Hemoptysis, Airway Obstruction, Bronchospasm, Cough, and Pulmonary Complications/Symptoms of Cancer and Its Treatment
Jaya Vijayan
J. Hunter Groninger
INTRODUCTION
Complications from malignancies abound in and around the pulmonary tree and chest cavity. Excepting primary brain malignancies, any cancer has the capacity to wreak havoc in vital organs and circulatory structures as well as potential spaces. For most of these malignancies, complications in the chest cavity or pulmonary tree suggest advanced, incurable disease. From the perspective of supportive oncology and/or palliative care, the clinical approach to the patient with such complications should reflect both evaluation of diseasemodifying treatment options and management of symptom burden, always considering the patient’s goals of care. Finally, many of the complications described here correlate with worsened functional status and prognosis and can lead directly to death. In addition to a comprehensive approach to managing these clinical situations, the supportive oncology or palliative care expert should always be prepared to counsel patients and families and to provide best end-of-life care when other interventions fail.
This chapter provides an overview of more common complications arising in the chest cavity in patients with malignancies and corresponding management strategies. It also broaches more common symptoms arising in the pulmonary system (of note, a most common symptom, dyspnea, is discussed elsewhere in this text). Finally, we summarize discussion points regarding noninvasive positive pressure ventilation (NIPPV), a treatment option that may often be overlooked, particularly in the palliative care setting. Although by no means exhaustive, this chapter should provide a sense of the breadth and depth to which malignancy can affect these critical organ systems and anatomy.
PLEURAL EFFUSIONS
Incidence
Malignant pleural effusions are a significant clinical problem in the management of the cancer patient. In any given general hospital patient population, up to 60% of all pleural effusions are malignant, the highest incidence seen in patients over 50 years old (1,2,3,4). In up to 50% of patients, it is the initial manifestation of cancer (4,5) but eventually, about half of all patients with disseminated cancer develop a malignant pleural effusion (4). Table 30.1 lists the frequency of the various tumor types that are associated with malignant pleural effusions.
Diagnosis
The approach to the diagnosis and subsequent treatment of a patient with a suspected malignant pleural effusion is shown in Figure 30.1. Initial screening begins with the posterior-anterior chest radiograph with decubitus views. Blunting of the costophrenic angle may suggest 175 to 500 mL of free fluid; a decubitus view may show as little as 100 mL (6). Computed tomography (CT) scans may be especially necessary if the hemithorax is opaque on chest radiograph, when a mesothelioma is suspected, or when the underlying primary tumor is unknown. Occasionally, chest ultrasonography can be employed to differentiate pleural fluid and pleural thickening (7), but this modality is more commonly used to localize smaller effusions en route to diagnostic or therapeutic thoracentesis (8).
If the patient is symptomatic, enough fluid should be drained by thoracentesis to relieve symptoms. Rapid removal of a large amount of fluid (especially over 1,500 mL) may result in life-threatening re-expansion pulmonary edema (9). A malignant effusion is frequently hemorrhagic (erythrocyte count >100,000/mm3), but this is nonspecific and occurs in only one-third of cases (5). Elevated levels of lactate dehydrogenase (LDH) or protein in the fluid, and ratios of fluid to concurrent serum levels of LDH and protein, distinguish transudate from an exudate (10). If findings suggest transudate, malignancy may be essentially excluded. However, an exudate with a negative cytology result necessitates a second diagnostic thoracentesis with cytology to improve sensitivity by another 10% (3). Cytology remains the cornerstone to diagnosing a malignant pleural effusion, although important variables contribute to its efficacy: tumor type, cytopathologist experience, and the volume of fluid sent for cytologic analysis (11). With
some cell types, such as Hodgkin’s disease, the rate of positive cytology results may prove as low as 23%, while with others, such as breast or lung cancer, remain as high as 73% (3).
some cell types, such as Hodgkin’s disease, the rate of positive cytology results may prove as low as 23%, while with others, such as breast or lung cancer, remain as high as 73% (3).
