Download 13 Hemoptysis, Cough, and Pulmonary Lesions

13
Hemoptysis, Cough, and
Pulmonary Lesions
John E. Langenfeld
Objectives
Hemoptysis
1. To know how to assess whether a patient has lifethreatening hemoptysis.
2. To list the differential diagnosis of a patient with
hemoptysis.
3. To discuss the initial stabilization of a patient presenting with hemoptysis.
4. To know the different diagnostic modalities available in the assessment of pulmonary bleeding.
5. To understand the risk and benefits of surgery
versus pulmonary embolization in the treatment
of hemoptysis.
Pulmonary Nodule
1. To discuss the differential diagnosis of nodules
presenting in the lung and mediastinum.
2. To describe the common risk factors for lung
cancer and the presenting symptoms.
3. To know the algorithm for the evaluation of a
patient with a lung nodule.
4. To be able to discuss the prognosis of patients
with different stages of lung cancer and how surgical and medical therapies affect on survival.
5. To understand which patients do not benefit from
a surgical resection.
6. To know how to evaluate a patient’s risk when
considering a pulmonary resection.
7. To discuss the surgical management of metastatic
tumors to the lung.
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Cases
Case 1
A 57-year-old man presents to the emergency room with the complaint
of hemoptysis. What is the initial workup of this patient and how
should he be treated?
Case 2
A 62-year-old man is referred to you because a routine chest x-ray
demonstrated a 1.2-cm asymptomatic nodule in the right upper lobe.
How should this patient be evaluated?
Hemoptysis
Hemoptysis most often is caused by bronchogenic carcinomas and
inflammatory diseases of the lung. Hemoptysis also can be caused
by interstitial lung disease, pulmonary embolism, cardiac disease,
coagulopathy, trauma, and iatrogenic causes. The most commonly
associated cardiac disease to cause hemoptysis is mitral stenosis.
The Swan-Ganz catheter is the most common iatrogenic cause of
massive hemoptysis in the hospital. See Table 13.1 for a thorough
listing of causes of hemoptysis.
Immediate Evaluation
The assessment of stability is the most important determination in the
initial evaluation of a patient who presents with hemoptysis. Massive
hemoptysis generally is defined as more than 250 mL of expectorated
blood within 24 hours and is associated with higher mortality rates.
Patients rarely exsanguinate from hemoptysis, but rather they asphyxiate from aspirated blood. Aspiration of even a small amount of blood
into the airways can lead to asphyxiation. See Case 13.1.
Table 13.1. Causes of hemoptysis.
Bronchogenic carcinoma
Inflammatory diseases
Tuberculosis
Aspergillosis
Cystic fibrosis
Lung abscess
Pneumonia
Bronchiectasis
Bronchitis
Cardiovascular
Mitral stenosis
Congestive heart failure
Congenital heart disease
Interstitial lung disease
Goodpasture’s syndrome
Wegener’s granulomatosis
Iatrogenic
Swan-Ganz catheter
Bronchoscopy
Pulmonary embolism
Arteriovenous fistula (rare)
Chest trauma
Pulmonary contusion
Gunshot wound
Stab wound
Transected bronchus
Miscellaneous
Coagulopathy
Epistaxis
Broncholithiasis
13. Hemoptysis, Cough, and Pulmonary Lesions
The initial immediate assessment should determine quickly whether
the patient has life-threatening hemoptysis. Patients should be considered to have potentially life-threatening hemoptysis if they have
an altered mental status, diminished blood pressure, rapid or slow
pulse, or labored breathing; give a history of aspiration or massive
hemoptysis; or have a room air O2 saturation below 90%. These
patients should be evaluated and treated emergently.
Fortunately, most patients do not present with massive hemoptysis
or with evidence of aspiration of blood. Most patients can be worked
up on a more elective basis, but they should be admitted to the
hospital for close observation. Consultants, who typically consist of a
pulmonologist and a thoracic surgeon, should be called upon early in
the patient’s evaluation.
Evaluation of a Stable Patient
The initial evaluation of a stable patient with hemoptysis consists of a
good history and physical. It is important when taking a history to
establish clearly that the bleeding is occurring from the lungs. Bleeding from the nose or upper gastrointestinal tract at times can be confused with hemoptysis. A good history usually can distinguish whether
the blood was coughed up from the lungs or whether it was regurgitated or vomited from the gastrointestinal tract.
History
The following information, obtained from a good history, can help
determine the etiology of the hemoptysis, help guide the diagnostic
evaluation, and help direct therapy:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
The amount of bleeding (greater than 250 mL/24 hours is massive)
Smoking or other risk factors for cancer
Fever, chills, productive cough (infectious)
Acute onset of shortness of breath prior to hemoptysis (pulmonary
embolism)
History of previous hemoptysis and pulmonary diseases
Cardiac history
Medications: Coumadin and platelet inhibitors; patients taking
immunosuppressive drugs (e.g., steroids, chemotherapy) are at risk
of developing fungal opportunistic infections
Alcohol use (patient at risk for aspiration pneumonia)
Prior history or exposure to tuberculosis
Travel history: (coccidioidomycosis in the Southwest, tuberculosis,
common in many countries, histoplasmosis in Mississippi,
Missouri, Ohio River Valley)
Trauma history
Physical Examination
Vital Signs
Heart rate, blood pressure, temperature, and respiratory rate should
be determined immediately. The oxygen saturation also should be
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determined using a pulse oxymeter (90% or below demonstrates severe
hypoxia).
Head, Eyes, Ears, Nose, Throat
Assess the presence of enlarged lymph nodes, which may signify
metastatic lung carcinoma. A carotid bruit suggests the presence of cardiovascular disease. Examine the nose for evidence of bleeding.
Chest/Lung
Assess whether breathing is labored, which may indicate pneumonia,
presence of blood in the tracheobronchial tree, or pulmonary embolus.
The presence of diminished breath sounds and vocal fremitus suggests consolidation of the lung. The presence of rales suggests congestive heart failure.
Cardiovascular
The rhythm, presence of a cardiac murmur or a jugular venous
distention, and the point of maximal impact should be determined.
Abdomen
Examine for the presence of an enlarged liver, which can occur in rightsided heart failure.
