(Chest. 1999;116:477S-479S.)
© 1999
American College of Chest Physicians
Treatment of Patients With Lung Cancer and Severe Emphysema*
Steven J. Mentzer, MD, FCCP and
Scott J. Swanson, MD, FCCP
*
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: sjmentzer{at}bics.bwh.harvard.edu
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Abstract
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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 long-term 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.
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Introduction
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Lung
cancer is the most commonly occurring cancer 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
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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
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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 increase in airway size can be
caused by an inherited predisposition, which is observed in
1-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
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Lung Volume Reduction Surgery
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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 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 quality-of-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.
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LVRS in Patients With Lung Cancer and Emphysema
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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 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
).
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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.
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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
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Indications or Early Results for LVRS in Lung Cancer
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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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Footnotes
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Abbreviation: LVRS = lung volume reduction surgery
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References
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Trends in lung cancer: morbidity and mortality. Epidemiology and Statistics Unit, American Lung Association 1998. Available at http://www.lungusa.org/data/tb/part1/pdf. Accessed July 29, 1999
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Current estimates from the National Health Interview Survey. Atlanta, GA: Centers for Disease Control and Prevention, National Center for Health Statistics, 1998
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National Health Interview Survey, 1982–1994. Atlanta, GA: Centers for Disease Control and Prevention, National Center for Health Statistics, 1998
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Mortality data, 1979–1995. Atlanta, GA: Centers for Disease Control and Prevention, National Center for Health Statistics, 1998
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Trends in chronic bronchitis and emphysema: morbidity and mortality. Epidemiology and Statistics Unit, American Lung Association; 1998; New York, NY
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Kabat, GC (1996) Aspects of the epidemiology of lung cancer in smokers and nonsmokers in the United States. Lung Cancer 15,1-20[CrossRef][ISI][Medline]
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Fletcher, CM (1959) Terminology, definitions, and classifications of chronic pulmonary emphysema and related conditions: a report of the conclusion of a CIBA Guest Symposium. September 24–28, 1958. Thorax 14,286-299
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Wiedemann, HP, Stoller, JK (1996) Lung disease due to 1-antitrypsin deficiency. Curr Opin Pulm Med 2,155-160[Medline]
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Reilly, JJ, Jr, Mentzer, SJ, Sugarbaker, DJ (1993) Preoperative assessment of patients undergoing pulmonary resection. Chest 103(suppl 4),342S-345S
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Reilly, JJ (1997) Preparing for pulmonary resection: preoperative evaluation of patients. Chest 112(suppl 4),206S-208S[Medline]
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Brantigan, OC, Mueller, E, Kress, MB (1959) A surgical approach to pulmonary emphysema. Am Rev Respir Dis 80,194-206[ISI][Medline]
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Knudson, RJ, Gaensler, EA (1965) Surgery for emphysema. Ann Thorac Surg 1,332-362
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Cooper, JD, Trulock, EP, Triantafillou, AN, et al (1995) Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg 109,106-119[Abstract/Free Full Text]
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Swanson, SJ, Mentzer, SJ, DeCamp, MM, Jr, et al (1997) No-cut thoracoscopic lung plication: a new technique for lung volume reduction surgery. J Am Coll Surg 185,25-32[CrossRef][ISI][Medline]
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Ingenito, EP, Evans, RB, Loring, SH, et al (1998) Relation between preoperative inspiratory lung resistance and the outcome of lung-volume-reduction surgery for emphysema. N Engl J Med 338,1181-1185[Abstract/Free Full Text]
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McKenna, RJ, Jr, Fischel, RJ, Brenner, M, et al (1996) Combined operations for lung volume reduction surgery and lung cancer. Chest 110,885-888[Abstract/Free Full Text]
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DeRose, JJ, Jr, Argenziano, M, El-Amir, N, et al (1998) Lung reduction operation and resection of pulmonary nodules in patients with severe emphysema. Ann Thorac Surg 65,314-318[Abstract/Free Full Text]
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TOP
Abstract
Introduction