TABLE 30.1 Tumor causes of malignant pleural effusions from collected series | ||||||||||||||||||||||
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When two exudative pleural fluid cytology results are negative for malignancy in the face of high clinical suspicion for malignancy, most clinicians move to video-assisted thoracoscopy surgery (VATS), which permits visually directed pleural biopsy and direct therapeutic intervention including lysis of adhesions, mechanical or chemical pleurodesis, or pleurectomy (12).
 Figure 30.1. Approach to the diagnosis and treatment of malignant pleural effusions. +, study result is positive; -, study result is negative. (From Ruckdeschel JC. Management of malignant pleural effusion: an overview. Semin Oncol. 1988;15:24-28, with permission.) |
Prognosis
Most patients with malignant pleural effusions have an incurable disease. Treatment should be targeted to the most effective palliation for maximal, comfortable time outside the hospital. For all patients, the overall mean survival time is 3 to 6 months. In general, mortality in the setting of this complication is high: from 54% at 1 month to 84% at 6 months (13,14,15).
Management
Management of Underlying Malignancy
Whenever indicated, a therapeutic thoracentesis should be followed by appropriate disease-modifying therapies such as systemic chemotherapy or hormonal therapy (16,17). If the malignancy is resistant to systemic therapies, then tube thoracostomy followed by intrapleural therapy may be appropriate, if the patient has a reasonable life expectancy. If the patient’s performance status is poor, simple prolonged drainage by an indwelling catheter may be more appropriate.
Management of Fluid Accumulation
While thoracentesis relieves symptoms briefly, fluid usually re-accumulates quickly—in up to 97% of patients by 1 month (18). Tube thoracostomy demonstrates a role in draining the pleural cavity and maintaining opposition of the pleural surfaces when a therapeutic agent is infused into the chest cavity for sclerotherapy.
Soft silastic indwelling catheters, often placed under local anesthesia, allow patient or caregiver to periodically drain the pleural space for symptomatic relief. When employed more than 6 weeks, these catheters facilitate spontaneous pleurodesis between 40% and 46% of the time (19—21).
Fibrinolytic Agents. Intrapleural instillation of a fibrinolytic agent such as urokinase may help to break up more gelatinous or fibrous fluid accumulations (22,23).
Pleurodesis. Drainage of the pleural space with re-expansion of the lung, followed by instillation of a chemical agent into the pleural cavity, remains the most common management strategy for malignant pleural effusions. The mechanism of this intervention, called pleural sclerotherapy or pleurodesis, is considered to be creation of an inflammatory pleuritis between visceral and parietal pleuras that facilitates more permanent closing of the potential space. A table of available agents used for pleurodesis is given in Table 30.2.
Pleuroperitoneal Shunt. Internal drainage of the malignant effusion into the abdomen using an implanted, valved, manually operated pump is occasionally an option in compliant, well-motivated patients with good performance status who have a trapped lung and an intractable effusion (5,17,24).
Recurrent Effusions. A common frustrating problem remains the refractory pleural effusion in which the first attempt at pleural sclerotherapy has failed. At times, a second tube thoracostomy, followed by intrapleural sclerotherapy, is attempted, usually employing a different agent. If this second attempt fails, and if the patient had a good performance status and a reasonable estimated life span, then VATS talc poudrage may be considered. In many instances, the placement of a silastic catheter with prolonged external drainage has become the treatment of choice.
TABLE 30.2 Available intrapleural sclerosing agents | ||||||||||||||||||||||||||||
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Summary
Patients with malignant pleural effusions generally have terminal disease with a very limited life span—often just a few months at best. Choice to pursue disease-modifying therapy
should reflect the clinician’s realistic understanding of the patient’s overall prognosis along with motivation to provide the maximum quality of life and function. A suggested treatment algorithm for malignant pleural effusions is shown in Figure 30.2.
should reflect the clinician’s realistic understanding of the patient’s overall prognosis along with motivation to provide the maximum quality of life and function. A suggested treatment algorithm for malignant pleural effusions is shown in Figure 30.2.
 Figure 30.2. Malignant pleural effusion—suggested treatment algorithm. |
PERICARDIAL EFFUSIONS
Incidence
In a collection of autopsy studies of patients with disseminated cancer, involvement of the heart and pericardium with metastatic malignancy is seen in up to 21% of cases (24,25,26,27,28,29), with the highest incidence occurring in patients with leukemia (69%), melanoma (64%), and lymphoma (24%) (29).
