A Case

1
A Case

• Mr. G
• 61 y/o male transferred from OSH for weakness, HA
• Had abnormal imaging discovered at OSH
• Sxs present for 3-4 months
• What else do you want to know?

2
Case continued

• HAs occur 3-4 times/day, lasting 10-15 minutes
  with a black spot in the center of his R eye
  visual field
• Was seen 2 months earlier in UCC, evaluated by
  neuro who recommended MRI, scheduled 11 days from
  now

3
Case continued

• Notes LUE weakness, intermittently dropping
  objects
• Intermittent LLE weakness and increased sense of
  smell
• Remainder of ROS unremarkable except for some
  mild increased SOB
• Next?

4
Case continued

• PMH migraines, depression, DLD
• Social handyman, former factory worker, remote
  EtOH (16 years ago), 1.5-2 ppd with 80 pack year
  hx
• Medications combivent, metoprolol, simvastatin,
  ASA, omeprazole, naproxen
• After history comes

5
Case continued

• Physical exam
• 97.2 88 20 138/82 95 RA
• GEN Alert, intermittent confusion
• HEENT NC/AT, PERRLA, EOMI, MMM
• RESP CTAB, occ wheeze
• CVS RRR No g/m/r
• ABD Soft. NT/ND BS
• EXTWarm, well-perfused. No c/c/e

6
Case continued

• NEUROGrossly non-focal with good motor strength
  bilaterally in upper and lower extremities.
  Sensation intact. Noted to have transient
  weakness/instability on ambulation by nursing
  staff.
• Now what?

7
Case continued

• Work-up includes
• Labs
• Na K Cl CO2 BUN Cr
  Glu Ca
• 137 4.6 105 23 21 0.83
  146 9.9
• TP Alb TB AP AST
  ALT
• 7.6 4.4 0.6 100 18
  17
• WBC Hgb Hct Plt
• 7.4 16.8 47.7 246

8
Case continued

• Imaging as follows
• CT head - at least two mass lesions in the right
  cerebral hemisphere resulting in extensive right
  cerebral edema and leftward subfalcine shift and
  ventricular effacement. There is sulcal
  effacement as well. No uncal herniation is
  identified. There is no associated hemorrhage."
• Also noted mass lesion posterior in the left
  parietal lobe w/ assd edema

9
Case continued

• MRI - Multiple supratentorial metastatic lesions
  with the largest lesion in the right parietal
  lobe with mass-effect and midline shift of 1
  cm. Focal area of chronic ischemic change/gliosis
  in the right cerebellar hemisphere

10
Case continued

• Next step?
• Treat the acute process
• Steroids Decadron 6mg Q6h
• SSI
• Neuro following
• So what about that CXR?

11
Case continued

• CXR - Right hilar soft tissue fullness, recommend
  CT chest as well as chronic appearing coarse
  interstitial densities in the lungs are likely
  reflecting sequela from smoking and/or emphysema
• CT Chest - Subcarinal and right hilar adenopathy
  with maximal diameter of 2.3 cm associated with
  several right lung nodules
• CT Abd/pelv unremarkable

12
Case continued

• A diagnostic test was performed
• Bronch showed
• Negative endobronchial bx
• BAL negative for malignant cells
• Subcarinal LN bx non-small cell lung ca

13
Case continued

• Pt discharged after acute process resolved and
  was seen by H/O in f/u completed course of
  radiation therapy to brain and initiated on
  Tarceva
• T1N1M1 stage IV
• Despite therapy had progression of disease so was
  initiated on carbo/taxol therapy
• Repeat MRI showed worsening cerebral edema

14
Case continued

• Three months later pt admitted for worsening
  fatigue/weakness
• Hospice services initiated and patient passed
  away 9 days later

15
Lung Cancer

• Matthew Knoch
• Senior Talk
• May 20th and 22nd, 2009
• University Hospitals Case Medical Center and VA,
  Cleveland OH

16
Objectives

• Identify background knowledge of lung cancer
  rates and incidence, including etiology and
  causal factors
• Learn the different types of lung malignancies
  and understand their diagnosis, staging and
  prognosis
• Understand the basic treatment options

17
Background Information

• Most common type of cancer in industrialized
  nations leading cause of mortality from cancer
• Accounts for 13 of all new cancer diagnoses and
  30 of cancer deaths in men and 7 of deaths
  among both sexes however incidence in women is
  increasing greatly
• Remains the most frequent fatal malignancy, 91K
  male and 71K female deaths/year

18
Background Information (Cont)

• Annual deaths have increased from 18,000 in 1950
  to 158,000 in 1997 in US and roughly 900,000
  deaths worldwide with gt50 of those in developed
  countries
• Death rate has also increased 3-fold from 19.9 to
  74 per 100,000 in men and 7-fold 4.5 to 31 per
  100,000 in women during same time period
• Spectrum of disease more deaths than the next 3
  most common cancers combined (colon/rectum,
  breast and prostate) 114,690 cases/90,810
  deaths in men and 182,460 cases/71,030 deaths in
  women in 2008

19
Background Information (Cont)

• Accounts for 13 of all malignancies in both
  sexes
• Most often occurs between ages 40-70, peaks in
  the 50-60 age range

20
So what causes lung cancer?

• Probably
  multifactorial (genetics?)
  
