13
Hemoptysis, Cough, and Pulmonary Lesions
John E. Langenfeld
Objectives
Hemoptysis
1. To know how to assess whether a patient has life- threatening hemoptysis.
2. To list the differential diagnosis of a patient with hemoptysis.
3. To discuss the initial stabilization of a patient pre- senting with hemoptysis.
4. To know the different diagnostic modalities avail- able 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 sur- gical 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 asphyx- iate 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
The initial immediate assessment should determine quickly whether the patient has life-threatening hemoptysis. Patients should be con- sidered 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.Bleed- ing from the nose or upper gastrointestinal tract at times can be con- fused with hemoptysis. A good history usually can distinguish whether the blood was coughed up from the lungs or whether it was regurgi- tated 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. The amount of bleeding (greater than 250 mL/24 hours is massive) 2. Smoking or other risk factors for cancer
3. Fever, chills, productive cough (infectious)
4. Acute onset of shortness of breath prior to hemoptysis (pulmonary embolism)
5. History of previous hemoptysis and pulmonary diseases 6. Cardiac history
7. Medications: Coumadin and platelet inhibitors; patients taking immunosuppressive drugs (e.g., steroids, chemotherapy) are at risk of developing fungal opportunistic infections
8. Alcohol use (patient at risk for aspiration pneumonia) 9. Prior history or exposure to tuberculosis
10. Travel history: (coccidioidomycosis in the Southwest, tuberculosis, common in many countries, histoplasmosis in Mississippi, Missouri, Ohio River Valley)
11. Trauma history
Physical Examination Vital Signs
Heart rate, blood pressure, temperature, and respiratory rate should be determined immediately. The oxygen saturation also should be
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 car- diovascular 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 sug- gests consolidation of the lung. The presence of rales suggests conges- tive 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 right- sided heart failure.
Extremities/Skin
Assess for the presence of a coagulopathy (petechia, bruises).
Unilateral leg swelling suggests deep venous thromboses. Bilateral leg edemais 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
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 carci- noma, 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 exam- ined for the presence of cancer cells. A rigid bronchoscopy most often Figure 13.1. Chest radiograph of a patient with non–small-cell lung cancer dis- closes right hilar enlargement.
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.
* *
*
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.
Table 13.3. Management of patients with hemoptysis.
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
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 anti- microbial agent. Any coagulopathies should be corrected. A flexible bronchoscopy should be performed to assess for the presence of a bron- chogenic 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 antibi- otics 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 accu- mulation of blood in the airways.
The treatment options for a patient presenting with massive hemop- tysis 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 recommenda- tions discussed below.
Bronchial lavagehas been reported to temporarily control massive hemoptysis in 97% of patients. The procedure is performed by irrigat- ing the major bronchi of the bleeding lung with ice-cold saline using a rigid bronchoscope. Following a brief period of lavage, the nonbleed- ing 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 signifi- cantly less than that of an emergent pulmonary resection. Arterial embolization is 87% to 94% successful in achieving effective homeo- stasis. A major criticism of systemic embolization is the rate of rebleed- ing. 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 hemop- tysis 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,
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 bleed- ing. 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 mor- tality 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 calcifi- cation, 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.
History
When evaluating a patient for possible lung cancer the following factors are of particular importance:
1. Symptoms
2. Prior history of cancer 3. Smoking history
4. Family history of cancer 5. 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 nodesshould be carefully examined for metastatic disease.
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
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
History and Physical + family history + smoking
Risk of Cancer CT Chest
1 cm or greater <1 cm
PET Scan Fine-Needle
Aspiration (FNA)
+
Surgery –
Possible observation;
Consider surgical biopsy
+
Lobectomy/Pneumonectomy
• May observe
• F/U 3 months If grows or if spiculated, then remove
Cancer:
Non–Small-Cell Lung Carcinoma (NSCLC)
Wedge resection if poor pulmonary function
Surgical Biopsy
Surgical
Biopsy +
Algorithm 13.1. Algorithm for the evaluation of a solitary pulmonary module.
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 pneu- mothorax, 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.
The decision to proceed with an FNA or a lung biopsy is largely based on physician preference.There are no studies proving one eval- uation 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 multi- modality 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 inhala- tion 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 inci- dence 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 adenocarci- noma, squamous cell carcinoma, large-cell carcinoma, or small-cell lung carcinoma (Table 13.5). The first three are referred to as
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 mul- tifocal nodules, or as a diffuse infiltrating tumor. Squamous cell carci- noma 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. Immunohisto- chemical 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 repre- sents 75% of all benign tumors of the lung and accounts for 8% of pulmonary neoplasm. Other causes of benign lung tumor occur only rarely.