Etiology
Nearly any primary malignancy can metastasize to the pericardium and cause an effusion (29) excepting primary brain tumors. As with malignant pleural effusions, the most common perpetrators are malignancies of the lung and breast and lymphoma or leukemia; together these account for almost 75% of all pericardial malignant events (30). Elucidating the cause of such an effusion is critically important, since approximately 40% of patients with an underlying cancer have a nonmalignant etiology (31).
Pathophysiology
The increase in pericardial fluid, threatening to cause tamponade, typically results from obstruction of the mediastinal lymphatic system, especially by cancers that commonly involve the mediastinal lymph nodes (26). With slow accumulation of fluid, the pericardium can distend to contain up to 2 L. Rapid accumulation does not allow such tissue distension and hemodynamic compromise may occur with as little an accumulation as 200 mL (32). The critical outcome is impaired diastolic filling of the right side of the heart. Cardiac tamponade occurs when accumulating pericardial contents overwhelm compensatory mechanisms leading to hemodynamic instability (33).
Clinical Presentation
The most common presenting symptom is dyspnea on exertion, which may progress to dyspnea at rest as cardiac function becomes compromised (26,31,33). Other common symptoms include chest pain or heaviness (63%), cough (30% to 43%), and weakness or fatigue (26%) (29). Less common symptoms include peripheral edema, low-grade fever, dizziness, nausea, diaphoresis, and peripheral venous constriction.
On examination, the classic signs associated with cardiac tamponade are often referred to as Beck’s triad: faint heart sounds, hypotension, and venous distention (33). Hypotension may be found in over 60% of patients, elevated venous pressure is seen in 50% to 60%, and resting tachycardia occurs in up to 90% (26). A central venous pressure >15 mm Hg along with hypotension is highly suggestive of tamponade. The pathophysiologic effects of cardiac tamponade tend to exaggerate the normal fall in systolic blood pressure (usually <10 mm Hg) and stroke volume that occur with inspiration, a phenomenon termed pulsus paradoxus. Other signs, less frequent, that may be present include a narrowed pulse pressure, a visible increase in venous pressure on inspiration (Kussmaul’s sign), hepatomegaly, hepatojugular reflux, peripheral edema, cyanosis, pericardial friction rub, arrhythmias, cold clammy extremities, low-grade fever, and ascites.
Diagnosis
Radiographic
In any patient with cancer, a change in the size and contour of the heart in the setting of clear lung fields on a standard
chest x-ray should provoke consideration of a pericardial effusion. The cardiac silhouette might resemble the so-called water-bottle heart with bulging of the normal contours. However, a normal-size heart shadow does not exclude the presence of a pericardial effusion or even a life-threatening tamponade. A chest CT scan is more sensitive and may suggest a malignant pericardial process if the effusion has a high density, there is pericardial thickening, masses are contiguous with the pericardium, or there is an obliteration of the tissue planes between the mass and the heart (26).
chest x-ray should provoke consideration of a pericardial effusion. The cardiac silhouette might resemble the so-called water-bottle heart with bulging of the normal contours. However, a normal-size heart shadow does not exclude the presence of a pericardial effusion or even a life-threatening tamponade. A chest CT scan is more sensitive and may suggest a malignant pericardial process if the effusion has a high density, there is pericardial thickening, masses are contiguous with the pericardium, or there is an obliteration of the tissue planes between the mass and the heart (26).
A more invasive diagnostic procedure is right heart catheterization. The findings from this procedure in true tamponade are depressed cardiac output and the equalization of diastolic pressures in all heart chambers (33).
Electrocardiography (ECG)
ECG changes—including sinus tachycardia, atrial and ventricular arrhythmias, low-voltage QRS, and diffuse nonspecific ST- and T-wave abnormalities—may reflect presence of an effusion. Electrical alternans (alternating large and small P wave and QRS complexes) is occasionally seen and generally resolves immediately with drainage of the effusion (27,33).