Extremities/Skin
Assess for the presence of a coagulopathy (petechia, bruises).
Unilateral leg swelling suggests deep venous thromboses. Bilateral
leg edema is more consistent with lymph edema or congestive heart
failure.
Diagnostic Evaluation (Table 13.2)
The history and physical help determine which diagnostic tests are
needed and the urgency with which you need to proceed. In general,
Table 13.2. Diagnostic evaluation for hemoptysis.
Vital signs
Arterial blood gas
Portable chest radiograph
Blood work
CBC
Electrolytes
BUN/creatinine
Liver function
PT/PTT
Type and crossmatch
Sputum cultures
Pulmonary function test
Computed tomography (CT) of the chest
Bronchoscopy
Flexible
Rigid (massive hemoptysis)
Echocardiogram
IF heart disease is suspected
13. Hemoptysis, Cough, and Pulmonary Lesions
Figure 13.1. Chest radiograph of a patient with non–small-cell lung cancer discloses right hilar enlargement.
all patients should receive a chest x-ray, an electrocardiogram (ECG),
arterial blood gases, and blood work consisting of a complete blood
count (CBC), electrolytes, blood ureanitrogen (BUN)/creatinine,
liver function tests, prothrombin time/partial thromboplastin time
(PT/PTT), and a type and crossmatch. Sputum cultures for bacteria
and fungus should be obtained on all patients.
A chest radiograph is the first diagnostic test that should be done
(Fig. 13.1). A chest x-ray may demonstrate the presence of an abscess,
lung nodule, consolidation, or atelectasis representing the possible
source of bleeding. It also can suggest the presence of heart disease,
showing enlargement of the ventricle or atrium and the presence of
Kerley B lines. Massive pulmonary hemorrhage may occur from an
area that appears normal on routine chest radiograph.
Computed tomography (CT) of the chest helps to delineate the
cause of hemoptysis (Fig. 13.2). In patients with bronchiogenic carcinoma, a CT scan may demonstrate the presence of a pulmonary mass,
determine the extent of local invasion, and assess metastatic spread to
the mediastinal lymph nodes, liver, or adrenal glands. A CT scan also
can identify a lung abscess, bronchiectasis, lung consolidation, and an
arteriovenous malformation.
A flexible bronchoscopy frequently is used in the evaluation of a
patient with hemoptysis. A flexible bronchoscopy can identify the site
of the bleeding, which is critical if surgery is contemplated as a means
of controlling the bleeding. A flexible bronchoscope can detect the
presence of a tumor obstructing a lobar bronchus. Bronchial washings
should be sent for cultures, and a cytology specimen should be examined for the presence of cancer cells. A rigid bronchoscopy most often
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**
*
Figure 13.2. Accompanying computed tomography (CT) scan confirms the
presence of extensive hilar and mediastinal adenopathy. In addition, a focal
peripheral lung opacity is present: the primary lung neoplasm. Atelecfic
changes also are seen in the right upper lung (**). The tumor invades the main
pulmonary artery (*). A right pleural effusion is seen. This is too small to be
visible on the posteroanterior (PA) chest radiograph.
is used in patients with massive hemoptysis. A rigid bronchoscope
basically is a hollow metal tube with a light source and a side port for
anesthesia. A rigid bronchoscopy is performed most frequently in the
operating room under general anesthesia. The larger size of the rigid
bronchoscope allows for better suctioning and control of the airway
than a flexible bronchoscope.
Management (Table 13.3)
The treatment options for controlling bleeding originating from the
lung include medical management, bronchial lavage, embolization of
bronchial arteries, and surgery. The management of patients with
hemoptysis is dependent on the amount of hemoptysis, the etiology
of the hemoptysis, the number of recurrent bleeding episodes, and
the general medical condition of the patient. The initial goal is to
control bleeding so the workup can proceed in an organized manner.
Table 13.3. Management
hemoptysis.
of
patients
Medical management
Bed rest
Antitussive agent
Postural drainage and antimicrobials
Correct coagulopathies
Prevent aspiration
Ice-cold bronchial lavage
Bronchial artery embolization
Surgical resection of the bleeding lung
with
13. Hemoptysis, Cough, and Pulmonary Lesions
Fortunately, bleeding in most patients is not massive and can be
controlled with conservative measures, which include bed rest and
controlling the cough. Patients with pulmonary infections should be
treated with postural drainage and started on the appropriate antimicrobial agent. Any coagulopathies should be corrected. A flexible
bronchoscopy should be performed to assess for the presence of a bronchogenic carcinoma. Surgery should be considered in patients who
present with recurring hemoptysis.
The objectives in treating patient with massive hemoptysis are to
prevent asphyxiation, localize the site of bleeding, and arrest the
hemorrhage. Medical therapy should be initiated promptly. Patients
are placed with the bleeding side down to prevent aspiration of blood
into the contralateral lung. A large-bore intravenous (IV) line is secured;
typed and crossmatched blood is made available. Prophylactic antibiotics have been recommended, but this remains controversial. Patients
with tuberculosis are treated with antituberculosis therapy. Effective
antituberculin therapy can control hemoptysis, and, if surgery becomes
necessary, the complication rate is reduced. Bronchodilators are not
used because they may cause vasodilatation. Patients with a violent
cough are treated with antitussives (codeine). However, the cough
should not be suppressed completely, because this may lead to accumulation of blood in the airways.
The treatment options for a patient presenting with massive hemoptysis include continued medical management, embolization of the
bleeding bronchial arteries, and a surgical resection of the lung. There
are no controlled studies demonstrating superiority of one modality
over another; however, the literature does support the recommendations discussed below.
Bronchial lavage has been reported to temporarily control massive
hemoptysis in 97% of patients. The procedure is performed by irrigating the major bronchi of the bleeding lung with ice-cold saline using a
rigid bronchoscope. Following a brief period of lavage, the nonbleeding lung is ventilated using the rigid bronchoscope. Bronchial lavage
is considered a temporizing measure, and definitive therapy should not
be delayed if required. The bleeding segmental bronchus can be
controlled by passing a Fogarty catheter (bronchial blocker) into the
appropriate segmental bronchus using a flexible bronchoscope. The
bronchial blocker can tamponade the bleeding and prevent blood from
accumulating into the nonbleeding lung.
