Quality of life after thoracic surgery

CONTENTS

Preface xiAnthony P.C. Yim

Risk Acceptance and Risk Aversion: Patients’ Perspectives on Lung Surgery 287Samuel Cykert

Many patients diagnosed with early-stage, non small cell lung cancer do not acceptpotentially curative lung resection surgery. Decisions for and against surgery often areinfluenced by patients’ perceptions of risk and prognosis. This article reviews the litera-ture pertaining to risk acceptance and risk aversion and discusses the influence of theserisk attitudes on lung cancer surgery decisions. The concept of numeracy is introduced,and future directions that could optimize cancer treatment decisions are suggested.

Optimization of Lung Function Before Pulmonary Resection: Pulmonologists’Perspectives 295 Aymarah M. Robles and Deborah Shure

Pulmonary resection for lung cancer carries a significant risk for patients with under-lying lung disease. Determinations of predicted postoperative lung function and exerciseendurance can help to reduce morbidity and mortality through appropriate patientselection. Other methods of risk reduction for patients with significant chronic obstruc-tive pulmonary disease include inspiratory muscle training, treatment of pulmonaryinfections, bronchodilators, and corticosteroids if needed. Smoking cessation also shouldbe encouraged.

Methodology for Quality-of-Life Assessment: A Critical Appraisal 305Benny Chung-Ying Zee and Tony S.K. Mok

Technologic advancements have transformed diseases such as cancer from a usuallyfatal disease to a curable illness for some patients and a chronic condition for many more.This change has resulted in an increasing appreciation for the health-related quality of lifeof patients diagnosed with cancer and the quality of care they receive. Knowledge ofhealth-related quality of life provides helpful information to primary care providers,specialists, other health care providers, patients, and families to understand and explorefurther their role in symptom management and appropriate means for providing specialcare for patients throughout the course of cancer. Partly due to the realization of thisneed, academic research on quality of life has been active since the 1980s and 1990s.Health-related quality of life has become an important end point in cancer clinical trials,and it has presented methodologic issues that have been areas of active research. Thisarticle discusses several methodologic issues in the research for health-related quality of life.

QUALITY OF LIFE AFTER THORACIC SURGERY

VOLUME 14 • NUMBER 3 • AUGUST 2004 v

Acute and Chronic Reduction of Pulmonary Function After Lung Surgery 317Ibrahim Bulent Cetindag, William Olson, and Stephen R. Hazelrigg

Thoracic surgeons are facing an increased number of complicated and elderly patientsfor consideration of pulmonary resection. Preoperative prediction of pulmonary func-tion changes is important in marginal patients. Several variables (ie, surgical approach,extent of resection, and postoperative management) play roles in lung function changes,especially in the early postoperative period. Pulmonary rehabilitation is helpful in therecovery of cardiopulmonary function for patients who are left with marginal respira-tory volumes.

Acute Postoperative Compromise in Cardiovascular Function After Chest Surgery 325 Joseph LoCicero, III

Major chest operations place a significant strain on all physiologic systems in the body.Strain on the cardiovascular system can lead to the most serious problems or even death.The problems are not limited to ischemia, arrhythmias, or heart failure, but also includecardiac herniation and hypertensive crisis. Attention to preoperative cardiovascular riskfactors, appropriate preparation, early recognition, and treatment are essential to pre-vent potential catastrophic cardiac events from leading to life-threatening situations inthe postoperative period.

Shoulder Function After Thoracic Surgery 331Wilson W.L. Li, T.W. Lee, and Anthony P.C. Yim

Thoracic procedures are considered to be among the most painful surgical incisions andare associated with considerable postoperative pain and shoulder dysfunction, severelyaffecting mobility and activities of daily living. Improper patient positioning, muscledivision, perioperative nerve injury, rib spreading, and consequent postoperative paininfluence the patient’s postoperative shoulder function and quality of life. To reduceaccess trauma and postoperative morbidity, various alternative modalities have beenproposed to replace the standard posterolateral thoracotomy, including muscle-sparingtechniques and video-assisted thoracic surgery. Initial evaluations suggest that thesealternatives are associated with significantly better postoperative shoulder function.

Postthoracotomy Pain Syndrome 345Manoj K. Karmakar and Anthony M.H. Ho

Postthoracotomy pain syndrome occurs in some 50% of patients. It manifests as chronicneuropathic and myofascial pain. Preemptive analgesia prior to surgery might reduce itsincidence. Surgical techniques that minimize intercostal nerve injury show promise, butno technique has emerged as the definitive answer. Treatment is seldom totally satisfac-tory and might require long-term multidisciplinary pain management.

Quality of Life After Lung Cancer Resection 353Wilson W.L. Li, T.W. Lee, and Anthony P.C. Yim

Lung cancer is the most common cancer in the world, with the highest cancer mortalityrate by far. Although resection remains the treatment of choice in early-stage non small-cell lung cancer, the prognosis remains grim even after surgical treatment. In a patientpopulation with such a high mortality rate, evaluation and preservation of quality of life(QOL) after treatment is imperative. More prospective, longitudinal studies with largerstudy populations and a longer follow-up period are needed to more accurately portraythe course of QOL in lung cancer patients and improve postoperative care.

vi CONTENTS

Quality of Life After Esophageal Surgery 367Hiran C. Fernando and James D. Luketich

Quality of life measurement (QOL) is being reported with increasing frequency in thesurgical literature. The authors and others have found that the use of a generic instru-ment such as the SF36 used in combination with a disease-specific instrument will pro-vide the most comprehensive information. Gastroesophageal reflux disease (GERD) is asignificant health problem that primarily affects the QOL of a large segment of the pop-ulation. New therapies for GERD continue to be developed and introduced into clinicalpractice. QOL assessment should be an important part of the evaluation of these newtherapies. Similarly, the management of esophageal cancer and high-grade dysplasia isalso controversial. QOL assessment should be a crucial factor in determining which sur-gical or nonoperative approach is used for these patients.

Quality of Life After Lung Volume Reduction Surgery 375Douglas E. Wood

Emphysema produces disabling symptoms with an enormous impact on quality of life.Physiologic and functional variables used to evaluate outcomes of lung volume reduc-tion surgery are poor surrogates for the outcomes that are important to patients—reliefof symptoms and improvement in quality of life. Disease-specific and general measure-ments of health-related quality of life have been reported in several series of lung vol-ume reduction surgery outcomes and uniformly show the benefit of lung volume reductionsurgery in relieving the symptoms of dyspnea and improving quality of life in patientswith emphysema.

Quality of Life After Lung Transplantation 385Cliff K. Choong and Bryan F. Meyers

Lung transplantation is an accepted form of treatment for many end-stage lung diseases.Numerous studies have reported improvements in pulmonary function and exerciseperformance after lung transplantation. The survival of lung transplant recipients alsohas improved as a result of improved patient selection, perioperative care, surgical tech-niques, and immunosuppression regimens. Despite the potential differences in patientcharacteristics, study designs, and types of instruments used, this review of the literatureshowed several common findings. Important improvements in quality of life are reportedafter lung transplantation. These improvements were observed when cross-sectionalcomparisons were made across the cohort of candidates and recipients and during longi-tudinal follow-up of patients pretransplant and posttransplant. The improvements inquality of life after transplantation seem to be sustained for 1 to 3 years after transplant.Lung transplant recipients generally were satisfied with their decision to have under-gone transplantation.

Return to Work After Thoracic Surgery: An Overlooked Outcome Measure in Quality-of-Life Studies 409 Chuong D. Hoang, Marc C. Osborne, and Michael A. Maddaus

An important, but poorly defined and often unrecognized aspect of global quality of lifeafter undergoing thoracic surgery is the patient’s ability to return to work. Furtherimprovement in postoperative quality of life is unlikely without a better understandingof the factors that influence the ability to work. The available data on return to work afterthoracic surgery highlight the urgent need for comprehensive clinical investigations tobe performed.

CONTENTS vii

Chronic Respiratory Failure After Lung Resection: The Role of Pulmonary Rehabilitation 417 Bartolome R. Celli

Pulmonary rehabilitation has become the cornerstone of treatment of symptomaticpatients with chronic lung disease. In several published randomized trials, rehabilitationhas been compared with optimal medical therapy and has been shown to have moreimpact on outcomes of importance to patients than any other therapy. The NationalEmphysema Therapy Trial reaffirmed the central role of rehabilitation in the manage-ment of patients with chronic obstructive pulmonary disease. Rehabilitation now is anintegral part of the overall selection process and treatment of patients to be offered lungreduction surgery and lung transplant. This article describes major advances in pul-monary rehabilitation, explains and documents why rehabilitation should be included inthe evaluation of patients with lung disease, and expands on its role in patients beingconsidered for high-risk surgery.

Index 429

viii CONTENTS

FORTHCOMING ISSUES

October 2004

MesotheliomaDavid J. Sugarbaker, MD, andMichael Chang, MD, Guest Editors

February 2005

Thoracic Anesthesia and Pain ManagementJerome M. Klafta, MD, Guest Editor

RECENT ISSUES

May 2004

Aggressive Surgery for Lung Cancer Valerie W. Rusch, MD, Guest Editor

February 2004

Imaging Modalities in General Thoracic SurgeryNasser K. Altorki, MD, andDavid F. Yankelevitz, MD, Guest Editors

November 2003

Surgery for EmphysemaKeith S. Naunheim, MD, Guest Editor

August 2003

Lung TransplantationG. Alexander Patterson, MD, Guest Editor

May 2003

Tracheal SurgeryDouglas J. Mathisen, MD, Guest Editor

THE CLINICS ARE NOW AVAILABLE ONLINE!

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Thorac Surg Clin 14 (2004) xi

Preface

Quality of Life After Thoracic Surgery

Anthony P.C. Yim, MD, FRCS, FACS, FCCP, FHKAM

Guest Editor

Traditionally, surgical mortality and major mor-

bidity have been the standard outcome parameters in

volume reduction surgery, and lung transplantation;

and the impact of functional impairment such as

studies involving chest operations. Although these

data continue to provide important information, with

the advances in anesthetic and surgical techniques

and technology, mortality and major morbidity fig-

ures alone are increasingly inadequate in meeting the

growing needs for detailed comparison of new sur-

gical approaches and rising expectations from

patients of surgery.

This issue of Thoracic Surgery Clinics of North

America focuses on the various aspects of post-

operative quality of life after thoracic surgery. The

carefully chosen topics cover preoperative patient

counseling and risk assessment; preoperative optimi-

zation of lung function; a critical appraisal of the

different health-related quality-of-life instruments

currently in use; impairment of pulmonary, cardio-

vascular, and shoulder functions after lung resection;

chronic pain syndrome; quality of life after different

procedures—lung resection, esophageal surgery, lung

1547-4127/04/$ – see front matter D 2004 Elsevier Inc. All right

doi:10.1016/S1547-4127(04)00027-1

chronic respiratory failure and loss of work on the

patients, their families, and society.

The articles in this issue have been written by

renowned experts in their fields. I would like to thank

all the authors for their contributions, which I trust

the readers will find both useful and educational.

I would also like to thank our consulting editor,

Dr. Mark Ferguson, for the privilege and opportunity

to put this issue together.

Anthony P.C. Yim, MD, FRCS, FACS, FCCP, FHKAM

Department of Surgery

Professor of Surgery and

Chief of Cardiothoracic Surgery

The Chinese University of Hong Kong

The Prince of Wales Hospital

Shatin, NT, Hong Kong SAR, China

E-mail address: [email protected]

s reserved.

Thorac Surg Clin 14 (2004) 287–293

Risk acceptance and risk aversion: patients’ perspectives on

lung surgery

Samuel Cykert, MDa,b,*

aDepartment of Medicine, Division of General Internal Medicine, The University of North Carolina School of Medicine,

Chapel Hill, NC USAbInternal Medicine Program, Moses Cone Hospital, 1200 North Elm Street, Greensboro, NC 27401, USA

Lung cancer is the leading cause of cancer death in exposure at some point in their lives and often are

the United States. Estimates derived from the National

Cancer Institute’s Surveillance Epidemiology and End

Results program suggested that during 2003, 172,000

new patients would be diagnosed with lung cancer,

and 157,000 attributable deaths would occur. Non–

small cell histology is the predominant lung cancer

type, representing 80% of all cases [1,2]. Surgical

resection during stage I and stage II disease remains

the only reliable cure, with a 5-year survival rate of

about 40% when considering all patients in these

clinical stages [3]. Patients who do not undergo ap-

propriate lung resection are limited to a median

survival of less than 1 year, during which time they

endure the consequences of progressive cancer and

death [4,5]. Despite the morbidity associated with the

choice against surgery, administrative data suggest

that 24% of white patients and 36% of black patients

who are diagnosed clinically with stage I or stage II

disease do not undergo surgery [3]. Despite facing

a rapidly progressive, fatal disease, many patients

and their physicians are deciding exclusively or mu-

tually that the only reliable curative treatment is not

worth pursuing.

By definition, patients diagnosed with non–small

cell lung cancer have experienced significant tobacco


doi:10.1016/S1547-4127(04)00016-7

This work was supported by the University of North

Carolina Project on Health Outcomes, the Education Com-

mittee of the Greensboro Area Health Education Center,

and the Moses Cone Health System.

* Internal Medicine Program, Moses Cone Hospital,

1200 North Elm Street, Greensboro, NC 27401.


affected by the pulmonary and cardiovascular con-

sequences of such exposure. Even with the high

prevalence of tobacco-associated comorbid conditions

among lung cancer patients, however, few have the

severe degree of these illnesses that represent absolute

contraindications to surgery. Many patients do not

pursue lung cancer surgery because of their physi-

cian’s clinical judgment or their own risk perceptions.

This article reviews the role of these risk perceptions

in decisions about lung cancer surgery. The following

questions relevant to this topic are addressed:

1. How accurately do patients understand con-

versations about risk?

2. How might risk aversion affect surgical

decisions?

3. Can prognostic accuracy alter patients’ treat-

ment decisions?

4. When patients’ preferences are measured for-

mally in a manner that takes risk attitudes into

account, what lung cancer outcomes do they

care about most?

5. What can clinicians tell patients about these

outcomes of interest?

6. What future directions should be pursued?

General risk perceptions and numeracy

The idea that numeracy (the construct that

describes facility with basic probability and numerical

concepts) affects the accuracy of patients’ risk per-

ceptions has been postulated and measured only more

s reserved.

S. Cykert / Thorac Surg Clin 14 (2004) 287–293288

recently. Schwartz et al [6] surveyed 287 female

veterans. Of these women, 96% were high school

graduates, and 36% had attended at least some col-

lege. Of the group, 85% had had a previous mammo-

gram. Numeracy of participants was tested using three

questions: (1) the number of times 1000 coin flips

would come up heads (about 500), the conversion of a

percentage (1%) to a proportion (10 of 1000), and a

proportion (1 in 1000) to a percentage (0.1%). Only

16% answered all three questions correctly compared

with 26% with two correct answers, 28% with one

correct answer, and 30% with no correct answers. The

participants were presented with data describing the

risk reduction of breast cancer death related to screen-

ing mammography. Of respondents who answered all

three numeracy questions correctly, 40% were able to

present accurately the breast cancer risk reduction,

compared with 9% who answered one question cor-

rectly and 6% who answered none correctly. Although

strong numeracy skills were associated with better

understanding of mammography benefit, most of

the high numeracy group still was not able to por-

tray accurately the effect of mammography on breast

cancer. The authors did not report the effect of

numeracy on the number of study participants who

then went on to get mammograms. Two other assess-

ments of numeracy have been published [7,8]. One

study showed that many highly educated patients have

numeracy difficulties [8], and the other study showed

that for patients with low numeracy scores, the mea-

surement of health preferences is less likely to be

reliable [7]. No reports connect level of numeracy to

real decisions concerning cancer or surgical care.

Authors of an article published in 2001 described

risk perceptions of 71 patients with symptomatic ca-

rotid artery disease who were awaiting endarterectomy

[9]. All patients in this study were given a scripted

presentation by the consulting surgeon. During the

presentation, patients were advised of the 3-year risk

of stroke without surgery, the reduction of risk attrib-

utable to surgery, and the immediate stroke risk during

operation. Numbers were quoted exactly and displayed

graphically during the consultation. Patients under-

stood that the operation would reduce their 3-year

stroke risk. The numbers quoted for risk without

surgery and the reduced risk after successful surgery

were markedly overestimated, however (57% versus

22% for baseline risk and 24% versus 8% for postsur-

gery risk). The risk of endarterectomy itself not only

was overestimated at initial survey (10% versus 2%),

but also when patients were resurveyed the day before

operation the surgical risk was quoted as even higher

(14%). There was a statistically significant correlation

of patients who perceived greater risk also perceiving

greater benefit. The authors did not offer a formal

analysis of the association of risk/benefit perceptions

with actual surgical decisions except to state that 15%

of patients who estimated surgical risk higher than

their baseline risk still opted for carotid endarterectomy.

The same authors now are investigating the use of

written pamphlets and computer aids to improve the

risk communication [9].

Risk aversion, risk acceptance, and patient

preferences

The role of risk aversion in surgical decisions has

been discussed in past reports. In a hypothetical

decision model used to evaluate transurethral prosta-

tectomy versus watchful waiting for benign prostatic

hypertrophy, Cher et al [10] showed that when the

complications of sexual dysfunction and urinary in-

continence were considered, risk-averse patients con-

sistently decided in favor of a watchful waiting

strategy rather than surgical intervention. For lung

cancer specifically, a similar analysis explored the

influence of risk aversion attitudes on the cost-effec-

tiveness of diagnostic algorithms for solitary pulmo-

nary nodules [11]. The base case used in this study

was a 50-year-old man with a 3-cm, peripheral pul-

monary nodule. The diagnostic strategies included im-

mediate thoracoscopy, sputum cytology followed by

thoracoscopy, fine-needle aspiration followed by thor-

acoscopy, sputum cytology followed by fine-needle

aspiration followed by thoracoscopy, and sputum

cytology followed by fine-needle aspiration; if strat-

egies were nondiagnostic, expectant management was

implemented. Besides the strategies themselves, com-

parisons also were made between patients who were

risk averse to procedures and patients who were

averse to waiting and worrying about cancer. The

results of the study are outdated in that positron

emission tomography was not a diagnostic option

for difficult cases, and the expectant management

strategy consisted of frequent chest x-rays at 3- to

6-week intervals with cost accounting for only a

2-month period. Despite these limitations, the authors

did show that whether a patient was more risk averse

toward procedures or more averse toward waiting for

and worrying about a diagnosis influenced cost-effec-

tiveness calculations and possibly actual decisions.

Another method used to assess the relationship of

risk aversion to surgical decisions is the measurement

of an individual’s perception of surgery as a treatment

alternative for a defined condition. The best example

of this method is the aversion to surgery score as

defined by Oddone et al [12] in their study pertaining

S. Cykert / Thorac Surg Clin 14 (2004) 287–293 289

to racial disparities in the use of carotid endarterec-

tomy. These investigators enrolled patients who had

at least a 50% carotid stenosis as shown by Doppler

ultrasound. As part of a predecision survey, partici-

pants were asked to ascertain the risk of immediate

death that they would be willing to accept to be

treated with a pill rather than an operation to reduce

10-year stroke risk by the same magnitude. Surgery

was assigned a fixed mortality risk of 5%. The

aversion to surgery score was determined using a

standard gamble approach in which the interviewer

determined the probability of death for taking the pill

to be indifferent compared with the 5% mortality risk

for surgery (probability of indifference [Pi]). The

surgical mortality risk was subtracted from Pi. This

percentage was converted to a decimal probability. If

the patient considered a 10% immediate death risk for

the pill to be equivalent to a 5% risk of surgery, Piwould be equal to 10%; the aversion to surgery score

would be 10% � 5% converted to the decimal score

of 0.05. Similarly, if Pi were 20%, the aversion to

surgery score would be 0.15, and if Pi were 5%, the

score would be 0. In the analysis, the aversion to

surgery score was divided into quartiles (0–0.025,

0.025–0.075, 0.075–0.250, and > 0.250). A logistic

regression model was used to identify predictors of

carotid endarterectomy while controlling for Rand

appropriateness rating and patient’s race, surgical

experience, self-rated health, Charlson comorbidity

score, evaluation site, and aversion to surgery quar-

tile. Patients in the highest aversion score quartile

(>0.250) were only 40% (95% confidence interval

20% to 90%) as likely to receive carotid endarterec-

tomy compared with the lowest quartile. These data

suggest that individuals who fear surgery are less

likely to accept invasive intervention. The author

used this concept in a pilot study of patients with

newly diagnosed stage I or II non–small cell lung

cancer (n = 29). The author was not able to show a

statistically significant effect ( P = 0.77) of the

aversion to surgery score on decisions for (n = 19,

aversion score 0.22) and against (n = 10, aversion

score 0.26) lung resection surgery (unpublished data).

As opposed to risk aversion, attitudes of risk

acceptance influence patient preferences toward more

aggressive therapies. Although most cancer patients

tend to be risk averse [13], Weeks et al [14] showed

that patients who overestimate their prognosis were

more accepting of aggressive life-extending therapy

compared with patients who did not overestimate

prognosis. Specifically the study population had meta-

static non–small cell lung cancer or metastatic colon

cancer. Patients who estimated their probability for

6-month survival as equal to or greater than 90%

were 2.6 times more likely to choose aggressive

treatments than patients who estimated this probabil-

ity as less than 90%. When patients in the overesti-

mation group were cared for by physicians whose

concomitant 6-month survival estimate for that pa-

tient was less than 10%, the odds ratio for aggressive

treatment increased to 8.5. These results suggest that

patients who do not understand the limitations of their

prognosis and treatment are more risk accepting and

pursue therapies that are overaggressive. The data

concerning discordant perceptions between patient

and physician pairs indicate that the larger the phy-

sician-patient communication gap, the more likely the

patient will choose potentially dangerous therapies

for minimal benefit. Because cancer patients often are

unjustifiably optimistic about their long-term survival

[15,16], these findings are likely important for pa-

tients making decisions about lung cancer surgery.

As these authors concluded, more accurate patient

perception of prognosis may be key to making

treatment decisions that are more consistent with

patients’ true values for risk and benefit.

Health utility scores (HUS) represent patient val-

ues assigned to potential outcomes of medical treat-

ments, including thoracic surgery. Classically, these

scores are anchored in such a way that 0 = death and

1 = normal health. The HUS is an indicator of the

quality of life that patients attach to a specific health

state. Although it is controversial which of the three

major methods of utility assessment is the most

accurate [17], the standard gamble approach is the

one that accounts most for patients’ risk attitudes [13].

The HUS derived from the standard gamble is deter-

mined in a manner similar to the aversion to surgery

score. The health state in question is presented, usu-

ally by a trained, face-to-face interviewer, as a guar-

anteed situation. To avert the guarantee, a patient is

asked the immediate risk of death that he or she would

accept to receive a therapy that would return the

patient to normal health. The concept of risk is

explained thoroughly, and patients are presented pos-

sible risk choices in a predefined manner. The percent

risk at which the patient is indifferent between imme-

diate death and the guaranteed health state determines

the HUS. The higher the risk the patient is willing to

take to avert the guaranteed health state, the lower the

value he or she places on that state. In a survey to

define patient values for possible outcomes of lung

resection surgery, the author and colleagues wanted to

determine the average HUS for progressive lung

cancer [18]. The following scenario was presented:

If you were to receive the diagnosis of lung cancer,

imagine that to cure the cancer and restore your

Table 1

Patients’ perception of possible outcomes of lung surgery as

represented by utility scores

Outcome

Utility score* (95%

confidence interval)

Pneumonia requiring

2 wk of hospitalization

0.81 (0.74–0.88)

Atelectasis requiring

bronchoscopic therapy

0.80 (0.72–0.88)

Ventilator dependence for 3 d 0.76 (0.68–0.84)



Permanent ventilator dependence

with estimated survival of 6 mo

0.10 (0.04–0.16)

Acute myocardial infarction 0.49 (0.40–0.59)

Can walk only 2 city blocks

without stopping

0.48 (0.40–0.56)

Current activity level reduced

by half

0.44 (0.37–0.51)

Oxygen dependence 0.33 (0.26–0.40)

Need assistance with activities

of daily living

0.19 (0.13–0.25)

Limited to bed-to-chair existence 0.17 (0.11–0.23)

Progressive lung cancer 0.17 (0.10–0.24)

Permanent nursing home placement 0.16 (0.10–0.22)

* Utility scores range from 0, representing death, to 1,

representing perfect health.

Adapted from Cykert S, Kissling G, Hansen C. Patients pre-

ferences regarding possible outcomes of lung resection: what

outcomes should pre-operative evaluation target? Chest

2000;117:1553; with permission.


normal life expectancy a hypothetical treatment is

available. The problem with this hypothetical treat-

ment is that there is a chance of dying immediately

when taking the treatment. If you do not have the

treatment, however, the cancer will progress, and

you likely will die in 18 months. The last 6 months

will involve physical weakening, such as an inability

to walk more than a few steps, and pain that some-

times requires narcotic medications for relief. In

other words, if you take no treatment, you are

guaranteed to live 18 months, but the last 6 would

involve weakness and pain. What percent risk of

dying right now are you willing to take to accept the

hypothetical treatment to cure the cancer and live a

normal life?

If the patient is indifferent between accepting a

70% risk of immediate death associated with taking

the treatment and remaining in the guaranteed health

state, the Pi is equal to 0.7. To calculate the HUS for

progressive lung cancer, Pi simply is subtracted from

1, yielding a value in this case of 0.3. If this Pi were

equal to 95%, the HUS for progressive lung cancer

would be 0.05. By forcing a decision on acceptable

death risk early on, a patient’s risk attitude is incor-

porated into the value placed on the given health state.

Patients can be risk averse concerning surgery but

may be risk accepting of surgery or any treatment

potentially causing immediate death if faced with the

prospect of progressive cancer. Somehow, these com-

peting patient attitudes and values need to be com-

bined into an approach that leads to the most rational

treatment decision.

Decisions about lung resection surgery

Most of the literature that describes preoperative

prediction for postoperative complications of lung

resection surgery uses a composite postoperative

complication outcome that largely includes transient

states, such as atelectasis, pneumonia, and prolonged

mechanical ventilation [19–27]. Using the standard

gamble approach, the author and colleagues docu-

mented that these transient complications were rela-

tively unimportant from a patient’s perspective

(Table 1) [18]. In Table 1, utility score decrements

for atelectasis, pneumonia, and time-limited ventila-

tor therapy apply only during periods that patients are

affected by these complications. Conversely, out-

comes that patients feared most—the outcomes for

which patients were willing to take an 80% risk of

immediate death to avoid—were limitation to a bed-

to-chair existence, the need for help in performance

of activities of daily living, permanent ventilator

dependence, and permanent nursing home placement.

Respondents believed that the HUS for progressive

cancer was just as poor, however, as the scores as-

signed to these severe treatment complications. After

expanding the respondent pool to 181, these HUS

data were used to construct a decision model to simu-

late the lung resection surgery decision for patients

who had stage I or stage II, non–small cell cancer

[28]. One of the goals of this decision analysis was to

identify factors in the decision process that most

powerfully sway patients away from surgery. Some

of the important results from this model output are

as follows:

1. Reasonable variation in the HUS for progres-

sive lung cancer affected the surgical decision

only if the patient was sure to have a disabling

complication combined with a life expectancy

of less than 8 months or if the patient faced a

perioperative mortality of 80% or greater.

2. If the patient was uncertain of the diagnosis or

believed in an alternate therapy for cure, he or

she was more apt to decide against surgery,


particularly if there was a chance of disabling

complications. The higher the predicted com-

plication rate, the greater the certainty of

diagnosis a patient required to decide in favor

of surgery.

The two-way sensitivity analysis presented in

Fig. 1 graphically shows the relationships described

in the second statement. The pcurenosurg variable

pictured on the x-axis of Fig. 1 can represent either

uncertainty of diagnosis (eg, if there is a 20% chance

that you do not have lung cancer, then there is a 20%

chance you will be free of cancer without lung

surgery) or the belief that an alternative cure, such

as prayer, would work.

Although results from decision modeling are

hypothetical, pilot data derived from newly diag-

nosed lung cancer patients support these concepts

[29]. HUS for progressive lung cancer was no differ-

ent (P = 0.6) for patients who had surgery (n = 19,

HUS = 0.30) compared with patients who did not

(n = 10, HUS = 0.25). In bivariate analysis, patients

who believed that prayer alone could cure their dis-

ease (4 of 10) underwent surgery less often than those

who did not hold this belief (14 of 18; P = 0.05).

Also, of patients who were asked on a 0-to-100 scale

how certain they were about the diagnosis of lung

cancer, patients who answered less than 90% (4 of

12) were less likely to undergo surgery than patients

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0

pnoc

omp

- P

roba

bilit

y of

NO

Per

iope

rativ

e C

ompl

icat

ions

0.0 0.1 0.2 0.3 0.4 0.5

pcurenosurg - Probability of Lung Cance

Fig. 1. Two-way sensitivity analysis on the probability of ‘‘cu

tive complications. (Adapted from Cykert S, Phifer N. Surgical d

racially sensitive perceptions of cancer are likely to explain rac

with permission.)

who conveyed a certainty of 90% or greater (15 of

17; P = 0.002). Although these data must be regarded

as preliminary, they re-emphasize the point that

misperception of diagnosis and prognosis potentially

can change risk attitudes and treatment decisions.

