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Kent J. Blanke D.O. FACOS

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Small cell lung cancer has a high response rate to chemotherapy and radiation, ... Smokers have a 10-25 fold increase in lung cancer incidence compared to nonsmokers. ... – PowerPoint PPT presentation

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Title: Kent J. Blanke D.O. FACOS


1
Kent J. Blanke D.O. FACOS
  • Bronchogenic Carcinoma

2
My Rules For Lung Masses
  • I am taught to think the worst.
  • Any lung mass is cancer until proven otherwise!!

3
Bronchogenic Carcinoma
  • Epidemiology
  • Etiology/risk factors
  • Pathogenesis
  • Pathology
  • Diagnosis
  • Staging
  • Management
  • Surgical Management
  • Prevention

4
Quick Pearls
  • Lung Cancer is the leading cause of cancer death
    in both men and women in the United States.
  • Bronchogenic Carcinoma is divided into two
    subgroups Small-cell lung cancer (SCLC) and
    non-small-cell lung cancer (NSCLC).
  • Non-small-cell includes adenocarcinoma, squamous
    cell, and large cell cancers.

5
Quick Pearls
  • The correct tissue diagnosis is critical to
    determine the appropriate therapy.
  • Small cell lung cancer has a high response rate
    to chemotherapy and radiation, and is rarely
    treated by surgery alone. It is highly
    aggressive, and tend to metastasize.
  • Non-small cell lung cancer can be cured by
    surgery alone in certain stages and is not
    curable by chemotherapy alone.

6
Epidemiology
  • Lung cancer is the second most common cancer in
    the U.S.
  • It accounts for 15 of all cancers.
  • Lung cancer accounts for approximately one-fourth
    of all cancer deaths.
  • In 2000 the deaths attributed to lung cancer were
    160,000, exceeding the combined total deaths of
    breast, prostate, and colorectal cancer.

7
Epidemiology
  • Historically lung cancer predominated in men,
    however with the increase in smoking rates among
    women, the estimated male to female ratio is 1.2
    1

8
Etiology/Risk Factors
  • Cigarette Smoking
  • Asbestos exposure
  • Radon exposure
  • COPD
  • Other carcinogens

9
Cigarette Smoking
  • Cigarette smoking is the most important risk
    factor in the development of lung cancer.
  • Smokers have a 10-25 fold increase in lung cancer
    incidence compared to nonsmokers.
  • Cigarette smoking accounts for 85 of lung
    cancer seen in the USA.

10
Cigarette Smoking
  • More than 40 carcinogens have been identified in
    cigarette smoke, some include polycyclic
    aromatic hydrocarbons, nickel, vinyl chloride,
    aldehydes, catechols, peroxides, and
    nitrosamines.
  • Smoking cessation causes a gradual drop in lung
    cancer risk, but not a complete normalization of
    risk

11
Cigarette Smoking
  • After 10-15 years of abstinence from smoking the
    life long risk of lung cancer approximates that
    of a nonsmoker.
  • Second hand smoke contains a significant amount
    of carcinogens.
  • Second hand smoke increases the chances of
    developing lung cancer with a relative risk of 1.3

12
Asbestos Exposure
  • Inhalation of asbestos fibers may cause both
    pulmonary and pleural malignancies, including
    bronchogenic carcinoma (all 4 types) and pleural
    mesothelioma.
  • The relative risk of lung cancer in an asbestos
    worker is approx. five fold.
  • The lag between time of first exposure to
    asbestos and the development of cancer ranges
    from 20-30 years.

13
Radon Exposure
  • In the US, as many as 30,000 lung cancer deaths
    may be attributable to radon exposure each year.
  • Mining of radioactive ores was the first
    occupation to be linked to the development of
    lung cancer.
  • The alpha particles of radon daughters are
    believed to deliver significant radiation to
    bronchial epithelium.
  • Significant radon exposure produces a 15 fold
    increase in the risk of developing lung cancer

14
COPD
  • The presence of COPD defined as either air flow
    obstruction on PFTs or symptoms of chronic
    bronchitis increases the risk of lung cancer
    several fold.
  • COPD is a risk factor by itself and is not just a
    reflection of the number of cigarettes smoked.