• Not the Only
  cause (90 of
• cases)but also based
  upon
• 1.
  Amount of daily smoking
• 2.
  Tendency to inhale
• 3.
  Duration of smoking
• 4. Age of initiation of smoking?
• Increases
  risk by about 10-20 fold
• over
  non-smokers in
• 
  retrospective studies compared
• with control
  subjects, shown by
• landmark epidemiologic studies
• in the 1950s in US/Britain

21
It doesnt stop there

• Cancers of the lip, tongue, oropharynx, throat,
  bladder and kidney cancer are all implicated in
  smoking
• So what helps?
• Smoking cessation 10 years out returns risk
  level to that of nonsmokers (dose response
  relationship exists)

22
Why are cigarettes so bad and how do they cause
cancer?

• Over 1200 chemical substances (50 identifiable
  carcinogens) found in the smoke of cigarettes
  including
• Initiators such as PAH
• Promoters such as phenol derivatives
• Radioactive elements polonium-210, carbon-14,
  potassium-40
• Others arsenic, nickel, molds, additives

23
More on Dose Response

• The Cancer Prevention Study II (CPSII) followed
  gt1,000,000 smokers for 6 years and found that
• 1 ppd 22x the risk of dying from lung cancer
• 2 ppd 45x the risk of dying from lung cancer

24
Also helpful, kind of

• At least in the US public health interventions,
  litigation and education have contributed to a
  decline in smoking and therefore lung cancer
  rates, however this is not the case in developing
  nations across the globe
• Roughly 20-25 of the American population
  continues to smoke

25
Cigarette Consumption, per capita in adults

26
More good news

• Experiments have been unsuccessful in causing
  lung cancer in laboratory animals through
  prolonged exposure to smoke
• On the other hand, bronchioloalveolar cancers
  have been demonstrated but these are not seen
  very often in human smokers

27
Other Risk Factors

• Industrial radiation exposure, asbestos,
  workers exposed to nickel/chromate/coal/ mustard
  gas/arsenic/berylium/iron/gold/ haloether and
  newspaper industry workers (9-15)
• Air pollution both indoor and outdoor (1-2),
  radon (10), difficult to determine though
• Second hand smoke nonsmoking women married to
  smokers had a 1.2x risk of developing cancer
  possible hormonal/metabolism effects, even higher
  if gt2 ppd (roughly 3000 case/year)
• Combined risk factors approach 100

28
Molecular Genetics

• So what does the cumulative effect of all of
  these risk factors mean?
• It is thought that by the time a tumor in the
  lung has developed that anywhere from 10 to 20
  genetic mutations have occurred before a tumor
  develops
• These include c-myc, K-ras and p53

29
Other factors implicated

• Scarring researchers have noted cancer
  formation in the region of prior lung scarring
• These include areas of old infarct, metallic
  foreign bodies, wounds and granulomatous
  infections
• Most of these cancers are histiologically
  adenocarcinomas

30
Types Of Lung Cancer

• Squamous cell 25-40, epidermoid derived
• Adenocarcinoma 25-40, bronchial, acinar,
  papillary, solid, broncioalveolar
• Small cell 20-25, oat, intermediate cell
• Large cell 10-15, undifferentiated, giant or
  clear cell
• Combined squamous and adenocarcinoma

31
So what about gender?

• Since the 1950s, a gt500 lung cancer mortality
  has been identified in women
• Partially due to increasing number of women
  smokers, but it has also been observed that dose
  for dose women have increased susceptibility to
  carcinogen exposure than men

32
Good News

• The most important risk factors implicated in
  lung cancer are modifiable, e.g. stop smoking

33
Mechanism of cancer formation

• Begins as in situ cytologic atypia that
  multiplies into tumor formation
• May progress into the lumen, spread to adjacent
  areas of carina or mediastinum with nodal
  involvement, pleural invasion
• Intraparenchymal mass formation
• Rapid growth may cause local obstruction,
  hemorrhage or necrosis depending on rate of
  growth and location

34
What lung cancer likes

• Adrenals - 50 of cancers
• Liver 30-50
• Brain 20
• Bone 20

35
Adenocarcinoma

• Includes bronchial-derived and bronchioloalveolar,
  80 contain mucin
• Incidence greatly increased in the past 20 years
• Most common form in women, probably in men too
  being seen more in smokers
• Cause for the increase? Perhaps related to
  addition of filters and deeper inhalation

