court
Allan Feingold MD, FRCP(C), FCCP
1
South Miami
Hospital
Dr. Allan Feingold
Chief, Division of Pulmonary Medicine,
6200 SW 70th Ave
Miami, Florida 33143
TEL:
786-662-5229
Email:
[email protected]
2
3
South Miami
Hospital
Dr. Allan Feingold
• Clinician: Chief
Division of Pulmonary
Medicine, South
Miami Hospital
• Assistant Voluntary
Professor of Medicine,
University of Miami
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South Miami
Hospital
Dr. Allan Feingold
• 5 x board certified
Internal and Pulmonary
Medicine
• 6 x NIOSH certified B
reader
• Licensed: NY, FL,
Quebec
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Dr. Allan Feingold
Clinical practice:
•
•
•
•
•
lung cancer
emphysema
pneumonia
asthma
forensics:
– occupational
– tobacco
– U.S., Florida
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… although we approve the Third District’s reversal of the
$145 billion class action punitive damages award, we quash
the remainder of the Third District’s decision. A majority of
the Court holds that the compensatory damages award in
favor of Mary Farnan in the amount of $2,850,000 and
Angie Della Vecchia in the amount of $4,023,000 should be
reinstated. However, the court unanimously agrees that the
compensatory damages award in favor of Frank Amodeo
must be vacated based on the statute of limitations.
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…We conclude that the date of the trial
court’s November 21, 1996, order that
recertified a narrower class is the
appropriate cut-off date.
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As for Angie Della Vecchia, she was diagnosed with lung cancer in
early 1997. However, at that time, it was also noted by her doctors
that she had a past medical history of chronic obstructive
pulmonary disease (“COPD”) and significant hypertension.
Because two of the diseases at issue in this case are coronary
heart disease and COPD, Della Vecchia’s medical records indicate
that she had been suffering from a tobacco related disease prior to
the time of certification and is therefore properly included as a class
member. The jury specifically found that her lung disease was
caused by smoking.
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Supreme Court of Florida
Conclusions
• Approved 3rd District’s reversal of
punitive damages award
• Reinstated compensatory damages in
favor of Mary Farnan and Angie Della
Vecchia
• Established cut off date November 21,
1996
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Supreme Court of Florida
Conclusions
• Unanimously agreed with 3rd District
that judgment in favor of Frank Amodeo
must be reversed because of statute of
limitations; but…
• Allowed award to Della Vecchia
because “she had been suffering from a
tobacco related disease prior to the time
of certification”
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TPLP Conclusions
Who can bring an action under Engle?
All Florida citizens and residents, and their
survivors, who have suffered, presently suffer
or who have died from diseases and medical
conditions caused by their addiction to
cigarettes that contain nicotine. The diseases
and medical conditions must have first
manifested themselves by the class cut-off
date of November 21, 1996.
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Supreme Court of Florida
• Smoking cigarettes causes aortic aneurysm, bladder
cancer, cerebrovascular disease, cervical cancer,
chronic obstructive pulmonary disease, coronary
heart disease, esophageal cancer, kidney cancer,
laryngeal
cancer,
lung
cancer
(specifically,
adenocarinoma, large cell carcinoma, small cell
carcinoma, and squamous cell carcinoma),
complications of pregnancy, oral cavity/tongue
cancer, pancreatic cancer, peripheral vascular
disease, pharyngeal cancer, and stomach cancer)
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Supreme Court of Florida
• Nicotine in cigarettes is addictive
• Cigarettes were placed upon the market as a
defective and unreasonably dangerous
product
• Manufacturers concealed or omitted material
information concerning the health effects and
addictive nature of smoking cigarettes with
the intention that the public would rely upon
misrepresentations about the health effects
and addictive nature of cigarettes
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Smoking-Induced Diseases
Malignant and non-malignant
What is the purpose of medical-legal
evaluation?
• Diagnosis and/or confirmation of
diagnosis
• Attribution – apportionment of causation
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Smoking-Induced Diseases
Malignant and non-malignant
The diagnostic method
• There is only one standard for diagnosis
• Medical and medical-legal diagnostic
standard is the same
• Doctors attempt to achieve diagnostic
certainty, or at least a reasonably
reliable diagnosis (much greater than
51% certainty).