15
Pathogenesis
  • The development of bronchogenic carcinoma follows
    a multi-step carcinogenesis process with the
    successive accumulation of mutations in a number
    of genes involved in regulating growth.
  • DNA damage occurs after exposure to carcinogens.

16
Pathogenesis
  • A progression of histologic change occurs.
  • 1. proliferation of basal cells
  • 2. development of atypical nuclei with prominent
    nucleoli
  • 3. stratification
  • 4. development of squamous metaplasia
  • 5. carcinoma in situ
  • 6. invasive carcinoma

17
Pathogenesis
  • Oncogenes (c-myc, N-ras, c-erbB-2)
  • Tumor suppresor genes ( p53, retinoblastoma gene
    Rb)
  • Abnormalities of p53 expression occur in up to
    100 of SCLC and 75 of NSCLC.

18
Pathology
  • There is a slight preponderance of lung cancer
    developing in the right lung because the right
    lung has approx. 55 of the lung parenchyma.
  • Lung cancer also tends to develop more commonly
    in the upper lobes than the lower lobes.

19
Pathology
  • Squamous cell accounts for one-third of all lung
    cancers. Until recently it was the most common
    cell type. It has been surpassed by
    adenocarcinoma which makes up approx. 45.
  • Large cell accounts for 15-20 of tumors.
  • Small cell makes up 20-25 of primary lung
    malignancies.

20
Squamous Cell
  • Squamous cell carcinoma tends to originate in the
    central airways. Its origin in the bronchial
    epithelium explains the occasional occurrence of
    positive sputum cytology in the absence of chest
    radiographic abnormalities

21
Adenocarcinoma
  • Most of these tumors are peripherally located
    (75). Tends to metastasize earlier than squamous
    cell. Due to the peripheral location of these
    tumors sputum cytology is rarely positive.
  • A subcategory of adenocarcinoma called
    Bronchioalveolar carcinoma also arises in the
    periphery. However, this sub type tends to be
    more indolent and offer a better prognosis. These
    tumors appear as interstitial infiltrates on
    radiograph and can be confused with infectious
    pneumonitis.

22
Large Cell
  • The location and behavior of large cell carcinoma
    is very similar to that of squamous cell
    carcinoma.
  • Two rare subtypes of large cell are the giant
    cell carcinoma assoc with peripheral
    leukocytosis, and clear cell carcinoma which
    resembles renal cell carcinoma.

23
Small Cell
  • Approximately 80 originate centrally.
  • They tend to expand against the bronchus causing
    extrinsic compression.
  • These tumors spread rapidly to regional hilar
    nodes, mediastinal lymph nodes, and distant sites
    especially bone marrow and the brain.

24
Diagnosis
  • Management of Solitary Pulmonary nodule
  • Symptomatic Presentation of Cancer Patients
  • Laboratory Evaluation
  • Imaging Evaluation
  • Obtaining Tissue Diagnosis

25
Management of Solitary Pulmonary nodules
  • A significant number of lung cancers are
    initially detected as asymptomatic radiographic
    abnormalities.
  • A solitary pulmonary nodule is defined as an
    asymptomatic mass within the lung parenchyma
    that is less than 3cm and is well circumscribed.
  • Overall 33 of these masses are malignant, and
    50 are malignant if the patient is older than
    50.

26
Management of Solitary Pulmonary nodules
  • Discovery of a new nodule on chest film should
    begin with the review of previous chest
    radiographs.
  • Lesions that are new or increasing in size should
    be treated as pulmonary malignancies.

27
Management of Solitary Pulmonary nodules
  • Fine needle aspiration should be performed
  • If FNA is positive then resection is recommended.
  • If the FNA is nondiagnostic, definitive treatment
    or other diagnostic measures should be
    undertaken.
  • A wedge resection of the nodule is not always
    possible and lobectomy may need to be utilized
    for both diagnosis and treatment
  • Mediastinal lymph node dissection should be
    performed as part of the definitive treatment.