Embolization of a bleeding bronchial artery is being used more
frequently as the initial treatment to control massive hemoptysis. The
morbidity and mortality of bronchial artery embolization is significantly less than that of an emergent pulmonary resection. Arterial
embolization is 87% to 94% successful in achieving effective homeostasis. A major criticism of systemic embolization is the rate of rebleeding. Some consider embolization only a temporizing measure. Control
of hemoptysis following bronchial artery embolization is 77% at 1 year
and 50% to 60% at 5 years. Patients presenting with massive hemoptysis from a fungal infection or abscess are thought to be at highest risk
of rebleeding. While the rate of rebleeding at 5 years is relatively high,
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bronchial artery embolization may represent the preferred method
to control bleeding in a critically ill patient. After controlling the
hemoptysis by embolization, a decision can be made as to whether a
lung resection should be performed as a more elective procedure.
A surgical resection of the involved lung also has been used to
control massive hemoptysis. The most commonly performed operation
is a lobectomy. The site of bleeding must be localized, which usually
can be achieved by bronchoscopy. Pulmonary resection has been
shown to be an effective method to control and prevent recurrent bleeding. Emergency pulmonary resection has substantial mortality and
morbidity rates. Spillage of blood or pus into the dependent lung
contributes to the morbidity and mortality. Major complications,
which include respiratory failure, bronchopleural fistula, empyema,
pulmonary edema, and pneumonia, occur in up to 60% of patients.
Adequate pulmonary reserve, which can be determined by a bedside
spirometer, must be assessed prior to surgery. The morbidity and mortality rates following surgical resection are significantly lower when
pulmonary resection is performed as an elective procedure.
Conservative measures using medical treatment and/or bronchial
artery embolization should be used initially to control bleeding. An
elective pulmonary resection then can be performed on medically
fit patients in order to prevent recurrent hemoptysis. Patients who
are typically considered for surgery are those with resectable lung
carcinomas and patients with recurrent bleeding from benign
disease.
Solitary Pulmonary Nodules
Evaluation of a Solitary Pulmonary Nodule (Table 13.4)
Solitary pulmonary nodules typically are found as an incidental
finding on a routine chest radiograph. See Case 13.2 and Algorithm
13.1. The incidence of a solitary pulmonary nodule being malignant
varies, ranging from 3% to 50%. The most common benign lesions
are hamartomas and granulomas. Although metastatic tumors to the
lung are frequently multiple, they can present as solitary lesions,
representing 5% to 10% of resected nodules. The noninfectious
granulomatous diseases sarcoidosis and Wegner’s granulomatosis
typically present with multiple pulmonary lesions but occasionally
can present as solitary pulmonary nodules.
If the nodule contains a central nidus of calcification, diffuse calcification, or ring-like calcification, it is most likely a granuloma. Lumps
of calcification throughout the lesion (popcorn calcification) suggest a
hamartoma. All old chest radiographs should be reviewed if available.
If the nodule had increased in size compared to a previous radiograph,
this is strongly suggestive of a malignancy. Typically, if no growth is
observed for 2 years, it is considered benign. However, some tumors,
especially bronchioloalveolar cell carcinoma, exhibit no growth for
over 2 years.
13. Hemoptysis, Cough, and Pulmonary Lesions
Table 13.4. Solitary pulmonary nodules.
Neoplasms
Malignant
Bronchial carcinoma
Carcinoid tumor
Metastasis
Other rare primary lung tumor: sarcomas,
lymphoma, melanoma, plasmacytoma
Benign
Hamartoma
Other benign lung tumors (uncommon)
Inflammatory
Infectious granulomas
Histoplasmosis
Tuberculosis
Aspergillosis
Cryptococcosis
Blastomycosis
Coccidioidomycosis
Noninfectious (usually multiple)
Sarcoidosis
Embolus
Rheumatoid nodule
Wegener’s granulomatosis
Bronchiolitis obliterans-organizing pneumonia
(BOOP)
Mucoid impaction
Granuloma
Benign lung tumor (hamartoma)
Metastasis
Arteriovenous malformation
History
When evaluating a patient for possible lung cancer the following
factors are of particular importance:
1.
2.
3.
4.
5.
Symptoms
Prior history of cancer
Smoking history
Family history of cancer
Prior medical history
Physical Examination
Since a solitary pulmonary nodule may represent a metastatic
nodule, a complete physical should be performed. Female patients
should be asked whether a recent mammogram and Pap smear have
been performed. Patients should be assessed for the presence of
metastatic disease.
Head and Neck
Lymph nodes should be carefully examined for metastatic disease.
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History and Physical
+ family history
+ smoking
Risk of Cancer
CT Chest
1 cm or greater
Fine-Needle
Aspiration (FNA)
PET Scan
+
<1 cm
–
Surgical
Biopsy
+
• May observe
• F/U 3 months
If grows or
if spiculated,
then remove
Possible observation;
Consider surgical biopsy
Surgical
Biopsy
+
Cancer:
Non–Small-Cell Lung Carcinoma
(NSCLC)
Surgery
Lobectomy/Pneumonectomy
Wedge resection if poor
pulmonary function
Algorithm 13.1. Algorithm for the evaluation of a solitary pulmonary module.
Cardiac
Assess risk of cardiac disease, murmurs, enlarged heart, and jugular
venous distention.
Lungs
Examine for accessory muscle use, wheezing, chest wall tenderness,
pleural effusion, consolidation, and presence of a barreled chest from
severe chronic obstructive pulmonary disease (COPD).
Extremities
Determine the presence of clubbing, peripheral vascular disease, and
bone pain.
Neurologic
Assess focal neurologic deficits from metastatic disease.
Imaging Studies
All patients with pulmonary nodules should have a CT scan of the
chest (Fig. 13.2). A more recently introduced imaging modality to
13. Hemoptysis, Cough, and Pulmonary Lesions
assess a patient’s risk of having lung cancer is a positron emission
tomography (PET) scan (Fig. 13.3); see Lung Neoplasms, below. Since
diagnostic studies cannot predict absolutely which pulmonary nodules
are cancerous, a histologic evaluation is required. The radiographic
studies can guide the physician in determining which patients
should have more invasive procedures to confirm a diagnosis. Small
nodules (less than 1 cm) are observed frequently with serial CT scans.
