Kent J. Blanke D.O. FACOS

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Kent J. Blanke D.O. FACOS

• Bronchogenic Carcinoma

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My Rules For Lung Masses

• I am taught to think the worst.
• Any lung mass is cancer until proven otherwise!!

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Bronchogenic Carcinoma

• Epidemiology
• Etiology/risk factors
• Pathogenesis
• Pathology
• Diagnosis

• Staging
• Management
• Surgical Management
• Prevention

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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.

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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.

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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.

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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
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Etiology/Risk Factors

• Cigarette Smoking
• Asbestos exposure
• Radon exposure
• COPD
• Other carcinogens

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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.

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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

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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

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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.

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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

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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.

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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.

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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

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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.

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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.

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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.

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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

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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.

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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.

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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.

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Diagnosis

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

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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.

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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.

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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.

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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.

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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).

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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

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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.

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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).

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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.

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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.

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Obstruction

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

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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.

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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.

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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.

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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.

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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.

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Digital Clubbing

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

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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

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Paraneoplastic Syndromes

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

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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.

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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.

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Laboratory Evaluation

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

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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.

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Imaging Evaluation

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

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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.

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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.

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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.

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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.

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Radiographic appearances characteristic of
malignant lesions

• Lobulation
• Shaggy margins
• Poorly defined margins
• Calcifications (Concentric, Popcorn pattern)

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Chest X-rays
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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.

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Lymph Node Involvement
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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.

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CT scan

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

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Adrenal and Liver Mets
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Brain mets
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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.

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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

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PET
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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.

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Bone Scan
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Tissue Diagnosis

• The definitive diagnosis of lung cancer requires
  histopathologic or cytologic confirmation.
• Methods for obtaining tissue include
  bronchoscopy, transthoracic needle aspiration,
  mediastinoscopy, thoracoscopy.

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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.

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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

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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.

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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.

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Bronchoscopy
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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.

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Mediastinoscopy

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

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VATS

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

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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.

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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.

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Regional Lymph Nodes Used For Staging
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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.

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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.

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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.

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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.

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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.

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Treatment of NSCLC

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

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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.

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Thoracotomy
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Thoracotomy
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Thoracotomy
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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.

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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.

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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.