How does the interaction of patients’ risk attitudes

toward progressive cancer and debilitating surgical

complications affect acceptance of operative mortal-

ity risk? Using the survey and decision model, if

surgery was the only possible cure, and the diagnosis

of lung cancer was absolutely certain, the model

output suggests that, in the setting of a 100% com-

plication rate, patients would accept an operative

mortality rate of 60% [28]. Dowdie and Wildman

[30] projected the mortality rate to be 40%, but these

authors empirically used much higher values for life

with progressive cancer than the author and col-

leagues obtained from the HUS survey. Further

analysis of the model reveals that with the assumption

of a 30% cure for nonsurgical treatment, the accept-

able operative mortality decreases to 10%. If this

nonsurgical cure rate is fixed at 30% (eg, radiation

therapy for stage Ia non–small cell cancer) [31], and

if a patient is guaranteed not to have any long-term

postoperative debility, the acceptable operative mor-

tality risk becomes 20% or less. If a long-term

debility risk of 30% or greater is assigned, however,

the model output does not yield any acceptable opera-

tive mortality risk.

0.6 0.7 0.8 0.9 1.0

r Resolving Without Surgery

surgery

no surgery

re’’ without surgery and the probability of no periopera-

ecisions for early stage, non-small cell lung cancer: which

ial variation in surgery. Med Decis Making 2003;23:172;


Which patients subjected to lung resection surgery

develop the extent of permanent debility that is un-

acceptable according to patients’ preferences? Two

reports agree that patients who are treated with lobec-

tomy experience a mild-to-moderate decrement in

forced expiratory volume in 1 second (FEV1) 3months

postoperatively that returns to near-baseline 6 months

later [32,33]. The average preoperative FEV1 in both

studies was greater than 2 L. Patients with lower

baseline FEV1 might or might not fare as well. Pneu-

monectomy resulted in much more significant pulmo-

nary function reductions that did not recover over

time. The authors did not correlate the reduced breath-

ing capacity with actual functional status. Investiga-

tors led by Handy and Myrdal [34,35] attempted to fill

this void by reporting on postoperative functional

measurements, including the physical functioning

scale of the SF-36. Both groups found significant

reductions in SF-36 physical functioning scores with

absolute values in the range of 55 to 60. These scores

are statistically different compared with the normal

population but do not represent significant clinical

impairment. A group of pulmonary rehabilitation

patients improved their SF-36 physical functioning

score from 26 to 31, and these values correlated with

an improvement of 6-minute walk test distance from

470 to 536 m [36]. Even with dismally low SF-36

scores (half of age-matched population norms), these

data do not describe a population limited to a bed-to-

chair existence or confined to a nursing home.

Summary

Patients express risk aversion toward surgery,

particularly if surgery can lead to lifelong debility

and loss of independence. When faced with a guar-

antee of progressive lung cancer and no alternatives

for cure, however, patients are willing to take ex-

tremely high risks of postoperative complications and

surgery-related death. This result occurs because risk

aversion toward unrelenting cancer death supersedes

patients’ risk attitudes toward almost all other health

states. By adding conditions such as misunderstand-

ing of prognosis, diagnostic uncertainty, a patient’s

denial of diagnosis, an actual alternative cure such as

radiation therapy, or a perceived alternative cure such

as prayer, decisions can be shifted so that risk

aversion to surgery can predominate. In practical

terms, the following statements can be made:

1. For patients who surely have operable stage I

or stage II non–small cell lung cancer, if

patient risk preferences are taken seriously, the

pulmonary function level and comorbidities

that are acceptable for the offer of surgical care

probably need to be liberalized. Patients with

short life expectancies because of advanced age

or comorbid illness and patients with severe

preoperative functional debility (eg, bed-to-

chair limitation as defined earlier) should not

be candidates, however.

2. The diagnosis of cancer needs to be confirmed

absolutely as often as possible before lung re-

section surgery.

3. Physicians or a staff member must communi-

cate prognosis to a patient as precisely and

numerically as possible and ensure the patient’s

understanding of the data presented.

4. This communicator also must explore a pa-

tient’s trust in the diagnosis and probe for be-

liefs in alternative solutions.

Important areas for future study include the search

for methods that most accurately communicate risk

information to patients, especially patients with low

numeracy skills. Part of this communication effort

should involve the exploration and discussion of

patients’ alternative beliefs and ways of using these

belief systems to help them make the best possible

decisions for their long-term health and quality of

life. Also, clinicians must identify pulmonary and

other predictors of mortality rates and the debility

states that patients’ cite as most important according

to their risk preferences and give up the predictors of

transient postoperative complications that patients

find acceptable.

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Optimization of lung function before pulmonary resection:

pulmonologists’ perspectives

Aymarah M. Robles, MD, FCCP, Deborah Shure, MD, Master FCCP*

4929 Travis, Houston, TX 77002, USA

Lung resection carries inherent risks for patients tobacco smoking. Tobacco smoking also is the major

with underlying pulmonary disease. Thoracotomy

alone, without resection, has long been known to

diminish lung volume postoperatively [1]. Resection

adds an additional burden depending on the extent of

the resection [1]. Lobectomy tends to decrease post-

operative forced expiratory volume in 1 second

(FEV1) by 10%, and pneumonectomy tends to de-

crease FEV1 by 33%, although exercise capacity does

not decrease proportionately to the loss in FEV1 [2].

Much attention has been focused on prediction of

postoperative lung function to determine an accept-

able level of risk, and although no single test can

determine definitively the safety of a surgical proce-

dure, much has been learned about relative risks. It

also is essential to understand the many risk factors

other than volume loss that relate to morbidity and

mortality from lung resection to prepare the patient

better preoperatively. Some risk factors are unalter-

able; the effects of others can be ameliorated. This

article reviews predictors of postoperative lung func-

tion, preoperative risk factors, and measures to opti-

mize lung function before surgery. The emphasis is

on chronic obstructive pulmonary disease (COPD)

because this disease has been the main area of

research. What information is lacking and needs for

further investigation also are reviewed.

Chronic obstructive pulmonary disease

Most lung resections are performed for broncho-

genic carcinoma, for which the major risk factor is


doi:10.1016/S1547-4127(04)00018-0

* Corresponding author.

E-mail address: [email protected] (D. Shure).

risk factor for the development of COPD. Most

candidates for resection for lung cancer have COPD

with its attendant functional impairment. Because the

only known cure for non–small cell bronchogenic

carcinoma currently is surgery, the concern of the

pulmonologist and the surgeon is determining which

patients can tolerate the necessary removal of lung

tissue without developing severe pulmonary disabil-

ity postoperatively.

Prediction of postoperative lung function

Currently a great deal is known about predictors

of postoperative lung function, but clinicians still are

in the same position they were in 1987, when Tisi [3]

observed that no single number or even combination

of numbers can predict a good individual outcome.

There is even no firm lower limit, although high risk

can be determined. Table 1 summarizes the results of

several studies since the 1980s and indicates the

variability among these studies.

Several methods have been used to predict post-

operative lung volumes. Quantitative lung perfusion

scans have been consistently reliable [4–7]. CT also

shows good correlation with actual results [6]. Three

other methods are based on anatomy: the postopera-

tive predicted remaining number of segments as a

percentage of total segments, the predicted remaining

segments as a percentage of total unobstructed seg-

ments (functional segments), and a similar method

based on the number of subsegments. Good correla-

tions have been claimed for all methods, but only one

prospective study has compared all five techniques

[6]. Lung perfusion scanning was found to be the

most accurate. Postoperative predicted FEV1 and

forced vital capacity (FVC) values were the same as

s reserved.

Table 1

Predictors of postoperative pulmonary function

Parameters Study design No. patients Method of prediction Results References

FEV1, FVC Prospective 35 Segments Actual postoperative values at 6 mo were lower than

predicted values for patients with main or lobar bronchial

obstruction; PPO values were accurate for segmental

obstruction

Foroulis et al [65]

FEV1 Prospective 32 Segments Actual postoperative values were higher than PPO values.

Actual values were much higher than PPO values with

inspiratory muscle training

Weiner et al [58]

FEV1, FVC,

TLC, DLCO, VO2max

Prospective 68 Lung scan Actual post-operative values at 6 mo were higher than

PPO values

Bolliger et al [4]

FEV1, DLCO, VO2max Prospective 25 Lung scan Actual postoperative FEV1 and VO2max were the same as

PPO values at 3 mo.

Bolliger et al [5]

Actual postoperative DLCO was higher than predicted.

All actual values were higher than PPO values at 6 mo

FEV1 Retrospective 60 Segments Actual FEV1 was higher than PPO values. Good

correlation for lobectomy, but not for pneumonectomy

Zeiher et al [66]

FEV1, FVC, DLCO,

VO2max

Prospective 44 Lung scan, CT,

segments, functional

segments, subsegments

Lung perfusion scanning was the most accurate followed by

CT. The segment method without regard for obstruction

was the least accurate.

Bolliger et al [6]

For lung scans, the predicted values were the same as the

actual values for all but the VO2max, for which the actual

values were higher than the PPO values.

For all other techniques, the actual values were higher than

PPO values.

The results were not influenced by the presence or absence

of COPD

FEV1, FVC Prospective 11 Lung scan Actual postoperative values 200 mL higher than PPO values Williams et al [7]

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; PPO, predicted postoperatives; TLC, total

lung capacity.

A.M

.Robles,

D.Shure

/ThoracSurg

Clin

14(2004)295–304

296

A.M. Robles, D. Shure / Thorac Surg Clin 14 (2004) 295–304 297

the measured values. Only the postoperative pre-

dicted VO2max was higher than the predicted value.

CT was the next most accurate technique. The seg-

ment method without regard for obstruction was the

least accurate. For all techniques other than lung

scanning, the actual values were higher than the

predicted values. In another prospective study by

the same investigators [5], actual values for FEV1

and VO2max were the same as postoperative pre-

dicted values at 3 months postoperatively but were

higher than postoperative predicted values at

6 months. The DLCO was higher than postoperative

predicted at both times. In general, most prediction

methods underestimate actual postoperative function

but serve as reasonable guides to risk.

Preoperative predictors of postoperative morbidity

and mortality

Many factors have been examined as predictors of

morbidity and mortality with lung resection, and

there is a great deal of variation among study results

(Table 2). Some investigators have found the pres-

ence of COPD to be predictive of complications [8,9],

whereas others have not [10]. The same discrepancies

hold true for most parameters with the exception of

stair climbing and predicted postoperative DLCO as a

percentage of predicted normal (ppoDLCO%) derived

from lung scanning, which have been found uni-

formly to be predictive of complications [11,12].

These studies vary in their design (retrospective and

prospective), the numbers of patients studied, the

numbers of parameters studied, and the level of

sophistication of the statistical analysis. Despite these

differences, some general patterns have emerged and

are reviewed for pulmonary function tests, exercise

tests, scoring systems, and other risk factors.

Pulmonary function tests

The FEV1 is the best standardized pulmonary

function test available. It forms an important part of

the basis of the definition of COPD and is used

commonly as a measure of the severity of the disease

[13]. The preoperative FEV1 has not been the best

predictor, however, of postoperative morbidity and

mortality, and patients with FEV1 values less than 1 L

(traditionally assumed to prohibit resection) have

survived lung resection without complications [14].

It generally is acknowledged that surgery should not

be withheld on the basis of a low FEV1 alone [13].

Predicted postoperative FEV1 (ppoFEV1) has been

a better indicator of postoperative morbidity and

mortality, but no lowest value has been identified

definitively. Even ppoFEV1 values less than 1 L (but

�700 mL) have been found acceptable. Because

criteria involving absolute values of FEV1 can be

biased against women and people of short stature,

who have lower normal absolute values and lower

values with disease, ppoFEV1% (predicted postoper-

ative FEV1 expressed as a percentage of the predicted

normal value) has been investigated and found to be a

better predictor of morbidity and mortality than

absolute values [15–18]. Still, there is no one value

that has been found to be prohibitive. Although some

studies have identified cutoff values of 40% [19],

others have found acceptable risk at values of 25%

[18]. Other studies have not identified increased risk

with ppoFEV1% less than 33% [14].

The DLCO expressed as a percentage of predicted

and, in particular, the ppoDLCO% have been found to

be the most reliable predictors of postoperative mor-

bidity and mortality. A ppoDLCO% less than 40% of

predicted normal values has been shown to be a good,

and often the only, predictor of morbidity and mor-

tality [11,16,20].

Arterial carbon dioxide retention, as defined by

PaCO2 equal to or greater than 45 mmHg, although a

marker of severe COPD, has not been found to be

independently predictive of increased risk of lung

resection [14,21–23]. Hypoxemia also has not been

found to be a predictor of increased surgical risk,

although conflicting data exist with respect to oxygen

desaturation during exercise [18–20,24].

Exercise tests

Although the ppoFEV1 has been found to be

useful and the ppoDLCO% even more so, many

studies suggest that some form of exercise testing,

particularly for borderline patients, can determine

high risk better. Exercise testing is believed to reflect

cardiac and pulmonary function. Study results have

varied (see Table 2). VO2max derived from expired

gas analysis during exercise has been a good predic-

tor of morbidity and mortality. Most studies have

found unacceptable risk associated with VO2max less

than 10 mL/kg/min [5,25,26]. There seems to be no

risk associated with VO2max equal to or greater than

20 mL/kg/min and an intermediate risk with values

between 10 mL/kg/min and 15 mL/kg/min.

Formal cardiopulmonary exercise testing is not

widely available. A simple and less costly assessment

of endurance is the time-honored practice of stair

climbing. Although results have varied with respect

to the number of steps or number of flights climbed,

increased risk is associated with poorer performance.

The inability to climb two flights of stairs is asso-

ciated with worse postoperative outcomes [12,27].

The inability to perform any exercise carries a poor

Table 2

Preoperative prediction of postoperative morbidity or mortality

Category Predictive of increased morbidity or mortality

Not predictive of increased morbidity

or mortality

Pulmonary

function tests

FEV1 <80% [9]

FEV1 <70% [67]

FEV1 <60% [16]

Low FEV1 [68,69]

PPOFEV1 <700 mL [25]

PPOFEV1 <55% [15]

PPOFEV1 <40% [11,16,19,20]

PPOFEV1 <30% [17]

PPOFEV1 <25% [18]

PPOFVC <55% [15]

DLCO <60% [16,70]

PPODLCO <40% [11,16,20]

Low PPODLCO% [19,71]

PPODLCO% — lack of increase with exercise [72]

PPOFEV1% � PPODLCO% [73]

Low maximal expiratory pressure [42,60]

FEV1 [1,23,24,28,38,41,71,74]

FEV1 <70% [75]

FEV1 <40% [14]

PPOFEV1 <35% [38]

PPOFEV1 <33% [14]

DLCO [1]

PaCO2 �45 mm Hg [14,21–23]

Exercise tests VO2max <15 mL/kg/min [14,16] VO2max [12,38,69,70]

VO2max <10 mL/kg/min [5,25,26] Oxygen desaturation during exercise [18]

VO2max <1.25 L/min [39] 12-min walk [68]

VO2max <60% [74,76]

Stair climb <3 flights [25,38,77]

Stair climb <2 flights [12,27]

6-min walk <1000 ft [12]

Inability to perform exercise [26]

Oxygen desaturation during exercise [19,20,24]

Ventilatory reserve <25 L [39]

Scoring systems ASA score �3 [28] QLI [39]

Poor POSSUM score [23,29] Comorbid indices [18]

Poor EVAD score [31]

CPRI score �4 [26,30]

Comorbid indices �4 [9]

Diseases COPD [8,9] COPD [10]

Interstitial lung disease [32] Interstitial lung disease [33,34]

Cancer [9] Cardiac disease [38]

Other Male gender [36,78,79] Male gender [9,23,41]

Older age [9,67] Older age [9,18,22,36,38]

Age �60 y [80] Weight loss [9]

Age �65 y [41] Poor nutrition [23,41]

Age �75 y [39] Preoperative chemotherapy [9,23]

Age �84 y [10] Preoperative radiation therapy [23]

Poor performance status [40] Corticosteroids [9]

Weight loss [40] Race [41]

Poor nutrition [42] Obesity [10,41]

Smoking, current [39]

Advanced stage [41]

Hemoglobin V10 g/dL [41]

Preoperative chemotherapy [9,45–48]

Preoperative radiation therapy [45,46]

Low institutional surgical volume [49]

Abbreviations: ASA, American Society of Anesthesiology; COPD, chronic obstructive pulmonary disease; CPRI, Cardio-

pulmonary Risk Index; FEV1, forced expiratory volume in 1 second; FVCS, forced vital capacity; PPO, predicted postoperative;

POSSUM, Physiological Operative Severity Score for Enumeration of Morbidity and Mortality; QLI, Quality of Life Index.

A.M. Robles, D. Shure / Thorac Surg Clin 14 (2004) 295–304298


prognosis [26]. Although other forms of exercise

testing have been advocated, such as the 6-minute

walk [12] and oxygen desaturation during exercise

[18,19], stair climbing or, if available, cardiopulmo-

nary exercise testing provides the most studied and

reliable assessment of cardiopulmonary function.

Scoring systems

Many scoring systems have been studied as

predictors of postoperative function (see Table 2).

American Society of Anesthesiology scoring and

Physiological Operative Severity Score for the Enu-

meration of Morbidity and Mortality scoring have

been used in general surgery and have been found to

be predictive in lung resection as well [23,28,29]. A

scoring system of comorbid indices also has been

found to be predictive of overall outcome [9]. A

cardiopulmonary index (Cardiopulmonary Risk In-

dex) and a pulmonary index (EVAD, using pulmo-

nary function data and age) also have been found

to be useful in prospective studies [26,30,31]. Al-

though these scoring systems can be useful, it is not

clear that they add information to that obtained by

exercise testing and ppoDLCO%.

Other risk factors

Many preoperative risk factors, other than those

related to pulmonary function, have been identified.

COPD itself has been found to be a risk factor in

some studies [8,9], but not all studies [10]. Similarly

the presence of interstitial lung disease was found to

increase the risk of resection in one study [32], but

not in others [33,34]. In these latter studies, mortality

and survival were the same as for lung cancer in

general or interstitial lung disease in general. Asthma

is not a risk factor, unless it is in exacerbation, in

which case preoperative treatment and control together

with good postoperative management reduce the

risk. Corticosteroids, a mainstay in the treatment of

asthma exacerbations, have been found to be safe in

the preoperative and perioperative periods [9]. They

do not lead to increase in infections and have no

clinically significant effect on wound healing [35].

Age has been a controversial issue in the past, but

it now seems clear that age is not an independent

predictor of significant risk of surgery [18,22,36–38].

Octagenarians have undergone resection for broncho-

genic carcinoma successfully [39,40].

Men seem to do worse than women with lung

cancer surgery. Men tend to present with more ad-

vanced disease, requiring pneumonectomy rather

than lobectomy, and have worse survival rates than

women [4,15,67]. This finding has not been borne out

in all studies, however [9,23,41]. Advanced stage of

disease is itself a risk factor for worse outcome [41].

Perhaps reflecting advanced disease or more aggres-

sive tumor biology, poor performance status, regard-

less of anatomic staging, is associated with increased

surgical morbidity and mortality [40].

Poor nutritional status also is associated with

increased risks [42]. This observation is important

because patients with COPD are known to have

poorer nutritional status; 25% to 50% of COPD

patients have been found to have impaired nutritional

status [43,44]. Another factor related to COPD is the

risk of current smoking. This risk decreases when

smoking has stopped 2 months or more before

surgery [39].

Preoperative chemotherapy and radiation therapy

have been associated with increased postoperative

morbidity and mortality [9,45–48]. These therapies

seem to inhibit bronchial stump healing by decreasing

bronchial mucosal blood flow [47].These findings

also are important because neoadjuvant therapy may

play a future role in the management of lung cancer

as new, more potent drugs become available. Ways

needs to be found to minimize their adverse effects on

surgical outcomes.

A particularly important risk factor is the lack

of institutional experience. One study found signifi-

cantly lower morbidity and mortality in institutions

with high volumes of lung resection [49].

Pulmonary hypertension has not been well studied

in this setting but has been assumed to be a contra-

indication to resection. Pulmonary hypertension as-

sociated with COPD is a contraindication to lung

volume-reduction surgery (LVRS) [50] and so can be

inferred to be a contraindication to resection for lung

cancer. What has not been well established is the

degree of pulmonary hypertension and whether or not

pulmonary hypertension is present only with exercise.

Preoperative optimization of function and

reduction of risk

With the understanding of the above-outlined

preoperative risk factors, measures can be taken to

reduce surgical risks. Focusing on COPD, several

areas can be optimized. Bronchitic infections, mani-

fested by increased cough and sputum production,

can be treated with a course of antibiotics with

improvement in postoperative outcomes [51,52].

Bronchospastic exacerbations of COPD or asthma

can be treated with bronchodilators and corticoste-

roids preoperatively, perioperatively, and postopera-


tively. Exacerbations should be controlled before

surgery, but treatment should continue during and

after surgery to decrease risks [51]. As mentioned

previously, corticosteroids do not increase the risk of

postoperative infection and may decrease morbidity

by decreasing inflammatory cytokine production

postoperatively [53].

Smoking is common in patients with lung cancer

and patients with COPD. Cessation has been shown

to decrease postoperative complications in coronary

artery bypass patients [54] and can be assumed to do

so in patients undergoing lung resection. This effect

can be inferred from the finding of increased post-

operative morbidity in current smokers, but not in

patients who have stopped smoking 2 months or more

before surgery [39]. Although it may not be practical

to defer surgery for 2 months, smoking cessation still

should be encouraged to decrease smoking-related

lung inflammation, which may have deleterious

effects in the postoperative period [55].

Although it commonly is believed that lung

function cannot be improved other than with bron-

chodilators if a reversible component is present,

inspiratory muscle training has been documented to

improve function and cause subjective improvement

in dyspnea [56,57]. One study of incentive spirome-

try and inspiratory muscle training initiated 2 weeks

preoperatively and continued for 3 months postopera-

tively found significant increases in postoperative

FEV1 over ppoFEV1 [58] compared with untrained

controls. The actual measured FEV1 was 570 mL

larger than the ppoFEV1 for lobectomies and 680 mL

for pneumonectomies. These numbers compare with

70 mL for lobectomies and 110 mL for pneumonec-

tomies in the controls. Actual lung function can be

improved. Pulmonary rehabilitation also may have

a role because it is known to improve function,

dyspnea scores, and quality of life [59]. It also is a

prerequisite for LVRS in the National Emphysema

Treatment Trial [50]. A full pulmonary rehabilitation

program may not be practical, however, in terms of

the imperative of surgery. Inspiratory muscle training

should be possible, however, in most cases.

Nutrition is another area worthy of attention.

Because poor nutrition is associated with worse sur-

gical outcomes [42,60], improvement in nutritional

status preoperatively may be helpful. This effect has

not been studied for lung resection, however.

As noted earlier, the volume of surgery performed

at an institution has been found in a large retrospec-

tive study (2116 operations) to be related to outcome

[49]. In this study, 5-year survival was highest at the

centers with the highest volume, 44% versus 33% at

the centers with lower volume. Differences also were

found in the incidence of postoperative complications

(20% versus 44%) and the 30-day mortality (3%

versus 6%). Choosing the most experienced center

may improve outcome.

Patient selection can be optimized in many in-

stances. Patients with no history of COPD and no

pulmonary symptoms are unlikely to be at signifi-

cantly increased risk. Pulmonary function tests are

recommended for patients undergoing resection [13].

If the FEV1 is equal to or greater than 60% of

predicted and the patient is asymptomatic, no further

evaluation is needed because the patient falls into a

low-risk category. If the FEV1 or the DLCO are less

than 60% or if the patient has pulmonary symptoms,

such as dyspnea (regardless of the FEV1), further

functional evaluation is needed to assess risk. Lung

scanning or CT is indicated to determine ppoFEV1%

and ppoDLCO. If these values are borderline or low

(<40%), some form of exercise testing is indicated

[61]. This testing can be the simple stair climb or the

more sophisticated VO2max. An inability to climb

two flights of stairs or a VO2max less than 10 mL/kg/

min or less than 40% of predicted indicates a high-

risk patient. Although high-risk patients have been

operated on successfully [14], the markedly increased

level of risk dictates that great caution be exercised in

recommending surgery in these individuals. Perhaps

the only exceptions to the VO2max level of less than

10 mL/kg/min would be the rare patient with the

simultaneous ability to stair climb or an adequate

ppoDLCO% (>40%). In these cases, the VO2max

expressed as a percentage of predicted is likely to

be a better indication of risk.

Possible exceptions to these guidelines have been

seen in patients who underwent LVRS and were

found incidentally to have lung cancers in the

resected tissue. Many of these patients experienced

improvement in function postoperatively as a result

of the LVRS despite having poor preoperative func-

tion [62]. The mean preoperative FEV1 was 654 mL

(21.7% predicted), and the mean postoperative FEV1

was 1097 mL (49% predicted). A subsequent study

examined patients with lung cancer who were candi-

dates for LVRS [63]. Patients with ppoFEV1 less than

40% had no change in FEV1 postoperatively, whereas

patients with ppoFEV1 greater than 40% experienced

a reduction postoperatively. The in-hospital mortality

was high in the group with worse preoperative

function, 14% versus 0% for the group with better

preoperative function, but the long-term survival rates

of the groups were the same. The finding of no

decrement in lung function in the group with the

lowest FEV1 is consistent with other studies that

have found a smaller proportional decrement in


lung function in patients with the lowest preoperative

FEV1 [64].

Future research

Although much information has become available

with respect to COPD, comparable information is

needed for the effects of resection on patients with

interstitial lung disease. The need for prediction of

postoperative lung function and the accuracy of these

predictions in the presence of interstitial lung disease

are not known. The presence of significant pul-

monary hypertension can be assumed to present a

risk similar to that in COPD, but in both cases a

tolerable level (if any) of pulmonary hypertension is

not known.

The optimal timing and duration of inspiratory

muscle training are not known and may be a profit-

able area of research. The risks of delaying surgery to

achieve optimal training by specific muscle training

or pulmonary rehabilitation in patients with lung

cancer also are not known and perhaps would be

difficult to study directly. Similarly the risks of

delaying surgery to achieve adequate nutritional sta-

tus are not known.

Summary

Many risk factors for morbidity and mortality with

lung resection have been identified. Factors such as

age, gender, and cancer stage cannot be altered, but

lung function can be optimized by treating COPD or

asthma with bronchodilators, corticosteroids, or anti-

biotics (when indicated) and by inspiratory muscle

training. Although smoking cessation 2 months in

advance of surgery may not be feasible, cessation

nevertheless should be encouraged because it may

decrease postoperative inflammation and in the long-

term may decrease the risk of recurrence. In addition,

morbidity and mortality can be minimized by careful

patient selection using lung scanning or CT to deter-

mine predicted postoperative functions (FEV1% and

DLCO%) and some form of exercise testing, such

as cardiopulmonary exercise testing or simple stair

climbing. When the risk of surgery is high, any

benefit from possible cure must be weighed against

the risk of long-term disability or death. Although

much data are available to guide clinicians in these

decisions, there still is no one test that provides the

answer in individual cases. The art and science of

medicine must merge at this point.

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Methodology for quality-of-life assessment:

a critical appraisal

Benny Chung-Ying Zee, PhDa,b,*, Tony S.K. Mok, MD, FRCPCc

aCentre for Clinical Trials, School of Public Health, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT,

Hong Kong SAR, ChinabComprehensive Cancer Trials Unit, Department of Clinical Oncology, Chinese University of Hong Kong,

Prince of Wales Hospital, Shatin, NT, Hong Kong SAR, ChinacDepartment of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT,

Hong Kong SAR, China

Technologic advancements in surgery and medi- as pain, dyspnea, and fatigue, which can be clearly

cine have transformed diseases such as cancer from a

usually fatal disease to a curable illness for some

patients and a chronic condition for many more. This

change has resulted in an increasing appreciation

about the health-related quality of life (HRQOL) of

patients diagnosed with cancer and the quality of care

they receive. Knowledge of HRQOL provides helpful

information to primary care providers, specialists,

other health care providers, patients, and families to

understand and explore further their role in symptom

management and appropriate means for providing

special care for patients throughout the course of

cancer. Partly due to the realization of this need, the

academic research on quality of life (QOL) has been

active since the 1980s and 1990s. HRQOL is widely

considered as multidimensional constructs describing

how illness and treatment affect patients’ ability to

function and the potential burden of symptoms from

treatment [1–3]. HRQOL has become an important

end point in cancer clinical trials, and it has presented

many methodologic issues that have been areas of

active research. This article discusses several meth-

odologic issues in the research for HRQOL.

One issue in HRQOL research is the definition

and the associated clinical meaning associated with

the QOL domains [4,5]. In contrast to symptoms such


doi:10.1016/S1547-4127(04)00028-3



(B.C.-Y. Zee).

defined, HRQOL sometimes refers to abstract con-

structs, such as social functioning. Instead of a mea-

surement of depression, HRQOL assesses emotional

functioning that may incorporate a much wider scope

of emotional distress due to the disease and treatment.

Within the clinical trial context, various methods

of symptom assessment have been studied exten-

sively with a long history of methodologic develop-

ment that has been accepted by regulatory agencies in

the drug approval process to deal with specific

symptoms. Some successful examples and future

directions of development for other HRQOL con-

structs are discussed.

Because HRQOL data usually are obtained through

patient self-administered questionnaires, missing val-

ues are common [6]. The way the data are processed

may make a difference in the analysis and may affect

the study conclusion. To deal with missing data, most

statistical software uses case-deletion method by

deleting cases with missing data, then applies stan-

dard complete-data methods for the analysis. A

disadvantage is that case-deletion method reduces

the sample size and produces less efficient and

possibly biased estimates leading to erroneous con-

clusions. This article discusses many commonly used

approaches in summarizing the QOL scores with

missing data.

Finally, the HRQOL outcome may have been

defined clearly with an optimal methodology of

dealing with missing data; however, the way the data

are analyzed may affect the conclusion. The difficulty

s reserved.