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Smoking-Induced Diseases
The diagnostic method
•
•
•
•
•
•
•
•
•
Detailed past medical history
Verified smoking history
Detailed occupational history
Residential history
Family history (including occupation)
Physical examination results
Good quality chest x-rays and CT scans
Pulmonary function test results
Adequate pathology
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Smoking-Induced Diseases
The diagnostic method
• Past medical history:
– Any prior malignancy
– Any history of obstructive lung disease
(asthma, chronic bronchitis, emphysema)
– Coronary artery disease
– Any prior significant disease
– Provide expert with ALL records
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Smoking-Induced Diseases
The diagnostic method
• Smoking history:
– Medical records
– Answers to interrogatories
– Depositions
– Onset, packs per day, date of cessation
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Smoking-Induced Diseases
Chest Radiology
University of Virginia Health Sciences
Center, Department of Radiology
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Smoking-Induced Diseases
Chest Radiology
University of Virginia Health Sciences
Center, Department of Radiology
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Smoking-Induced Diseases
Chest Radiology
University of Virginia Health Sciences
Center, Department of Radiology
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Smoking-Induced Diseases
Computed Tomography (CT)
Radiological Society of North America
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Smoking-Induced Diseases
Computed Tomography (CT)
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PET-CT
Positron Emission Tomography + Computed Tomography
University of Virginia Health Sciences
Center, Department of Radiology
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Smoking-Induced Diseases
Pulmonary Function Testing (PFT)
National Heart Lung and Blood Institute
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Smoking-Induced Diseases
Pulmonary Function Testing (PFT)
Wikimedia
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Smoking-Induced Diseases
Pulmonary Function Testing (PFT)
Wikimedia
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Lung Cancer Pathology
Non-small cell lung cancer
• Squamous cell
• Adenocarcinoma
– Bronchioloalvelolar cell carcinoma
– Adenosquamous
• Large cell undifferentiated
Small cell or “oat cell”
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Brambilla, Travis, Colby et al
WHO classification
European Resp J 2001
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Right
upper lobe
squamous
cell lung
cancer
Univ Utah
Dept of
Pathology
http://medlib.med.utah.edu/WebPath/LUNGHTML/LUNG067.html
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Right
upper lobe
squamous
cell lung
cancer
Univ Utah
Dept of
Pathology
http://medlib.med.utah.edu/WebPath/LUNGHTML/LUNG067.html
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Lower
lobe lung
cancer
Peripheral
adenoCA
Univ Utah
Dept of
Pathology
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Lobectomy – pulmonary adenocarcinoma
U.S. Armed
Forces
Institute of
Pathology
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Small cell
lung cancer
obstructing
left main stem
bronchus
Univ Utah
Dept of
Pathology
http://medlib.med.utah.edu/WebPath/LUNGHTML/LUNG067.html
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Diagnostic Samples
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Sputum cytology
Bronchoscopy: cytology and/or biopsy
Transthoracic needle biopsy
Thoracoscopy or open lung biopsy
Pathological examination of lobectomy
Biopsy of metastatic lesion
– peripheral lung
– distal e.g. liver, brain
• Autopsy
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Pathology and Cytology
• Pathology:
– Usually adequate: sample from
thoracoscopy, lobectomy, pnuemonectomy
or autopsy.
– Sometimes adequate: core needle biopsy
of pulmonary, pleural or metastatic lesion
– Sometimes adequate: cytology from
bronchoscopy, pleural fluid
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Keratinizing squamous cell CA
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Keratinizing squamous cell CA
Bronchial cytology
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Adenocarcinoma
Lobectomy
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TTF-1 immunohistochemistry
Malignant cells which stain positive with immunostains are
typically brown. For adenoCA, only lung and thyroid are
positive, other adenoCA (e.g. breast) are negative
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TTF-1 immunohistochemistry
Another example of a primary pulmonary adenocarcinoma which
shows strong nuclear staining with TTF-1.
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CK7/CK20 immunohistochemistry
Strong cytoplasmic staining: cytokeratin 7 (CK7) in pulmonary
adenocarcinoma. Colon cancers are typically CK7 negative.
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CK7/CK20 immunohistochemistry
Cytokeratin 20 (CK20) negative in pulmonary adenocarcinoma.
Colon cancers are typically CK20 positive.