Larger lesions should have a confirmatory histologic diagnosis.
Histologic Diagnosis of a Solitary Lung Nodule
Although not commonly used today, a diagnosis of lung cancer can be
made by examining the sputum cytologically for the presence of
cancer cells. Bronchoscopy can make the diagnosis of lung cancer for
central lesion by direct biopsy, brushing and washings. A transthoracic
fine-needle aspiration (FNA) can yield a diagnosis in 80% to 95% of
patients. Patients with intermediate FNA results have a 20% to 30%
chance of having cancer. Therefore, patients with a nondiagnostic FNA
should have a lung biopsy. The main complication with FNA is a pneumothorax, which occurs in 25% of patients. More invasive methods
include a wedge resection via video-assisted thoracoscopic surgery
(VATS) or a thoracotomy. Surgery is being used more frequently to
make the diagnosis of a solitary pulmonary nodule since the VATS
procedure is less invasive than a thoracotomy incision, which had been
used previously.
Figure 13.3. Positron emission tomography (PET) scan of patient with lung lesion.
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The decision to proceed with an FNA or a lung biopsy is largely
based on physician preference. There are no studies proving one evaluation strategy is better than another. The proponents of early surgery
argue that VATS can be performed with a low morbidity and a short
hospital stay, and will always obtain a diagnosis. An FNA does carry
a lower risk and usually does not require hospitalization, but it is not
always diagnostic. An FNA should be encouraged strongly in patients
with multiple medical problems. Another important consideration is
patients with central tumors. Due to their location to hilar vessels,
central tumors may require a lobectomy instead of wedge resection in
order to obtain a diagnosis.
Lung Neoplasms
Lung cancer is the leading cause of cancer deaths in the United States
among both men and women. Approximately 180,000 patients are
diagnosed with lung cancer per year in the United States. The average
age at the time of diagnosis is 60 years. The long-term survival for lung
cancer remains poor, with only a 14% overall 5-year survival. High cure
rates following resection can be expected with patients who present
with early disease. It is imperative for physicians treating lung cancer
to properly evaluate their patients to determine which patients may
benefit from surgical resection and which may benefit from multimodality therapy.
Epidemiology
Studies have confirmed that 80% to 90% of lung cancers are caused by
tobacco use. Risk factors include the age at which smoking is started,
the frequency, and the duration. The duration of smoking is the most
important risk factor. Studies have demonstrated an increased risk of
lung cancer in people exposed to secondhand smoke. Several studies
also have demonstrated an increased risk of lung cancer in uranium
miners. Occupational exposure linked to lung cancer includes inhalation of asbestos and polycyclic aromatic hydrocarbons, and exposure
to arsenic, chromates, and bis(chloromethyl)ether.
Cancer Prevention
Studies have linked diets high in fruits and vegetables to lower incidence of lung cancer, suggesting that vitamin A may help prevent lung
cancer. However, the vitamin A derivative beta-carotene did not show
an improvement in survival or in the prevention of lung cancer in
prospective randomized studies. Ongoing studies are evaluating other
agents that may reduce the risks of lung cancers.
Malignant Tumors
The majority of lung tumors that are malignant consist of adenocarcinoma, squamous cell carcinoma, large-cell carcinoma, or small-cell
lung carcinoma (Table 13.5). The first three are referred to as
13. Hemoptysis, Cough, and Pulmonary Lesions
Table 13.5. Histologic classification of malignant epithelial lung tumors.
Squamous cell carcinoma
Variant:
Papillary
Clear cell
Small cell
Basaloid
Small-cell carcinoma
Variant:
Combined small-cell carcinoma
Adenocarcinoma
Acinar
Papillary
Bronchioloalveolar carcinoma
Solid adenocarcinoma with mucin
Large cell carcinoma
Source: Reprinted from World Health Organization. Histological typing of lung and pleural tumours, 3rd ed.,
1999:21–22, with permission.
non–small-cell lung carcinoma (NSCLC) and present 80% of all lung
carcinomas. The best chance for cure for NSCLC remains surgical
resection. Adenocarcinoma is the most common cause of lung cancer,
accounting for 46% of the cases. Adenocarcinoma most frequently
presents as a peripheral lung nodule and has the tendency to spread
via the lymphatics and hematogenously. Bronchoalveolar carcinoma,
an adenocarcinoma subtype, may present as a discrete nodule, as multifocal nodules, or as a diffuse infiltrating tumor. Squamous cell carcinoma is the second most common cause of lung cancer. Squamous cell
carcinoma typically presents as a central tumor, which can occlude a
proximal bronchus.
Small-cell lung carcinomas also are known as “oat cell” carcinomas.
At times, the differentiation among carcinoids, lymphocytic tumors,
and poorly differentiated NSCLC may be difficult. Immunohistochemical staining should allow for proper identification of these
tumors. Small-cell lung carcinomas have a propensity for early spread
and are typically treated by chemotherapy. However, patients with
small-cell lung carcinomas can present with a small tumor (less than
3-cm) without metastasis and have 5-year survivals of 50% following
surgical resection.
Benign Tumors
Benign tumors of the lung represent only 5% of lung tumors. The most
common cause of benign tumor is a hamartoma. Hamartoma represents 75% of all benign tumors of the lung and accounts for 8% of
pulmonary neoplasm. Other causes of benign lung tumor occur only
rarely.
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Bronchial Gland Tumors
Five tumors comprise bronchial gland tumors: bronchial carcinoid,
adenoid cystic carcinoma, mucoepidermoid carcinoma, bronchial
mucous gland adenoma, and pleomorphic mixed tumors. Bronchial
carcinoid constitutes 85% of this group of tumors. Ninety percent of
carcinoid tumors present in the main stem or lobar bronchi, with less
than 10% presenting as a solitary nodule. Because carcinoid tumors frequently present in major bronchi, patients may present with symptoms
secondary to an obstructed airway.
Bronchial carcinoids are classified as neuroendocrine tumors, the
amine precursor uptake decarboxylase (APUD) tumors that arise
from Kulchitsky cells in the respiratory epithelium. The more common
typical carcinoid tumor only metastasizes in 5% to 6% of patients. The
more aggressive atypical variant metastasizes more frequently. Carcinoid tumors are a common cause of lung tumors presenting in young
patients. Ninety percent of patients with typical carcinoids are cured
with a surgical resection. Atypical carcinoids occur in 15% of patients
and have a higher incidence of metastasis when compared to typical
carcinoids.