1

0.8

0.6

0.4

0.2

0

–0.2

–0.4

–0.6Phys Role Emot Cogn Glob

QOLNaus Appe

–0.32

–0.01–0.06

–0.27 –0.3

0.78

0.38

Fig. 1. Spearman correlations between average diary nausea

score and selected European Organization for Research and

Treatment of Cancer (EORTC) Core Quality of Life

Questionnaire (QLQ-C30) domains and symptoms. Phys,

physical functioning; Role, role functioning; Emot, emo-

B.C.-Y. Zee, T.S.K. Mok / Thorac Surg Clin 14 (2004) 305–315306

encountered in the analysis is due to the longitudinal

nature of the HRQOL data coupled with practical

issues, such as appointment scheduling. The analysis

methods of using growth curve modeling are dis-

cussed and compared with the results of the analysis

of using a HRQOL response variable to summarize

longitudinal HRQOL data [7,8].

Throughout this article, a cancer-specific question-

naire, the European Organization for Research and

Treatment of Cancer (EORTC) Core Quality of Life

Questionnaire (QLQ-C30) is used for illustration

purposes [9]. This is a patient self-administered ques-

tionnaire with 30 items. It has been psychometrically

validated and used in many studies. Embedded in the

questionnaire are dimensions assessing physical func-

tioning, role functioning, emotional functioning, cog-

nitive functioning, social functioning, and overall or

global QOL. In addition, there are three symptom

domains, including fatigue, nausea and vomiting and

pain, and six single items on dyspnea, insomnia, ap-

petite loss, constipation, diarrhea, and financial diffi-

culties. The whole QLQ-C30 questionnaire normally

takes about 10 to 15 minutes to complete.
tional functioning; Cogn, cognitive functioning; Glob QOL,
global quality of life; Naus, nausea and vomiting; Appe,

appetite loss.

Symptom assessment and health-related quality

of life

Clinical trials on symptom control have been

successful in the past. One example is in the area of

antiemetic drug development. Pharmaceutical com-

panies and academic institutions have done many

well-designed studies assessing the antiemetic effect

of treatments such as ondansetron and dexametha-

sone [10–13]. One reason for these successes is that

nausea and vomiting, although considered as a sub-

jective response, can be understood easily from a

clinical point of view, which facilitates the regulatory

approval process. In a study assessing chemotherapy-

induced nausea and vomiting [14], 5-day average

nausea scores captured by patient diary on a 100-mm

visual analogue scale was significantly correlated with

QLQ-C30 nausea and vomiting domain (P < .01),

appetite loss (P < .05), physical functioning (P < .05),

and global QOL (P < .05) (Fig. 1). An important

observation of this result is that the high correlation

between 5-day average of nausea scores from patient

diary and the one-time assessment of the HRQOL at

the end of day 5 implies that the assessment of nausea

and vomiting can be done at one point of time,

although it was believed that the daily assessment

of nausea and vomiting is more accurate, and daily

diary assessment has been a preferred end point in

antiemetic studies. Kaizer et al [11] captured daily

measurements of nausea and vomiting for 5 days and

a one-time measurement of HRQOL at day 8 after

starting chemotherapy; there was a significant differ-

ence between the maintenance ondansetron arm and

the no maintenance ondansetron arm with respect to

complete response (59.6% versus 42.1%; P = .012,

one-sided test). The 5-day average of severity of nau-

sea also was significant in favor of the ondansetron

maintenance arm, with a mean of 9.4 mm differ-

ence (P = .002). Similarly the comparison between

EORTC QLQ-C30 nausea and vomiting domain was

significant in favor of the maintenance ondansetron

arm (17.8 versus 29.2; P < .001). The benefit of

nausea and vomiting assessment for the maintenance

arm was not strong enough, however, to translate into

a global QOL benefit (53.9 versus 49.4; P = .217).

The above-mentioned observations have been

noted repeatedly in other studies. In a phase II,

prospective randomized study, patients with stage

IIIb/IV, histologically confirmed non–small cell lung

carcinoma with an age range of 18 to 75 and with

bidimensionally measurable disease were randomized

to receive either gemcitabine, 1 g/m2, on days 1, 8,

and 15 and cisplatin, 75 mg/m2, on day 15 (GP)

versus gemcitabine, 1 g/m2, on days 1, 8, and 15 and

oral etoposide, 50 mg, on days 1 to 14 (GE) [15].

B.C.-Y. Zee, T.S.K. Mok / Thorac Surg Clin 14 (2004) 305–315 307

Patient HRQOL was assessed using EORTC QLQ-

C30 at baseline and the beginning of each cycle.

After the first cycle of treatment, nausea and vomiting

(5.1 for GE versus 16.7 for GP; P = .004) was

significantly worse in the GP arm, and alopecia

(52.5 for GE versus 11.5 for GP; P < .001) was

significantly worse in the GE arm. Nausea and

vomiting as assessed by the common toxicity criteria

was not significantly different (38% versus 39%

grade 2 or greater; P = .93). These results showed

that symptoms measured by a patient self-adminis-

tered tool such as QLQ-C30 are more sensitive than

common toxicity criteria. The QOL questionnaire can

be used as a valid clinical trial end point; the amount

of information required to show improvement is

dramatically reduced compared with a patient diary.

Other symptoms of interest in these patients are

cough, hemoptysis, sore mouth, and pain. Interven-

tion that could alleviate these symptoms may have a

greater impact on global QOL.

Summarizing health-related quality-of-life scores

with missing data

The ease of interpretation for the symptom

domains within a HRQOL questionnaire and the

evidence that a less frequent measurement schedule

may be sufficient do not come without a price. The

most obvious problem of using a patient self-admin-

istered questionnaire is missing data. The types of

missing data in HRQOL studies include data missing

due to patients inadvertently missing the item or

choosing not to answer the item for a specific reason.

Another type of nonresponse may be due to the fact

that patients with poor QOL may have a higher

likelihood of missing items or may be incapable of

answering the whole questionnaire. In a study on

palliative therapy for patients with poor-prognosis

small cell lung cancer, the proportion of patients

completing the QOL assessments decreased from

92% to 31% in patients whom physicians rated as

normal compared with patients who were confined to

bed or a chair [16]. The consequence of this type of

missing data is that serious bias may be generated. To

choose an optimal method of handling missing data

in a HRQOL study, the authors formally evaluated

many different imputation approaches through a

simulation method.

Methods of imputation

Six methods were examined in this study: (1) case

deletion, (2) subscale mean, (3) subscale mean 50%,

(4) item mean, (5) single imputation, and (6) matched

item mean. The most primitive method of handling

missing data is the case-deletion method. In this

method, a complete data set is generated by deleting

all subjects with incomplete items. The subscale-

mean method can be applied to instruments with

domains or subscales that have multiple items. The

imputed value of a missing item is the average of all

the completed items in that subscale for a particular

subject. The major characteristic of this method is

that it does not depend on the availability of data

from other subjects. The subscale-mean 50% method

is similar to the previous subscale-mean method

except that it requires at least 50% of the items within

the imputing domain to be answered before an

average value can be computed and used as the

imputed value. The items-mean method imputes the

missing items of a subject by an average of the items

of the subjects who answered that particular item.

This method does not depend on the availability of

data in each domain or subscale, but rather it depends

on the availability of data from other subjects and is

suitable only for large studies. The next two methods

use sets of similar subjects to model the missing

data. The criteria for defining the set of similar sub-

jects are discussed subsequently. The single-imputa-

tion method imputes a randomly selected value

from the corresponding item in the set of similar

subjects for the missing item. The matched items-

mean method also uses the set of similar subjects, but

similar to the imputed items-mean method. Instead

of imputing a value randomly selected from the

corresponding items, as in single imputation, the

missing items are imputed by the mean of the cor-

responding items.

For single-imputation and matched items-mean

methods, the selection criteria include a series of

comparisons between pairs of subjects. The sum of

the absolute differences between all nonmissing

items, within each domain, is calculated, as follows:

0 V dijk ¼XNk

l¼1

j Iikl � Ijkl jnikðak � bkÞ

V1;

k ¼ 1; . . . ; 15; I ¼ 1; . . . ; n; j ¼ 1; . . . ; n; and iaj

where Iikl and Ijkl are the lth item values of the kth

domain for the ith and jth individuals, nik is the

number of nonmissing items in the kth domain for

the ith individual, and the values ak and bk are the

maximum and minimum of the item value for the kth

domain. Nk is the total number of items in the kth

domain, and n is the total number of subjects in the

study. After the standardized distances (dijk) for each

Table 1

Average deviations for random missing data (N = 177)

10% data missing 20% data missing 30% data missing

Imputation method SSD PMD SSD PMD SSD PMD

Case deletion Nil .0107 Nil .0176 Nil .0701

Subscale mean .0401 .0004b .0567b .0004a .0855b .0061b

Subscale mean 50% .0348a .0001a .0559a .0014b .0705a .0071

Item mean .0610 .0046 .1151 .0024 .1597 .0007a

Single imputation .0377b .0039 .0871 .0092 .1004 .0343

Matched item mean .0703 .0025 .1195 .0113 .1474 .0354

Abbreviations: PMD, population mean deviation; SSD, sum of squared deviation.a Refers to the smallest p-value among the imputation methods.b Refers to the second smallest p-value among the imputation methods.


of the domains are calculated, an average is taken,

as follows:

0V Dij ¼X15k¼1

dijk

!=15

" #V1;

i ¼ 1; . . . ; n; j ¼ 1; . . . ; n; and iaj

where Dij is the average standardized distance (ASD).

Based on ASD, a probability (prob = 1 � ASD) was

assigned to the compared subject, and this probability

represents the chance the subject will be included

in the set of similar subjects. Subjects with a small

ASD value have a high probability, which represents

a higher likelihood of being included in the set of

similar subjects.

Simulation study

A data set was used to evaluate the performance of

the imputation methods. The data set was obtained

Table 2

Average deviations for random missing data (N = 452)

10% data missing 20

Imputation method SSD PMD SS

Case deletion Nil .0114 N

Subscale mean .0372 .0001a .0

Subscale mean 50% .0368b .0005b .0

Item mean .0411 .0021 .1

Single imputation .0282a .0009 .0

Matched item mean .0806 .0008 .1

Abbreviations: PMD, population mean deviation; SSD, sum of sqa Refers to the smallest p-value among the imputation methodb Refers to the second smallest p-value among the imputation

from samples of two symptom control studies (SC.8

and SC.9) of the National Cancer Institute of Canada

Clinical Trials Group [11,17]. In this data set, a total of

820 subjects were obtained, and 673 had complete

QOL data. A sample of 177 patients and a larger set of

452 patients were chosen from the complete QOL data

set for performing the evaluation. Among the patients

with complete QOL data, a comparison of the day

8 QOL data between two treatment arms was used.

To evaluate the performance of various imputation

methods, missing data were generated from the

complete data set using random and nonrandom

processes. In a workshop on ‘‘Missing Data in

Quality of Life Research in Cancer Clinical Trials,’’

most cooperative groups reported that the baseline

compliance rates were greater than 90% [18]. The

compliance rate while patients were receiving treat-

ment was about 80% and after patients completed

treatment was in the 70% range. Based on these

generally acceptable ranges of missing data during

different phases, the proportion of missing items

% data missing 30% data missing

D PMD SSD PMD

il .0192 Nil .0255

675b .0046b .1144b .0023

648a .0058 .1027a .0014b

052 .0020a .1562 .0010a

748 .0070 .1148 .0121

469 .0053 .1816 .0090

uared deviation.

s.

methods.

Table 3

Average deviations for nonrandom missing data (N = 177)

10% data missing 20% data missing 30% data missing

Imputation method SSD PMD SSD PMD SSD PMD

Case deletion Nil .0136 Nil .0235 Nil .0282a

Subscale mean .0120 .0015b .0375 .0012b .0579b .0035b

Subscale mean 50% .0116b .0012a .0369b .0027 .0535a .0052

Item mean .0206 .0031 .0465 .0045 .0864 .0090

Single imputation .0113a .0015b .0294a .0008a .0604 .0052

Matched item mean .0357 .0046 .0988 .0071 .1465 .0086

Abbreviations: PMD, population mean deviation; SSD, sum of squared deviation.a Refers to the smallest p-value among the imputation methods.b Refers to the second smallest p-value among the imputation methods.


generated for this study has been decided and set at

10%, 20%, and 30%. For the nonrandom process,

missing data were generated using a mechanism such

that the probability of a nonresponded item is a

function of the score of a patient’s global QOL,

which ranged from 1 to 7, and a predefined rate of

nonresponses, 10%, 20%, and 30%. The percentage

of nonresponse for ith subject is (NR)I, as follows:

ðNRÞi ¼ Rð8� GiÞ=7; i ¼ 1; . . . ; n

where R is the predefined rate of nonresponse, and Gi

is the global QOL score for the ith patient among a

total of n patients. Because a small Gi is associated

with poor global QOL, the percentage of nonresponse

is higher for a patient with poorer global QOL.

Evaluation criteria

In assessing the accuracy of the imputation meth-

ods, the precision of the imputed individual total

score is evaluated by the average sum of squared

Table 4

Average deviations for nonrandom missing data (N = 452)

10% data missing 20

Imputation method SSD PMD SS

Case deletion Nil .0135 N

Subscale mean .0188b .0026a .0

Subscale mean 50% .0188b .0026a .0

Item mean .0231 .0046 .0

Single imputation .0141a .0029b .0

Matched item mean .0351 .0048 .0

Abbreviations: PMD, population mean deviation; SSD, sum of sqa Refers to the smallest p-value among the imputation methodb Refers to the second smallest p-value among the imputation

deviation (SSD) between the imputed values and the

actual values, as follows:

SSD ¼XNi¼1

XKj¼1

ðYij � YijÞ2

nj

0BBBB@

1CCCCA;

i ¼ 1; . . . ; n; and j ¼ 1; . . . ;K

where Yij is the sum of the jth subscale of the ith

subject from the imputed data set, Yij is the total for

the individual subscale of complete data, nj is the

number of complete cases in the jth subscale, N is the

number of subjects in the data, and K is the number

of subscales.

Another evaluation index is the deviation of the

averaged population mean deviation (PMD) between

the imputed data set and the actual complete data set.

The accuracy of the imputation methods is measured

by the absolute difference between the sample mean

% data missing 30% data missing

D PMD SSD PMD

il .0184 Nil .0246

175a .0036b .0298a .0034a

177b .0057 .0298a .0051b

451 .0063 .0856 .0100

256 .0027a .0537b .0081

503 .0061 .1078 .0077

uared deviation.

s.

methods.

Table 5

Health-related morality-of-the data response rates

Worsened Stable Improved Fisher’s p-valueb MH c2 P valuec

Physical functioning GE 11 (32%) 12 (35%) 11 (32%) .346 .477

GP 11 (32%) 7 (21%) 16 (47%)

Role functioning GE 10 (29%) 4 (12%) 20 (59%) 1.000 .785

GP 9 (26%) 4 (12%) 21 (62%)

Emotional functioning GE 9 (26%) 25 (74%) 0 .369 .234

GP 5 (15%) 29 (85%) 0

Cognitive functioning GE 13 (38%) 8 (24%) 13 (38%) .321 .154

GP 7 (21%) 10 (29%) 17 (50%)

Social functioning GE 14 (41%) 7 (21%) 13 (38%) .574 .277

GP 10 (29%) 7 (21%) 17 (50%)

Global QOL GE 13 (38%) 11 (32%) 10 (29%) .215 .783

GP 15 (44%) 5 (15%) 14 (41%)

Fatigue GE 14 (41%) 2 (6%) 18 (53%) .409 .516

GP 10 (29%) 5 (15%) 19 (56%)

Nausea and vomiting GE 15 (44%) 15 (44%) 4 (12%) .022a .032a

GP 26 (76%) 5 (15%) 3 (9%)

Pain GE 12 (35%) 7 (21%) 15 (44%) .810 .496

GP 10 (29%) 6 (18%) 18 (53%)

Dyspnea GE 13 (38%) 13 (38%) 8 (24%) .106 .036a

GP 7 (21%) 11 (32%) 16 (47%)

Insomnia GE 13 (38%) 9 (26%) 12 (35%) .136 .049a

GP 7 (21%) 7 (21%) 20 (59%)

Appetite loss GE 21 (62%) 13 (36%) 0 1.000 .806

GP 20 (59%) 14 (41%) 0

Constipation GE 13 (38%) 14 (41%) 7 (21%) 1.000 1.000

GP 13 (38%) 14 (4%) 7 (21%)

Diarrhea GE 5 (15%) 29 (85%) 0 .003a .180

GP 7 (21%) 19 (56%) 8 (24%)

Financial difficulties GE 8 (24%) 19 (56%) 7 (21%) .003a .001a

GP 2 (6%) 12 (35%) 20 (59%)

Abbreviations: GE, gemcitabine plus etoposide; GP, gemcitabine plus cisplatin.a Refers to p <0.05.b Fisher’s exact test with 2 degrees of freedom.c Mantel-Haenszel test with 1 degree of freedom.


of the questionnaire when there are no missing data,

as follows:

lf ¼

XNi¼1

Xnjj¼1

ðYij=njÞ=N

where N is the total number of subjects, nj is the

number of items in the jth subscale, and Yij is the total

for the individual and subscale of complete data. The

sample mean of the questionnaire when the missing

data are handled by the imputation methods is

as follows:

l ¼XNi¼1

Xnyj¼1

ðYij=njÞ=N

where Yij is the total of the completed and imputed

values for subjects with missing items. The absolute

deviation of the population means is PMD.

Comparisons of results among methods

In the simulation, missing rates of 10%, 20%, and

30% were used. The precision of the imputed values

was evaluated using the average SSD method of

individual items and the method of PMD. In SSD

and PMD approaches, values that are closer to 0

indicate smaller differences between the imputed

and actual values. The smaller the value, the better

the performance of the corresponding imputation

method. Results for missing items generated using a

random process are shown in Tables 1 and 2. Results

for missing items generated using a nonrandom

process are shown in Tables 3 and 4. The results of

average deviations all were close to zero in the

average SSD and the PMD; multiple imputation has

shown its accuracy and ability to minimize potential

biases caused by the missing data.


The results in Tables 1 and 2 revealed that when

missing data are ignorable and in cases in which the

sample size is small, the performance of subscale

50% is superior in the SSD but not in the PMD

measure. As the sample size increases (see Table 2),

subscale mean 50% still outperforms other methods

most of the time. When the missing data were gen-

erated based on a nonrandom process, the average

SSD indicated results in favor of subscale mean 50%

(Tables 3 and 4). As sample size increases for non-

random missing data cases, the methods subscale

mean, subscale mean 50%, and single imputation

showed similar performance. The subscale mean

50% approach to summarize HRQOL data outper-

forms other methods. When the HRQOL data are not

missing at random, the subscale-mean 50% method

still has a good performance, but other methods, such

as single imputation or more complicated methods,

may be needed. The case-deletion, item-mean and

matched item-mean methods are not recommended.

Analysis of health-related quality of life data

In the analysis stage, in addition to using imputa-

tion methods to deal with missing data problems and

applying conventional cross-sectional analysis for

complete data, two proposed approaches are dis-

cussed. The first approach is to summarize the

longitudinal HRQOL data into a HRQOL response

variable [8]. The second approach is modeling using

the growth curve method [7].

The HRQOL response variable method takes into

account the longitudinal nature of the data. It is

1 20

80

60

0

20

40

−20

−40

QO

L S

core

Cyc

Treatmen

Third degree gro

p=0.0001 p<0.

Fig. 2. Growth curve models for nausea and vomiting between g

cisplatin (GP) arm. QOL, quality of life.

defined based on the change scores along time and

a prespecified, clinically significant difference D for

the change score and summarizes the longitudinal

data into a single variable. The longitudinal HRQOL

data for a particular patient are categorized into an

‘‘improved’’ category if at least one postbaseline

change score is greater than D. The longitudinal

HRQOL data for a particular patient are categorized

into a ‘‘worsening’’ category if all the postbaseline

change scores are less than or equal to D, but there is

at least one postbaseline change score that is less

than �D. A HRQOL response variable is defined

as stable if all postbaseline change scores are be-

tween �D and D. A simple c2 test or Fisher’s exact

test with 2 degrees of freedom or a Mantel-Haenzsel

(MH) c2 test with one degree of freedom can be used

to compare the differences between treatment arms.

The growth curve modeling approach is designed

to handle dropout and missing data in QOL data [19].

It requires only a missing at random (MAR) assump-

tion to be satisfied and to be able to use all data

without artificially forcing patient HRQOL data into

fixed time intervals. It also describes the average

HRQOL patterns along time for the two treatment

arms in a clinical trial. The graphic representation of

the various HRQOL domains provides comparative

information visually to evaluate the likely impact

of treatments.

The randomized, phase II non–small cell lung

cancer trial mentioned earlier [15] is used to illustrate

the methods. Table 5 shows the HRQOL response

rates for the QLQ-C30 domains. The GP arm has a

significantly higher proportion of patients with wors-

ening of nausea and vomiting and a lower proportion

3 4

les

t-by-time interaction p=0.001

wth curve model GEGP

p=0.00130001 p<0.0001

emcitabine plus etoposide (GE) arm and gemcitabine plus

1 2 30 4

100

80

60

0

20

40

−20

QO

L S

core

Cycles

Treatment-by-time interaction p=0.0125

Third degree growth curve modelGEGP

p=0.0291 p=0.0431p=0.0726 p=0.0356

Fig. 3. Growth curve models for dyspnea between gemcitabine plus etoposide (GE) arm and gemcitabine plus cisplatin (GP) arm.

QOL, quality of life.


of patients with stable response and improvement

(P = .022, 2 degrees of freedom). Dyspnea and

insomnia are significant only in the Mantel-Haenzsel

c2 test (P = .036 and P = .049 with 1 degree of

freedom) and not in Fisher’s exact test (P = .106 and

P = .136 with 2 degrees of freedom), showing that

GP has more improvement in both of these symptoms

and less in the stable and worsening categories. In

general, the Mantel-Haenzsel c2 test is more power-

ful at detecting linear trends and less powerful at

detecting nonlinear relationships.

10

80

60

0

20

40

−20

QO

L S

core

Cy

Treatme

Second degree gro

p=0.8850 p=0.

Fig. 4. Growth curve models for insomnia between gemcitabine

(GP) arm. QOL, quality of life.

When the results are assessed using growth curve

models, nausea and vomiting at baseline is close to 0,

indicating that there is no nausea and vomiting before

patients receive chemotherapy. There are significant

differences in each of the first four cycles, all of them

in favor of the GE arm after treatment started (Fig. 2).

For dyspnea, the sample size is relatively small for a

randomized phase II study with only 34 patients in

each of the two arms. The dyspnea score at baseline

for GE is 23.5 (SD = 25.33) and 46.1 (SD = 30.72)

for GP (P = .0026). The growth curve shows an

2 3 4

cles

nt-by-time interaction p=0.117

wth curve model GEGP

p=0.33977285 p=0.4701

plus etoposide (GE) arm and gemcitabine plus cisplatin

1 2 30 4

40

20

−20

0

−40

QO

L S

core

Cycles

Treatment-by-time interaction p=0.8996

Second degree growth curve model GEGP

p=0.0255 p=0.3537p=0.1066 p=0.2294

Fig. 5. Growth curve models for diarrhea between gemcitabine plus etoposide (GE) arm and gemcitabine plus cisplatin (GP) arm.

QOL, quality of life.


improvement for the GP arm but a slight worsening

then a gradual improvement for the GE arm (Fig. 3).

The treatment by time interaction is significant at

P = .0125. The improvement in the GP arm is sig-

nificant, which agrees with the Mantel-Haenzsel c2

test from the HRQOL response analysis. For insom-

nia, there is no difference at early time points, and the

GE arm shows a slight worsening where the GP arm

shows a slight improvement, but the effect is not

large enough to be significant (Fig. 4).

For diarrhea, as shown in Fig. 5, the GP arm has a

higher proportion of patients with improvement and a

lower proportion of patients with stable responses,

10

80

60

0

20

40

−20

QO

L S

core

Cy

Treatm

Second degree grow

p=0.2268 p=0

Fig. 6. Growth curve models for financial difficulties between g

cisplatin (GP) arm. QOL, quality of life.

but a higher proportion of patients with worsening

(P = .003, 2 degrees of freedom). The proportion of

patients with improvement and worsening may cancel

out the linear trend on the treatment effect for

diarrhea. This phenomenon is shown in the signifi-

cant P value of the Fisher’s exact test, but a non-

significant P value when Mantel-Haenzsel c2 test

was used. Lastly, both tests show a significant result

for financial difficulties (P = .003 and P = .001).

For financial difficulties, the average baseline scores

between the GE arm of 28.4 (SD = 37.72) and the GP

arm of 48 (SD = 36.87) were significant (P = .0204)

due to chance in a small study. The growth curve

2 3 4cles

ent-by-time interaction p=0.003

th curve model GEGP

p=0.3397.7165 p=0.9314

emcitabine plus etoposide (GE) arm and gemcitabine plus


shows a clear difference in favor of the GE arm at

baseline; the GP arm is shown to improve quickly to

the same level of the GE arm after starting treatment

(Fig. 6). The difference in the rates of change

between the two arms is shown in the treatment by

time interaction test (P = .003).

In general, the Mantel-Haenzsel c2 test for the

HRQOL response shows the test of trend between the

two treatment arms with respect to the corresponding

domain. Fisher’s exact test provides an indication of

any differences between arms. The HRQOL response

approach is simple to understand and to carry out. It

lacks the visual presentation of the growth curve,

however, that provides more details to explain some

of the average patterns and potential disparity of

HRQOL scores at the baseline.

Summary

The methodology for QOL assessment covers a

wide range of topics. It involves a proper choice of

instruments with appropriate psychometric properties,

the administration of these instruments, frequency

of measurements, missing data problems, and the

method of analysis. There are currently debates on

the meaning and interpretation of the HRQOL

domains taking the form of arguing how to define

minimal clinically meaningful difference and whether

this can be used in regulatory approval for drug

development [20]. From a practical point of view,

the authors proposed that a disease-specific checklist

or symptom domains incorporated within a HRQOL

questionnaire may be a middle ground to gain general

agreements among academic institutions, manufac-

turers, and regulatory agencies to use a specific

symptom checklist or domain as the primary end

point for clinical trials together with other HRQOL

domains as ancillary data for the study. Antiemetic

trial with HRQOL assessments is an example. Most

would agree, however, that no matter what HRQOL

domains or symptoms are being studied, it should be

based on a patient self-administered questionnaire as

shown by the lack of sensitivity in the example in this

article [15]. Missing data are a problem in the data

collection and handling. The authors have examined a

few commonly used approaches and performed simu-

lation to study their properties. The subscale-mean

method when one has more than 50% of the infor-

mation on a subscale generally reflects the true

values. In practice, one still would have missing data

that cannot be handled completely by imputation. The

method of analysis must be flexible enough to

incorporate the nature of these data. Two approaches

have been discussed, and they are both flexible in

terms of using all available information being ob-

tained in a longitudinal fashion with variable visiting

schedules and potential missing data. The HRQOL

response variable approach is simple and easy to

understand. The growth curve models approach pro-

vides more detailed information on average trends

between treatment arms. In general, these two meth-

ods agree on the results of the example. They can be

used to report clinical trial results using HRQOL data

as end points.

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Acute and chronic reduction of pulmonary function after

lung surgery

Ibrahim Bulent Cetindag, MDa, William Olson, MDa,Stephen R. Hazelrigg, MDb,*

aDivision of General Surgery, Southern Illinois University School of Medicine, 800 North Rutledge, Room D319,

Springfield, IL 62702, USAbDivision of Cardiothoracic Surgery, Southern Illinois University School of Medicine, 800 North Rutledge, Room D319,

Springfield, IL 62702, USA

Thoracic surgeons are facing an increased number mal disease requires the use of a combination of

of complicated and elderly patients for consideration

of pulmonary resection. In evaluating these patients,

surgeons continually must balance the benefits of

resection with the operative risks. Today the peri-

operative mortality rate for lung resection is low, but

it increases with the magnitude of the lung resection

planned. For pneumonectomies, reported periopera-

tive mortality and morbidity rates are 6% to 15%

and 36% to 70% [1–7], whereas for lobectomies,

mortality is much lower (3–7%) [1–7]. Respiratory

failure remains the leading cause of mortality and

morbidity after lung surgery, and the preoperative

estimation of pulmonary function is important to

aid in predicting the likelihood of postoperative

complications. The preoperative evaluation may

alter the extent of lung resection, preoperative pul-

monary preparation, surgical approach, or analgesic

strategy [8].

Many different tools are used simultaneously for

predicting the acute and long-term changes in pul-

monary functions after lung surgery (Box 1) [9–15].

This preoperative assessment can be done easily for

patients with good pulmonary function by using one

pulmonary function test, such as forced expiratory

volume in 1 second (FEV1). The decision with regard

to the type of resection for patients with severe

chronic obstructive pulmonary disease or parenchy-


doi:10.1016/S1547-4127(04)00019-2


E-mail address: [email protected] (S.R. Hazelrigg).

several different tests. The surgeon strives to ensure

that the planned procedure will provide the patient a

reasonable outcome without chronic respiratory in-

sufficiency. This article reviews the literature pertain-

ing to acute and chronic lung function changes after

lung surgery.

Preoperative evaluation

The literature abounds with data and opinions on

the question of which pulmonary function test is most

predictive for postoperative outcome.

Spirometry is one of the oldest and most practical

tests for pulmonary mechanical function. Although

modern spirometry is able to report a multitude of

flows and volumes, the most often used parameters

for preoperative evaluation include forced vital ca-

pacity (FVC), FEV1, and the FEV1/FVC ratio. All

values are reported before and after bronchodilator

therapy, as milliliters, and as a percent predicted for

the patient’s age and body surface. A 15% improve-

ment with bronchodilators is considered a significant

improvement suggesting reactive airway disease.