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Adenocarcinoma metastatic to
cerebellum
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Adenocarcinoma of breast
metastatic to lung
http://medlib.med.utah.edu/WebPath/LUNGHTML/LUNG080.html
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Metastatic
disease
involving the
lung
Univ Utah
Dept of
Pathology
http://library.med.utah.edu/WebPath/LUNGHTML/LUNG078.html
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Bronchioloalveolar Carcinoma
http://medlib.med.utah.edu/WebPath/LUNGHTML/LUNG124.html
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Large cell undifferentiated
metastatic to inguinal nodes
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Small cell lung cancer
http://medlib.med.utah.edu/WebPath/LUNGHTML/LUNG075.html
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Small cell lung cancer
Small core biopsy
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Small cell lung cancer
Malignant pleural effusion
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Lung cancer cell types
% attributable to smoking
Sridhar et al, Am J Clin Oncol 1991
100
50
0
Squam SCLC Adeno Large
Non-smoker
Ad-Sq
BAC
Smoker
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Lung Cancer Cell Types
Male Smokers vs. Non-smokers
Barbone et al Chest 1997 112:1474
100
50
Smoker
Non-smoker
0
All
Squam
SCLC
Adeno
Non-smoker
Large
Smoker
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Changes in Lung Cancer Cell Type
Males and Females 1964 compared to 1985
Squamous
AdenoCA
Small cell
Large cell
Males
1964
56
4
4
36
Males
1985
37
27
17
29
Females
1964
6
41
6
47
Females
1985
23
40
30
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El-Torky et al, Cancer 1990 65:2361
56
Michael Thun, Epidemiology and
Surveillance Research Division
American Cancer Society, JNCI 1997
• Smoking is the major cause of
adenocarcinoma, and other lung cancer
cell types.
• Death rates from adenocarcinoma
remained low and essentially unchanged
from CPS-I (1959-1961) to CPS-II (19821984) in lifelong nonsmokers, but they
increased markedly in smokers.
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Michael Thun, Epidemiology and
Surveillance Research Division
American Cancer Society, JNCI 1997
Adenocarcinoma incidence in
Connecticut increased nearly 17
fold in women and nearly 10 fold in
men from 1959-1991.
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Levi, Switzerland, Cancer 1997
Reported on lung cancers diagnosed
from 1974 to 1994 in pop of 760,000:
• “adenocarcinoma incidence increased
in both genders by approximately 2.5
fold; and during the period 1990-1994,
in young adults of both genders, it was
more than 3 fold higher than the
incidence of squamous cell carcinoma.”
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Levi, Switzerland, Cancer 1997
6
5
4
3
2
1
0
1974-79
1980-84
1985-89
1990-94
Adenocarcinoma
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Rubin: Use of cytokeratins 7 and 20 in determining the
origin of metastatic carcinoma of unknown primary, with
special emphasis on lung cancer. Eur J Cancer Prev 2001.
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Smoking cessation does not
reduce risk of lung cancer
• Age at smoking cessation “locks”
patient onto persistent lung cancer risk
curve.
• The earlier that you quit smoking, the
smaller is your lifetime risk, but risk
persists.
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Smoking cessation
and lung cancer
Cumulative risk of
death by age 75
Peto, BMJ 2000
Halpern, JNCI 1993
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Long term smoking cessation
in an asbestos worker
Example of risk calculations
• Mr. W.C.M. born 08/14/1922, died at
age 77 of squamous cell lung cancer.
• Smoked 2-3 packs per day from age 18
until age 57, 20 years prior to the
diagnosis of his lung cancer.
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Lung cancer mortality in 77 year
old men
CPSII data Halpern: J Natl Cancer Inst 1993
• Ongoing smokers: 859/100,000 per
year.
• Ex-smokers stopped age 57:
354/100,000 per year.
• Never smokers: 39.5/100,000 per year.
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Lung cancer despite long term smoking
cessation in 77 yr old asbestos worker
• Although risk of lung cancer was
reduced by smoking cessation at age
57, 40 years of smoking 2-3 packs of
cigarettes per day prior to cessation
resulted in a large, persistent lung
cancer risk, estimated to be:
(354-39.5)/39.5 or 800% greater than
a never smoker.
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Attributable risk: The proportion of disease in exposed
individuals that can be attributed to exposure to an agent, as
distinguished from the proportion of disease attributed to all
other causes.
Incidence due
to exposure
Incidence not
due to exposure
Exposed
Un-exposed
AR = (incidence in the exposed) - (incidence in the unexposed)
incidence in the exposed
AR = (354-39.5)/354
AR = 89%
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Carcinogen
Benzo[a]pyrene
4-Methylnitrosamino)-1(3-pyridyl)-1-butanone
(NNK)
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Denissenko M. Science, October 1996
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Denissenko M. Science, October 1996
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K-ras Mutations in AdenoCA
Ahrendt 2001
Cancer gene
Smokers
Non-smokers
K-ras
43%
0%
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Sanchez-Cespedes et al.
Chromosomal Alterations in Lung
Adenocarcinoma
Cancer Research 61,1309–1313,
February 15, 2001
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Fractional
allelic loss
or gain
Sanchez-Cespedes et al. Chromosomal Alterations in Lung
Adenocarcinoma. Cancer Research 2001. 61:1309–1313
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Playboy Magazine
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South Miami
Hospital
Dr. Allan Feingold
Chief, Division of Pulmonary Medicine,
6200 SW 70th Ave
Miami, Florida 33143
TEL:
786-662-5229
Email:
[email protected]
79