Metastatic Tumors
Sarcomas and carcinomas arising from the breast, kidney, and colon
have a propensity to metastasize to the lung. The lung may be the
only site of distant spread. Although never studied in a prospective
randomized trial, several studies have suggested a survival advantage
in patients whose lung metastases are surgically resected. The recommendation for surgical resection results from the following criteria:
the lung is the only site of metastatic spread, the primary tumor is
controlled, there is no effective medical treatment available, and the
metastatic tumor can be resected completely. Survival appears to be
dependent on the tumor type, number of metastasis, and the latency
between the diagnosis of the primary tumor and the development of
metastatic spread to the lung. The best survival has been in patients
with solitary tumors and a latency over 1 year. However, 5-year
survivals up to 20% are reported with multiple pulmonary metastasis
presenting as synchronous disease.
Tumors of the Mediastinum
Tumors presenting in the chest cavity that are not originating from the
lung or pleural surface are classified according to their location within
the mediastinum (Table 13.6). The mediastinum anatomic alley is
divided into the anterior, middle, and posterior compartments. The
anterior compartment extends from the undersurface of the sternum to
the anterior borders of the heart and great vessels. The posterior compartment extends from the anterior border of the vertebral bodies to
the ribs posteriorly. The middle mediastinum includes all structures
between the anterior and posterior mediastinum. These anatomic
boundaries serve as an excellent means to develop an accurate differ-
13. Hemoptysis, Cough, and Pulmonary Lesions
Table 13.6. Tumors of the mediastinum.
Anterior
Thymus
Thymoma
Thymic carcinoma
Carcinoid
Lymphoma
Germ cell tumor
Thyroid
Most commonly a benign goiter
Parathyroid adenoma
Posterior mediastinum
Neurogenic tumors
Benign
Schwannoma (neurilemmoma)
Neurofibroma
Ganglioneuroma
Pheochromocytoma
Paraganglioma
Malignant
Malignant schwannoma
Neuroblastoma
Malignant paraganglioma
ential diagnosis. The anterior mediastinum consists mainly of tumors
of the thymus (predominantly thymomas), lymphomas, and germ cell
tumors. The majority of posterior mediastinal tumors are neuroendocrine in origin and usually are benign in adults.
Clinical Presentations
Primary Tumor
Patients with lung cancer typically present with symptoms (Table
13.7). Symptoms at presentation are from the primary tumor in 27% of
patients and are dependent on the location of the tumor. Central
tumors may cause a cough, hemoptysis, obstructive pneumonia, or
wheezing. Peripheral tumors are more likely to present with chest pain,
dyspnea, or pleural effusion. The primary tumor may cause symptoms
by direct extension into mediastinal structures. Patients may present
with pain from direct rib involvement, or a tumor in the superior sulcus
(Pancoast) can cause radicular arm pain and weakness from invasion
of the brachial plexus. Invasion of the superior vena cava (superior
vena cava syndrome) may cause facial and upper torso venous
engorgement. Hoarseness from recurrent laryngeal nerve invasion also
may occur.
Metastatic Tumor
Metastatic disease from mediastinal tumors is the presenting symptom
in 32% of the cases. The most common sites of distant lung metastasis are the adrenal gland, lung, bone, liver, and brain. Bone pain from
metastatic spread occurs in 20% to 25% of patients. Ten percent of
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Table 13.7. Initial symptoms at presentation of
lung cancer.
Symptoms
Cough
Weight loss
Dyspnea
Chest pain
Hemoptysis
Lymphadenopathy
Bone pain
Hepatomegaly
Clubbing
Intracranial
Superior vena cava syndrome
Hoarseness
Percentage (%)
74
68
58
49
29
23
25
21
20
12
4
18
Source: Reprinted from Hyde L, Hyde CI. Clinical manifestations of lung cancer. Chest 1974;65:300.
patients present with brain metastasis; however, 25% of patients eventually develop brain metastasis.
Paraneoplastic Syndromes
Paraneoplastic syndromes occur most commonly with small-cell carcinomas and squamous cell carcinomas (Table 13.8). Paraneoplastic
syndromes include hypertrophic pulmonary osteoarthropathy,
inappropriate secretion of antidiuretic hormone (ADH), hypercalcemia, Cushing’s syndrome, and neurologic and myopathic syndromes. Inappropriate secretion of ADH and Cushing’s syndrome
most commonly are related to small-cell carcinomas. Hypercalcemia
from the production of either a parathyroid hormone or a parathyroidlike substance is associated most commonly with squamous cell
carcinomas.
Superior Sulcus Tumor
Superior sulcus tumors arise from the apex of the lung and can invade
the upper ribs or brachial plexus. Patients frequently complain of arm
or shoulder pain and may have T1 nerve root weakness or present with
Horner’s syndrome. All patients presenting with a superior sulcus
tumors should have their mediastinal lymph nodes evaluated by mediastinoscopy. The survival is extremely poor when this group of patients
presents with mediastinal lymph metastasis. Patients are treated with
radiotherapy (30 to 45 Gy), followed by en bloc resection in 4 weeks.
Recent studies suggest a benefit to neoadjuvant chemotherapy, in addition to radiotherapy.
Diagnosis and Staging
Patients who are being considered for a potentially curative resection
must be properly staged clinically. Diagnostic and staging modalities
include chest radiograph, CT scan of the chest and brain, PET scan,
bone scan, and lymph node sampling by mediastinoscopy or anterior thoracotomy. The extent of the workup often is dependent on
13. Hemoptysis, Cough, and Pulmonary Lesions
Table 13.8. Paraneoplastic syndromes in lung
cancer patients.