Levels that have been associated with increased

pulmonary complications early after surgery are less

than 50% predicted for FVC and less than 60% for

FEV1/FVC ratio [16]. FEV1 has been studied exten-

sively and probably is the most common single

spirometric parameter used to predict postoperative

respiratory insufficiency [17–19]. The desired level

s reserved.

Box 1. Preoperative tools for prediction ofpostoperative lung function changes

1. Function testsSpirometry (FEV1)Parenchymal function (DLCO,arterial blood gasesCardiopulmonary function (exercisetolerance, VO2max, 6-minutewalk test)

2. Ventilation/perfusion scan3. CT or MRI4. Bronchoscopy

I.B. Cetindag et al / Thorac Surg Clin 14 (2004) 317–323318

of postoperative FEV1 is approximately 800 mL in an

average-size adult. The percent-predicted values

should be used in clinical practice because they

provide a more accurate assessment. Predicted post-

operative (PPO) FEV1 ideally should be greater than

30% to 40% predicted for the patient’s size and age.

The formula for PPO FEV1 is as follows [16]:

PPOFEV1

¼ preoperative FEV1ðas percent predicted valueÞ

� ð1�%functional lung tissue removed=100Þ

For patients with homogeneous lung parenchyma,

the right lung is considered roughly 10% larger than

the left, and the right upper and middle lobes can be

considered as one lobe [16]. The calculation for PPO

FEV1 is based on functional segments, with value

assigned as follows: Right upper lobe (RUL) is 6 (ap-

proximately 14%), right middle lobe (RML) is 4

(approximately 10%), right lower lobe (RLL) is 12

(approximately 30%), and left upper lobe (LUL) and

lower lobe (LLL) are 10 (approximately 23%) each.

A PPO FEV1 greater than 40% is a safe level to

prevent postoperative pulmonary complications. The

PPO FEV1 levels of 30% and less are associated with

a high incidence of prolonged postoperative ventila-

tory support due to respiratory insufficiency [17,18].

The overall condition of the patient always should be

considered with the FEV1. Gass and Olsen [19] in

their review showed 21% PPO FEV1 might be well

tolerated by young men, whereas 48% is the lower

limit for elderly women. Evaluating by the patient’s

exercise capacity along with their FEV1 is often

enough for surgical clearance with regard to the

preoperative evaluation of lung function in good-risk

patients. For patients with a marginal PPO FEV1 and

exercise capacity, other lung function and preopera-

tive evaluations should be performed.

The DLCO is another common lung function test

that is reported with spirometry results. Preoperative

DLCO less than 60% predicted is associated with an

increased incidence of pulmonary complications [20].

PPO DLCO of 40% or less also has a higher mortality

and morbidity [21,22]. PPO DLCO is calculated

similar to PPO FEV1 [23]. Patients with severe

emphysematous disease and lesions located in the

emphysematous parts of the lungs often can undergo

resection safely even with a preoperative DLCO less

than 60% predicted. Because these emphysematous

areas are not contributing to gas exchange (and they

may compress potentially functional lung), there

often is little change in postoperative pulmonary

function values [23].

The simplest and most important assessment is

cardiopulmonary function. A valuable and easy way

to assess cardiopulmonary function is with a careful

history pertaining to the patient’s exercise capacity.

A traditional test for ambulatory patients is the stair-

climbing test. Olsen et al [24], in their retrospective

review, found that patients unable to climb two flights

of stairs were more likely to have postoperative

pulmonary morbidity. Usually one flight is defined

as 20 steps with each step 6 inches in height [16].

Rao et al [25], in their retrospective study, investi-

gated the value of spirometry and exercise oximetry

in predicting postoperative home oxygen require-

ments. They found that simple exercise oximetry is

a better tool than FEV1 for predicting postoperative

home oxygen requirements and intensive care unit

admissions. They also showed the cost-effectiveness

of this method.

A more sophisticated laboratory test for cardio-

pulmonary function is VO2max. This test may be a

useful tool in marginal patients with pulmonary

insufficiency. Walsh et al [26] showed that patients

with VO2max of 15 mL/kg/min and greater with

marginal FEV1 could be operated on with a reason-

able risk of pulmonary morbidity and no mortality.

Another useful cardiopulmonary function test is the

6-minute walk distance test, which has been used as a

routine in the authors’ lung volume reduction

patients. A 6-minute walk 2000 feet and less is

associated with a higher incidence of postoperative

pulmonary insufficiency [27].

The ventilation/perfusion scan, bronchoscopy, and

imaging (CT and MRI) studies also may contribute to

a surgeon’s estimation of postoperative lung function.

Although predictive postoperative values of different

spirometry calculations is possible to predict based on

the formula explained earlier t, it can be predicted

I.B. Cetindag et al / Thorac Surg Clin 14 (2004) 317–323 319

more accurately in patients with significant bullous

disease by using the ventilation/perfusion scan [25].

Ventilation/perfusion scans can give accurate infor-

mation about the distribution of functional areas of

the lung [28]. Bronchoscopy may show bronchial

obstruction that would affect calculations of post-

operative pulmonary function. The lung segment

beyond these areas should not be taken into consid-

eration in the calculation. Tracheomalacia also can be

visualized with bronchoscopy in an awake setting.

Patients with tracheomalacia have an abnormally low

FEV1 but often tolerate the resection of the lung

beyond this area [16].

CTandMRI give information about nonfunctional,

air-filled bullous regions and the magnitude and num-

ber of lung masses. Patients with large tumors may

have little function loss after pulmonary resection

depending on how much functional lung needs to be

resected. Patients with significant emphysema may

improve after upper lobectomies because of the

removal of space-occupying nonfunctional lung. Se-

lected patients with lung cancer and disabling emphy-

sema (with suitable anatomy for lung volume

reduction) may benefit from a combined lobectomy

and lung reduction [23,29]. The degree of heteroge-

neous or homogeneous disease on high-resolution CT

scan can be assessed to predict how a resection would

be tolerated [30].

Surgical approach and postoperative lung

function changes

Pain and the amount of lung tissue removed are

the two most important factors in early postoperative

respiratory problems. Chest wall injuries affect the

compliance of the thoracic cage and lead to depres-

sion of total volumes for about 3 weeks. Chest wall

mechanics and pain are at their worst in the early

postoperative period and can result in significant

decreases in pulmonary volumes. The specific type

of thoracic incision can affect respiratory compro-

mise [31].

Thoracotomy is considered one of the more pain-

ful approaches among surgical incisions [32]. Several

different modifications of posterolateral thoracotomy

(PLT) have been suggested in the literature to dimin-

ish the pain and functional deterioration after this

approach [32–40]. These modifications include

limited lateral thoracotomy (LLT), muscle-sparing

thoracotomy (MST), anterior limited thoracotomy

(ALT), vertical axillary thoracotomy, anteroaxillary

thoracotomy (AAT), and axillary thoracotomy. Hazel-

rigg et al [40] evaluated the effects of MST versus

PLT on pulmonary function, pain, and muscle

strength. That prospective study concluded that the

MST is associated with improved postoperative pain

but no significant effects on postoperative FEV1 at

1 week and 1 month. Nomori et al [41] compared

ALT, AAT, video-assisted thoracoscopic surgery

(VATS), and PLT after lobectomy. The PLT approach

was associated with significantly lower vital capacity

between the first week and 24 months. These inves-

tigators also found better 6-minute walk distances in

the first postoperative week after ALT and VATS

approaches. There were no significant differences

between ALT and VATS in terms of 6-minute walk

and vital capacity at any time point after lobectomy.

The superiority of VATS in terms of preservation

of lung function in the immediate postoperative

period has been noted [42–52]. Outcome in lung

biopsy patients has been improved after VATS versus

open lung biopsy [42]. Similarly, there has been

better outcome in other patient populations using

VATS [45]. Reduced pain after VATS is associated

with a faster recovery in vital capacity and cardio-

pulmonary function [41,52]. Circulating cytokine

levels during and after surgery (which are associated

with systemic organ injury, such as adult respiratory

distress syndrome) have been shown to be signifi-

cantly lower with VATS compared with the conven-

tional approach [50]. Video-assisted thoracoscopic

procedures also may be associated with better oxy-

genation and diffusion capacity after surgery. Nomori

et al [41] compared the ALT approach with VATS in a

separate study. Their initial study (mentioned previ-

ously in the thoracotomy section) failed to show

significance between the two approaches. Their sec-

ond study showed superior 6-minute walk results

with the VATS approach. This difference did not

reach significance (P = .06), however [49]. Land-

reneau et al [48] reported similar findings; however,

in their study there was a change in FEV1 in the first

week that was significantly better with VATS versus a

limited thoracotomy.

Median sternotomy is another favorable approach

for preservation of lung function. It was noted that

patients who underwent sternotomy preserved their

total lung capacity [31]. It is speculated that because

respiratory muscles are left intact and pain is less after

this approach, the chest wall mechanics are better

preserved. Because of these favorable effects, median

sternotomy became the incision of choice for some

surgeons [53,54]. Hazelrigg et al [43] showed no

significant difference between median sternotomy

and staged VATS in terms of 6-minute walk and

dyspnea scores after lung volume reduction surgery

for pulmonary emphysema. The authors’ preliminary


observation with a similar ongoing study on bilateral

VATS and median sternotomy for lung reduction

patients supports these findings. Cooper et al [55]

showed that the recovery of spirometric function is

significantly faster after median sternotomy than after

lateral thoracotomy.

Degree of lung resection and lung function

changes

For thoracic surgeons, there are two questions

to answer preoperatively in deciding the extent of

the resection:

1. What is the optimal resection for the pathology?

2. What resection can be tolerated by the patient?

The second question is the focus of this review.

In practice, the correlation between lung tissue

resected and the change in lung function is not linear.

Ali et al [56] showed good correlation in lung

function changes and resected lung when three or

more segments are removed. In smaller resections

(wedge resection or segmentectomy), pulmonary

function tests were better preserved than predicted.

Wedge resection, on patients with marginal FEV1

levels, often can be done in patients with less than

3 cm peripheral malignancies with low risk. Careful

evaluation of x-ray studies and cardiopulmonary

function is mandatory [57]. In high-risk patients,

the minimally invasive approach may be the choice

to minimize early postoperative respiratory insuffi-

ciency [23,29].

Postoperative management

Inadequate pain control not only creates discom-

fort for the patient, but also it may cause an additional

reduction in lung function by impairment of respira-

tory effort and atelectasis. This impairment is promi-

nent in patients with obesity, a significant history of

smoking, old age, and preexisting cardiovascular

disease [32]. The VATS approach often is tolerated

well in terms of postoperative pain–related pulmo-

nary morbidity [41,42,52].

Pain control strategies are an important determi-

nant of postoperative pulmonary function [32,57–59].

Of pain regimens, thoracic epidural analgesia seems to

be the most practical and favorable method in terms of

preservation of lung function [32,57]. The lung func-

tion is preserved in the 40% to 60% range with

thoracic epidural analgesia after thoracotomy. Tho-

racic epidural analgesia also has been shown to im-

prove outcomes significantly with regard to length of

hospital stay and postoperative pulmonary complica-

tions [58,60,61].

Systemic opioid analgesia has some depressive

effects on lung function even though in some studies

pain control is as good as the epidural analgesia [32].

The authors’ approach for patients with marginal lung

function is to use thoracic epidural analgesia with

ketorolac to avoid or minimize the depressive effects

of opioids.

Long-term changes in pulmonary function

After lung resections, the remaining lung expands,

the mediastinum shifts, and the diaphragm rises to

lessen the size of the thorax. Vital capacity and total

lung capacity typically decrease. In marginal patients,

this decrease may lead to an increase in oxygen

requirement in the short-term [31].

In the perioperative period, postoperative physical

reconditioning and anemia can augment the magni-

tude of functional loss. After the acute phase, this

reconditioning of lung function reaches a steady state.

This steady state is related to the extent of lung

resection and other concomitant disability. Although

a change in lung volume occurs, the exercise capac-

ity may not correlate [62]. The overall exercise tole-

rance depends on the matched blood flow, diffusion

through the capillaries, affinity of hemoglobin to

oxygen, and mitochondrial activity. The VO2max,

which is a reflection of the patient’s physical and

cardiopulmonary function, depends more on the car-

diac output and peripheral oxygen extraction and

uptake than maximal ventilation and diffusing ca-

pacity [63]. Enhancing the cardiac output and oxy-

gen extraction with regular exercise improves the

patient’s overall functional status and oxygenation

without changing the chronic restrictive changes after

lung resection. This is the concept behind pulmonary

rehabilitation in marginal patients in the preoperative

and postoperative periods [62]. For all of the previ-

ously mentioned reasons, cardiopulmonary disability

after lung surgery depends on the preoperative exer-

cise tolerance, postoperative physical recovery, and

regular exercise more than the preoperative spiromet-

ric volumes. A less invasive procedure may provide

faster recovery and better postoperative cardiopulmo-

nary function in the acute phase of the postoperative

period [41,49]. Conversely, large resections, such as

a pneumonectomy, have profound effects on cardio-

pulmonary function in the long-term. Nezu et al


[64] showed that lobectomy patients recover more

quickly than pneumonectomy patients during the first

6 months after surgery. The VO2max continues to

decrease for 6 months after surgery, after which time

it stabilizes.

Summary

Pulmonary function is affected by several varia-

bles. The more marginal the patient, the more impor-

tant the preoperative and perioperative assessment

becomes. VATS might be tolerated well with regard

to pulmonary function in the early postoperative

period. It has allowed thoracic surgeons to expand

surgical indications to patients that previously would

not have been considered.

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Acute postoperative compromise in cardiovascular function

after chest surgery

Joseph LoCicero III, MD

Department of Surgery, Center for Clinical Oncology, and Center for Interventional Technology, University of South Alabama,

2451 Fillingim Street, Mastin 719, Mobile, AL 36617, USA

Major chest operations place a significant strain recommend that pericardial defects, regardless of the

on all physiologic systems in the body. Strain on the

cardiovascular system can lead to the most serious

problems or even death. The problems are not limited

to ischemia, arrhythmias, or heart failure, but also

include cardiac herniation and hypertensive crisis.

Cardiac herniation

Unless promptly diagnosed and treated, cardiac

herniation can be a fatal complication of any lung

procedure. Although herniation most often occurs

after right pneumonectomy [1], it can occur after left

pneumonectomy [2] or even after lobectomy on either

side [3]. Small defects are the most dangerous.

Because of the rhythmic rocking of the heart, it

literally can jump through the defect. On the right

side, the superior and inferior vena cavae become

twisted, and blood return is severely compromised.

On the left side, the cavae are stretched and cause

diminished blood return. The patient immediately

becomes hypotensive, hypoxemic, tachypneic, and

tachycardic. Diagnostic tests should not be necessary,

but the characteristic chest radiograph confirms sus-

picions (Fig. 1) [4]. The patient should be turned with

the operative side up. The heart may return to the

normal position. Immediate return to the operating

room and repair of the pericardial defect is necessary.

If the patient is unstable, emergency thoracotomy in

the postanesthesia care unit may be necessary. To

prevent this devastating complication, most authors


doi:10.1016/S1547-4127(04)00020-9


defect size, should be closed with a prosthetic patch.

Arrhythmias

Postoperative cardiac arrhythmias and ischemia

are common problems after thoracotomy. Groves et al

[5] monitored the heart rates of 82 patients having a

major thoracotomy. They discovered that the number

of patients with silent myocardial ischemia doubled

after thoracotomy. Patients who had ischemia had an

average postoperative resting heart rate of 93 beats/

min as opposed to patients without ischemia who

had an average postoperative resting heart rate of

82 beats/min. The investigators noted 12% of patients

developed atrial arrhythmias, none of which were

associated with myocardial ischemia.

The treatment of postoperative arrhythmias is

controversial. A brief review of the most commonly

used medications is presented in Table 1 [6]. Ventricu-

lar arrhythmias are rare after thoracotomy, and the

treatment relies primarily on resuscitation of the

hemodynamically unstable patient. The principles of

correcting electrolyte abnormalities and oxygenation

deficits and ruling out myocardial ischemia should

be paramount for patients showing ventricular ectopy

or tachycardia.

For atrial tachyarrhythmia, when the diagnosis has

been established, the first priority is to assess hemo-

dynamic stability. If the patient experiences syncope

or if the blood pressure is less than 80 mmHg systolic,

synchronous electrical cardioversion should be per-

formed. The first shock typically is delivered at 200 J,

with subsequent shocks at 300 J and 360 J. Conscious

s reserved.

Fig. 1. Postoperative radiograph of cardiac herniation after

right pneumonectomy. (From Montero CA, Gimferrer JM,

Fita G, Serra M, Catalan M, Canalis E. Unexpected postop-

erative course after right pneumonectomy. Chest 2000;117:

1184–5; with permission.)

J. LoCicero III / Thorac Surg Clin 14 (2004) 325–330326

sedation should be administered before cardiover-

sion. Sometimes sedation depresses the blood

pressure further, requiring intravenous fluid adminis-

tration or short-term vasopressors.

If the patient is hemodynamically stable, the next

priority should be to achieve ventricular rate control.

Drugs such as digoxin, verapamil, diltiazem, and

metoprolol all depress atrioventricular nodal conduc-

tion and are most useful here. Because many thoracic

surgical patients exhibit bronchospasm, b-adrenergicblocking drugs are contraindicated. b-Blockers fre-

quently are longer acting than calcium channel block-

ing drugs and are not as easy to reverse should an

adverse effect occur. For these reasons, digoxin

(0.5 mg intravenous bolus, followed by two 0.25-mg

intravenous boluses spaced 4 hours apart) combined

with verapamil (5–10 mg intravenous bolus every

Table 1

Commonly used antiarrhythmic agents

Drug Class Loading dose

Adenosine Unassigned 6–12 mg rap

Digoxin Unassigned 1–1.5 mg/4

Procainamide I-A 17 mg/kg (lo

Metoprolol II 5–10 mg IV

Verapamil IV 5–10 mg IV

Diltiazem IV 0.25 mg/kg (

Amiodarone III 800–1600 m

Class refers to Vaughan-Williams [6] classification.

b-Blockers are contraindicated in patients with bronchospastic dise

5–10 minutes) or diltiazem (0.25–0.35 mg/kg intra-

venous bolus every 5–10 minutes) to control ventric-

ular rate is a reasonable choice. If these drugs are not

successful or if the patient is hemodynamically unsta-

ble, synchronous cardioversion should be performed.

When rate control has been achieved, the drugs are

converted to equivalent doses of oral medication over

the next 24 hours. During this time, electrolytes, such

as potassium and magnesium, should be assayed and

corrected. Myocardial ischemia should be ruled out by

electrocardiogram (ECG) and enzymatic assay.

In the absence of ongoing ischemia, the natural

history of postoperative atrial tachyarrhythmias is

self-termination. Usually nothing more than 1 or

2 days of rate control is required. If the patient does

convert spontaneously back to normal sinus rhythm

over the next 24 hours, the medication can be dis-

continued, and no further treatment is required. When

the patient remains in a rate-controlled fibrillation or

flutter beyond 24 hours, cardioversion should be

attempted. Usually cardioversion is begun as a trial

of chemical cardioversion with antiarrhythmic medi-

cation. There is no single drug that showed high

efficacy at converting postoperative atrial fibrillation

or atrial flutter to sinus rhythm. The class I-A agents,

such as procainamide and quinidine, exhibit approxi-

mately a 30% conversion rate, similar to placebo. The

class I-C agents, such as flecainide and propafenone,

claim a higher conversion rate (about 40–60%), but

their use is contraindicated in patients after a recent

myocardial infarction or with a known depressed

ejection fraction. The new class III agent, ibutilide,

claims a high conversion rate of approximately 60%,

but is associated with a high relapse rate and the

appearance of malignant ventricular arrhythmias, such

as torsades de pointes. One of the older class III

agents, d-sotalol, has been shown to be effective at

converting atrial fibrillation to sinus rhythm, but the

racemic mixture of d-sotalol and l-sotalol has signifi-

Maintenance dose

id IV push None

doses/12 h 0.125–0.25 mg/d PO or IV

ad over 20 min) 2 mg/min IV infusion

bolus 5–10 mg IV q1–2h

bolus 5–10 mg IV q1–2h

load over 10 min) 5–10 mg/min IV infusion

g PO 400 mg PO

ase or known hypersensitivity to the drug.

J. LoCicero III / Thorac Surg Clin 14 (2004) 325–330 327

cant b-blocking activity and is relatively contraindi-

cated in thoracic surgical patients.

Despite its relative lack of efficacy, the most often

used and recommended drug for chemical cardiover-

sion is procainamide. It is easy to give a loading dose

(17 mg/kg intravenously over 20 minutes), has rela-

tively few acute limiting side effects (hypotension,

nausea), and is quickly metabolized. In contrast to

quinidine, which has anticholinergic side effects, pro-

cainamide has some antiadrenergic effects and can

‘‘double’’ as an atrioventricular nodal blocking drug.

When the patient has been given a loading dose of

procainamide, he or she is started on a continuous

infusion of 2 to 4 mg/min. If the patient is taking oral

medications, Procanbid (Monarch Pharmaceuticals,

Bristol, Tennessee) can be started by mouth when

the loading dose is completed. The infusion is

stopped after the second oral dose.

Although used mainly for ventricular arrhythmias,

amiodarone is increasingly popular for rate control in

atrial tachyarrhythmias. After acute intravenous dos-

ing in humans, amiodarone may have a mild negative

inotropic effect. After oral dosing, however, amiodar-

one produces no significant change in left ventricular

ejection fraction, even in patients with depressed left

ventricular ejection fraction. Amiodarone increases

the cardiac refractory period without influencing rest-

ing membrane potential except in automatic cells, in

which the slope of the prepotential is reduced, gen-

erally reducing automaticity. These electrophysiologic

effects are reflected in a decreased sinus rate of 15%

to 20%, increased P-R and QT intervals of about 10%,

development of U waves, and changes in T-wave

contour. Rarely, QT prolongation has been associated

with worsening of arrhythmia. Amiodarone has

many potential side effects, including pulmonary

toxicity, worsening arrhythmias, liver failure, and loss

of vision.

Myocardial infarction

Perhaps the most feared postoperative complica-

tion is a myocardial infarction. The World Health

Organization definition of myocardial infarction re-

quires two of the following three conditions be met:

(1) symptoms, (2) myocardial enzyme release, and

(3) compatible ECG changes. This definition poses a

dilemma, however, to categorize the many postopera-

tive patients who exhibit myocardial enzyme release

but are devoid of symptoms or ECG changes. Most

clinicians consider a significant enzyme release as a

myocardial infarction despite the failure to meet strict

criteria. Several conditions may result in the release

of troponin, including blunt myocardial trauma, aortic

dissection, pulmonary embolism, esophageal rupture,

peptic ulcer disease, pancreatitis, and cholecystitis.

Unstable angina, non–ST segment elevation myo-

cardial infarctions, and ST segment elevation myocar-

dial infarctions represent a continuum of degree of

coronary artery occlusion and amount of myocardial

necrosis, with ST segment elevation infarctions rep-

resenting 100% occlusions and significant necro-

sis. ST segment elevation myocardial infarctions

usually are treated aggressively with aspirin, oxygen,

b-blockers, morphine, intravenous nitroglycerin, and

early cardiac catheterization with percutaneous inter-

vention. These myocardial infarctions are exceedingly

rare in the postoperative patient. For acute non–ST

segment elevation myocardial infarctions and unstable

angina, the treatment is largely medical, only rarely

requiring urgent percutaneous intervention. The risks

of hemorrhage in the surgical patient must be weighed

against the potential benefits of each therapy to make

an informed decision as to which treatments to use.

Several randomized trials have shown the benefits

of aspirin in unstable coronary syndromes with a

relative risk reduction of death or myocardial infarc-

tion of more than 50% by the Research on Instability

in Coronary Artery Disease (RISC) study group in

1990 [7]. A meta-analysis of six randomized trials by

Oler et al in 1996 [8] showed that patients treated

with a combination of aspirin and heparin had a

33% reduction in death or myocardial infarction com-

pared with patients treated with aspirin alone. A meta-

analysis by Yusuf et al [9] showed a 13% reduction in

the progression to acute myocardial infarction with

the use of these agents in unstable angina.

Low-molecular-weight heparins have several ad-

vantages over conventional unfractionated heparin,

including ease of subcutaneous administration, reli-

able bioavailability and anticoagulant effect, lower

rates of heparin-induced thrombocytopenia, and de-

creased sensitivity to platelet factor 4 inhibition.

These agents inhibit thrombin and possess potent

anti–factor Xa activity. The largest studies to date in

patients with unstable angina/non–ST segment eleva-

tion myocardial infarctions, ESSENCE (Efficacy and

Safety of Subcutaneous Enoxaparin in Non-Q Wave

Coronary Events) with 3171 patients [10] and throm-

bolysis in myocardial infarction (TIMI) IIB with

4020 patients [11], found that the primary end points

of death, myocardial infarction, or recurrent ischemia

are reduced significantly with enoxaparin compared

with unfractionated heparin. In the ESSENCE trial,

the 30-day end point was reached in 19.8% in the

enoxaparin group compared with 23.3% in the unfrac-


tionated heparin group (P = .016). In TIMI IIB, there

was a 15% relative risk reduction in the primary end

point at 14 days (P = .03).

Glycoprotein IIb/IIIa inhibitors have been shown

to be useful in acute coronary syndromes. These

agents inhibit platelet aggregation, reducing distal

embolization and preventing subsequent myocardial

infarctions. They also display late benefit (3 years),

which may be due to anti-inflammatory properties

caused by inhibition of MAC-1 on white blood cells

and by plaque stabilization, which reduce long-term

target vessel revascularization. These agents reduce

adverse cardiac events by 22% to 56% at 30 days in

high-risk and low-risk patients undergoing percuta-

neous coronary interventions. In patients with acute

coronary syndromes not undergoing percutaneous

interventions, there is more modest evidence of bene-

fit with these agents.

b-Blockers also have been shown to improve

mortality in acute coronary syndrome patients. In

the ISIS-1 (First International Study of Infarct Sur-

vival) trial, 16,027 patients were randomized to

receive intravenous atenolol, 5 to 10 mg, followed

by oral atenolol, 100 mg daily [12]. The atenolol

patients had a 7-day reduction in mortality from 4.3%

to 3.7%. Another study showing the benefits of

b-blockers in acute myocardial infarction was the

MIAMI (Metoprolol in Acute Myocardial Infarction)

trial, in which more than 5700 patients were random-

ized to receive intravenous metoprolol, 15 mg or less,

followed by oral metoprolol or placebo [13]. The

b-blocker patients had a 13% reduction in mortality

at 15 days. Compared with aspirin, heparin, and

b-blockers, there is no clear mortality benefit associ-

ated with use of nitroglycerin.

The goals of managing patients who have had

demand myocardial infarctions either before or after

operation are simple: decrease myocardial oxygen

demand, and increase myocardial oxygen supply.

The simplest and most effective way to decrease

demand is to decrease heart rate and blood pressure

using b-blockers. The mortality benefits of this agent

were discussed previously. It also is important to pay

attention to the intravascular volume status of the

postoperative patient because increased filling pres-

sures can cause increased oxygen demand and lead

to increased catecholamine levels, creating a vicious

cycle. Another factor that significantly increases myo-

cardial oxygen demand is fever. Elevation of the body

temperature by 2�C can result in an increase of energy

consumption of greater than 20% as reported by

Kluger et al [14]. Standing doses of antipyretics should

be considered in a patient with a recent myocardial

infarction (or stroke) in whom fever is present.

Hypertension

Perioperative hypertension is especially important

because of the potential for producing myocardial

ischemia. Weitz [15] noted that perioperative hyper-

tension or hypotension occurs in 25% of hyper-

tensive patients who undergo surgery. Hypertensive

events occur most frequently in patients with a resting

diastolic blood pressure greater than 110 mm Hg

undergoing carotid, abdominal aortic, peripheral

vascular, intraperitoneal, or intrathoracic surgeries.

A multivariate analysis performed by Browner et al

[16] in male veterans after thoracic surgery found

a 3.8 odds ratio for postoperative death in hyperten-

sive patients compared with normotensive patients.

Other data are conflicting, however. A prospective

randomized multicenter study by Forrest et al [17]

of more than 17,000 patients found that preopera-

tive hypertension was associated with bradycardia,

tachycardia, and hypertension but had no impact

on mortality.

Weitz [15] noted that perioperative hypertension

tends to occur at four different times: (1) during

intubation and induction of anesthesia (owing to

sympathetic stimulation with adrenergic mediated

vasoconstriction); (2) intraoperatively secondary to

pain; (3) early postoperatively secondary to pain,

hypothermia, hypoxia, and volume overload or hypo-

volemia; and (4) 24 to 48 hours postoperatively as

fluid is immobilized. Hypertension often occurs with-

in 48 hours of stopping preoperative antihypertensive

agents and sedatives. b-Blocker withdrawal some-

times occurs 4 days postoperatively, however.

The treatment of perioperative hypertension

depends on the cause. If hypertension occurs during

intubation, surgical incision, or emergence from

anesthesia, it often is due to increased sympathetic

tone, and the treatment is generally short-acting

b-blockers or narcotics. If the hypertension occurs 24

to 96 hours postoperatively, the preoperative anti-

hypertensives should be restarted as a first line of

therapy. Prevention is paramount. Often long-acting

preparations can be given before surgery, or if an

extended period of bowel rest is expected postopera-

tively, standing intravenous antihypertensive therapy

should be considered. It generally is indicated to

continue the outpatient antihypertensive regimen

throughout the perioperative period, especially with

regard to b-blockers and clonidine because these

medications tend to cause the most severe with-

drawal reactions. Lastly, congestive heart failure is

a frequent cause of postoperative hypertension. A

combination of nitrates and diuretics is effective first-

line therapy.