28
Conservative treatment in certain populations
  • Patients with a mass unchanged for more than 2
    years. Needs to be documented by serial
    radiography.
  • Patients with benign patterns of calcification
    such as hamartomas.
  • Patient with masses clearly caused by
    inflammatory causes.

29
Symptomatic Presentation of patients
  • Patients are usually 50-70 years of age.
  • Lung cancer is clinically silent for most of its
    course. The presentation of symptoms is
    associated with later-stage disease and a worse
    prognosis.
  • Most patients have bronchopulmonary symptoms
    cough(75), dyspnea(60), chest pain(50), and
    hemoptysis(30).

30
Signs and Symptoms
  • Cough 75
  • Weight loss 68
  • Dyspnea 60
  • Chest pain 50
  • Sputum production 45
  • Hemoptysis 30
  • Malaise 26
  • Bone pain 25
  • Lymphadenopathy 23
  • Fever 21
  • Hepatomegaly 21
  • Clubbing 20
  • Neuropathy 10
  • Superior Vena Cava 4 syndrome
  • Dizziness 4
  • Hoarseness 3
  • Asymptomatic 12

31
Symptomatic Presentation of patients
  • Other symptoms may include hoarseness, superior
    vena cava syndrome, chest wall pain, Horner
    syndrome, dysphagia, pleural effusion, or phrenic
    nerve paralysis.
  • Nonspecific symptoms such as anorexia, malaise,
    fatigue, and weight loss may occur in 70 of
    patients.

32
The Silent Killer
  • Because the pulmonary parenchyma does not contain
    nerve endings, many lung cancer grow to a large
    size before they cause local symptoms
    (hemoptysis, change in sputum production,
    dyspnea, obstruction, or pain).

33
Cough
  • Either a new cough or a change in the nature of a
    chronic cough is the most common presenting
    symptom of bronchogenic carcinoma.
  • This symptom in a smoker should always cause
    concern.

34
Hemoptysis
  • Hemoptysis, either gross or minor, commonly
    occurs when mucosal lesions ulcerate.
  • Although the most common cause of hemoptysis is
    bronchitis, this sign should always lead to
    further investigation.

35
Obstruction
  • Tumors that obstruct major airways can produce
    wheezing, and unilateral wheezing suggests a
    localized obstruction

36
Lung Abscess
  • Lung cancer is often associated with cavitation
    and lung abscess formation, due either to airway
    obstruction with postobstructive pneumonia or to
    necrosis of a large tumor mass.
  • Clinical signs particularly indicative of
    malignancy associated lung abscess include
    chronicity of symptoms, lack of high fever, and
    lack of leukocytosis.

37
Pleural Effusions
  • Pleural effusions occur in approx 10-20 of
    patients at the time of diagnosis.
  • It is the most frequent sign that a tumor is
    non-operable.
  • Invasion of the pericardium can lead to cardiac
    tamponade as well as arrhythmia.

38
Superior Vena Cava Syndrome
  • Due to obstruction of the superior vena cava
    either by tumor or associated thrombosis.
  • Should be treated promptly following
    establishment of tissue diagnosis.

39
Horner Syndrome
  • Results from involvement of the superior cervical
    ganglion.
  • Characterized by unilateral facial anhidrosis,
    ptosis, and miosis.
  • Hoarseness can occur from invasion of the
    recurrent laryngeal nerve either from the mass
    directly or by regional lymph nodes.
  • Hoarseness is most commonly assoc with
    unresectability.

40
Pancoast Syndrome
  • Occurs in tumors involving the apex and superior
    sulcus of the lung.
  • Results from local invasion into the brachial
    plexus as well as the cervical sympathetic chain.
  • Clinical manifestations are dominated by shoulder
    and arm pain.
  • Can include Horner Syndrome and superior vena
    cava syndrome.
  • Delay in diagnosis is common due to the
    musculoskeletal component.