Metabolic
Hypercalcemia
Cushing’s syndrome
Inappropriate antidiuretic hormone production
Carcinoid syndrome
Gynecomastia
Hypercalcitonemia
Elevated growth hormone level
Elevated prolactin, follicle-stimulating hormone,
luteinizing hormone levels
Hypoglycemia
Hyperthyroidism
Neurologic
Encephalopathy
Subacute cerebellar degeneration
Peripheral neuropathy
Polymyositis
Autonomic neuropathy
Lambert–Eaton syndrome
Opsoclonus and myoclonus
Skeletal
Clubbing
Pulmonary hypertrophic osteoarthropathy
Hematologic
Anemia
Leukemoid reactions
Thrombocytosis
Thrombocytopenia
Eosinophilia
Pure red cell aplasia
Leukoerythroblastosis
Disseminated intravascular coagulation
Cutaneous and muscular
Hyperkeratosis
Dermatomyositis
Acanthosis nigricans
Hyperpigmentation
Erythema gyratum repens
Hypertrichosis lanuaginosa acquisita
Other
Nephrotic syndrome
Hypouricemia
Secretion of vasoactive intestinal peptide with
diarrhea
Hyperamylasemia
Anorexia-cachexia
Source: Reprinted from Shields TW. Presentation, diagnosis,
and staging of bronchial carcinoma and of the asymptomatic
solitary pulmonary nodule. In: Shields TW, ed. Thoracic
Surgery. Malvern, PA: Williams & Wilkins, 1994. With permission from Lippincott Williams & Wilkins.
249
250
J.E. Langenfeld
symptoms. All patients should receive a CT of the chest that includes
the liver and adrenal gland. Patients with complaints of bone pain or
neurologic changes should receive a bone scan or CT of the brain,
respectively. A PET scan is being used more often in the evaluation of
patients with lung cancer.
Chest Radiograph
A posteroanterior and lateral chest radiograph can determine the size
of the tumor, bone metastasis, collapsed lung, and pleural effusion.
Mediastinal nodal involvement can be assessed if it is large, but a chest
radiograph is not as sensitive as a CT scan.
Computed Tomography
A CT scan determines the size of the primary tumor, tumor growth into
the chest wall and mediastinum, enlarged lymph nodes, and liver and
adrenal metastasis. A mediastinal lymph node larger than 1 cm is considered suspicious for metastasis; if it is less than 1 cm, it is considered
normal. The false-negative rate in assessing mediastinal metastasis is
10% to 20% when using these criteria. The false-negative rate increases
the larger and more central the tumor is. The false-positive rate is 25%
to 30%. Therefore, a tissue diagnosis is required to confirm the presence or absence of mediastinal metastasis.
Positron Emission Tomography
The PET scan determines the presence of tissue that has increased
glucose metabolism when compared to the surrounding normal tissue.
Enhanced glucose metabolism occurs with malignant tumors and
inflammatory lesions. The PET scan measures the uptake of a positron
emission analogue (2–18 F) fluoro-2-deoxy-d-glucose (FDG). The FDGPET has a reported sensitivity of 95% and specificity of 80% in determining whether a solitary pulmonary nodule is benign or malignant.
False-positive results can occur with inflammatory conditions. The PET
scan also has been shown to be more sensitive and specific than a CT
scan in detecting mediastinal metastasis. A whole-body PET scan
detects unsuspected distant metastasis in 11% to 14% of patients.
Cervical Mediastinoscopy
Cervical mediastinoscopy is used extensively to examine the presence
of metastasis to the mediastinal lymph nodes. (See Algorithm 13.2.)
Mediastinoscopy examines the paratracheal, subcarinal, and tracheobronchial lymph nodes. This technique provides histology from N2 and
N3 lymph nodes (see section on staging, below), which would dictate
treatment. N3 lymph node metastases are considered inoperable, and
N2 lymph node metastasis may require preoperative chemotherapy.
Staging of Non–Small-Cell Lung Carcinoma
The staging of lung cancer is based on the TNM classification: (see
Algorithm 13.3). The T determines the size of the primary tumor, distance from carina, pleural involvement, and invasion into the chest wall
or mediastinum. The presence and location of hilar and mediastinal
lymph node metastasis and metastasis outside the involved hemithorax are assessed. The TNM descriptors are shown in Table 13.9.
13. Hemoptysis, Cough, and Pulmonary Lesions
251
INDICATOR FOR MEDIASTINOSCOPY
CT: Lymph Nodes
N2 – N 3 > 1 cm
PET (+)
Mediastinal Lymph Nodes
N2 – N 3
Control Tumor
Tumor > 2 cm
Algorithm 13.2. Algorithm for the use of mediastinoscopy.
Surgical Management of Non–Small-Cell Lung Carcinoma
Surgical resection remains the most effective treatment for NSCLC.
Surgery should be performed only in patients in whom complete
excision of the tumor can be performed. Patients with N1 disease and
selected patients with N2 nodal metastasis are surgical candidates.
Patients with contralateral mediastinal lymph node metastasis, malignant pleural effusions, or metastatic spread to other organs are not
surgical candidates. Patients with N2 disease are treated with
chemotherapy prior to surgery. Two small prospective randomized
Stage
Treatment
IL
Lobectomy with hilar and mediastinal lymph node dissection;
postop. chemotherapy and irradiation (RT) not indicated
II
Lobectomy with hilar and mediastinal lymph node dissection;
postop. chemotherapy/RT does not prolong survival
If clinically stage IIIA, preop. chemotherapy; possible RT
followed by surgery*
IIIA
T3N0–1
T1–3N2
IIIB
T4N0
T4N1–2
Any T, N3
Chemotherapy/RT (+surgery in highly selected cases)
Chemotherapy/RT
Chemotherapy/RT
IV
All other M+
Chemotherapy/RT
Pantumor
Preop. chemotherapy/RT followed by surgery
}
Special cases
*If stage IIIA disease is diagnosed only after surgery, postoperative irradiation and
chemotherapy are given; the combination yields significantly longer disease-free survival than
irradiation alone. Postoperative irradiation alone improves local control but has no appreciable
effect on survival.
Algorithm 13.3. Algorithm for staging of non–small-cell carcinoma of the lung. (Reprinted from
Warren WH, James TW. Non-small cell carcinoma of the lung (continued). Reprinted from Saclarides
TJ, Millikan KW, Godellas CV, eds. Surgical Oncology: An Algorithmic Approach. New York: SpringerVerlag, 2002, with permission.)
252
J.E. Langenfeld
Table 13.9. Lung cancer TNM descriptors.