J. LoCicero III / Thorac Surg Clin 14 (2004) 325–330 329

Heart failure

Chronic heart failure

Chronic heart failure usually is known preopera-

tively, and the patient can be prepared well in advance

of the surgery to be in optimal condition. The usual

maneuvers of judicial fluid administration, afterload

reduction, rate control, and use of inotropic agents

help most patients through the postoperative period.

According to data on perioperative congestive

heart failure in the 1950s and 1960s, most exacerba-

tion of heart failure developed within 1 hour of

cessation of anesthesia; this was due to a combination

of hypertension/hypotension, ischemia, intraoperative

fluid administration, sympathetic stimulation, ces-

sation of positive-pressure ventilation, and hypoxia.

According to Weitz [15], a second peak occurred

between 24 and 48 hours and may be related to

the reabsorption of interstitial fluid, myocardial is-

chemia, and possibly withdrawal of long-term oral

medications. Insertion of a pulmonary artery cathe-

ter perioperatively is controversial. In January 2003,

Sandham et al reported a randomized trial in 1994

high-risk elderly patients undergoing major surgery

[18]. In-hospital mortality at 6 months and at

12 months did not differ appreciably between the

two groups. The only significant difference obtained

was the development of pulmonary embolism in eight

patients with a pulmonary artery catheter versus none

in the standard care group (P = .004). Another

interesting finding was a trend toward improved

survival in New York Heart Association class III or

class IV patients, although the number of patients in

this category was small.

The appropriate course of action depends on the

cause, with a crucial distinction made between acute

management and long-term therapy. To understand

this distinction better, one needs to understand the

neurohumoral paradigm for treating chronic heart

failure patients. When the heart is failing, many

neurohormones circulate at high levels, which help

the body maintain perfusion of the brain and organs.

In the short-term, this circulation of neurohormones

conveys a survival benefit by maintaining an ade-

quate cardiac output and blood pressure. These neu-

rohormones are toxic to the heart over the long run,

resulting in fibrosis, apoptosis, and remodeling, while

increasing the myocardial propensity to fibrillate.

Examples of these potentially toxic substances in-

clude angiotensin 2, aldosterone, epinephrine, and

possibly endothelin. The majority of the medications

used in chronic heart failure are antagonists of the

above-mentioned toxins. Angiotensin-converting en-

zyme inhibitors are used not only for their benefits in

afterload reduction; but rather as general inhibitors of

the generation of angiotensin II. Hydralazine is a

much more potent afterload reducer, but it lacks the

antitoxin effects of the aforementioned agents and has

little, if any, mortality benefits.

The neurohumoral paradigm is in contradistinction

to acute heart failure management theory. Here the

paradigm is a simple pump theory. The pump theory

treats the heart as a pump, which is affected by preload,

inotropy and afterload. The first step in managing

heart failure in the perioperative period is to identify

destabilizing factors, such as fluid overload, anemia,

or fever, and remedy these if possible. The next step

is simple pump theory with various medical and

mechanical tools at the clinician’s disposal.

Nitroglycerin is a potent preload reducer that

works by venodilation. Other agents that reduce pre-

load include diuretics (including hemodialysis) and

positive-pressure ventilation, including biphasic posi-

tive airway pressure.

Digoxin is too weak to be considered an inotrope

in the acute management phase. Dobutamine, a non-

selective b-agonist, is a potent inotrope and an

afterload reducer. Dopamine also is a nonselective

b-agonist in doses of 5 to 10 mg/kg/min. Dopamine

tends to increase afterload, however, due to its

a1-agonist activity, making it a less desirable agent

in acute heart failure. Milrinone, a phosphodiesterase

inhibitor, is a potent inotrope and an afterload reducer.

Diuretics also decrease afterload.

Nitroprusside is the most potent afterload reducer.

This agent must be used with caution and usually

with an arterial line because of its ability to cause

severe hypotension. Additionally, thiocyanate levels

should be checked in all patients taking this drug for

more than 24 hours, especially in patients with renal

failure. Hydralazine is another suitable pure afterload-

reducing agent, which can be given intravenously or

orally. Nesiritide is a recombinant human brain type

of natriuretic peptide, which acts as a venodilator and

arterial dilator and a diuretic. Additionally, this agent

antagonizes the renin-angiotensin-aldosterone system

and the sympathetic nervous system.

Acute right heart failure

Large pulmonary resections may produce acute

right heart failure even in patients who are thought to

have normal ventricular function before operation.

The small pulmonary bed may limit the flow of blood

out of the right heart producing pulmonary hyperten-

sion and increased right ventricular afterload. In some

cases, patients develop significant pulmonary edema,


which increases the pulmonary resistance. Positive-

pressure ventilation may limit the pulmonary edema,

but also may increase right heart strain. Inhaled nitric

oxide has not shown long-term success in adults.

Drugs that reduce pulmonary artery pressure may

be beneficial, however, such as nitroprusside, nitro-

glycerin, prostacyclin, and iloprost. Galie et al [19]

reviewed three trials showing efficacy of the prosta-

cyclin analogues. Specifically, inhaled iloprost im-

proved symptoms, exercise capacity, and clinical

events in patients with pulmonary hypertension and

inoperable chronic thromboembolic pulmonary hy-

pertension. Although none of the studies involved

critically ill patients, the favorable effects of prosta-

noids observed in all studies coupled with different

profiles of adverse events and tolerability for each

prostacyclin analogue allow the unique opportunity

to select the most appropriate compound for the

individual patient with pulmonary hypertension.

Summary

Attention to preoperative cardiovascular risk fac-

tors, appropriate preparation, early recognition, and

treatment are essential to prevent potential cata-

strophic cardiac events from leading to life-threaten-

ing situations in the postoperative period.

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123–37.


Shoulder function after thoracic surgery

Wilson W.L. Li, MSc, T.W. Lee, FRCS,Anthony P.C. Yim, MD, FRCS, FACS, FCCP, FHKAM*

Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital,

Shatin, NT, Hong Kong SAR, China

For most thoracic procedures, posterolateral tho- ability to use the upper extremity depends on the

racotomy (PLT) has long been the standard surgical

approach. This incision provides excellent access into

the chest cavity, but it may require the division of

several major chest wall muscles and spreading of the

ribs. Experience has shown that this incision may lead

to serious postoperative morbidity, including chronic

pain, compromised pulmonary function, and restric-

tion of shoulder function [1,2]. The disabling effect of

thoracic surgery on shoulder function is a commonly

overlooked and rarely accurately investigated compli-

cation. Proper shoulder function is a prerequisite,

however, for effective arm and hand function and

for performing multiple tasks involving mobility,

ambulation, and activities of daily living [3]. Postop-

erative shoulder dysfunction is an important factor in

determining return to normal preoperative functioning

and could become a serious long-term disability if

neglected. This article describes the common causes

of shoulder dysfunction after thoracic surgery, the

available data on postoperative shoulder dysfunction

comparing different access modalities, and the poten-

tial contribution of upper extremity revalidation for

the postoperative recovery course.

Causes of postoperative shoulder dysfunction

The shoulder is composed of the glenohumeral

joint and scapulothoracic articulation and is served by

various muscles, together providing the complex

movements of the human upper limb [4]. A person’s


doi:10.1016/S1547-4127(04)00021-0


E-mail address: [email protected] (A.P.C. Yim).

strength and range of motion (ROM) of the shoulder,

both of which could be affected by pain [3]. Shoulder

dysfunction after thoracotomy is a frequently encoun-

tered complication in the early postoperative period

[1,2,5–8]. Although the exact prevalence has not

been defined, it has been reported that disability in

shoulder function occurs in 10% to 26% of the pa-

tients in the first year after surgery [9]. More than

1 year after thoracotomy, 15% to 33% of patients still

experience subjective restriction of ipsilateral shoul-

der function [9,10].

It has never been investigated whether shoulder

dysfunction occurs disproportionately more often

after thoracic surgery compared with other surgical

specialties. Nevertheless, postoperative shoulder dys-

function after other nonthoracic surgical procedures

directly affecting the chest wall and shoulder area

seems to be common. In breast cancer surgery, radi-

cal mastectomy removes the breast along with the

underlying pectoralis major and pectoralis minor

muscles. It is well established that this procedure is

associated with considerable early and late postoper-

ative impairment of shoulder ROM and shoulder

strength. Axillary dissection, potentially complicated

with lymphedema, further worsens postoperative

shoulder function [11–13]. Even with muscle-spar-

ing techniques, 2% to 51% of patients after surgical

treatment of early-stage breast cancer have long-

term impairment of shoulder ROM [14], and 17%

to 33% of patients have prolonged decreased shoul-

der strength [14]. Significant correlation has been

found in this group of patients between upper limb

morbidity and poorer quality of life [14]. In cardiac

surgery, it has been reported that 1.5% to 24% of

patients undergoing median sternotomy experience

s reserved.

W.W.L. Li et al / Thorac Surg Clin 14 (2004) 331–343332

brachial plexus injury, significantly affecting postop-

erative shoulder function [15–20]. It is believed that

this injury is caused by compression of the brachial

plexus secondary to sternal retraction [15–20], es-

pecially when internal mammary artery harvesting

occurs [19,20]. Additionally, median sternotomy can

cause first rib fractures, which also could be associ-

ated with brachial plexus injury [15,16,20]. In con-

trast, shoulder dysfunction after surgical procedures

not affecting the chest wall or shoulder area is rare.

Reported cases are sporadic and are related mainly

to peripheral nerve injury [21–23]. Retrospective

studies have reported that the incidence of upper

extremity nerve palsies after total hip arthroplasty

was only 0.15% to 0.22% [22,23].

It seems that shoulder dysfunction after surgical

procedures directly affecting the chest wall or shoul-

der area and shoulder dysfunction after surgical

procedures not affecting the chest wall or shoulder

area are two separate entities. Shoulder dysfunction

after the latter is rare. It is caused almost solely by

peripheral nerve injuries, frequently as a result of im-

proper patient positioning [21–23], and has an ex-

cellent chance of full functional recovery [22–24].

Shoulder dysfunction after thoracotomy or breast

cancer surgery is far more common and often be-

comes a long-term complication [9,10,14]. Various

aspects of thoracic procedures can contribute to

postoperative shoulder dysfunction, including posi-

tioning of the patient, muscle division, injury to the

long thoracic nerve, and postoperative pain.

Positioning of the patient

Most patients undergoing thoracic surgery need to

be placed in a full lateral decubitus position. This

includes all PLTs, lateral thoracotomies, and video-

assisted thoracic surgery (VATS) procedures. The

operating table should be flexed at the level of the

nipples, to widen the intercostal spaces on the oper-

ated side. Especially with VATS procedures, this sim-

ple procedure could render excessive rib retraction

unnecessary, potentially reducing postoperative pain

[25,26]. Anterolateral and axillary thoracotomies

usually require the patient to be in a supine position,

with the side to be operated tilted at 30� to 45�.Whether in full lateral decubitus position or su-

pine position, shoulder abduction greater than 90�should be avoided at all times to prevent brachial

plexus neuropathy [27–30]. In addition, in the full

lateral decubitus position, chest rolls should be placed

under the ‘‘down-side’’ lateral thorax, potentially

decreasing the risk of brachial plexus neuropathy

in the down arm [28]. Regardless of the position,

attention should be given to potential pressure areas.

After placing the arms in a comfortable position, care

should be taken to ensure that both ulnar nerves are

protected from pressure damage to prevent periopera-

tive ulnar nerve injury.

Improper positioning of the upper extremity of the

patient can lead to peripheral nerve injuries and

frozen shoulder syndrome, limiting postoperative

shoulder function [21,28–31]. The exact contribution

of patient malpositioning to shoulder dysfunction

after thoracic procedures has not been investigated.

Nevertheless, proper positioning of the patient is im-

perative in all surgical procedures to reduce the oc-

currence of perioperative neuropathies [28,29]. Ulnar

neuropathy is the most common perioperative nerve

injury, followed by lesions of the brachial plexus

[21,30,31]. Particularly brachial plexus neuropathy

could affect postoperative shoulder function severely,

causing decreased muscle strength of shoulder and

arm, shoulder pain, and numbness and abnormal

sensations of the shoulder area [27]. It has been

suggested that lesions at the brachial plexus are likely

to be stretch induced [27–30]. Several positions of

the upper extremity have been associated with an

increased risk for brachial plexus neuropathy, includ-

ing shoulder depression, shoulder abduction greater

than 90�, lateral rotation of the arm, full elbow ex-

tension, forearm supination, and lateral flexion of

the patient’s head to the opposite site [27–30]. The

American Society of Anesthesiologists has formulated

empirically based recommendations on patient posi-

tioning to prevent some of these positions [28]. These

position strategies are proposed mainly for the supine

or prone position, however, and essentially are estab-

lished based on expert opinion rather than evidence-

based data. Whether these protective measures are

truly effective in preventing perioperative peripheral

neuropathies needs to be evaluated. The relevance of

these position strategies for patients in the full lateral

decubitus position needs to be investigated further.

Muscle division

The shoulder girdle is served by various muscles,

together providing stability and the complex move-

ments of the human upper limb [4]. Depending on the

chosen approach of chest entry, several of the shoul-

der girdle muscles have to be divided (Table 1).

PLT is the standard thoracic incision for most

major procedures on lung, esophagus, and other

posterior mediastinal structures. It requires the divi-

sion of the lateral edges of the lower part of the

trapezius at the back of the incision and a large section

of the lattisimus dorsi in the front. The latissimus dorsi

Table 1

Standard thoracic incisions and shoulder girdle muscle division

Thoracic incision Muscles divided

Approximate length

of incision (cm) Rib spreading

Posterolateral thoracotomy Trapezius (lateral edge

of lower portion)

15–30 Yes

Lattisimus dorsi

Serratus anterior

Muscle-sparing thoracotomy None 8–20 Yes

Anterolateral thoracotomy Pectoralis major 8–20 Yes

Pectoralis minor

Serratus anterior

Axillary thoracotomy None 6–15 Yes

Median sternotomy None 15–25 Sternum spreading

VATS (utility thoracotomy) Lattisimus dorsi 6–10 No

Serratus anterior

Table 2

Direct actions of shoulder girdle muscles affected by

thoracic surgery

Muscle divided Supported shoulder girdle action

Lattisimus dorsi Upper arm

Adduction

Extension

Internal rotation

Accessory breathing muscle

Serratus anterior Scapula

Protraction

Upward rotation

Fixation of scapula against

thoracic wall

Trapezius (lower portion) Scapula

Static support

Retraction

Pectoralis major Upper arm

Adduction

Flexion

Internal rotation

Accessory breathing muscle

Pectoralis minor Scapula

Protraction

Downward rotation

From Halder AM, Itoi E, An KN. Anatomy and biome-

chanics of the shoulder. Orthop Clin North Am 2000;31:

159–76; with permission.

W.W.L. Li et al / Thorac Surg Clin 14 (2004) 331–343 333

muscle is divided at the level of the skin incision, and

the vascular pedicles are cauterized carefully. The

inferior portion of the muscle is denervated. The

serratus anterior muscle is divided in a slightly inferior

level to preserve the innervation of its main bulk. The

serratus anterior occasionally can be spared (as in a

lateral thoracotomy), although transection is impor-

tant for a wider exposure of the chest cavity. Most of

these muscles have no unique line of action (Table 2)

[4]. The latissimus dorsi is the main adductor of

the shoulder, but also functions as an extensor and

internal rotator. Its innervation is supplied by the tho-

racodorsal nerve. When the arm is fixed, the latis-

simus dorsi also can raise the lower ribs, acting as

an accessory breath muscle. The serratus anterior,

innervated by the long thoracic nerve, protracts and

upwardly rotates the scapula. It keeps the scapula

applied to the thoracic wall and maintains the stabil-

ity of the scapula during arm elevation and pushing

[32–34]. Of the trapezius muscle, usually only the

lateral edges of the ascending part is divided, respon-

sible for depression and static support of the scapula.

It is reasonable to assume that dividing one or more

of these muscles could affect significantly postopera-

tive shoulder strength and ROM in various directions.

Preservation of major chest wall muscles repeatedly

has been suggested to preserve postoperative shoulder

ROM and shoulder strength in various types of mus-

cle-sparing thoracotomies [1,2,7,35–39]. Alternative,

less invasive access modalities include anterolateral

thoracotomy, axillary thoracotomy [39–42], ausculta-

tory triangle thoracotomy [36,37], and muscle-sparing

PLT [1,7,35].

The lateral (muscle-sparing) thoracotomy is the

only real substitute for PLT. The consistent difference

between PLT and muscle-sparing thoracotomy is the

preservation of the latissimus dorsi and serratus ante-

rior muscles. Location, length of incision, and amount

of rib spreading are similar [1,2,7,35]. Various modi-

fications exist with different skin incisions. One

common incision is a transverse one, which starts

from the anterior axillary line to below the scapular

tip. Soft tissue is dissected to facilitate posterior

mobilization of the latissimus dorsi and preservation


of the long thoracic neurovascular bundle. The serra-

tus anterior is split along its fibers over the selected

intercostal space. The intercostal muscles are divided

well beyond the incision to allow maximal rib spread-

ing. This incision is as versatile as PLT in experienced

hands, but not for most surgeons on most common

procedures because the operative field can be reduced

greatly [1,7,35,38]. Although studies have reported

significant benefits regarding postoperative shoulder

dysfunction with muscle-sparing techniques [1,2,7,

37,38], the exact contribution and importance of

division of each shoulder girdle muscles have not

been elucidated properly [39].

With VATS procedures, only a minithoracotomy

is necessary for retrieval of the specimen. The inci-

sion is placed over the fourth intercostal space in

the anterolateral chest and generally is 6 to 8 cm in

length. In this location, only a small portion, if any, of

the latissimus dorsi muscle needs to be divided,

whereas the serratus anterior muscle is split along

the direction of its fibers [26]. Differences between

VATS and the more traditional thoracotomy include

the length of the incision and amount of muscle

division and, more importantly, the avoidance of rib

spreading. It has been reported that VATS patients

experience significantly less early postoperative

shoulder dysfunction compared with PLT patients

[5,6,8,9]. Whether VATS is associated with less

shoulder dysfunction compared with muscle-sparing

thoracotomy needs to be investigated.

In addition to muscle division, it has been reported

that PLT causes postoperative atrophy of the latissi-

mus dorsi and serratus anterior, objectified by CT

[43]. This phenomenon most likely is caused by

denervation of these muscles [44]. It is unclear,

however, whether these radiologic findings correlate

with significant postoperative shoulder dysfunction.

Injury of the long thoracic nerve

Perioperative injury to the long thoracic nerve is

an uncommon, but important and easily avoidable

cause of shoulder dysfunction after thoracic surgery

[32–34]. Perioperative injury to the long thoracic

nerve can result in serious postoperative shoulder

dysfunction through weakness or paralysis of the

serratus anterior muscle. Subsequent scapular wing-

ing and loss of scapular rotation cause inability to flex

or abduct the shoulder fully [32–34,45,46] and

potentially disabling limitation of activities of daily

living [33].

The long thoracic nerve is a pure motor nerve,

innervating the serratus anterior muscle. It originates

from the anterior branches of the fifth, sixth, and sev-

enth cervical roots. The fifth and sixth roots, along

with the dorsal nerve of the scapula, pass across the

fibers of the scalenus medius muscle, whereas the

seventh cervical root passes anteriorly. The nerve runs

from behind the clavicle to reach the first rib, and from

there it descends along the lateral wall of the thorax

down to the eighth and ninth ribs to supply the serratus

anterior muscle with nerves.

The nerve’s long and superficial course makes it

susceptible to damage at various levels [33,34,46].

Given the location of the long thoracic nerve, it may

be especially prone to injury with axillary thoraco-

tomy incisions, VATS port insertion, first rib resec-

tions, and chest tube placement [46]. The risk of long

thoracic nerve injury should be minimal, however, if

the anatomy is considered when operating in the an-

terior scapular region.

In addition to perioperative damage, long thoracic

nerve injury by extreme abduction during general

anesthesia has been reported [32–34]. It is recom-

mended to avoid extreme abduction during patient

positioning at all times.

Postoperative pain and shoulder dysfunction

It is well established that thoracic procedures are

considered to be among the most painful surgical

incisions [1,2,47–50]. Acute postoperative wound

pain is anticipated as with all surgical procedures

and is caused by local tissue trauma, muscle division,

and peripheral and intercostal nerve injury [47–50].

Postoperative pain has significant overlap with post-

operative shoulder dysfunction [1,3,5,9,47,51,52].

It is reasonable to assume that pain can cause func-

tional limitations of the ipsilateral shoulder. Corre-

spondingly, movements of the shoulder girdle can

provoke or aggravate postoperative wound pain [1,5,

9,47,51–53]. Postoperative frozen shoulder, with or

without preexistent shoulder disease, also might be an

aggravating or causative factor to chronic post-thora-

cotomy pain [47,51–53]. The exact relationship

between postoperative shoulder function and pain is

complex. The precise impact of postoperative pain on

shoulder dysfunction, but also conversely of shoulder

dysfunction on postoperative pain, is elusive.

Less invasive access modalities, such as muscle-

sparing techniques, have been suggested to reduce

access trauma and consequently decrease postopera-

tive pain. Although muscle-sparing techniques have

significant benefits regarding postoperative shoulder

dysfunction [1,2,7,37,38], it has not reduced signifi-

cantly the incidence of acute and chronic postopera-

tive pain. Muscle division is unlikely to be the sole

contributing factor determining postoperative pain.


In addition to muscle division, all traditional tho-

racotomy incisions require a certain amount of rib

spreading, causing direct intercostal nerve damage

and rib injury. Excessive spreading could lead to pain-

ful rib fractures and costochondral separations. There

now is increasing evidence that the excessive morbid-

ity of a thoracotomy is mainly the result of intercostal

nerve damage after rib spreading [1,54–57]; this is

illustrated by the fact that pain-related morbidity after

VATS procedures, in which rib spreading is unneces-

sary or minimized, is significantly less compared with

PLT and muscle-sparing alternatives [5,9,26,47,58].

The exact contribution to postoperative shoulder

function needs to be investigated.

In addition to postoperative wound pain, ipsilateral

shoulder pain is a contributing factor to postoperative

shoulder dysfunction [59,60]. It is a well-recognized

and separate entity from incisional wound pain, with a

reported incidence of 75% to 78% [59–61]. It has

been hypothesized that this phenomenon is caused by

referred pain through the phrenic nerve due to irrita-

tion of the pericardium, mediastinum, and dia-

phragmatic pleural surfaces [60,61]. It also has been

suggested that the suprascapular nerve plays an im-

portant role, transmitting pain signals caused by

excessive strain of the shoulder joint capsule as a re-

sult of positioning the patient in the lateral decubitus

position [62,63]. It has been shown, however,

that suprascapular nerve block has no effect on ipsi-

lateral shoulder pain, making this theory highly de-

batable [61].

Postoperative outcome

The available data on shoulder dysfunction after

thoracic surgery are limited. Shoulder dysfunction

has long been an overlooked entity, and substantiat-

ing assessments were scarce. With the emergence of

alternative, less invasive thoracic incisions, however,

clinical comparison between different access modali-

ties has become more proficient and comprehensive.

Studies increasingly include proper evaluation of

shoulder function as an important postoperative out-

come for comparison, either between standard PLT

and muscle-sparing techniques (Table 3) or more

recently between VATS and the traditional access

modalities (Table 4).

Posterolateral thoracotomy versus muscle-sparing

thoractomy

In a prospective, randomized, blinded study, Ha-

zelrigg et al [1] assessed early postoperative shoulder

strength and shoulder ROM in 50 patients who had to

undergo thoracotomy for various thoracic procedures,

comparing standard PLT with a latissimus dorsi–

sparing and serratus anterior–sparing thoracotomy.

Location and length of the incision were similar for

both procedures [35]. They found that both groups

had significant decrease in shoulder ROM at 1 week

postoperatively, without significant differences be-

tween the two groups. Strength of the latissimus

dorsi and serratus anterior was better preserved in

the muscle-sparing group at 1 week postoperatively.

ROM and shoulder strength seemed to return to

preoperative levels at 1 month after surgery in both

groups. In another prospective, randomized study

with 30 patients using similar surgical techniques,

Sugi et al [7] found significantly better ROM for

patients from the muscle-sparing group 2 weeks after

surgery. Shoulder ROM returned to baseline values at

1 month after surgery in both groups. These findings

are supported by a more recent prospective, random-

ized, blinded study assessing 60 patients [2]. The

authors found that shoulder ROM returned to preop-

erative values 2 weeks after muscle-sparing thoracot-

omy, whereas this was the case in the PLT group only

1 month after surgery. Although shoulder strength

was significantly impaired in the PLT group 1 week

postoperatively, shoulder strength was preserved in

the muscle-sparing group. As suggested by previous

studies [1,7], shoulder ROM and shoulder strength

returned to preoperative values 1 month after surgery

in both groups. Conversely, Kutlu et al [38] reported

that shoulder strength did not return to preoperative

levels 3 months after surgery. They suggested that the

benefits of a muscle-sparing thoracotomy on shoulder

strength persist at least 3 months postoperatively.

Significant shoulder function benefits have not been

found when only the serratus anterior was spared [64].

The available data show that latissimus dorsi–

sparing and serratus anterior– sparing procedures

benefit early postoperative shoulder strength and

ROM compared with standard PLT [1,2,7,38], espe-

cially in the first month after surgery. It is unclear,

however, until when these benefits persist. Data on

long-term postoperative shoulder function are scarce.

In a large prospective, nonrandomized study with

335 patients, Landreneau et al [65] found that patients

after a muscle-sparing thoracotomy had similar per-

ceived level of shoulder strength 1 year after surgery

compared with patients from the PLT group (97%

versus 92% of preoperative level; P = .07). In a cross-

sectional study, Khan et al [37] compared 10 patients

undergoing PLT with 10 matched patients who un-

derwent an auscultatory triangle thoracotomy. They

assessed postoperative shoulder strength using a

Table 3

Comparative studies on shoulder function after thoracotomy (non–muscle sparing versus muscle-sparing techniques)

Author Year Study design Access modalities N

Shoulder function

evaluation

A essments

ti e frame Results

Early postoperative results

Hazelrigg et al [1] 1991 Prospective

randomized

blinded

PLT vs MS

(LD + SA)

24 vs 26 Physician assessment

(physiotherapist)

P op

P top

wk

mo

Shoulder strength

Significant decrease at 1 wk

postop in PLT group

Returns to preop levels at

1 month postop in PLT group

Preservation of shoulder strength

at 1 wk and 1 mo postop in

MS group

ROM


postop in both groups


1 mo postop in both groups

No significant differences

between groups

Sugi et al [7] 1996 Prospective

randomized

PLT vs MS

(LD + SA)


(physiotherapist)

P op

P top

ay 1,3,5,7,14

mo

ROM

Significantly better shoulder

ROM for MS patients up

to 14 days after surgery


1 mo postop in both groups

Mouton et al [64] 1999 Prospective

blinded

PLT vs MS (SA) 14 vs 14 Physician assessment

(physiotherapist)

P op

P top

wk

mo

y

Shoulder function


between groups at 2 wk, 3 mo

and 3 y after surgery

Kutlu et al [38] 2001 Prospective

randomized

blinded

PLT vs MS

(LD + SA)


(+ dynamometer)

P op

P top

mo

Shoulder strength

Significant decrease at 3 mo

postop in PLT group

No significant decrease at 3 mo

postop in MS group


strength for MS patients at

3 mo postop

W.W.L.Liet

al/ThoracSurg

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14(2004)331–343

336

ss

m

re

os

1

1

re

os

d

1

re

os

2

3

3

re

os

3

Akcali et al [2] 2003 Prospective

randomized

blinded

PLT vs MS

(LD + SA)


(physiotherapist)

Preop

Postop

1 wk

2 wk

1 mo

Shoulder strength


postop in PLT group

Returns to preop levels at 1 mo

postop in PLT group

Preservation of shoulder strength

at 1 wk and 1 mo postop in

MS group

ROM


postop in both groups

Returns to preop levels at 1 mo

postop in PLT group

Returns to preop levels at 2 wk

postop in MS group

Significantly better in MS group

at 1 wk and 2 wk postop

Late postoperative results

Landreneau et al [65] 1996 Prospective LT vs MS

(LD + SA)

187 vs 148 Questionnaire Postop

1 y

Shoulder strength

No significant differences between

groups (92% vs 97% of preop

level, P = .07)

Khan et al [37] 2000 Cross

sectional

case-matched

PLT vs ATT 10 vs 10 Physician assessment

(+ muscle strength

testing machine)

> 1 y postop

(mean 37 mo, range

12–60 mo)

Shoulder strength

Significantly better shoulder strength

for ATT patients >1 y postop

(78% vs 102% of preop level,

P = .04)

Abbreviations: ATT, auscultatory triangle thoracotomy; LT, lateral thoracotomy; MS (SA), serratus anterior-sparing thoracotomy; MS (LD + SA), latissimus dorsi and serratus anterior-

sparing thoracotomy; PLT, poterolateral thoracotomy; ROM, shoulder range of motion.