36
Squamous Cell Ca

• More often found in men, usually associated with
  long smoking history
• Centrally located lesions and spread locally
• Later metasteses

37
Small Cell Ca

• Oat cells given small histologic appearance
• High neuroendocrine activity
• PTH-like peptides
• Neuron-specific enolase
• Strongly associated with Tob exposure
• Centrally located

38
Large Cell Ca

• Likely represent squamous cell and
  adenocarcinomas that are undifferentiated

39
Complications of Lung Ca

• Obstruction emphysema vs. atelectasis
• PNA abscess formation
• SVC syndrome
• Pericarditis
• Pleuritis
• Neuroendocrine abnormalities
• Hypercoagulable states

40
Diagnosis

• Start with HP
• Illicit good history, especially social including
  exposure risks
• Cough, hemoptysis, weight loss, chest pain, SOB
• Physical exam

41
Diagnosis

• CXR identifies nodules usually gt1cm
• CT Chest more definitive view of lung
  parenchyma and adjacent lymph nodes
• PET scan helpful in staging to determine degree
  of metastases
• MRI/CT brain useful in looking at CNS
  involvement

42
Differential

• Other than cancer
• TB
• PE
• MI
• Other lung pathology PTX
• Simple PNAs
• Sarcoid

43
Symptoms of Lung Ca

• PNA
• Effusions
• Hoarseness/dysphagia
• SOB, diaphragm paralysis, chest pain, rib
  involvement
• SVC Syndrome
• Horners Syndrome Pancoast tumors
• Pericarditis/tamponade

44
Paraneoplastic syndromes

• SIADH small cell
• ACTH-producing tumors small cell
• PTH/PTH-rp squamous cell
• Calcitonin
• Gonadotropin
• Serotonin
• Lambert-Eaton syndrome small cell

45
Work-up

• If cancer is the answer, tissue is the issue
• i.e. bronch vs. VATS vs. CT-guided bx or
  peripheral bx

46
Staging - TNM

• Tumor size
• T1 lt or to 3cm
• T2 gt 3cm
• T3 local extension (parietal pleura, chest wall
  or within 2cm of carina)
• T4 spread to great vessels, trachea,
  mediastinum, esophagus or malignant effusion
  (nonresectable)

47
Staging - TNM

• Lymph Node
• N0 no involvement
• N1 hilar nodes
• N2 mediastinal nodes
• N3 contralateral nodes or ipsilateral
  supraclavicular (nonresectable)

48
Staging - TNM

• Metastases
• M0 none
• M1 presence (nonresectable)

49
Staging Continued

• Stage IA - T1 N0 M0
• Stage IB - T2 N0 M0 (T gt 3cm)

50
Staging Continued

• Stage IIA - T1 N1 M0
• Stage IIB - T2 N1 M0
• T3 N0 M0

51
Staging Continued

• Stage IIIA - T3 N1 M0
• T1-3 N2 M0
• Stage IIIB - Any T N3 M0
• T4 Any N M0

52
Staging Continued

• Stage IV - Any T Any N M1

53
Treatment Options

• Thoracotomy with resection is the only curative
  treatment available
• Surgical options available if NOT a small cell ca
• Chemotherapy (platinum based, topoisomerase and
  mitotic inhibitors), radiation and adjuvant
  debulking surgery (usually only palliative unless
  used in conjunction with curative resection)

54
Contraindications for Surgery

• MI within past 3 months, within 6 months only
  relative
• Major arrhythmias
• Severe pulmonary HTN
• Pre-op hypoxia
• Pre-op FEV1/FVC lt 80
• Pre-op FEV1 lt 1L
• Predictive post-op FEV1 /FVC lt 40 OR
• FEV1 lt1L

55
Prognosis
56
5-Year Relative Survival Rates by Year of
Diagnosis
 
57
Conclusions

• Lung cancer is a common malignancy in our society
  and throughout the world with the overall highest
  morbidity/mortality in terms of malignancies that
  unfortunately has not seen a significant increase
  in survival rates over the past several decades
• Bottom line, the best thing we can do as
  physicians to prevent this disease is to promote
  smoking cessation

58
Conclusions

• Finally, more research needs to be done for the
  treatment of lung cancer and perhaps the
  development and implementation of a screening
  tool for earlier diagnosis and treatment of the
  disease

59
Thank You

• Questions?
• Food for thought
• If you want to smoke
• something, smoke a
• banana

60
References

• Cotran, Kumar, Collins. Robbins Pathologic Basis
  of Disease. 6th edition, pages 741-753.
• American Cancer Society www.cancer.org
• Uptodate
• George, Light, Matthay, Matthay. Chest Medicine
  Essentials of Pulmonary and Critical Care
  Medicine, pages 316-344.
• Carpenter, Griggs, Loscalzo. Cecil Essentials of
  Medicine, 6th edition, pages 213-221.