1. health and fitness
2. disease
3. cancer

Treatment of Patients With
Lung Cancer and Severe
Emphysema*
Steven J. Mentzer, MD, FCCP; and
Scott J. Swanson, MD, FCCP
The development of lung cancer and emphysema is
associated with the destructive chemical milieu that
occurs with smoking. The recent interest in lung
volume reduction surgery (LVRS) has stimulated a
reassessment of the indications for surgery in patients with early stage lung cancer or emphysema.
For patients with both diseases, the issues surrounding LVRS are simplified. The major concern is that
the lung cancer can be surgically removed without
the need for postoperative ventilation or mortality. A
secondary consideration is the potential for longterm postoperative respiratory morbidity. These
risks can be estimated by evaluating the anatomic
location of the tumor, as well as the physiology of the
underlying emphysema. Early results of combined
LVRS and lung cancer resections suggest a favorable
outcome in carefully selected patients.
(CHEST 1999; 116:477S– 479S)
Abbreviation: LVRS 5 lung volume reduction surgery
cancer is the most commonly occurring cancer
L ung
and the most common cancer-related cause of death
among men and women.1,2 Although the rate of lung
cancer in white men in the United States appears to be
declining (Fig 1),3,4 it continues to increase among African-American men and both white and African-American
women. It is estimated that . 170,000 new cases of lung
cancer will be diagnosed and . 160,000 deaths will result
from lung cancer in the United States in 1999.1,2
Smoking is associated with . 80% of lung cancers.5
Male and female smokers have a 22-fold and 12-fold
increased risk, respectively, of developing lung cancer.1
This risk increases with age and duration of smoke exposure. Although the association between smoking and lung
cancer is clear, the mechanism of carcinogenesis remains
unclear.6 Cigarette smoke contains . 4,000 different
chemicals, many of which are proven carcinogens. Hundreds of other chemicals in cigarette smoke appear to
promote carcinogenesis as well as the destruction of lung
parenchyma. It is this destructive chemical milieu that
results in the concomitant development of lung cancer and
emphysema.
Emphysema is commonly defined as a condition of the
lung characterized by an abnormal increase in the size of
the airspaces distal to the terminal bronchiole.7 This
* From the Division of Thoracic Surgery, Department of Surgery,
Brigham and Women’s Hospital, and the Dana-Farber Cancer
Institute, Harvard Medical School Boston, MA.
Correspondence to: Steven J. Mentzer, MD, FCCP, Division of
Thoracic Surgery, Brigham and Women’s Hospital, 75 Francis
Street, Boston, MA 02115; e-mail: [email protected].
harvard.edu
Figure 1. Prevalence of emphysema and the incidence of lung
cancer in the past 15 years. The prevalence of all people with
emphysema is shown. The incidence of lung cancer in white men
is shown; the incidence of lung cancer in African-American and
white women (not shown) continues to rise. The incidence of
lung cancer in African-American men has been relatively stable
(not shown). Data from the National Center for Health Statistics.3,4
increase in airway size can be caused by an inherited
predisposition, which is observed in a1-antitrypsin deficiency.8 An estimated 50,000 to 100,000 Americans currently have this enzyme deficiency. Alternatively, airway
dilatation may result from destruction of the airway walls
after smoke-related damage. Smoking is responsible for
82% of all chronic obstructive pulmonary disease (COPD),
including emphysema. An estimated 2 million Americans
suffer from emphysema,3 and emphysema ranks as the
15th most common chronic condition that contributes to
activity limitation.2 Almost half of the patients with emphysema report that their daily activities are substantially
limited by the disease.2
The common etiologic factor of cigarette smoke results
in an increased risk of bronchogenic carcinoma in patients
with emphysema. Epidemiologic studies suggest that 90%
of patients with bronchogenic carcinoma have signs and
symptoms of COPD. In most cases, symptoms include
shortness of breath and cough. With disease progression,
the shortness of breath will further decrease activity and
exercise. The resulting deconditioning, combined with the
diminished underlying lung function, increases the risk of
any surgical intervention. An estimated 20% of patients