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Table 4

Comparative studies on shoulder function after thoracic surgery (thoracotomy versus VATS)

Author Year Study design Access modalities N

Shoulder function

evaluation

Assessm nts

time fra e Results

Early postoperative results

Radberg et al [6] 1995 Retrospective PLT vs VATS 25 vs 24 Questionnaire

(visual analogue scale)

Postop

1 wk

ROM

Significantly less ROM complaints

at 1 wk after surgery for VATS

patients (75 vs 35, P < .05)

Reduced ROM lasted median 3 wk

in VATS patients and 10 wk in

PLT patients

Furrer et al [66] 1997 Prospective PLT vs VATS 15 vs 15 Physician assessment Postop Shoulder function

4 mo Shoulder function was normal in

all but one patient after PLT


between groups

Li et al [8] 2003 Prospective PLT vs VATS 11 vs 18 Physician assessment

(physiotherapist)

Questionnaire

Preop

Postop

1 wk

1 mo

3 mo

ROM

Significantly better ROM for

VATS patients at 1 wk and

1 mo postop

Shoulder strength


strength for VATS patients at

1 wk postop

Shoulder function-related QOL


between groups

Landreneau et al [5] 1993 Prospective (MS) LLT vs

VATS


(dynamometer)

Preop

Postop

day 3

day 2

Shoulder strength

Significant decrease at postop day 3

in both groups (56% vs 59%

of preop level, P = NS)


strength for VATS patients at

postop day 21 (59% vs 85%

of preop level, P = .01)

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e

m

1

Late postoperative results

Sugiura et al [67] 1999 Cross-sectional PLT vs VATS 22 vs 22 Questionnaire >5 mo postop Shoulder function

PLT mean 34 mo

(range 11–32 mo)


between groups

VATS mean 13 mo

(range 5–20 mo)

Significantly longer follow-up

time for PLT group

Li et al [10] 2002 Cross-sectional PLT vs VATS 24 vs 27 Questionnaire >6 mo postop (mean 36 mo

range 6–84 mo)

Shoulder function

33% of patients in both groups

experience subjective shoulder

dysfunction

No significant differences between

groups

Landreneau et al [9] 1994 Cross-sectional (MS) LLT vs VATS 97 vs 142 Questionnaire 3–12 mo postop Shoulder function

Significantly less VATS patients

have shoulder dysfunction

compared with thoracotomy

group (26% vs 10% of patients,

P = .001)

Landreneau et al [9] 1994 Cross-sectional (MS) LLT vs VATS 68 vs 36 Questionnaire >1 y postop

(range 13–31 mo)

Shoulder function

No significant differences in

incidence of shoulder dysfunction

between groups (15% vs 14% of

patients, P = NS)

Abbreviations: LLT, limited lateral thoracotomy; (MS) LLT, muscle-sparing limited lateral thoracotomy; PLT, posterolateral thoracotomy; QOL, quality of life; ROM, shoulder range of

motion; VATS, video-assisted thoracic surgery.

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muscle strength testing machine measuring maximal

strength throughout the ROM of that muscle and

found that even after more than 1 year after surgery,

the auscultatory triangle thoracotomy group still had

24% greater shoulder adduction strength than the

PLT group.

Video-assisted thoracic surgery

The fact that access trauma is reduced with VATS

has been well documented. There is general consen-

sus on the benefits of this approach with respect to

less postoperative pain, better preservation of pulmo-

nary function, and earlier return to normal activities

[26,58]. The available data on shoulder function after

VATS are inconclusive, however, originating mainly

from cross-sectional and retrospective studies. In one

of the few prospective studies available, Li et al [8]

assessed early postoperative shoulder strength, ROM,

and shoulder function–related quality of life compar-

ing PLT with VATS. They found that VATS patients

had significantly better shoulder strength 1 week

postoperatively and significantly better ROM 1 week

and 1 month after surgery. These differences did not

lead to significant differences in shoulder function–

related quality of life between the two groups, how-

ever. In another small prospective study comparing

PLT with VATS, Furrer et al [66] reported no signif-

icant differences between the two groups 4 months

after surgery.

Radberg et al [6] analyzed 25 patients who had

undergone thoracoscopy and compared the outcome

with 24 patients who had undergone conventional

surgery for spontaneous pneumothorax. Using a ques-

tionnaire and visual analogue scales to grade postop-

erative shoulder ROM complaints, patients in the

thoracoscopy group reported significantly less impair-

ment of shoulder movement 1 week after surgery

(35 versus 75 on visual analogue scale; P < .05) and

were able to return to work and daily activities earlier

(3 weeks versus 8 weeks after surgery; P < .001).

Regarding late postoperative shoulder function,

two small, cross-sectional, questionnaire-based stud-

ies [10,67] found no significant differences between

VATS and PLT patients more than 6 months after

surgery. The available data seem to indicate that

VATS has significant benefits for early postoperative

shoulder function compared with thoracotomy poten-

tially 1 month after surgery [5,6,8]. The level of

evidence is poor, however, and the number of patients

studied is limited. Prospective randomized compar-

isons with large groups of patients and proper long-

term follow-up are necessary to evaluate the potential

benefits of VATS for postoperative shoulder function.

There has been no published report so far on a

study comparing VATS with muscle-sparing tho-

racotomy with respect to shoulder function. Ne-

vertheless, studies comparing VATS with lateral

thoracotomy (with or without muscle sparing)

showed that the former is associated with less short-

term shoulder dysfunction [5,9]. In a prospective,

nonrandomized study with 138 patients, Landreneau

et al [5] measured the strength of the latissimus dorsi

and serratus anterior muscle groups with a standard

dynamometer. They found that VATS was associated

with significantly better short-term shoulder strength

3 weeks after surgery (59% versus 85% of baseline

value; P = .01). In a follow-up study in an expanded

group of patients [9] using self-developed question-

naires to assess shoulder restriction, the same inves-

tigators reported that these benefits persist 1 year after

surgery. No significant differences were found be-

tween the two groups more than 1 year after surgery.

Postoperative shoulder rehabilitation

Various factors contribute to an improved out-

come after thoracic surgery, including early mobili-

zation [68,69], chest physiotherapy [70], breathing

exercises [71], and incentive spirometry [71,72], all

of which would be more effective given good anal-

gesia with minimal side effects [47–50]. Chest drains

should be removed as soon as clinically acceptable.

Physiotherapy exercises also are advised to im-

prove mobility of the shoulder, prevent frozen shoul-

der syndrome, and reduce postoperative shoulder

dysfunction. Specifically with upper extremity exer-

cise modalities, improvement in shoulder strength

and function can be expected [73,74]. It is suggested

that exercise training can lead to improvement in the

ability to perform activities of daily living, exercise

endurance, pulmonary function, and quality of life

[73,74]. The exact contribution of upper extremity

training to the above-mentioned variables is unclear,

however, and should be explored further.

Summary

Thoracic procedures are considered to be among

the most painful surgical incisions and are associated

with considerable postoperative pain and shoulder

dysfunction, severely affecting mobility and activities

of daily living. Improper patient positioning, muscle

division, perioperative nerve injury, rib spreading,

and consequent postoperative pain influence the

patient’s postoperative shoulder function and quality


of life. To reduce access trauma and postoperative

morbidity, various alternative modalities have been

proposed to replace the standard PLT, including

muscle-sparing techniques and VATS. Initial evalua-

tions suggest that these alternatives are associated

with significantly better postoperative shoulder func-

tion. Proper comparative studies using standardized

questionnaires, objective evaluations, or quality-

of-life assessments are scarce, however. Proper post-

operative care, including early mobilization and

effective physiotherapy, is a cornerstone in successful

patient rehabilitation and rapid return to normal daily

activities. Whether upper extremity exercises can

contribute to improvement in postoperative shoulder

function and the ability to perform activities of daily

living needs to be studied further.

Acknowledgments

The authors are indebted to Shirley Lam, Division

of Cardiothoracic Surgery, Department of Surgery,

Prince of Wales Hospital, Hong Kong SAR, for her

help and dedication in data collection and preparation

of the manuscript.

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Postthoracotomy pain syndrome

Manoj K. Karmakar, MD, FRCA, FHKCA, FHKAM*,Anthony M.H. Ho, MS, MD, FRCPC, FCCP, FHKCA, FHKAM

Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin,

Hong Kong, China

Thoracotomy not only causes severe pain in the Incidence

immediate postoperative period but in a significant

number of patients it also produces long term post-

thoracotomy pain [1–3] that often lasts for months or

even years after surgery. The International Associa-

tion for the Study of Pain defines postthoracotomy

pain syndrome (PTPS) as pain that recurs or persists

along a thoracotomy incision for at least 2 months

following the surgical procedure [4]. Pain in this

condition is unrelated to infection or persistent or

recurrent tumor. Postthoracotomy pain syndrome has

also been referred to as chronic postthoracotomy pain

[5–7], postthoracotomy intercostal neuralgia [8], or

postthoracotomy neuralgia [3,5,9] in the literature.

Although recognized as a sequela of thoracotomy

since 1944 [10], when the first reference to this con-

dition was made by two United States army surgeons,

Blades and Dugan [10], a lack of data in the literature

until the 1990s suggests that it had been overlooked

or neglected as a clinical entity. In 1991 Dajczman

et al [11] published the first report on the preva-

lence, severity, and functional significance of PTPS.

Since then there has been growing interest on

this subject and postthoracotomy pain syndrome is

now a well-recognized long-term morbidity of tho-

racic surgery. Nevertheless, there is still a paucity of

objective data in the literature on PTPS. This article

presents the current understanding of postthoracot-

omy pain syndrome.


doi:10.1016/S1547-4127(04)00022-2

Financial support was entirely from departmental/ins-

titutional resources.



(M.K. Karmakar)

It is difficult to quote the true incidence of post-

thoracotomy pain syndrome. Widely varying inci-

dence rates have been reported (Table 1), ranging

from 5% to 80% [2,3,9,11–19]. Different definitions

used to describe and assess pain, lack of large,

prospective studies, small sample size, varying sur-

gical techniques, nonstandard perioperative manage-

ment, varying periods of follow-up care, and so forth

have made the estimation of the incidence of PTPS

difficult. Nonetheless, published data suggest that

PTPS is a fairly common condition and can affect

more than 50% of patients who undergo thoracotomy.

It is a chronic condition, and as many as 30% of

patients might still experience pain 4 to 5 years after

surgery [11]. There is a decrease in the severity of

pain with time [2,13], although in the unfortunate few

there might be worsening of pain [13].

Characteristics of pain in postthoracotomy pain

syndrome

Most patients experience pain along the general

area of the thoracotomy scar [6,14], but pain can also

occur elsewhere in the chest [6,14], in the back [6,14],

or in more than one location [6,14]. Pain can occur

spontaneously or can be evoked by a particular

stimulus or activity. Allodynia, the sensation of pain

in response to a normally nonpainful stimulus, is a

frequent feature of PTPS [1]. The majority of patients

report their pain as an aching sensation [3,6,14–16, 9]

or tenderness [6,14], but it can also be described as

a continuous dysesthetic burning and aching [3,6,

14–16,19], lancinating pain [6], or a combination of

s reserved.

Table 1

Incidence of postthoracotomy pain syndrome

Reference Study design No. of patients studied

Time elapsed since

thoracotomy Incidence of PTPS

Dajczman et al, 1991 [11] Retrospective 56 Median 19.5 mo 54%

Cohort

Questionnaire

Kalso et al, 1992 [14] Retrospective

Cohort

134 Mean 30.3

(range 15–48) mo

44%

Questionnaire

Follow up

Conacher, 1992 [9] Retrospective 3109 �3 mo 5%

Records survey

Richardson et al, 1994 [3] Retrospective 883 �2 mo 22.3% at 2 mo

Cohort 14% at 1 y

Questionnaire

Landreneau et al, 1994 [16] Retrospective

Cohort

68 3–31 mo 44% at < 1 y

and 29% at > 1 y

Questionnaire

Keller et al, 1994 [12] Retrospective 238 �3 mo 11%

Cohort

Katz et al, 1996 [15] Retrospective 30 1.5 y 52%

Cohort

Telephone interview

Perttunen et al, 1999 [2] Prospective 84 �3 mo 80% at 3 mo

Standardized

Letter interview

75% at 6 mo and

61% at 1 y

Hu et al, 2000 [19] Retrospective, 372 28F12 mo 41% at 21F12 mo

Cohort

Telephone interview

Gotoda et al, 2001 [13] Retrospective 85 1 y 41%

Cohort

Questionnaire

Senturk et al, 2002 [17] Prospective 69 6 mo 62% at 6 mo

Randomized

Ochroch et al, 2002 [18] Prospective 157 12 mo 21.2% at 12 mo

Randomized

Double-blind

M.K. Karmakar, A.M.H. Ho / Thorac Surg Clin 14 (2004) 345–352346

sensations [14]. The involved site can have altered

sensation [14,19] and might be sensitive to touch or

change in temperature [1]. Pain is constant in 33%

to 80% of cases [3], but it can also be intermittent

in nature or come on ‘‘a few times a week’’ or ‘‘few

times a month’’ [11].

The severity of pain varies, but in the majority of

patients (80%) it is usually mild [11], often described

only as discomfort by patients and scoring 4 or less on

a 10-point visual analogue pain scale [11]. The

majority of patients do not seek medical advice and

declare it only on direct questioning [5,16]. Only a

small number of patients consider their pain to be

bothersome enough to seek medical advice [1,11].

Most declare it only on direct questioning [5]. Severe,

persistent, and debilitating pain only affects 4% to 5%

of patients suffering from PTPS [1,2,5,14]. Shoulder

movement worsens pain in a significant number of

patients (23.7%) [3]. In some cases movement of the

ipsilateral shoulder is so painful that frozen shoulder

can result from disuse [1]. Other factors that have been

cited to aggravate or induce pain in PTPS include

emotional stress [1,2], change in the weather [2], and

such activities as carrying heavy objects [2], lying on

the operated side [2], sitting [2], and working with the

hands on the operated side [2].

Etiology/pathogenesis

The exact mechanism for the pathogenesis of

PTPS is still not clear, but cumulative evidence sug-

gests that it is a combination of neuropathic and

nonneuropathic (myofascial) pain. The burning, dys-

M.K. Karmakar, A.M.H. Ho / Thorac Surg Clin 14 (2004) 345–352 347

esthesia, and allodynia sensation that is commonly

reported by sufferers of PTPS is typical of neuropathic

pain (ie, pain that is initiated or caused by a primary

lesion or dysfunction in the nervous system) [20].

Trauma to the intercostal nerve during thoracotomy is

the most likely cause and might occur because of

direct surgical trauma, stretching of the nerve during

rib retraction, suture entrapment of the nerve, or local

inflammation, edema, and fibrosis. Based on experi-

mental peripheral nerve injury data, a combination of

peripheral and central nervous system pain-related

phenomena contribute to neuropathic pain [20]. Pe-

ripheral nervous system changes include ectopic and

spontaneous neuronal discharge, ephaptic conduction

or crossexcitation, alteration in ion channel expres-

sion, collateral sprouting of primary afferent neurons,

and sprouting of sympathetic nerves into the dorsal

root ganglion and nociceptor sensitization [20]. Cen-

tral nervous system changes include central sensitiza-

tion, spinal reorganization, decrease in inhibitory

activity within the spinal cord, and cortical reorgani-

zation [20].

PTPS can also originate from the muscle and fas-

cia, producing myofascial pain syndrome [1,21,22],

which is characterized by steady aching muscle pain,

stiffness, limited range of movement, and trigger

points [1]. Two types of trigger points are seen: one

adjacent to the wound (44%) and the other in the

scapular region in a taut muscular band (67%) [21]. It

is difficult to differentiate the neuropathic from the

nonneuropathic component of pain when they coexist

[21]. Trigger point injection with local anesthetic is

considered to be the most effective treatment of

myofascial pain; the presence of a trigger point in the

scapular region in patients who have PTPS increased

the chance of success of treatment significantly [21].

Several local factors can also cause PTPS and

must be considered when evaluating these patients,

such as healing rib fracture, frozen shoulder, local

infection/pleurisy, costochondritis/costochondral dis-

location, and local tumor recurrence [16]. Local

tumor recurrence can cause pain in the area of the

incision by direct invasion of the chest wall, ribs, or

pleura and by compression of the intercostal nerves,

nerve roots, or spinal cord [1]. Vertebral collapse as a

result of tumor invasion can also be involved. Tumor

recurrence must therefore be excluded as a cause of

persistent pain when managing these patients.

Predictors for postthoracotomy pain syndrome

Several factors have been identified as predictors

for developing PTPS. Pain intensity 24 hours after

surgery [14,15] and analgesic consumption during the

first postoperative day [2] and week [2] are signifi-

cantly higher in patients who develop PTPS. A strong

association has been found with the female gender

[18], preoperative narcotic usage [12], chest wall

resection [12], pleurectomy [12] and postoperative

radiotherapy [23]. d’Amours et al, in their review on

the pathogenesis and management of persistent post-

thoracotomy pain, reported that the healing pattern of

the postthoracotomy scar has no influence on the

occurrence of PTPS [1]. Patients who have well-

healed scars might have as much pain as patients

who have keloid scars [1]. Sabanathan et al, in their

retrospective review, also found that cryoprobe neu-

rolysis of the intercostal nerve and benign esophageal

disease increased the likelihood of developing PTPS,

whereas rib resection and continuous extrapleural

intercostal nerve block with bupivacaine decreased

the likelihood of developing PTPS [23]. Adding a

nonsteroidal anti-inflammatory drug (NSAID) to the

above regimen brought about a further reduction in

the incidence of PTPS [3]. Others have also reported

that the nature of disease (benign or malignant) does

not influence the incidence or severity of PTPS [2].

Influence of acute pain management on the

development of postthoracotomy pain syndrome

Since reports of a predictive relationship between

a more intense acute pain experience [15] and greater

analgesic usage [2] in the postoperative period after

thoracotomy and PTPS, it has been suggested that

adopting an aggressive and effective postoperative

analgesic regimen and protecting the central ner-

vous system from sensitization after thoracotomy

[3] might reduce the incidence of PTPS. To date

only a few studies have evaluated the effects of anal-

gesic regimens or techniques on the incidence of

PTPS objectively.

Richardson et al., in a retrospective review of

1000 postthoracotomy patients over a 10-year period,

assessed the influence of acute postoperative pain

management on the incidence of PTPS at 2 months

after surgery [3]. The use of systemic opiates alone

was associated with a 23.4% incidence of PTPS [3].

Cryoprobe neurolysis of the intercostal nerve in-

creased the likelihood of developing PTPS (31.6%)

[3]. In contrast, using a continuous extrapleural para-

vertebral infusion of bupivacaine in conjunction with

systemic opiates reduced the incidence of PTPS

(14.8%) [3]. Adding an NSAID to this regimen

further reduced the incidence of PTPS (9.9%) [3].


Hu et al [19] retrospectively reviewed 372 patients

who had undergone posterolateral thoracotomy. Of

these, 159 were finally analyzed. One hundred nine-

teen patients received thoracic epidural anesthesia

(TEA) in combination with general anesthesia (GA)

and 40 patients received only GA. TEA was initiated

before the skin incision and continued intraoperatively

using bupivacaine 0.5%. Epidural morphine, injected

intermittently every 12 hours, was used for analgesia

for 3 days after surgery [19]. The overall incidence of

PTPS was 41%, lasting for approximately 21 F12 months. The incidences of PTPS in patients who

received GA or GA plus TEAwere comparable (39%

versus 42%) [19]. More recently, Obata et al [24], in a

prospective, randomized, double-blind study, com-

pared the effects of a continuous thoracic epidural

infusion, initiated 20 minutes before (pre group) or on

completion of thoracotomy (post group) and contin-

ued for 72 hours, on early and long-term postthor-

acotomy pain [24]. The pre group not only

experienced less acute pain but the incidence of

long-term pain was also significantly lower 6 months

after surgery [24]. There were also a greater number of

pain-free patients in the pre group than in the post

group at 3 and 6 months after surgery [24]. Senturk

et al [17], in a prospective, randomized, single-blind

study of 69 patients, compared the effects of three

analgesic regimes: (1) thoracic epidural analgesia

initiated before (pre-TEA) or (2) after surgical incision

(post-TEA) and (3) intravenous patient-controlled

analgesia (IVPCA) on acute postoperative pain and

on the incidence of PTPS 6 months after thoracotomy

[17]. Patients in the pre-TEA group experienced

significantly less pain compared with the IVPCA or

post-TEA group during the first 48 hours after surgery

[17]. The overall incidence of PTPS 6 months after the

thoracotomy was 62% [17]. The incidence and inten-

sity of PTPS was also significantly lower in the pre-

TEA (45%) group than in the post-TEA (63%) and

IVPCA (78%) groups [17]. Although Obata et al [24]

and Senturk et al [17] demonstrated a preemptive

analgesic effect and a reduction in the incidence of

PTPS in the groups in which TEA was commenced

before the surgical incision [17], Ochroch et al [18]

were unable to demonstrate comparable results. In a

prospective, randomized, double-blind study they

compared PTPS in 157 patients who were randomly

assigned to receive TEA initiated prior to incision or

at the time of rib approximation [18]. The overall

incidence of PTPS was 21.2% [18] and there was no

difference in the incidence between the two study

groups 1 year after surgery [18].

The method of acute pain management therefore

has a variable effect on the incidence of PTPS. This

variable result is not surprising considering what is

involved in afferent nociception after a thoracotomy.

Pain after thoracotomy is conveyed to the central

nervous system not only by way of the intercostal

(somatic) nerves but also by way of the sympathetic

chain, phrenic nerve, vagus nerve, and (in the case of

ipsilateral shoulder pain) by way of the brachial

plexus. Moreover, TEA is unable to abolish somato-

sensory-evoked potentials to thoracic dermatomal

stimulation, suggesting that the blockade produced

by a TEA is incomplete [25,26]. Thus, no single

analgesic technique can provide total pain relief or

prevent central sensitization of the nervous system

after thoracotomy. A multimodal analgesic regimen,

or balanced analgesia [3], comprising of a regional

anesthetic technique initiated before thoracotomy

incision and continued into the postoperative period

in conjunction with a systemic opiate and a NSAID

might be more effective for postthoracotomy analgesia

and preventing central sensitization, thereby reducing

the incidence of PTPS. Richardson et al [3] certainly

believed that this balanced analgesic approach,

together with gentler surgical handling of the chest

wall aided by rib resection, was what contributed to the

low incidence of PTPS (9.9%) in their retrospective

series [3]. Future research should evaluate the effects

of a balanced analgesic regimen on the incidence of

PTPS in a prospective, randomized setting.

Influence of surgical technique on the

development of postthoracotomy pain syndrome

To reduce the impact of a standard posterolateral

thoracotomy on tissue injury and thereby acute and

long-term postthoracotomy pain, several investigators

have modified their surgical approach while per-

forming thoracic surgery. These modifications include

muscle-sparing thoracotomy [27,28], rib resection [3],

different types of suturing techniques to close the

chest [29], and video-assisted thoracoscopic surgery

(VATS) [30– 34]. Objective data on how these

technical modifications affect PTPS are still sparse,

however, and the results of these studies must be

interpreted with caution.

During a standard posterolateral thoracotomy, the

lattisimus dorsi and the serratus anterior muscles are

cut, whereas in a muscle-sparing thoracotomy these

two muscles are retracted. A muscle-sparing thora-

cotomy, when compared to a standard posterolateral

thoracotomy, has been shown to reduce acute post-

operative pain [27], but it does not influence the

frequency of long-term pain when assessed 1 year

after the operation [28].


Rib resection is often performed during thoracot-

omy to allow rib spreading with a reduced likelihood

of rib fracture and disruption of the posterior costo-

vertebral elements. A small segment of rib is excised

between the angle of the rib and its articulation with

the transverse process of the vertebra. The only study

that had evaluated the effect of rib resection on the

incidence of PTPS is a retrospective review Richard-

son et al of 1000 patients after thoracotomy by [3].

Rib resection was identified as one of the interven-

tions that reduced the likelihood of developing PTPS

[3]. With no further objective data or data from ran-

domized studies it is not possible to draw any firm

conclusion regarding whether or not rib resection in-

fluences the incidence of PTPS.

At the level of thoracotomy or at the adjacent in-

tercostal spaces, the intercostal nerve can often be

entrapped in the sutures that are used to close the

thoracotomy wound, resulting in PTPS [8]. A recent

nonrandomized study [29] found that patients who had

pericostal sutures (stitches placed on top of the fifth

rib and on top of the seventh rib), as opposed to intra-

costal sutures (stitches placed on top of the fifth rib and

through small holes drilled in the bed of the sixth rib) to

close their thoracotomy wound experienced more pain

at 2 weeks, 1 month, 2 months, and 3 months after

surgery [29]. The pericostal group of patients also

more commonly reported their pain as hot/burning,

shooting, or stabbing in nature [29], suggesting a

higher incidence of intercostal nerve damage.

VATS is a minimally invasive approach of per-

forming thoracic surgery and has been touted as a

way of reducing postoperative pain-related morbidity

associated with standard thoracotomy. Most surgical

procedures for benign or malignant diseases of

the chest, which in the past would have required a

thoracotomy, can now be performed safely using a

VATS approach. Patients who undergo thoracic sur-

gery by way of a VATS approach experience signifi-

cantly less acute postoperative pain [33] and require

fewer doses of narcotics postoperatively [33] when

compared with patients who undergo standard thora-

cotomy. Despite these early benefits, a significant

number (20–36%) of patients undergoing VATS still

suffer from PTPS [16,30,31,34]. Few studies have

compared the incidence of PTPS after VATS and

standard thoracotomy objectively. Landreneau et al

[16], in their retrospective review of patients under-

going VATS (n = 178) or lateral thoracotomy (n =

165) for pulmonary resection, found that patients who

underwent VATS experienced significantly less pain

throughout the first year after surgery [16]; however,

after the first year the incidence of pain was compa-

rable between the two groups [16]. Others have also

reported that the incidence of PTPS is comparable

between VATS and thoracotomy patients [30,32].

Current evidence therefore suggests that VATS re-

duces early postoperative pain but does not influence

the incidence of PTPS. Long-term pain after VATS is

neuropathic in nature and commonly reported in the

area of the trocar insertion site [34] or along the

thoracoabdominal dermatomal distribution of the in-

tercostal nerve involved at the intercostal space where

the camera port was inserted [35], which indicates that

inadvertent injury to the intercostal nerve during blind

trocar insertion, blunt dissection of the intercostal

space, or excessive torquing of the instruments (trocar)

in the intercostal space are involved. To reduce the

likelihood of intercostal nerve injury, Richardson and

Sabanathan [36] resected an ellipse of the superior

aspect of the rib with a device called the sari punch

prior to inserting the ports and aligned all of their

instruments along one intercostal space [36]. None of

the 40 patients who had this modification in their series

reported pain 2 months after surgery [36]. Yim et al

[35] reported several other maneuvers to minimize

intercostal nerve trauma during VATS: [1] flexing the

operating table 30� between the level of the nipples

and the level of the umbilicus (with less flexion in

elderly patients) to open up the intercostal spaces [2],

absolutely avoiding torquing of the thoracoscope

and switching to a 30� lens when visualization of the

lateral chest wall is required [3], not using rigid ports

(except staple cutters), introducing the instruments

directly through the wound [4], using smaller tele-

scopes (5 mm) for simpler procedures, and [5] deliv-

ering surgical specimens through the anterior port as

the anterior intercostal spaces are wider. By adopting

these maneuvers Yim et al observed an overall im-

provement in the incidence of PTPS in their VATS

patients [35] and only 15% of their patients were

reporting some discomfort in the clinic [35].

Postthoracotomy pain syndrome and quality of

life

In 1944 Blades and Dugan identified that soldiers

who sustained war wounds of the thorax suffered from

intercostal pain that interfered with rehabilitation and

return to duty [10]. Nearly six decades later there are

still limited objective data on how PTPS affects

patient’s quality of life. Published data suggest that

PTPS can adversely affect patient’s quality of life.

Fortunately, pain only ‘‘slightly or moderately’’

[11] interferes with normal daily living in 23% to

50% of patients [2]. The most frequently reported

complaint is sleep disturbance, which is seen in 20%


to 63% of PTPS sufferers [2,3,6,19]. Pain can also

affect patients’ ability to exercise [3], go shopping [3]

or even work in some cases [3]. In a small subset of

patients pain can be severe and can be described as a

true disability to the extent that these patients are

incapacitated [5]. In these cases even the gentlest of

tactile stimulation on the affected side (eg, wearing

clothes or a gust of wind) can provoke paroxysms of

intense pain in the area of the thoracotomy wound

[1]. Although pain variably affects activities of nor-

mal daily living in patients who have PTPS, Perttu-

nen et al observed that the severity of limitation

diminished with time [2].

Ochroch et al [18] objectively evaluated physical

activity 4, 8, 12, 24, 36, and 48 weeks after thoracot-

omy in patients who were managed using TEA during

the postoperative period [18]. Physical activity was

assessed with the 10-question subset of the Quality-

of-Life Short Form Health Survey (SF-36), which

rates each activity on a three-point scale such that

the possible physical activity range is 10 to 30 [18].

The physical activity score was significantly lower

than preoperative values throughout the study period

and it was significantly lower in patients who reported

pain than in patients who reported no pain [18].

Although women were found to experience greater

postoperative and long-term pain than men, there was

no gender difference in physical activity [18].

Based on the functional status, Dajczman et al [11]

grouped patients after thoracotomy into three groups:

Group 1—individuals who are asymptomatic beyond

a brief period but might admit on questioning to numb-

ness at the incision site;Group 2—(the bulk of patients)

are those who experience mild, frequent chest pain that

can persist for years. Pain, being mild in intensity,

does not interfere with daily living or require medical

intervention; Group 3—a small subset of patients who

have debilitating pain that requires regular analgesics

and ongoing medical intervention [11].

Apart from the physical limitation that PTPS can

cause, as in most chronic pain syndromes, psycho-

logical morbidity can occur and can affect patient’s

quality of living. This is particularly true for PTPS

because patients might interpret the resurgence of

pain after a pain-free period after thoracotomy as

recurrence of malignancy. Chronic depression [19]

and anxiety are common presentations and might

manifest as suicidal tendencies.

Management

When patients present at follow-up clinics after

thoracotomy with symptoms suggestive of PTPS,

one must first exclude any recurrence of their primary

disease or malignancy as a cause for the persistent

pain. If there is a recurrence then it should be treated

appropriately. Otherwise, management should be

based on how much disability the PTPS is causing.

If pain is not causing any disability, then patients

should be managed conservatively. The majority of

patients who have PTPS can be managed conserva-

tively. If pain is causing disability, it is an indication

for referral to a pain management specialist.