Primary tumor (T)
TX Primary tumor cannot be assessed, or tumor proven by the presence of malignant cells in
sputum or bronchial washings but not visualized by imaging or bronchoscopy
T0
No evidence of primary tumor
Tis Carcinoma in situ
T1
Tumor £3 cm in greatest dimension, surrounded by lung or visceral pleura, without
bronchoscopic evidence of invasion more proximal than the lobar bronchus* (i.e., not in
the main bronchus)
T2
Tumor with any of the following features of size or extent:
>3 cm in greatest dimension
Involves main bronchus, ≥2 cm distal to the carina
Invades the visceral pleura
Association with atelectasis or obstructive pneumonitis that extends to the hilar
region but does not involve the entire lung
T3
Tumor of any size that directly invades any of the following: chest wall (including
superior sulcus tumors), diaphragm, mediastinal pleura, parietal pericardium; or tumor
in the main bronchus <2 cm distal to the carina, but without involvement of the carina;
or associated atelectasis or obstructive pneumonitis of the entire lung
T4
Tumor of any size that invades any of the following: mediastinum, heart, great vessels,
trachea, esophagus, vertebral body, carina; or tumor with a malignant pleural or
pericardial effusion,† or with satellite tumor nodule(s) within the ipsilateral primary
tumor lobe of the lung
Regional lymph nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and
intrapulmonary nodes involved by direct extension of the primary tumor
N2 Metastasis to ipsilateral mediastinal and/or subcarinal lymph node(s)
N3 Metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral
scalene, or supraclavicular lymph node(s)
Distant metastasis (M)
MX Presence of distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis present‡
* The uncommon superficial tumor of any size with its invasive component limited to the bronchial wall, which
may extend proximal to the main bronchus, is also classified T1.
† Most pleural effusions associated with lung cancer are due to tumor. However, there are a few patients in whom
multiple cytopathologic examinations of pleural fluid show no tumor. In these cases, the fluid is nonbloody and is
not an exudate. When these elements and clinical judgment dictate that the effusion is not related to the tumor, the
effusion should be excluded as a staging element and the patient’s disease should be staged T1, T2, or T3. Pericardial effusion is classified according to the same rules.
‡ Separate metastatic tumor nodule(s) in the ipsilateral nonprimary tumor lobe(s) of the lung also are classified M1.
Source: Reprinted from Mountain CF. Revisions in the international system for staging lung cancer. Chest
1997;111:1711, with permission.
studies have shown that patients with N2 disease who receive preoperative chemotherapy (neoadjuvant) have a survival advantage over
those who do not.1 It remains to be determined whether neoadjuvant
chemotherapy is beneficial for only selected patients with N2 disease.
1
Rosell R, Gomez-Codina J, Camps C, et al. A randomized trial comparing preoperative
chemotherapy plus surgery with surgery alone in patients with non-small cell lung
cancer. N Engl J Med 1994;330:153–158. Roth JA, Fossella F, Romaki R, et al. A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in
resectable stage IIIA non-small cell lung cancer. J Natl Cancer Inst 1994;86:673–680.
13. Hemoptysis, Cough, and Pulmonary Lesions
253
The primary tumor and surrounding intrapulmonary lymphatics
must be removed. Lobectomy is considered the operation of choice, but
a pneumonectomy may be required to obtain negative margins. Wedge
resection has a higher incidence of local recurrence and is not recommended unless the patient cannot tolerate a lobectomy. Patients who
are not considered surgical candidates because of extensive disease
or general medical condition are treated with chemotherapy and/or
radiation.
Preoperative Pulmonary Evaluation
An assessment should be made to determine whether the patient can
tolerate surgery. Most patients should have a pulmonary function test
prior to surgery. (See Algorithm 13.4.) Patients with a forced expira-
Peak O2 consumption > 15 mL/kg
Fall in SaO1 of <2% with exercise
Predicted DLCO of >40%
Preop. FEV1 > 2 L
Pneumonectomy or
Good exercise tolerance lobectomy should be
Normal chest radiography
tolerated
Calculated postoperative
FEV1 > 40%
Preop. FEV1 < 2 L
Calculated postoperative
FEV1 30–40%
Measure quantitative
VQ to predict
postop. FEV1
Measure gas
exchange at rest
and during
exercise (VO1 max)
Peak O2 consumption 10–5 mL
Fall in SaO1 >2%
Predicted DLCO <40%
If these conditions are satisfied,
consider limited resection
Calculated postoperative
FEV1 < 30%
Avoid
pneumonectomy,
consider lobectomy
Peak O2 consumption <10 mL/kg
FVC, forced vital capacity
FEV1, forced expiratory volume (I second)
DLCO, diffusing capacity for carbon monoxide
Vo1 max, maximum oxygen consumption
VQ, ventilation/perfusion scan
SaO1, saturation of oxygen in arterial blood
Pulmonary resection
not indicated
Algorithm 13.4. Evaluation of pulmonary function prior to surgery for non–small-cell carcinoma of
the lung. (Reprinted from Warren WH, Jomes TW. Non-small cell carcinoma of the lung (continued).
Reprinted from Saclarides TJ, Millikan KW, Godellas CV, eds. Surgical Oncology: An Algorithmic
Approach. New York: Springer-Verlag, 2002, with permission.)
254
J.E. Langenfeld
tory volume in 1 second (FEV1) of greater than 2.00, or greater than 60%
of predicted normal value, are thought to have sufficient pulmonary
reserves to tolerate a pneumonectomy. Patients with a predicted postoperative FEV1 of greater than 1.0, or greater than 40% of predicted,
should have sufficient pulmonary reserve to tolerate a lobectomy. A
quantitative ventilation perfusion scan also may be helpful to predict
postoperative FEV1. Arterial blood gases should be drawn to assess for
arterial hypoxia and hypercapnia. The pulmonary status also can be
assessed clinically by ambulating the patient. Patients who are short of
breath at rest or upon minimal activity are considered poor surgical
candidates. Patients who can walk a flight of stairs typically can tolerate a lobectomy.