with bronchogenic carcinoma have pulmonary dysfunction
sufficiently severe to be considered inoperable by conventional criteria.9,10
Lung Volume Reduction Surgery
The development of lung volume reduction surgery
(LVRS) for the treatment of emphysema has stimulated a
reassessment of the indications and contraindications for
surgery in early stage lung cancer. LVRS was first introduced for patients with diffuse emphysema by Brantigan
et al11 in the late 1950s. These investigators suspected that
the floppy airways in emphysematous lungs resulted from
lung hyperinflation. With a loss of elastic recoil caused by
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smoke-induced lung destruction, there was a concomitant
loss in airway tethering or “parenchymal interdependence.” By surgically reducing the lung volume, these
investigators expected a restoration of parenchymal interdependence with improved expiratory airflow and shortness of breath. However, few supportive data, as well as a
relatively high perioperative mortality, limited the initial
acceptance of the procedure.12
The reintroduction of LVRS by Cooper et al13 was
based on the similar concept of reversing the pathophysiologic effects of emphysema. In their initial report, these
investigators reported on 20 patients who underwent
LVRS via median sternotomy. There was no perioperative
mortality, and postoperatively, the patients demonstrated
an 82% improvement in FEV1, a 22% increase in 6-min
walk distance, and a significant improvement in qualityof-life assessments.13 Subsequent reports have suggested
similar benefits in selected patients. The procedure has
also been validated using minimally invasive or thoracoscopic approaches.14
Major questions regarding LVRS that remain unanswered include (1) which patients benefit most from
LVRS, (2) how durable is the response to LVRS, and (3)
what are the relative risks and benefits for any given
patient with emphysema? To address these questions,
several major clinical trials are currently underway, including the National Emphysema Treatment Trial. The National Emphysema Treatment Trial is a unique collaboration between the administrative agencies for Medicare and
the National Institutes of Health. The results of the
National Emphysema Treatment Trial are expected in 5 to
7 years. Other regional clinical trials, such as the Overholt
Blue Cross/Blue Shield Emphysema Surgery Trial in New
England, should offer additional insights into the relative
benefits of LVRS.
LVRS in Patients With Lung Cancer and
Emphysema
For the patient with a tumor growing in an emphysematous lung, the issues surrounding LVRS are simplified.
The duration and magnitude of the benefits of LVRS are
a small consideration. The major concern is that the lung
cancer can be surgically removed without postoperative
mechanical ventilation or mortality. A secondary consideration is the potential for long-term postoperative respiratory morbidity. These risks can be estimated by evaluating the anatomic location of the lung cancer, as well as
the physiology of the underlying emphysema.
Although many patients with emphysema will have
diffuse involvement of all portions of the lung, the majority
of patients will demonstrate differential destruction of the
apical portions of the lung. Both gas retention and hypoperfusion of the lung apices characterize the apical predominance of this type of emphysema. Resection of the
dysfunctional apical lung tissue is relatively well tolerated
because the apical portions contribute little or nothing to
gas exchange. In selected patients, reducing the overall
lung volume by resecting the apex has several beneficial
effects. First, the decreased volume of lung tissue allows
the distended chest wall and diaphragm to return to more
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normal anatomic positions. The improved position of the
chest wall and diaphragm can result in a significant
improvement in ventilatory mechanics. Second, the
smaller lung more effectively tethers the small airways,
which results in improved expiratory airflow. Thus, the
patient with apical emphysema and a lung cancer in the
upper lobe is a potential candidate for surgical resection
(Fig 2).
In addition to the anatomic location of the tumor, an
important consideration is the underlying cause of
airflow obstruction. The vast majority of patients with
emphysema have airflow obstruction, which is reflected
by their relatively slow expiratory flow (eg, low FEV1).