Table 13.5. Histologic classification of malig- nant 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. Histo- logical typing of lung and pleural tumours, 3rd ed., 1999:21–22, with permission.
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 fre- quently 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. Carci- noid 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 rec- ommendation 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 com- partment 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-
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 neuroen- docrine 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 metasta- sis are the adrenal gland, lung, bone, liver, and brain.Bone pain from metastatic spread occurs in 20% to 25% of patients. Ten percent of
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
patients present with brain metastasis; however, 25% of patients even- tually develop brain metastasis.
Paraneoplastic Syndromes
Paraneoplastic syndromes occur most commonly with small-cell carci- nomas and squamous cell carcinomas (Table 13.8). Paraneoplastic syndromes include hypertrophic pulmonary osteoarthropathy, inappropriate secretion of antidiuretic hormone (ADH), hypercal- cemia, Cushing’s syndrome, and neurologic and myopathic syn- dromes. 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 parathyroid- like 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 medi- astinoscopy. 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 addi- tion 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 ante- rior thoracotomy. The extent of the workup often is dependent on
Table 13.7. Initial symptoms at presentation of lung cancer.
Symptoms Percentage (%)
Cough 74
Weight loss 68
Dyspnea 58
Chest pain 49
Hemoptysis 29
Lymphadenopathy 23
Bone pain 25
Hepatomegaly 21
Clubbing 20
Intracranial 12
Superior vena cava syndrome 4
Hoarseness 18
Source: Reprinted from Hyde L, Hyde CI. Clinical manifesta- tions of lung cancer. Chest 1974;65:300.
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 per- mission from Lippincott Williams & Wilkins.
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 con- sidered 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 pres- ence 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 FDG- PET has a reported sensitivity of 95% and specificity of 80% in deter- mining 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 tracheo- bronchial 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, dis- tance 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 hemitho- rax are assessed. The TNM descriptors are shown in Table 13.9.
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, malig- nant 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 INDICATOR FOR MEDIASTINOSCOPY
PET (+) Mediastinal Lymph Nodes
N2– N3
CT: Lymph Nodes
N2– N3 > 1 cm Control Tumor Tumor > 2 cm
Algorithm 13.2. Algorithm for the use of mediastinoscopy.
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
IIIA T3N0–1
} If clinically stage IIIA, preop. chemotherapy; possible RT T1–3N2 followed by surgery*
IIIB T4N0 Chemotherapy/RT (+surgery in highly selected cases)
T4N1–2 Chemotherapy/RT
Any T, N3 Chemotherapy/RT
IV All other M+ Chemotherapy/RT
*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.
Special cases
Pantumor Preop. chemotherapy/RT followed by surgery
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: Springer- Verlag, 2002, with permission.)
studies have shown that patients with N2 disease who receive pre- operative chemotherapy (neoadjuvant) have a survival advantage over those who do not.1It remains to be determined whether neoadjuvant chemotherapy is beneficial for only selected patients with N2 disease.
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 £3cm 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:
>3cm in greatest dimension
Involves main bronchus, ≥2cm 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 <2cm 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. Pericar- dial 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.
1Rosell 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 random- ized 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.
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 recom- mended 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-
Preop. FEV1 > 2 L Good exercise tolerance Normal chest radiography
Preop. FEV1 < 2 L
Measure quantitative VQ to predict
postop. FEV1
Pneumonectomy or lobectomy should be
tolerated
Calculated postoperative FEV1 > 40%
Calculated postoperative FEV1 30–40%
Measure gas exchange at rest
and during exercise (VO
1 max)
Avoid pneumonectomy, consider lobectomy
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 SaO
1, saturation of oxygen in arterial blood
Calculated postoperative FEV1 < 30%
Peak O2 consumption > 15 mL/kg Fall in SaO1 of <2% with exercise Predicted DLCO of >40%
Peak O2 consumption 10–5 mL Fall in SaO1 >2%
Predicted DLCO <40%
If these conditions are satisfied, consider limited resection
Peak O2 consumption <10 mL/kg
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.)
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 post- operative FEV1of 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 toler- ate 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.)
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.2These 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.3The M.D. Anderson trial ran- domized 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 radia- tion. 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 follow- ing 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 random- ized 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.
Summary
When evaluating patients with hemoptysis, it is important to deter- mine 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 clin- ical 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 surgi- cal 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
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