Survival
The 5-year survival following resection for a stage I NSCLC is between
38% and 85% (Fig. 13.4). A significantly worse survival occurs in
patients with tumors greater than 3 cm (stage IB) than in those patients
presenting with tumors less than 3 cm (stage IA). Surgical resection of
stage II tumors results in survival rates between 22% and 55%. Prior to
neoadjuvant chemotherapy, patients with N2 mediastinal lymph node
metastasis (stage IIIA) had a 5-year survival of only 7%. With the
advent of multimodality treatment, an improvement in the 5-year
survival to 25% has been reported in completely resected disease
stage IIIA patients. Studies currently are evaluating which patients
with mediastinal (N2) lymph node metastasis will benefit from
surgical resection. Patients with clinical stage IIIB or stage IV disease
are not considered surgical candidates. The 1-year survival for these
patients is 20% to 37% and 5-year survival is 1% to 7%.
Figure 13.4. Duke University Medical Center data, 1980–1992. Survival curves
for stage I NSCLC based on tumor size. Graphs truncated at 72 months with
148 patients alive. (Reprinted from Lau CL, Harpole DH, Jr. Lung neoplasms.
In: Norton JA, Bollinger RR, Chang AE, et al., eds. Surgery: Basic Science and
Clinical Evidence. New York: Springer-Verlag, 2001, with permission.)
13. Hemoptysis, Cough, and Pulmonary Lesions
Neoadjuvant and Adjuvant Therapy
Prospective randomized studies demonstrate there is no advantage
of adjuvant (postoperative) chemotherapy for stage I NSCLC
patients. Four prospective randomized studies have analyzed the
effects of postoperative chemotherapy and/or radiotherapy for
patients with stage II to III NSCLC.2 These studies all showed that
there was no survival benefit for adjuvant therapy.
Two phase III neoadjuvant trials in stage IIIA lung cancer patients
demonstrated a significant improvement in survival in those patients
receiving chemotherapy prior surgery.3 The M.D. Anderson trial randomized 60 patients to preoperative and postoperative chemotherapy
and surgery versus surgery alone. The 3-year survival was 56% in the
neoadjuvant group compared to 15% in the control group. The Spanish
trial randomized 60 patients to preoperative chemotherapy followed
by surgery and postoperative radiation, or surgery followed by radiation. This study also demonstrated a significant improvement in
survival in the chemotherapy-treated group.
Management of Small-Cell Lung Carcinoma
Most patients with small-cell lung carcinoma (SCLC) present with
advanced disease, with 70% of patients presenting with extrathoracic
metastasis. Therefore, the majority of patients with SCLC infrequently
are treated with surgery. Chemotherapy is the main therapeutic
modality used to treat SCLC, although thoracic irradiation may be
valuable. Rarely, patients with SCLC present with a solitary nodule.
Surgery alone provides a curative therapy in 25% of patients. With the
addition of postoperative chemotherapy, 5-year survival rates up to
80% have been reported in patients with T1, N0, M0 disease. However,
at present, surgery is not recommended even in patients with very
limited disease.
Surveillance Following Surgical Resection
There has been no proven benefit to routine chest radiographs following a surgical resection of lung cancer. However, patients frequently are
followed with chest radiographs every 4 months for the first 2 years,
followed by chest radiographs every 6 months. Whether routine CT
scans after surgical resection add a benefit to the patient survival
remains to be determined.
2
Lau CL, Harpole DH Jr. In: Norton JA, Bollinger RR, Chang AE, Lowry SF, et al.
Surgery: Basic Science and Clinical Evidence, New York: Springer-Verlag, 2001.
3
Rosell R, Gomez-Codina J, Camps C, et al. A randomized trial comparing preoperative
chemotherapy plus surgery with surgery alone in patients with non-small cell lung
cancer. N Engl J Med 1994;330:153–158. Roth JA, Fossella F, Romaki R, et al. A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in
resectable stage IIIA non-small cell lung cancer. J Natl Cancer Inst 1994;86:673–680.
255
256
J.E. Langenfeld
Summary
When evaluating patients with hemoptysis, it is important to determine whether the bleeding is massive and if the airway is secure. The
treatment options used to control bleeding originating from the
lung include medical management, bronchial lavage, embolization of
bronchial arteries, and surgery.
Critical in treating patients with lung cancer is determining the clinical stage. Patients with stage I and stage II non–small-cell carcinoma
are best treated with surgical resection, while patients with stage IIIA
non–small-cell carcinoma should receive chemotherapy prior to surgical resection. More advanced lung cancer is treated with chemotherapy
with or without radiotherapy.
Basic guidelines for the evaluation, staging, and treatment of lung
cancer are highlighted (see Algorithm 13.1).
Selected Readings
International Registry of Lung Metastases, Ginsberg RJ, et al. Long-term results
of lung metastasectomy: prognostic analyses based on 5,206 cases. J Thorac
Cardiovasc Surg 1997;37–49.
Kato A, Kudo S, et al. Bronchial artery embolization for hemoptysis due to
begin immediate and long-term results. Cardiovasc Intervent Radiol 2000;
23(5):1–7.
Lau CL, Harpole DH Jr. In: Norton JA, Bollinger RR, Chang AE, Lowry SF,
et al. Surgery: Basic Science and Clinical Evidence, New York: SpringerVerlag, 2001.
Lee TW, Wan S, et al. Management of massive hemoptysis: a single institution
experiment. Cardiovasc Surg 2000;6(4):232–235.
Mal H, Rullon I, et al. Immediate and long-term results of bronchial artery
embolization and life threatening hemoptysis. Chest 1999;115(4):996–1001.
Pierson FG, Deslauries J, Ginsberg RJ, et al. Thorac Surg 1995.
Rosell R, Gomez-Codina J, Camps C, et al. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with
non-small cell lung cancer. N Engl J Med 1994;330:153–158.
Roth JA, Fossella F, Romaki R, et al. A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA
non-small cell lung cancer. J Natl Cancer Inst 1994;86:673–680.
Rusch VW, Giroux DJ, et al. Induction chemoradiation and surgical resection
for non-small cell lung carcinomas of the superior sulcus: initial results of S.
Oncology Group Trial 9416 (Intergroup Trial 0160). J Thorac Cardiovasc Surg
2001;121(3):472–483.
Shields TW, LoCicero J, Ponn RB. General Thoracic Surgery, 5th ed, vol 1. 2000.