The generally accepted definition of emphysema suggests that expiratory flow limitation is caused by the
collapse of floppy airways. Dilated, floppy airways
appear to be the mechanism of flow limitation in most
patients. There is evidence, however, that a subset of
patients have a different mechanism of expiratory flow
limitation.15 These patients appear to have high-resistance airways secondary to inflammation or scarring.
Despite two distinct mechanisms of airflow obstruction,
patients with emphysema will have indistinguishable
expiratory spirometry. The practical clinical problem is
that patients with dilated and floppy airways have a
potential to respond to LVRS. In contrast, patients with
fixed small airway disease appear unlikely to benefit and
may worsen on lung volume reduction. To distinguish
between these two groups of patients, Ingenito and
colleagues15 at the Brigham and Women’s Hospital are
studying airflow obstruction during both inspiration and
expiration. Patients with scarred small airways would be
expected to have high resistance during both inspiration
and expiration. Patients with floppy airways would be
expected to have airflow obstruction limited to expiration. Early clinical results support these predictions.15
Figure 2. Chest CT scan showing a squamous cell carcinoma in
the left upper lobe of a patient with a baseline FEV1 of 430 mL.
The combined tumor resection and LVRS resulted in a 3-day
hospital stay, negative margins, and slightly improved dyspnea.
Multimodality Therapy of Chest Malignancies—Update ’98
Table 1—Combined LVRS and Nodule Resection
Inclusion Criteria
Severe dyspnea
Hyperinflation with flow
obstruction
Oxygen requirement
Heterogeneous emphysema
Pulmonary nodule
Ambulatory potential
Exclusion Criteria
Irreversible small airway
obstruction
Obliterated pleural space
Intractable hypercarbia
Unresectable locoregional disease
Evidence of metastatic disease
Hilar tumor
Indications or Early Results for LVRS in
Lung Cancer
The indications for combined LVRS and resection of a
bronchogenic carcinoma are based on the generally accepted criteria for LVRS (Table 1). Patients may have
severe dyspnea. The arterial blood gas abnormalities can
include hypoxemia and hypercarbia. In addition, conventional spirometry may demonstrate FEV1 , 20% of predicted values. However, the most important predictor for
improvement after LVRS is the presence of recruitable
elastance, which is the relatively preserved tissue remaining in the lung. It is these relatively preserved areas of lung
tissue that are compromised by the hyperinflated emphysematous portions of the lung.
In addition to the exclusion of metastatic disease,
contraindications for combined LVRS and cancer resections include total disability because of lung disease (Table
1). Patients who are largely wheelchair bound but have
ambulatory potential can be enrolled in a pulmonary
rehabilitation program. Pulmonary rehabilitation can result in substantial improvements in preoperative condition
and surgical risk. Patients who do not have ambulatory
potential are at prohibitive risk for postoperative respiratory failure. Relative contraindications include the presence of hilar masses and large masses that require the
anatomic resection of residual functioning lung tissue.
The early results of combined LVRS and lung cancer
resections suggest a favorable outcome in most patients.
McKenna and colleagues16 reported the resection of 51
masses in 325 patients undergoing LVRS. Eleven of these
lesions were non–small cell lung cancer. The mortality
from this operation was 3.5%, and there was no evidence
of recurrent carcinoma during a 9-month follow-up period.14 DeRose et al17 resected 14 patients with lung cancer
with combined LVRS. Nine of resected lesions were
non–small cell lung cancer. There was one mediastinal
recurrence at 12 months, but substantial improvements in
dyspnea indexes, expiratory spirometry (FEV1), and functional capacity (6-min walk test) were reported. These and
other early results suggest that the indications and contraindications for the resection of bronchogenic carcinoma
must be carefully reassessed. In particular, patients with
end-stage emphysema must be evaluated in the context of
their physiologic potential and the possible benefits of
LVRS.
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