At the pain clinic, management is multidiscipli-

nary and involves the pain specialist, social worker,

psychologist or psychiatrist, and the physical thera-

pist. It is important to inform the patient at the out-

set of treatment that there is no singular treatment

modality that is curative for PTPS and the focus

must be on reducing disability and improving qual-

ity of life. A through psychological evaluation must

be performed on initial evaluation by a psycholo-

gist or psychiatrist. As with most forms of neuro-

pathic pain, treatment of PTPS is also difficult and

often unsatisfactory. First-line management includes

physical therapy, NSAIDs, transcutaneous electrical

nerve stimulation, tricyclic antidepressants, antiepi-

leptics, sodium channel blockers, and opioids. Tri-

cyclic antidepressants are effective in managing

neuropathic pain and are used in doses and at

plasma levels that are much lower than that required

to treat depression. Amitriptyline, the drug most

commonly used, is started at relatively low doses

and increased slowly until an improvement is seen or

when excessive side effects ensue. Anticonvulsants

(eg, carbamazepine, phenytoin, valproic acid) are the

other group of drugs that are useful in managing

neuropathic pain because they suppress ectopic im-

pulse generation [1]. Gabapentin, a new anticonvul-

sant, has recently been used to treat neuropathic pain,

but data on its efficacy in patients who have PTPS

are still not available. Sodium channel blockers (eg,

lidocaine and mexilitine) also suppress abnormal

impulse generation in the nervous system and bring

about an improvement in symptoms in patients who

have neuropathic pain. The use of opioids to manage

noncancer pain is somewhat controversial because of

the potential for abuse. It is best used as part of a

multimodal treatment plan. Patients might often re-

quire more than one form of treatment for controlling

their pain.

If these measures are ineffective in controlling

pain, then more invasive measures such as nerve

blocks (intercostal nerve block, paravertebral block,

sympathetic nerve block), trigger point injection,

and long-term neuromodulation using epidural anal-

gesia or spinal cord stimulation can be tried.


Throughout the course of management there must be

continued surveillance for the recurrence of disease

or malignancy.

Summary

Postthoracotomy pain syndrome is relatively

common and is seen in approximately 50% of

patients after thoracotomy. It is a chronic condition,

and about 30% of patients might still experience pain

4 to 5 years after surgery. In the majority of patients

pain is usually mild and only slightly or moderately

interferes with normal daily living. In a small subset

of patients pain can be severe and can be described

as a true disability to the extent that these patients

are incapacitated. The exact mechanism for the

pathogenesis of PTPS is still not clear, but cumula-

tive evidence suggests that it is a combination of

neuropathic and nonneuropathic (myofascial) pain.

Trauma to the intercostal nerve during thoracotomy

is the most likely cause. Because pain does not cause

disability in the majority of patients, management is

usually conservative. If pain is causing disability

then multidisciplinary pain management involving

the pain specialist, social worker, physical therapist,

and a psychologist is required. It is mandatory to

exclude recurrence of disease or malignancy as a

cause for the pain prior to initiating treatment. As

with most forms of neuropathic pain, treatment of

PTPS is also difficult and patients might require

more than one form of therapy to control pain and

reduce disability. Based on current evidence, it is

not possible to draw any firm conclusion regarding

whether any form of analgesic or surgical technique

can influence the generation of PTPS. Preemptive

analgesia initiated prior to surgery shows promise

and might help reduce the incidence of PTPS.

Scientific evidence is steadily growing but there is

still a need for large, prospective, randomized trials

evaluating PTPS. Until more is known about this

condition and how to prevent the central and

peripheral nervous system changes that produce

long-term pain after thoracotomy, patients must

be warned preoperatively about the possibility of

developing PTPS and how it might affect their

quality of life after surgery. In addition, measures

such as selecting the least traumatic and painful

surgical approach, avoiding intercostal nerve trauma,

and adopting an aggressive multimodal perioperative

pain management regimen commenced before the

surgical incision should be performed to prevent

postthoracotomy pain syndrome.

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Quality of life after lung cancer resection

Wilson W.L. Li, MSc, T.W. Lee, FRCS,Anthony P.C. Yim, MD, FRCS, FACS, FCCP, FHKAM*

Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital,

Hong Kong SAR, China

Lung cancer continues to be the most common on preoperative and postoperative QOL in NSCLC

cancer in the world, with the highest cancer mortality

rate by far [1,2]. For early-stage, stage I and II non–

small-cell lung cancer (NSCLC), surgical resection

remains the treatment of choice and offers the best

chance of cure [3–7]; however, only a minority of pa-

tients have resectable disease [8]. Furthermore, prog-

nosis remains grim even after surgical treatment.

Only 46% to 79% of stage I and 33% to 58% of

stage II lung cancer patients survive at 5 years after

lung cancer resection [8–11].

In a patient population that has such a high

mortality rate, evaluation and preservation of quality

of life (QOL) after treatment is imperative. Tradition-

ally, the main interest of the oncologic surgeon is the

long-term survival rate after tumor resection; how-

ever, from the patient’s point of view, survival statis-

tics inadequately deal with important issues regarding

daily life that arise before and after surgical treatment.

Patients are often more interested how surgery will

affect their physical functioning and performance of

activities of daily living [12]. Therefore, postopera-

tive QOL and factors influencing postoperative QOL

should be identified to facilitate preoperative guid-

ance and improvement of care. Furthermore, with

the advent of minimal access techniques in thoracic

surgery [13,14], QOL measurement could play an

important role in selecting the optimal access modal-

ity to perform lung cancer resection.

This review presents the basic concepts of QOL

research, several commonly used QOL measurement

instruments, and a summary of the available data


doi:10.1016/S1547-4127(04)00023-4


E-mail address: [email protected] (A.P.C. Yim).

patients. This article also discusses the potential

role of minimal access surgery in the management

of NSCLC.

Quality of life and health-related quality of life

QOL is a subjective, dynamic, multidimensional

concept incorporating all aspects that have impact on

a person’s life [15–19]. Although there is no con-

sensus on the definition of QOL, there is general

agreement that it should include health status and

social and psychological well-being [15–20]. In a

study in which 108 newly diagnosed lung cancer

patients were asked to define good QOL, family life

(55%) was considered to be as important as health

(56%), followed by social life and leisure activities

(42%) [21]. In addition, some argue that spirituality

and environment health, as expressed by safety of the

environment and accessibility of health care and

social services, are also important factors to consider

[18–20].

Health, which is defined by the World Health

Organization as ‘‘a state of complete physical, mental

and social well-being, and not merely the absence of

disease and infirmity’’ [22], has a significant impact

on QOL. While QOL covers all imaginable aspects

of a person’s well-being, health-related QOL more

specifically focuses on aspects of life that are affected

by disease and medical intervention [23,24]. Never-

theless, QOL and health-related QOL are often used

interchangeably in medical literature. Therefore, the

term QOL is used in this article to indicate health-

related QOL for consistency with the majority of

available literature.

s reserved.

Surg Clin 14 (2004) 353–365

Measuring quality of life

QOL is a subjective measurement of a person’s

well-being and should therefore be assessed based

upon the patient’s point of view [25]. Proxy or sur-

rogate evaluations should be avoided whenever pos-

sible; it has been shown that family members or

professional caregivers systematically underestimate

QOL and underreport the amount of symptoms of the

subject [25–29].

QOL assessments can be performed through sev-

eral modes of administration, all with advantages and

disadvantages in terms of costs, response rate, patient

burden, interviewer bias, and amount of missing

items [30–35]. Traditional methods to collect QOL

data are face-to-face interviews, self-administration

by mail, and telephone interviews. While face-to-face

interviews ensure compliance, decrease errors, and

decrease the amount of missing items [30,31], it is

much more expensive when compared with other

modes of QOL assessment. Phone interviews appear

to be an appropriate alternative, being cost-effective

and providing low rate of missing items and high

consent rates [31–33]. It has been suggested that

these different methods of collecting QOL data pro-

vide similar and directly comparable results [35];

however, one should be cautious when interpreting

QOL data from clinical studies collected with mixed

methods [33,34]. More recently, various electronic

modes of administration have become a subject of

interest in the collection of QOL data. Initial reports

have suggested that computer administration [36,37]

and QOL assessment through the Internet [38] can

avoid the occurrence of missing data and are cost

effective. Furthermore, results can be automatically

entered into an electronic database, saving time on

entering and verifying data from paper question-

naires [36–39]; however, it remains be to confirmed

whether or not electronic versions of existing QOL

instruments produce data comparable with traditional

paper questionnaires.

QOL is a dynamic concept [40], varying over time

and depending on changes over time, changes be-

cause of treatment effects, or alterations in the disease

situation. These changes are also modified by psy-

chological phenomena such as adaptation, coping,

expectancy, and optimism [40], which can vary with

time and experience. Although cross-sectional studies

yield valuable information, the dynamic characteristic

of QOL is best assessed in a longitudinal setting.

Before treatment, baseline assessments should be

undertaken followed by regular evaluations at proper

time intervals depending on the type of QOL instru-

ment and purpose of the study [17].

W.W.L. Li et al / Thorac354

QOL is measured with QOL instruments that

must conform to certain attributes and review criteria

[41,42]. Because QOL is a multidimensional con-

struct that involves physical functioning and psycho-

logical and social aspects of well-being [15–20], an

important facet of QOL measurement instruments

is that they measure all of these domains [20,25,

41–43]. Unidimensional instruments evaluating a sin-

gle domain are simply not comprehensive enough to

measure QOL adequately [25,43]. Proper QOL in-

struments must also comply with certain psycho-

metric properties, including reliability, validity, and

sensitivity [41,42]. Reliability estimates the extent

to which an instrument is free of measurement error

and involves test– retest reliability and internal con-

sistency. Test– retest reliability indicates that the same

scores should be obtained from the same patient in

repeated measurements, assuming the subject has

remained unchanged in the meantime. Furthermore,

in a questionnaire in which multiple items are com-

bined into separate scales, items within a single scale

should show an adequate degree of internal consist-

ency—this is assessed using the Cronbach’s coeffi-

cient alpha and should be above the range of 0.7

[23,42,44]; however, a reliability coefficient ap-

proximating 1.0 indicates that there is too little dis-

crimination among the separate items, suggesting that

the items are measuring the same (or nearly the

same) thing.

Validity refers to the extent to which an instrument

measures what it is supposed to measure, and

involves content, construct, and criterion validity.

Content validity is the appropriateness of the items

to the purpose of the instrument. Construct validity is

the ability of the instrument to be sensitive to differ-

ent levels of QOL in a variety of patient groups.

Criterion validity refers to the extent the scores of the

instrument correlate to other, already validated or

‘‘gold standard’’ instruments.

Finally, QOL instruments should be responsive

to change [41,42,45]. Especially when evaluating

the effects of medical interventions in a longitudinal

setting, it is essential that the questionnaire can

detect any changes in QOL resulting from disease

or treatment.

Quality of life instruments

QOL measurement instruments can be divided

into two main categories: generic instruments and

specific instruments (Table 1). Generic instruments

are designed to measure QOL in a broad range of

populations, conditions, and interventions. While ge-

neric instruments allow comparison between popu-

Table 1

Commonly used instruments for assessing quality of life in lung cancer patients

Instrument Items Scales/domains Reference

General

Medical Outcome Study 36-Item

Short-Form Health Survey (SF-36)

36 Eight health concepts: physical functioning (PF), role

limitations because of physical problems (RP), bodily

pain (BP), general health (GH), vitality (VT), social

functioning (SF), role limitations because of emotional

problems (RE), mental health (MH)

[46,47]

One additional item on health transition

Items can be combined into one physical component

summary and one mental component summary

Ferrans and Powers Quality of Life

Index (QLI)

66 Four subscales: health and functioning, social and

economic, psychological/spiritual, family

[48]

Items can be combined into one Total Quality of Life Score

Sickness Impact Profile (SIP) 136 Two overall domains (physical, psychosocial) with 12

categories (sleep and rest, eating, work, home management,

recreation and pastimes, ambulation, mobility, body care

and movement, social interaction, alertness behavior,

emotional behavior, communication)

[49–51]

Nottingham Health Profile (NHP) 45 Six domains: physical abilities, pain, social isolation,

emotional reactions, energy level, sleep

[52]

World Health Organization Quality

of Life Instrument (WHOQOL-100)

100 Six domains: physical, psychological, independence, social,

environment, spiritual

[18,19]

One general health/QOL facet

Cancer-specific

European Organization for Research

and Treatment of Cancer Quality

of Life Questionnaire ‘‘Core’’ 30

items (EORTC QLQ-C30)

30 Five functioning scales (physical, role, cognitive,

emotional, social)

Eight symptom scales (fatigue, nausea/vomiting,

pain, dyspnea, sleep disturbance, appetite loss,

constipation, diarrhea)

[54]

Financial impact of disease and treatment

One Global health + 1 global QOL scale

Functional Assessment Of Cancer

Therapy (FACT-G, version 3)

34 Five domains: physical well-being, social/family well-being,

relationship with doctor, emotional well-being, functional

well-being

[56]

Items can be combined into a FACT-G Total Score

Functional Living Index-Cancer (FLIC) 22 Five domains: physical well-being and ability, emotional

state, sociability, family situation, nausea

[57]

Rotterdam Symptom Checklist (RSC) 39 Three domains: physical symptom distress, psychological

distress, activities of daily living level

[58]

One item on overall quality of life

Lung cancer-specific

EORTC Lung Cancer-Specific

Questionnaire module (EORTC

CLC-LC13) used in combination

with EORTC QLQ-C30

13 Lung cancer-associated symptoms (coughing, haemoptysis,

dyspnea, pain)

Side effects from chemo- and radiotherapy (sore mouth,

trouble swallowing, neuropathy, hair loss)

[55]

Functional Assessment Of Cancer

Therapy — Lung (FACT-L,

version 3)

44 Five domains: physical well-being, social/family well-being,

relationship with doctor, emotional well-being, functional

well-being

[59]

Lung cancer subscale (lung cancer symptoms, cognitive

function, regret of smoking)

Items can be combined into a FACT-G Total Score, a Lung

Cancer Subscale Score, and a Trial Outcome Index

Lung Cancer Symptom Scale (LCSS) 15 Four patient scales: symptoms, total symptomatic

distress, activity status, overall quality of life

[60]

One observer scales: symptoms



lations and disease states, they might not be sensitive

enough to detect changes caused by specific treat-

ments or conditions in a particular clinical setting.

Examples of generic instruments are the Medical

Outcomes Study 36-Item Short-Form Health Survey

(SF-36) [46,47], Ferrans and Powers Quality of Life

Index (QLI) [48], Sickness Impact Profile (SIP)

[49–51], Nottingham Health Profile (NHP) [52],

and the World Health Organization Quality of Life

Instrument (WHOQOL-100) [18,19]. The Ferrans and

Powers QLI should not be confused with the Spitzer

QL-Index [53], which is essentially a proxy evalua-

tion of QOL as QOL is objectified through an inter-

view with the physician including topics such as

activity, living, health, support, and outlook on life.

Specific instruments are focused on the impact of

a particular disease, condition, or symptom on QOL.

Because disease-specific instruments are designed to

assess specific effects of the disease or its treatment,

they are more likely to be responsive to change. In

oncology, one of the most widely used instruments is

the European Organization for Research and Treat-

ment of Cancer Quality of Life Core Questionnaire

(EORTC QLQ-C30) [54], which can be supplemented

with the site-specific lung cancer module (EORTC

QLQ-LC13) [55]. Other commonly used cancer-spe-

cific instruments are the Functional Assessment of

Cancer Therapy scale (FACT-G) [56], Functional

Living Index–Cancer (FLIC) [57], and the Rotterdam

Symptom Checklist (RSC) [58]. Lung cancer-specific

instruments include the Functional Assessment of

Cancer Therapy–Lung questionnaire (FACT-L) [59]

and the Lung Cancer Symptom Scale (LCSS) [60].

The choice of QOL instrument depends on the

purpose of the study [23]. When evaluating the effect

of a particular treatment of a specific disease, a

disease-specific instrument should be adequate.

When comparing results between different popula-

tions or between different diseases, generic instru-

ments might be more suitable. For the assessment of

QOL in lung cancer patients, the EORTC QLQ-C30

is the best-developed and most frequently reported

instrument, often supplemented with the EORTC

QLQ-LC13 [61,62]. More specifically for lung can-

cer patients receiving surgical treatment, the SF-36

is the most commonly used instrument (Table 2)

[63–67], acknowledged for its well-established reli-

ability, validity, and responsiveness in various surgi-

cal populations [63]; however, general instruments or

even lung cancer-specific instruments might not be

sensitive enough to identify areas that are likely to be

affected by lung cancer surgery, including postopera-

tive shoulder dysfunction [68,69] and postthora-

cotomy pain [68–72]. These problems could be

resolved by designing new lung cancer surgery-spe-

cific questionnaires, by developing specific modules

to supplement existing instruments (eg, FACT-G and

EORTC QLQ-C30), or by the addition of a small

number of items to existing questionnaires. Li et al

attempted to develop nine additional surgery-related

items to supplement the EORTC CLC-QLQ30 and

EORTC CLC-LC13 [73]; however, these items re-

main to be properly validated in a larger population.

Until lung cancer surgery-specific QOL instruments

or other solutions are available, a reasonable option is

the selection of a lung cancer-specific questionnaire

(eg, EORTC QLQ-C30 supplemented with EORTC

QLQ-LC13) or a well-validated general instrument

(eg, SF-36) supplemented with additional items on

postoperative shoulder dysfunction, postthoracotomy

pain, and other thoracic surgery-related complaints.

Previous studies

QOL data concerning lung cancer patients after

surgical treatment are reported infrequently. In an ex-

tensive review on QOL in lung cancer patients

covering literature from 1970 to 1995, 42 studies

were identified on QOL in NSCLC patients [61];

however, only one study focused on QOL after

surgical treatment [74]. Fortunately, QOL has been

noted as an increasingly important outcome measure-

ment after surgical treatment of NSCLC [75], and a

growing number of studies has been published on this

matter in recent years (Table 2).

Dales et al [74] were one of the first groups to use

standardized questionnaires to assess QOL in lung

cancer patients after surgical treatment in a prospec-

tive manner. In patients who have possible lung

cancer undergoing thoracotomy, QOL was measured

using the SIP and Spitzer QL-Index complemented

with the Clinical Dyspnea Index and Pneumoconiosis

Research Unit Index to measure perceived dyspnea.

The questionnaires were administered preoperatively

and 1, 3, 6, and 9 months after surgery. One hundred

seventeen patients were entered into the study, 26

(22%) of whom did not have a postoperative diag-

nosis of lung cancer. Dales et al found that dyspnea

and QOL significantly worsened at 1 and 3 months

postoperatively. In the first 3 months after surgery,

40% to 50% of the patients had dyspnea at rest or

with light activities and required major assistance in

managing household. Furthermore, 20% of patients

required assistance in basic activities of daily living

such as washing, toileting, and eating; however, QOL

and the degree of dyspnea returned to preoperative

levels at 6 to 9 months after surgery. Old age,


magnitude of surgery, and the presence of cancer

were found to be independently associated with lower

levels of postoperative QOL. Unfortunately, no data

on postoperative pain or its effect on QOL were re-

ported in this study.

Similar findings were reported by Zieren et al [76],

who also used the Spitzer QL-Index with the EORTC

QLQ-CLC36 (an older version of the EORTC QLQ-

CLC30 questionnaire) to assess QOL in lung cancer

patients after surgical resection through an antero-

lateral thoracotomy. Fifty-two patients were assessed

on one occasion 12 months after surgery and 20 pa-

tients were followed prospectively. In the prospective

part of the study QOL assessments were performed

preoperatively, at discharge (median 11 days post-

operatively), and at 3 months, 6 months, 9 months,

and 12 months after surgery. Preoperatively, disease

symptoms and limitations relating to job and house-

hold tasks were the most frequent dysfunctions. These

restrictions in role functioning and limitations in

physical functioning increased in the first 3 months

postoperatively but improved again within 6 to

9 months after surgery. QOL scores in all domains

returned to baseline values at 12 months postopera-

tively despite the high prevalence of distressing

symptoms. At 1 year after surgery 73% of patients

still experienced dyspnea on running and 21% had

dyspnea at rest. In addition, 69% of patients com-

plained of coughing, 62% of fatigue, and 60% of pain.

Fatigue and pain were the symptoms most highly

correlated with a lower global QOL score. Restriction

in role functioning was common, with 54% reporting

a partial and 21% a complete incapacity to perform

household tasks. Eighty-five percent of patients could

not perform strenuous activities and 27% of patients

had trouble walking even a short distance. On the

other hand, 15% of the patients reported no physical

limitations at all and 25% of patients had no difficulty

in performing household tasks. The majority of

patients (81%) had no social or financial problems.

Pneumonectomy was significantly associated with

lower physical functioning and higher frequency of

symptoms in the first 3 months after surgery.

Mangione et al [63] prospectively assessed QOL

in three different surgical groups, including patients

undergoing lung cancer resection (n = 123), hip ar-

throplasty, and abdominal aortic aneurysm repair.

QOL was assessed using the SF-36 and evaluations

were performed before and 1, 6, and 12 months after

surgery. These researchers found that lung cancer pa-

tients before surgery have significantly lower scores

on the mental QOL scales (including social function-

ing, role limitations caused by mental problems,

mental health, health perception, and vitality) when

compared with the healthy population; however,

physical functioning between the two groups was

similar. The authors suggested that this is because

only patients who have localized disease were con-

sidered as candidates for surgical treatment. In the

first year after surgery QOL deteriorated in all sub-

scales, contributing to the physical construct of the

SF-36. Physical functioning worsened and bodily

pain and role limitations because of physical health

problems increased significantly. Furthermore, post-

operative vitality and health perception also declined

significantly. These changes persisted at least up to

12 months after surgery. On the other hand, subscales

contributing to the mental construct improved at

1 year after surgery. No further data were reported

on which symptoms or aspects of the postoperative

course could be responsible for the decline in QOL.

Handy et al [66] also used the SF-36 in combina-

tion with the Ferrans and Powers QLI to prospec-

tively assess QOL in 139 patients before and 6 months

after lung cancer resection through various access

modalities. They also found that lung cancer patients

before surgical treatment had poorer QOL when com-

pared with a healthy control group, and they reported

significantly lower scores in role limitations because

of emotional problems, mental health, and energy

subscales. Furthermore, in contrast to the previously

mentioned findings by Mangione et al [63], signifi-

cantly lower levels of preoperative physical function-

ing were also reported. After lung cancer resection,

QOL deteriorates even further at 6 months after

surgery. A significant persistent decline was found

in physical functioning, role limitations because of

physical problems, social functioning, mental health,

and bodily pain when compared with preoperative

levels. Although not worsened after surgery, post-

operative emotional role functioning remained signifi-

cantly lower when compared with a healthy control

population. On the other hand, levels of energy and

general health status at 6 months after surgery were

similar with the healthy control group. Postoperative

subjective dyspnea scores and visual analog pain

scores were also significantly worse when compared

with the preoperative baseline values; however, it

remains unclear whether or not a significant rela-

tionship was present between higher dyspnea and

pain scores and lower QOL scales. DLCO less than

45% predicted was the sole predictive clinical pa-

rameter and was associated with worse preoperative

physical functioning and QOL and worse postopera-

tive QOL, health and functioning, and psychological/

spiritual status.

In a recent study on cost and QOL after lung

cancer surgery, Welcker et al [67] measured QOL

Table 2

Available data on quality of life studies in patients who have non–small-cell lung cancer after surgical treatment

Article Year Design N Access modalities QOL instrument(s)

Assessment

time frame QOL outcome

Dales et al [74] 1994 Prospective

Descriptive

117 Thoracotomy SIP

Spitzer QL-Index

Preoperative

Postoperative

QOL significantly worsened at 1 and 3 mo after surgery and

returned to preoperative levels at 6 and 9 mo postoperatively

1 mo

3 mo

6 mo

9 mo

Older age, larger extent of surgery, and the presence of

cancer were independently associated with lower levels of

postoperative QOL

Zieren et al [76] 1996 Descriptive 52 Anterolateral

thoracotomy

EORTC QLQ-CLC36

Spitzer QL-Index

Postoperative

12 mo

Most limitations of QOL were related to physical and

role functions

High prevalence of distressing symptoms (73% exertional

dyspnea, 69% coughing, 62% fatigue, 60% pain)

Fatigue and pain were the symptoms most highly correlated

with a lower global QOL score

Majority of patients (81%) had no social or financial problems

Prospective

Descriptive

20 Anterolateral

thoracotomy

EORTC QLQ-CLC36

Spitzer QL-Index

Preoperative

Postoperative

11 d

QOL (especially role and physical functioning) deteriorated

in the first 3 mo after surgery and returned to preoperative

levels at 6–9 mo postoperatively

3 mo

6 mo

9 mo

Pneumonectomy was significantly associated with more

disease symptoms and greater limitations in physical

functioning when compared with lobectomy

Mangione et al [63] 1997 Prospective

Descriptive

123 PLT SF-36 Preoperative

Postoperative

1 mo

6 mo

12 mo

Lung cancer patients before surgical treatment have significantly

lower scores on the mental QOL scales when compared with the

healthy population (including social functioning, role limitations

because of mental problems, mental health, health perception and

vitality) but similar scores on physical functioning

QOL deteriorated in the first year after surgery in all

subscales contributing to the physical construct of the

SF-36 (physical functioning, role limitations because of

physical health problems, bodily pain, vitality, and health

perception)

Subscales contributing to the mental construct improved

at 1 y after surgery

W.W.L.Liet

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14(2004)353–365

358

Handy et al [66] 2002 Prospective

Descriptive

139 PLT (57.6%)

Sternotomy

(36.7%)

MS (5.0%)

VATS (0.7%)

SF-36

QLI

Preoperative

Postoperative

6 mo

Lung cancer patients before surgical treatment have

sig ificantly lower QOL when compared with a healthy

co rol group (regarding the physical functioning,

em tional role functioning, mental health, and energy

su cales)

QO deteriorates even further at 6 mo after surgery

(si ificant persistent decline in physical functioning,

ph ical role functioning, social functioning, mental

he th, and bodily pain)

DL O <45% predicted was the sole predictive clinical

pa meter (associated with worse preoperative physical

fu tioning and QOL and worse postoperative QOL,

he th and functioning, and psychological/spiritual status)

Welcker et al [67] 2003 Descriptive 22 Anterolateral

thoracotomy

SF-36 Postoperative

12 mo

Lu cancer patients at 12 months after surgery have

lo r scores on almost all SF-36 subscales (except bodily

pa ) when compared with normal healthy population and

pa nts who have other forms of cancer or chronic diseases

Myrdal et al [64] 2003 Cross-sectional

Descriptive

112 MS SF-36 + three

self-developed lung

specific questions

Median follow-up time:

23 mo postoperatively

(range 4–48)

Pa nts after lung cancer resection have significantly

wo e scores in most QOL domains (except bodily pain)

wh n compared with a healthy control group

Pa nts after lung cancer resection have significantly

wo e physical function when compared with matched

pa nts who had undergone CABG

Pn monectomy and FEV1 <60% before surgery had a

sig ificant correlation with lower scores for the physical

su mary component

Co tinued smoking after surgery was associated with

lo r scores for mental health and vitality

Sarna et al [65] 2002 Cross-sectional

Descriptive

142 Not reported SF-36

QOL-Survivor

Mean follow-up time:

10.4 y postoperatively

(range 5–22)

Lo -term survivors of lung cancer after surgical resection

ha worse physical function but better mental health when

co pared with patients who have other forms of cancer

an chronic lung disease

Lo -term survivors of lung cancer after surgical resection

be ve they have good QOL (50% viewed the cancer

ex rience as contributing to positive life changes and

71 described themselves as hopeful about the future)

Di essed mood was the strongest predictor of poor

lo -term QOL

(continued on next page)

W.W.L.Liet

al/ThoracSurg

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359

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Table 2 (continued)

Article Year Design N Access modalities QOL instrument(s)

Assessment

time frame QOL outcome

Sugiura et al [77] 1999 Cross-sectional

Comparative

44 PLT vs VATS Self-developed

questionnaire

(six items)


PLT 34 mo

(range 11–32)

VATS 13 mo

(range 5–20)

VATS patients had an earlier return to preoperative activity

(2.5 versus 7.8 mo, P = 0.03)

Significantly fewer VATS patients had acute and chronic

chest pain requiring medication (0 versus 4 patients, P= 0.01)

VATS patients were more satisfied with the size of the

scar and the operation as a whole

Li et al [73] 2002 Cross-sectional

Comparative

51 PLT vs VATS EORTC CLC-30

EORTC CLC-LC13

+ nine self-developed

lung cancer surgery-

specific questions


PLT 39.4 mo

(range 7–75)

VATS 33.5 mo

(range 6–84)

Both groups of patients enjoyed good QOL and high

levels of functioning without significant differences between

the groups

Most common symptoms were fatigue (74–92%), dyspnea

(75–85%), coughing (75–82%), and pain (67–71%)

All three self-developed multi-item QOL scales demonstrated

good reliability

Abbreviations: MS, muscle-sparing thoracotomy; PLT, posterolateral thoracotomy.

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360


using the SF-36 in 49 subjects. One year postopera-

tively, lung cancer patients had lower scores on all

QOL subscales when compared with healthy volun-

teers, chronic obstructive pulmonary disease patients,

and patients who had other forms of cancer. Lesser

extent of resection and lower tumor stage correlated

significantly with higher quality-adjusted life years.

Lung cancer and lung cancer resection cause

significant deterioration of early postoperative QOL

[63,66,74,76]; however, the long-term effect of lung

cancer resection on QOL remains unclear given that

the available data originate mainly from a few retro-

spective analyses. Myrdal et al [64] compared long-

term QOL in 112 lung cancer patients after surgical

resection with patients undergoing coronary artery

bypass grafting (CABG) and a healthy control group.