41
Digital Clubbing
  • Digital clubbing is seen in a variety of
    pulmonary conditions but occurs most commonly in
    association with bronchogenic carcinoma.

42
Other poor prognostic indicators
  • Esophageal obstruction
  • Vertebral body invasion
  • Distant extrathoracic tumor effects commonly
    involving lymph nodes, CNS, liver, bone and bone
    marrow, and the adrenal glands

43
Paraneoplastic Syndromes
  • Occur in 10 of patients with bronchogenic
    carcinoma.
  • Can be divided into systemic, endocrine,
    neurologic, cutaneous, hematologic, and renal
    categories.

44
Endocrine Abnormalities
  • Are relatively common in lung cancer.
  • Hypercalcemia is most commonly assoc with
    squamous cell and may occur directly due to bone
    invasion or indirectly due to Parathyroid
    Hormone.
  • SIADH and Cushing syndrome can be associated with
    small cell.
  • Elevations in ACTH may be found in 30-50 of
    small cell carcinomas.
  • Cushing syndrome is manifested by muscle
    weakness, hypokalemia, metabolic alkalosis, and
    diabetes.

45
Neurologic disorders
  • There is an association between small cell lung
    cancer and the Eaton-Lambert Myasthetic
    syndrome.
  • This syndrome is characterized by proximal muscle
    weakness, decreased or absent deep tendon
    reflexes, paresthesias, and autonomic dysfunction.

46
Laboratory Evaluation
  • CBC
  • Electrolyte panel
  • Liver function tests
  • Serum calcium assay
  • Tumor Markers

47
Tumor Markers
  • Carcinoembryonic antigen (CEA)
  • Creatine Kinase BB (CK-BB)
  • Neuron-specific enolase (NSE)
  • Bombesin/gastrin-releasing peptide (GRP)
  • Tissue Polypeptide antigen (TPA)
  • CA-125
  • NSE and CEA are the markers used most frequently.

48
Imaging Evaluation
  • Chest X-ray
  • Computed Tomography
  • Magnetic Resonance Imaging
  • Positron Emission Tomography
  • Bone Scan

49
Imaging Evaluation
  • Radiologic evaluation is an integral part of the
    diagnosis and treatment of lung cancer.
  • Chest radiography and CT of the chest and upper
    abdomen to assess Liver and adrenals are the
    standard for initial imaging.
  • Bone scan and MRI of the brain are reserved for
    organ specific or nonspecific symptoms.

50
Imaging Evaluation
  • CT and MRI can identify the location of the
    primary tumor with respect to the other
    mediastinal structures.
  • However, it is difficult to determine if the mass
    merely abuts adjacent structures or if it invades
    them.
  • Often this distinction can only be made at the
    time of surgical exploration.

51
Chest X-ray
  • Chest films provide information regarding the
    size, shape, density, and location of the tumor.
  • Can also evaluate for the presence of thoracic
    lymphadenopathy, pleural effusion, pulmonary
    infiltrates, pneumonia, or consolidation.
  • Changes in the contour of the mediastinum
    secondary to lymphadenopathy, and mets to ribs or
    other bony structures may also be visualized.

52
Chest X-ray
  • Most asymptomatic lung cancers are detected on
    chest radiographs.
  • Lesions smaller than 5-6mm are rarely noticed.
  • The radiographic appearance of a lesion cannot
    reliably distinguish between a benign and
    malignant process.

53
Radiographic appearances characteristic of
malignant lesions
  • Lobulation
  • Shaggy margins
  • Poorly defined margins
  • Calcifications (Concentric, Popcorn pattern)

54
Chest X-rays
55
CT scan
  • CT scan of the chest reveals small nodules
    undetectable on routine chest X-ray.
  • CT provides more detail than chest X-ray
    regarding the surface characteristics of the
    tumor, relationships of the tumor to the
    mediastinum and mediastinal structures, and mets
    to lung, bone, liver, and adrenals.