Echocardiography
Echocardiography may detect as little as 15 mL of fluid as well as identifying myocardial masses and even loculations of fluid.
Pericardial Fluid Examination
Percutaneous, ultrasound-guided pericardiocentesis can safely be performed in patients with larger effusions (>1 cm anterior clear space on echocardiogram), yielding fluid sample for examination in approximately 90% of patients and temporary tamponade relief (26,34). In a malignant effusion, the result of cytology will be positive for malignant cells in 65% to 90% of cases (35). False-negative cytologic results can frequently be seen with lymphoma and mesothelioma. Negative cytology alone does not exclude neoplastic pericarditis, and it may be necessary to obtain pericardial tissue for histology if clinical suspicion remains high.
Differential Diagnosis of Pericardial Effusion
Up to 40% of patients with a symptomatic pericardial effusion and cancer will have a benign etiology of the effusion (31). Generally, the pericardial fluid analysis together with the patient’s history will exclude most of the potential diagnoses and will pinpoint the actual cause of the effusion.
Prognosis
Quality of life and functional status depend largely on malignancy cell type and stage. In general terms, prognosis is limited at best; for example, after surgical drainage of an effusion, patients with breast cancer have a mean survival of 8 to 18 months (36,37), patients with lymphoma have a mean survival of 10 months (36), and patients with lung cancer have a mean survival of 3 to 5 months (38,36).
Management
Pericardiocentesis
This is the initial procedure of choice in the emergency management of life-threatening tamponade. When combined with echocardiography the success rate in obtaining fluid for diagnosis and relieving symptoms rises to almost 97% with a decrease in the complication rate to 2.4% (26,37). Most (39% to 56%) malignant effusions will recur even after single or repeated taps (26,37). During initial drainage, insertion of a small pigtail catheter into the pericardial space can facilitate intermittent drainage over several days (26).
Intrapericardial Sclerosis
The logic extension of pericardiocentesis with catheter drainage is injection of a sclerosing agent into the pericardium through the indwelling catheter to prevent a recurrence of the effusion, much like that practiced with malignant pleural effusions. Agents used in small studies include tetracycline, doxycycline, minocycline, bleomycin, and talc.
Radiotherapy
Surgical Approaches
The most popular approach to surgical treatment of a malignant pericardial effusion is the subxiphoid pericαrdiectomy (i.e., “pericardial window”), which offers the distinct advantages of very low mortality (1% or less), 1% major morbidity, and 100% immediate efficacy in relieving tamponade. The longterm effusion recurrence rate is low (3% to 7%) (26,40,41,42,43). Diagnostic accuracy approaches 100% because fluid and pericardial tissue are both removed and sent for pathologic evaluation. If necessary, a left anterior thoracotomy for pericardiectomy has a low morbidity and mortality and allows examination and biopsy of the contents of the left pleural cavity if desired. More extensively, the median sternotomy with pericardiectomy gives very wide exposure to most of the pericardium. Alternatively, the advent of VATS has allowed a minimally invasive approach to pericardiectomy; one series of 28 patients demonstrated 100% long-term success, no significant morbidity, and 0% mortality (44). Finally, more novel attempts to maximize fluid drainage while minimizing surgical risks include the pericardioperitoneal shunt (45) and the percutaneous balloon pericardiotomy (46).
Summary
Malignant pericardial effusion is not uncommon in advanced cancers, especially with cancers of the lung and breast and with leukemia or lymphoma. In general, these patients have incurable disease. Nonetheless, most patients with symptomatic effusions deserve treatment evaluation, as they may respond rapidly to pericardial decompression. Therapy must
be individualized, taking into consideration tumor cell type and sensitivity to disease-modifying therapies, patient performance status and prognosis, and presence/absence of pericardial tamponade, leading to some meaningful period of palliation. A suggested treatment algorithm for patients with chemosensitive tumor is shown in Figure 30.3.
be individualized, taking into consideration tumor cell type and sensitivity to disease-modifying therapies, patient performance status and prognosis, and presence/absence of pericardial tamponade, leading to some meaningful period of palliation. A suggested treatment algorithm for patients with chemosensitive tumor is shown in Figure 30.3.
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