56
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57
Lymph Node Involvement
58
CT scan
  • CT of the chest has a 65 specificity and an 85
    sensitivity for identifying mediastinal
    lymphadenopathy.
  • When lymph nodes are greater than 1.5 cm in
    diameter, CT in approx 85 specific in
    identifying mets to mediastinal lymph nodes.

59
CT scan
  • CT scan for lung cancer should include the
    abdomen for evaluation of the liver, adrenals,
    and kidneys for metastasis.

60
Adrenal and Liver Mets
61
Brain mets
62
MRI
  • MRI is helpful for evaluating apical lung lesions
    where the coronal reconstruction may be help to
    identify proximity to the brachiocephalic vessels
    and the brachial plexus and the spine.
  • MRI is particularly useful to detect vertebral,
    spinal cord, and mediastinal invasion in selected
    patients.

63
PET scan
  • Cancer cells metabolize glucose more rapidly than
    normal cells.
  • The 18-fluorodeoxyglucose (FDG) given
    intravenously is trapped within malignant cells
    and can be imaged with PET

64
PET
65
PET scan
  • PET scanning can often discriminate between
    benign and malignant parenchymal nodules.
  • The sensitivity and specificity of PET with FDG
    for detecting nonmalignant lesions ranges form
    94-97 for benign lesions and 80-100 for
    malignant lesions.
  • Active inflammation may yield false results.
  • Carcinoid tumors as well as bronchioalveolar
    tumors take up the radiolabeled glucose poorly,
    leading to false negative scans.

66
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67
Bone Scan
68
Tissue Diagnosis
  • The definitive diagnosis of lung cancer requires
    histopathologic or cytologic confirmation.
  • Methods for obtaining tissue include
    bronchoscopy, transthoracic needle aspiration,
    mediastinoscopy, thoracoscopy.

69
Tissue Diagnosis
  • Sputum cytology is positive in more than 50 of
    cases, especially in centrally located tumors.
  • Results of sputum samples are highly variable and
    interpretation my be difficult due to poor
    samples, purulence, malignant cell degeneration,
    poor sample preparation, and inexperienced
    cytologists.

70
Tissue Diagnosis
  • Negative sputum cytology in a suspicious setting
    should not be the basis for ending the
    evaluation.
  • Needle biopsy of suspicious pulmonary masses
    under either fluoroscopic of CT guidance is
    highly accurate, with a sensitivity of 90-95

71
Bronchoscopy
  • For endoscopically visible lesions, bronchoscopy
    is diagnostic in over 90 of cases.
  • The sensitivity for peripheral lesions is lower
    than for directly visualized airway lesions.
  • Transbronchial biopsy may be performed with a
    special 21-gauge needle through the bronchoscope.

72
Bronchoscopy
  • Bronchoscopy is recommended before any planned
    pulmonary resection if the sputum is positive
    with a negative chest X-ray or if atelectasis or
    an infiltrate fail to clear with medical
    management.
  • The surgeon always performs bronchoscopy to
    independently assess the endobronchial anatomy,
    exclude other tumors, and ensure all known cancer
    will be encompassed by the planned pulmonary
    resection.

73
Bronchoscopy
74
Mediastinoscopy
  • Cervical mediastinoscopy with sampling of lymph
    nodes is also highly accurate in selected
    patients with lymphadenopathy.
  • A mediastinoscopy should be a part of the
    evaluation in all patients with clinically
    suspicious lymph nodes on CT.
  • Lymph nodes 1.5 cm are more likely to involved
    with metastasis from lung cancer.

75
Mediastinoscopy
  • Complications of mediastinoscopy are infrequent
    but include massive hemorrhage, injury to the
    trachea or bronchi, esophageal injury, and
    pneumothorax.

76
VATS
  • Video assisted thoracic surgery can evaluate
    enlarged aortic and inferior mediastinal lymph
    nodes

77
NSCLC Staging
  • The most widely accepted system of staging for
    NSCLC is the TNM anatomic classification.
  • Stage I and II tumors are completely contained
    within the lung and may completely be resected
    with surgery.
  • Stage IV disease includes metastatic disease and
    is not typically treated by surgery except in
    those requiring surgical palliation.

78
NSCLC Staging
  • Stage IIIA and IIIB are locally advanced tumors
    with mets to the ipsilateral mediastinal
    structures or involving the mediastinal
    structures.
  • These tumors may be mechanically removed with
    surgery, however, surgery does not control the
    micromets.

79
Regional Lymph Nodes Used For Staging
80
SCLC Staging
  • Small cell carcinoma is not generally included in
    the TNM classification system.
  • The majority of small cell tumors are systemic at
    the time of diagnosis.
  • The two-stage system devised by the Veterans
    administration lung cancer study group is used
    for small cell staging.
  • The two-stage system classifies small cell as
    either limited or extensive.

81
Management
  • Options include
  • Surgery for localized disease
  • Chemotherapy for metastatic disease
  • Radiation for local control in patients not
    amenable to surgery
  • Radiation and chemotherapy together are better
    than either one alone for primary treatment of
    advanced cancer.

82
Management
  • The most important prognostic factors identified
    to date are disease stage, performance status,
    and extent of weight loss.
  • Patients who have lost 5 or more of body weight
    in the preceding 2-6 months have a poor
    prognosis.

83
Treatment of NSCLC
  • Stage I and II
  • Surgical resection is the treatment of choice in
    early stage lung cancer.
  • Wedge and segmental resections are safer but lead
    to a higher incidence of recurrence than
    pneumonectomy or lobectomy
  • 5 year survival rates for stage I and II disease
    are 60-70 and 40-55 respectively.

84
Treatment of NSCLC
  • Stage IIIA
  • Stage IIIA is included chest wall invasion,
    mediastinal nodal disease, and direct invasion of
    mediastinal structures.
  • IIIA is potentially resectable
  • 5 year survival rates are up to 40 with surgery
  • Unfavorable factors include gross extranodal
    disease and multiple nodal level involvement.
  • Studies indicate increased survival with either
    chemo or a combination of chemo and radiation
    before surgery.

85
Treatment of NSCLC
  • Stage IIIB
  • Patients with IIIB disease are generally
    unresectable.
  • Treatment with chemotherapy and/or radiation
    without surgery may improve survival rates.

86
Treatment of NSCLC
  • Stage IV
  • Disseminated disease occurs in the majority of
    patients with lung cancer.
  • At the time of presentation two thirds of
    patients already have disseminated disease.
  • Median survival time of 4 months
  • 1 year survival rate of approx 10-15
  • Palliative treatment is the main option for the
    majority of these patients.

87
Thoracotomy
88
Thoracotomy
89
Thoracotomy
90
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91
Treatment of Small Cell
  • Small cell cancer is assumed to be a systemic
    disease at the time of presentation.
  • Systemic chemotherapy is the treatment modality
    most commonly employed in these patients.
  • Combined chemo and radiation is the accepted
    standard of care for limited stage SCLC.
  • Surgery should only be considered for resection
    of solitary pulmonary nodules and must be
    followed by adjuvant chemotherapy.

92
Novel Therapies
  • Laser therapy
  • Useful for palliation of patients with
    obstructing disease
  • Nd-YAG is the most common type
  • Brachytherapy
  • Useful for palliation of patients with
    obstructing disease
  • Involves the placement of an ionizing
    radioactive source into the airway through
    catheters placed adjacent to the tumor.

93
Novel Therapies
  • Photodynamic therapy
  • Involves the injection and subsequent uptake and
    selective retention of a hematoporphyrin
    derivative into the tumor cells
  • The compound is then photoactivated by light at
    630nm to cause cell death.
  • Patients with localized stage I endobronchial
    lesions.
  • The majority of patients have a complete response
    of the tumor.
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