The SF-36 was used to assess QOL, supplemented

with three additional lung-specific questions on the

presence of pain in the chest, breathlessness, and

cough. In addition, the Hospital Anxiety and Depres-

sion Scale (HAD) was used to measure anxiety and

depression. At a median follow-up of 23 months

after surgery (range 4–48 months), patients after lung

cancer resection had significantly worse physical

function when compared with the CABG group.

Correspondingly, lung cancer patients also had sig-

nificantly higher levels of breathlessness on physical

effort. Furthermore, pneumonectomy and FEV1 less

than 60% before surgery had a significant correlation

with lower scores for the physical summary compo-

nent. Continued smoking after surgery was associated

with lower scores for mental health and vitality. No

differences were found between the two groups

regarding depression or anxiety. Both groups also

reported significantly worse scores in most QOL

domains when compared with the healthy control

group. Surprisingly, bodily pain was the only sub-

scale that did not differ from the healthy control

group. The authors concluded that patients after lung

cancer surgery have a QOL comparable to that of

CABG patients; however, lung cancer patients have

lower levels of physical functioning, possibly be-

cause of reduced pulmonary function. Furthermore,

despite having been operated on because of a serious

malignancy, they report no significant impairment of

social function, mental status, anxiety, or depression.

In a similar report Sarna et al [65] reported that

long-term survivors of lung cancer after surgical

treatment have good QOL. They assessed QOL in

142 patients who had been disease-free for at least

5 years (mean 10.4 years, range 5–22 years) using the

SF-36, the QOL-Survivor questionnaire, and the

Center for Epidemiologic Studies Depression Scale.

When asked about their QOL, 50% of patients viewed

the cancer experience as contributing to positive life

changes and 71% described themselves as hopeful

about the future. Then again, 27% of patients re-

ported fatigue, 24% of patients reported aches or

pains, and 30% of patients reported problems with

anxiety. Furthermore, FEV1 was only 68% of pre-

dicted value. Nevertheless, despite having decreased

pulmonary function, multiple symptoms, and comor-

bidities, this did not seem to affect their overall QOL.

Also, distressed mood was shown to be the strongest

predictor of poor long-term QOL.

In summary, lung cancer and lung cancer resec-

tion cause significant deterioration in postoperative

QOL [63,66,74,76]. The available data suggest that

early-stage lung cancer patients already have signifi-

cantly lower QOL when compared with the normal

population before surgical treatment [63,66]. Signifi-

cant impairment was not only observed in physical

functioning [66] but also in mental health and emo-

tional functioning [63,66]. After lung cancer resec-

tion QOL deteriorates even further at 3 to 6 months

after surgery [63,66,74,76]. Postoperative pain [63,66]

and dyspnea [66,74] could be important causes of

disability. While some studies suggest that QOL

returns to baseline levels 6 to 9 months postopera-

tively [74,76], others report that QOL is still signifi-

cantly impaired at 6 months [66] and at 1 year after

surgery [63].

Prospective data analyzing long-term postopera-

tive QOL are not available. Nevertheless, available

data suggest that long-term survivors after lung cancer

surgery enjoy good QOL despite impaired physical

functioning [64,65]; however, although cross-sec-

tional studies yield valuable information, QOL is a

dynamic concept that is best assessed in a longitudi-

nal, prospective setting. Without preoperative baseline

evaluations, the effect of lung cancer and its treatment

on long-term QOL cannot be properly defined.

Despite recent increasing interest in QOL assess-

ment in lung cancer patients after surgical treatment,

available data remain limited. Postoperative QOL

data (collected in a prospective manner) of only

399 patients have been published so far. Moreover,

timing of assessment, the QOL instruments, and

access modalities used have been variable, compli-

cating interpretation and generalization of the infor-

mation at hand. Future studies need to be prospective

and longitudinal, and should include larger study

populations and a longer follow-up period to portray

the course of QOL in lung cancer patients more

accurately before and after surgical treatment. Fur-

thermore, it should be clarified which symptoms are

responsible for the deterioration of QOL after surgery

to improve postoperative care.

Surg Clin 14 (2004) 353–365

Minimal access surgery and quality of life

The application of video-assisted thoracic surgery

(VATS) for lung cancer resection remains controver-

sial [13,14]. The early postoperative benefits of this

approach such as less postoperative pain, less shoul-

der dysfunction, preservation of pulmonary function,

and earlier return to preoperative activity are well

documented [13,14]; however, the success of a cancer

operation is firstly judged by the long-term survival

of patients. Although there was initial skepticism

regarding the oncologic adequacy of VATS lung can-

cer resection, an increasing number of reports now

show consistently that the intermediate to long-term

survival is at least as good as—if not superior to—

the standard approach [13,14]. Given the apparent

equivalent survival outcome between the two access

modalities, QOL assessments become increasingly

important to help guide clinical decision making re-

garding selection of treatment option.

Data on QOL after VATS lung cancer resection are

extremely limited. In the previously mentioned pro-

spective study by Handy et al [66], only 0.7% of the

139 patients studied had lung cancer resection per-

formed through VATS. The sample size was too small

to provide helpful comments or multivariate analysis.

No other studies are available that assess the early

postoperative QOL in patients after VATS lung cancer

resection. Two small cross-sectional studies have

compared long-term QOL after lung cancer resection

through VATS with lung cancer resection through

thoracotomy [73,77]. Sugiura et al [77] compared

QOL in patients after lung cancer resection through

VATS or posterolateral thoracotomy (PLT). They used

a self-designed questionnaire with six items on time to

return to preoperative activity, narcotic medication

requirement, numbness in or around the incision,

shoulder function restriction, satisfaction with the size

of the scar, and satisfaction with the operation as a

whole. Twenty-two patients were recruited in both

groups. At a mean follow-up time of 21 months (range

5–43 months) they found that VATS patients had

an earlier return to preoperative activity (2.5 versus

7.8 months, P = 0.03), and significantly fewer VATS

patients had acute and chronic chest pain requiring

medication (zero versus four patients; P = 0.01).

Furthermore, VATS patients were more satisfied with

the size of the scar and the operation as a whole.

No significant differences between the groups were

found on shoulder dysfunction. However, all these

results should be interpreted with caution; there was a

significantly shorter follow-up for VATS patients

(12.6 months versus 33.6 months; P = 0.0001),

making comparison between the two groups less

W.W.L. Li et al / Thorac362

valid. Moreover, one should argue whether or not

QOL was really measured [41–43]; global QOL or

functioning status was not assessed and psychometric

properties (eg, validity and reliability) of the ques-

tionnaire used was not evaluated.

Li et al [73] used the EORTC QLQ-C30 and the

EORTC QLQ-LC13 supplemented with nine self-

developed lung cancer surgery-specific items on

shoulder dysfunction, scar-related complaints, post-

thoracotomy pain, and satisfaction with the surgical

procedure. They found that both groups of patients,

after a mean follow-up time of 33.5 months in the

VATS group and 39.4 months in the PLT group,

enjoyed good QOL and high levels of functioning

despite a fairly high incidence of symptoms. The most

common symptoms were fatigue (74–92%), dyspnea

(75–85%), coughing (75–82%), and pain (67–71%).

Furthermore, the three self-developed multi-item

QOL scales demonstrated good reliability.

Summary

Lung cancer continues to be the most common

cancer in the world, with the highest cancer mortality

rate by far. Although resection remains the treatment

of choice in early-stage NSCLC, the prognosis

remains grim even after surgical treatment. In a

patient population with such a high mortality rate,

evaluation and preservation of QOL after treatment

is imperative.

Early-stage lung cancer patients already have sig-

nificantly lower QOL when compared with the normal

population before surgical treatment, with significant

impairment in physical and emotional functioning.

Lung cancer resection causes further deterioration of

QOL, especially in the first 3 to 6 months after sur-

gery. While some studies suggest that QOL returns to

baseline levels at 6 to 9 months postoperatively, others

report that QOL is still significantly impaired at

6 months and 1 year after surgery. Although pros-

pective studies analyzing long-term postoperative

QOL are not available, retrospective data suggest that

long-term survivors after lung cancer surgery enjoy

good QOL despite impaired physical functioning.

QOL studies on VATS lung cancer resection are

extremely limited.

More prospective, longitudinal studies with larger

study populations and longer follow-up periods are

needed to portray the course of QOL in lung cancer

patients more accurately and to improve postopera-

tive care. Furthermore, comparative studies between

VATS and the standard thoracic incisions (including

QOL assessments) must be performed to guide clini-


cal decision making regarding selection of optimal

access modality for performing lung cancer resection.

Acknowledgments

The authors are indebted to Shirley Lam, Division

of Cardiothoracic Surgery, Department of Surgery,

Prince of Wales Hospital, Hong Kong SAR, for her

help and dedication in data collection and preparation

of the manuscript.

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Quality of life after esophageal surgery

Hiran C. Fernando, MD, FRCS, FACS, James D. Luketich, MD, FACS*

Division of Thoracic and Foregut Surgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Suite C-800,

Pittsburgh, PA 15213, USA

Maintaining an acceptable quality of life (QOL) is One of the oldest instruments to measure QOL is

a key factor after any surgical operation; however, for

diseases of the esophagus, QOL assumes unparalleled

importance compared with other organs because

nutritional intake is so crucial to patient satisfaction.

The incidence of adenocarcinoma of the esophagus is

increasing significantly in the Western world. Most

patients will have significant impairment of QOL

because of the dysphagia associated with an obstruct-

ing tumor. Although esophagectomy can improve

QOL [1], concerns over the high morbidity and

mortality associated with this operation have led to

a reluctance by some physicians to refer patients to

surgery, and in some cases nonresectional treatments

such as photodynamic therapy are favored [2,3].

QOL is also a key issue when treating benign

esophageal diseases. In contrast to esophageal cancer,

in which palliation of dysphagia and cure are impor-

tant issues, gastroesophageal reflux disease (GERD)

is a disease that primarily affects QOL. A number of

new treatment modalities are becoming available for

GERD [4]. As these are introduced into clinical

practice, QOL measurement should be an important

part of their evaluation.

Despite the importance of QOL, this outcome

measure is rarely measured in surgical practice. Most

surgical publications typically report only standard

outcomes such as mortality and morbidity. This can,

in part, be explained by the lack of a gold standard

instrument to measure QOL and the perception that

QOL measurement is difficult to define objectively

and too time-consuming to collect.


doi:10.1016/S1547-4127(04)00024-6


E-mail address: [email protected] (J.D. Luketich).

the Karnofsky index [5,6]. This venerable tool has

been most useful to measure performance status and

predict ability to tolerate therapy in oncology patients;

however, it is insufficient in many aspects because it

exclusively evaluates physical functioning and does

not give significant weight to other domains of QOL.

Another disadvantage of the Karnofsky index is its

reliance on an observer’s assessment of a patient’s

level of independence and activity rather than the

patient’s own assessment of their QOL.

Recently, a number of newer instruments have

been developed to measure QOL. These include the

Sickness Impact Profile [7], the Functional Living

Index in Cancer [8], and the MOS-SF36 [9]. These

newer instruments all rely on subjective assessment

by the patient rather than assessment by a potentially

biased observer. Subjective assessment of QOL by

the patient rather than objective evaluation by a

doctor or other caregiver has been demonstrated to

provide a more accurate assessment of QOL [10].

This article provides an overview of instruments

used to measure QOL and their increasing application

following esophageal surgery for cancer and GERD.

Overview of quality of life instruments

QOL is a concept that is easy to grasp intuitively

but difficult to measure reliably. In the everyday sense

of the phrase, QOL can include such aspects as

personal income, location of residence, leisure time

and activities, interpersonal relationships, meaningful

work, and spiritual fulfillment, among other nonmedi-

cal aspects of life. In medicine, however, what one

attempts to assess is health-related QOL (HRQOL),

which measures the impact of disease on physical,

s reserved.

H.C. Fernando, J.D. Luketich / Thorac Surg Clin 14 (2004) 367–374368

psychological, and social health. The World Health

Organization previously defined QOL as an absence

of infirmity and a state of physical, social, and mental

well-being [11]. Although these definitions might be

obvious, their measurement might not be.

QOL instruments have internal characteristics that

should be assessed more rigorously. These qualities

include reliability, validity, responsiveness, appropri-

ateness, practicality, and interpretability. Reliability

implies that the instrument must produce the same

result on repeated assessment of the same level of

QOL. Validity implies that the instrument measures

what it is purported to measure. Responsiveness (sen-

sitivity to change) is the ability of the instrument to

detect clinically important changes in QOL as a result

of treatment or over time. The appropriateness of an

instrument depends on how well the instrument

measures the relevant aspects of QOL for a given

health problem. Practicality reflects the ease with

which the instrument can be used by health care

professionals and patients. Interpretability is how

well the result of the questionnaire can be understood

by the clinician using the results. All of these factors

should be considered when selecting a QOL instru-

ment for use in clinical practice or research.

QOL instruments can generally be categorized as

generic or disease-specific. Generic instruments mea-

sure global QOL and are broadly applicable across

several diseases, whereas disease-specific instruments

assess specific diagnostic groups to measure clinically

important changes within these diseases. This sensi-

tivity to change (responsiveness) might be one of the

most important characteristics of instruments used to

evaluate the effects of treatments. The advantages of

a generic instrument are that a single instrument can be

used in several settings, detecting differential effects

on the various aspects of health status, and that

comparisons after interventions for different diseases

are possible. Additionally, generic instruments allow

comparisons to normal populations and patients who

have other chronic diseases. The disadvantages of

generic instruments are that they might not focus ade-

quately on an area of interest (eg, severity of symp-

toms) and they might not be responsive enough (ie,

might not measure changes as a result of an interven-

tion), which might be important for a study on the

effects of a particular treatment. Disease-targeted

instruments focus on a specific condition and its re-

lated symptoms. The specificity of condition-specific

instruments can increase their responsiveness to detect

small treatment changes over time; however, many of

these instruments have not been as extensively vali-

dated by longitudinal studies, as generic instruments

have. Many practitioners are reluctant to use a variety

of instruments for multiple disease types (eg, a spe-

cific questionnaire for each digestive disease).

A third group of QOL instruments are those that

measure specific symptoms. These instruments do

not take into consideration other QOL issues such

as social interactions or psychological stresses; how-

ever, these are still of value if a primary endpoint of

treatment or a common major complication of treat-

ment is the symptom being evaluated. The authors

have previously used symptom-specific instruments

to evaluate dysphagia after esophagectomy [12] or

photodynamic therapy [3] and pain severity after

thoracotomy [13].

Generic quality of life instruments

Probably the most well known generic instrument

is the Medical Outcomes Study Short Form 36 (SF36)

[9]. This instrument was originally developed by John

Ware and the Medical Outcomes Trust and has gained

increasing popularity in several clinical settings. This

36-item questionnaire has been validated extensively

and normal values for various populations have been

well defined. When originally developed, scores were

expressed as eight domains of QOL, including physi-

cal functioning, role physical, bodily pain, general

health, vitality, social functioning, role emotional, and

mental health. Subsequently, these eight-domain

scores were combined into two scores [14], a physical

component summary (PCS) and mental component

summary (MCS) score.

The SF36 has become one of the most popular

and widely used QOL instruments in the United

States and worldwide, with several foreign trans-

lations available.

The Psychological General Well-Being Index

(PGWB) was developed to measure subjective well-

being or distress [15]. Since its introduction in 1984 it

has been used in many studies, including the evalua-

tion of QOL in upper gastrointestinal diseases [16].

It assesses six dimensions of QOL: anxiety, depressed

mood, positivewell-being, self-control, general health,

and vitality. These are then combined to give an overall

score. This instrument has been popular in several

European studies of GERD.

Disease-specific instruments used to evaluate

gastroesophageal reflux disease and esophageal

cancer

The Gastrointestinal Symptom Rating Scale

(GSRS) was constructed initially to measure severity

H.C. Fernando, J.D. Luketich / Thorac Surg Clin 14 (2004) 367–374 369

of symptoms in peptic ulcer disease and irritable

bowel syndrome [16]. It is a seven-grade Likert scale

questionnaire that contains 15 items. It has been

found to be satisfactory with respect to internal con-

sistency, validity, and responsiveness. It has been

used to assess GERD and seems to be adequate for

this purpose [17].

The Gastroesophageal Reflux Disease–Health

Related Quality of Life Scale (HRQOL) was devel-

oped by Velanovich to assess GERD severity [18].

The HRQOL is a disease-specific instrument that

consists of 10 questions. Nine questions relate to

different aspects of GERD with each response scored

from 0 to 5. The best possible score is 0 (no sym-

ptoms) and the worst possible score is 5 (most severe

symptoms). The tenth question relates to an overall

assessment of satisfaction. In a study comparing the

HRQOL to the SF36 performed in 43 patients who

had GERD, 59% of patients preferred the HRQOL,

62% felt it was easier to understand, and 86% felt

it was more reflective of their symptoms [19].

The authors’ group’s preference has been to use the

HRQOL in combination with the SF36 because the

authors feel that the combination of a disease spe-

cific and generic instrument is advantageous [20].

Another instrument, the Reflux-Related Visual Ana-

logue Scale, has been developed recently. Data about

its validity and reliability have yet to be published,

although Blomqvist et al [21] showed that there is a

good correlation with specific symptoms of GERD

assessed preoperatively and after antireflux surgery.

The European Organization for Research and

Treatment of Cancer (EORTC) has developed a

disease-specific instrument for application in esopha-

geal cancer [22]. This instrument uses an esophageal

module (QLQ-OES18) with items specific to aspects

of esophageal cancer. The esophageal module is used

in combination with the EORTC core questionnaire

(the QLQ-C30). The QLQ-C30 has been used previ-

ously for lung, breast, and ovarian cancer [23].

Quality of life measurement in esophageal cancer

Comparison of esophagectomy to palliative treatment

of esophageal cancer

A few studies have compared QOL after palliative

treatment and resection of esophageal cancer. As may

be expected, one of the concerns with this approach is

that patients who receive palliative care tend to be

older and have poorer baseline QOL scores [24]. In a

study of 69 patients who underwent resection or

palliation with radiation and stent placement, QOL

was measured using a cancer-specific scale (Rotter-

dam Symptom Checklist) and a dysphagia score [24].

After treatment, QOL scores initially deteriorated in

both groups, but at 16 weeks improvements were

seen in the resection group only. Dysphagia scores

improved in both groups at 6 weeks, but at 16 weeks

further improvements were seen in the surgical

group only.

Another study involved 59 patients who under-

went esophagectomy and 26 who were palliated with

radiation with or without stent placement. This study

used the QLQ-C30 and a dysphagia score [25].

Statistically significant differences were found be-

tween the two groups with respect to the physical,

emotional, and cognitive function scores, favoring the

resection patients. Additionally, posttreatment dys-

phagia scores were worse in the patients who had

palliative treatment only. The dysphagia scores did

not correlate with any of the individual QOL scales or

items, indicating that although dysphagia is an im-

portant issue, other factors contribute to overall

QOL in esophageal cancer. Although these studies

are biased in favor of the functionally better surgical

groups, the superior results with esophagectomy sup-

port the role of esophagectomy in providing palliation

and relief of dysphagia when feasible.

Outcome after open esophagectomy

A study by Wong et al [1] compared 49 patients

who underwent curative open esophagectomy (OE)

to 39 patients who underwent palliative OE. There

were no significant differences between these groups

with respect to preoperative risk factors, although

Eastern Cooperative Oncology Group (ECOG) per-

formance status was worse in the palliative group

preoperatively. Although pain and overall QOL scores

were worse in the palliative group at 9 months, there

were no differences with regard to sleep and leisure

activity between the groups. Additionally, the type and

quantity of oral intake improved significantly in both

groups after surgery with no differences seen at 18

months of follow-up care. This study again demon-

strates the positive impact of esophagectomy on QOL

even if resection is incomplete.

Esophagectomy is a complex and challenging

operation. Total morbidity rates are usually not docu-

mented in surgical series, but when they are reported

they appear to be around 60% [26,27]. The signifi-

cant physiological challenges to the patient and the

possibility of increased morbidity after esophagec-

tomy lead clinicians to expect that QOL will initially

decrease during the immediate postoperative period


but will improve eventually. A few studies have

addressed the issue of intermediate and long-term

follow-up care after OE. Zieran et al [28] followed a

cohort of 30 patients over a 1-year period using the

EORTC QOL questionnaire and the Spitzer index

after OE. All patients had curative operations and

were disease-free during this 12-month period Dys-

phagia was the most severe symptom before surgery

and had improved by discharge from the hospital.

Global QOL, however, deteriorated significantly after

operation and did not recover until about 6 months

after operation. At 12 months, QOL scores were

slightly higher than preoperative values. A study by

Blazeby et al [27] used the QLQ-C30 and the EORTC

QLQ-OES24 in 17 patients who survived for at least

2 years after OE and compared these to 38 patients

who survived for less than 2 years after OE. At

6 weeks all patients reported decreased functional,

symptom, and global QOL scores compared with

preoperative scores. In both groups dysphagia im-

proved after surgery and was maintained until death

or the duration of the study. In the patients who

died within 2 years, former QOL levels were never

regained, whereas in patients who survived for more

than 2 years, QOL scores had recovered by 9 months

after operation.

Probably the best-reported long-term QOL data

come from the Mayo clinic experience [29]. They

reported on 107 patients who had survived for 5 or

more years after OE. The median survival time was

10.2 years. At the time of follow-up, 60% of patients

complained of reflux, 53% of dumping, and 25% of

dysphagia to solid food. Only 17% were completely

asymptomatic. A cervical anastomosis was associated

with significantly (P < 0.05) less reflux, and dumping

occurred more frequently (P < 0.05) in younger

patients and women. QOL was measured using the

SF36. Physical function scores were significantly less

than national norms; however, scores measuring abil-

ity to work, social interaction, daily activity, emotional

dysfunction, and health perception were similar to

national norms. Surprisingly, mental health scores

were better than national norms. This study illustrates

that even though a high percentage (83% in this study)

of long-term survivors after OE will complain of

gastrointestinal symptoms such as reflux or dumping,

most aspects of QOL will still be preserved.

The Mayo clinic also reviewed their long-term

follow-up care after OE with a preoperative diagnosis

of high-grade dysplasia [26]. This is a challenging

group of patients because most will be relatively

asymptomatic compared with patients who have more

advanced cancers. There were 54 patients in this

series, of whom 35% were found to have an invasive

cancer. Using the SF36 they found that the role

physical and role emotional scores in the high-grade

dysplasia patients were better than norms, whereas

the patients who had cancer had poorer health per-

ception scores. Physical function, social function,

mental health, bodily pain, and energy/fatigue were

similar. Despite the high operative morbidity (57%)

seen in this group of patients, the findings of a 35%

incidence of unsuspected cancer and the acceptable

QOL seen at follow-up support the role of resection

for patients who have high-grade dysplasia.

Outcomes after minimally invasive esophagectomy

A number of approaches to esophagectomy are

used by surgeons. The mortality from OE has been

reported to be in the range of 6% to 7% in published

series [30]. It appears that mortality is related to the

experience and volume of esophagectomy cases per-

formed at individual centers rather than the approach

used. In a report summarizing nationwide statistics,

mortality ranged from 8% in high-volume centers to

as high as 23% in low-volume centers [31]. In view

of the high chance of morbidity and mortality, it is

perhaps not surprising that some patients might be

treated nonoperatively without evaluation by a sur-

geon. The authors’ group explored the role of mini-

mally invasive esophagectomy and now favors this

approach to esophagectomy. The authors recently

published the results of their first 222 cases [12].

The authors’ standard approach includes a right

video-assisted thoracic surgery (VATS) mobilization

of the thoracic esophagus combined with a lapa-

roscopic transhiatal approach and neck anastomosis

[12]. Minimally invasive esophagectomy (MIE)

offers the potential to lower morbidity and allow

quicker return to normal function than OE. If mor-

tality and morbidity are reduced, a greater number of

patients might be referred and benefit from MIE. In

the authors’ series of 222 patients, mortality occurred

in 1.4% of patients and major morbidity occurred in

32%. The median hospital stay was 7 days, which is

lower than that reported in most series of OE. QOL

was measured using the SF36 and dysphagia was

measured using a scale from 0 (no dysphagia) to

5 (severe dysphagia). Because reflux is often reported

after esophagectomy [29], the authors also recorded

heartburn severity using the HRQOL [18]. At a mean

follow-up of 19 months the mean HRQOL score was

4.6, which represents a normal (no reflux) score.

Only 4% of patients complained of significant reflux

(HRQOL score �15), supporting the continued use of

a neck anastomosis. SF36 scores were compared with


age-matched norms. PCS scores were not significantly

different, whereas MCS scores were slightly but

statistically (P = 0.001) lower than United States

norms (49.67 versus 52.68). Pre- and postoperative

scores were only available in 57 patients. In these

patients PCS and MCS scores were not significantly

different from preoperative values, suggesting preser-

vation of QOL. Dysphagia scores were excellent

(mean 1.4). The authors previously reviewed the

results of MIE in a cohort of 41 patients aged 75 years

or older [32]. There were no preoperative deaths,

major morbidity occurred in 19% of patients, and

median length of stay was 7 days. These data also

support the use of MIE in older patients who have

esophageal cancer.

Based on these data the authors believe that MIE

(performed in centers experienced in minimally in-

vasive surgical techniques and malignant esophageal

surgery) is a good therapeutic option that can be

performed with acceptable morbidity and mortality

and result in a preserved QOL.

Quality of life measurement in gastroesophageal

reflux disease

Quality of life measurement after surgical therapy of

gastroesophageal reflux disease

Laparoscopic fundoplication has been shown to

be a safe procedure that can be performed with ac-

ceptable results; however, the role of the operation

remains controversial and continues to be debated in

the literature. Before the routine use of laparoscopic

fundoplication, a study by Pope demonstrated the

benefits of open fundoplication on QOL [33]. Over

the last 12 years, larger and larger series of laparo-

scopic fundoplication have been reported using QOL

measures. In an earlier study, QOL measurements

using the PGWB index (generic) and the GSRS (dis-

ease-specific) were reported in 40 patients and dem-

onstrated improvement after operation [34]. More

recently, reports of 300 patients (using the SF36)

and 500 patients using another disease-specific in-

strument, the Gastrointestinal Quality of Life Index,

have been reported [35,36]. These single-center

studies demonstrated improved QOL after operation.

A study from Pittsburgh used a disease-specific GERD

score, symptom-specific heartburn and dysphagia

scores, in 297 patients before and after operation

[37]. At a mean follow-up of 31.4 months, symp-

tom-specific and disease-specific scores improved,

with only 10% of patients requiring proton pump

inhibitor (PPI) for typical GERD symptoms.

Other studies have compared open and laparo-

scopic approaches. In one nonrandomized study

Bloomqvist compared open and minimally invasive

approaches, with similar outcomes demonstrated be-

tween groups [21]. In another study Velanovich [38]

compared open and laparoscopic antireflux operation

and found superior physical function and bodily pain

scores at 6 weeks in the laparoscopic group, indicat-

ing that these patients had a quicker recovery com-

pared with patients who underwent open operation.

The group from the University of Southern California

used the SF36 to compare 72 patients who had a

laparoscopic Nissen fundoplication to 33 patients

who had more complex hiatal hernias and strictures

who underwent transthoracic Nissen fundoplication

[39]. Although the laparoscopic group recovered

more quickly with less postoperative discomfort at

long-term follow-up, QOL scores were similar and

were only significantly decreased for patients who

(not surprisingly) had recurrent reflux symptoms. The

laparoscopic group was more likely to use acid

suppression medications and tended to be less satis-

fied, arguing that an open operation is preferred, at

least for patients who have advanced gastroesopha-

geal reflux disease.

The authors’ group has previously reported their

experience with 200 giant hiatal hernia repairs per-

formed laparoscopically [40]. These complex hiatal

hernias had at least 30% of the stomach within the

mediastinum. In most cases, in the later part of the

series, a laparoscopic Collis gastroplasty was per-

formed because the authors believe that this proce-

dure helps prevent problems with recurrence of the

hernia when a shortened esophagus is present [41].

HRQOL was used to evaluate patients in follow-up

(mean scores 2.4), and scores were felt to be in the

excellent or good range in 92% of patients.

Another group of patients who have complex

GERD are patients who have previously undergone

antireflux operation. It is often argued that these

complex operations should be approached using open

techniques because results will be worse than with

primary repair and have been reported ranging from

66% to 76% [42]; however, if the same principles as

open surgery are employed (ie, full workup of the

patient preoperatively, complete takedown of the

previous repair, assessment for the presence of a

shortened esophagus with appropriate use of a Collis

gastroplasty), results will be as good as with an open

operation. The authors’ series of 80 laparoscopic

reoperations included the use of the SF36, HRQOL,

and a dysphagia score ranging from 1 (no dysphagia)

to 5 (severe dysphagia—unable to tolerate saliva) at a

mean follow-up period of 18 months [43]. SF36 PCS


and MCS scores were similar to normal values and

mean HRQOL scores were 6, which is within the

normal range. Dysphagia scores improved signifi-

cantly (from 2 to 1.3) and only 18% of patients

reported that they were dissatisfied.

Age is sometimes felt to be a contraindication to

laparoscopic antireflux surgery. GERD primarily af-

fects QOL, and the operation might have a significant

positive effect even in the elderly, higher surgical risk

patient who has severe GERD. The authors recently

compared outcomes between an older and younger

group of patients, all of whom had complete fundo-

plications [44]. Despite a longer length of stay in the

older population, follow-up HRQOL, SF36, and

dysphagia scores were excellent and similar between

the two groups of patients, supporting the role of the

operation for older patients.

Medical versus surgical therapy: how does quality

of life compare?

This question continues to be an area of intense

discussion, particularly with the introduction of

newer medications and the increasing availability of

the laparoscopic antireflux operation. In one of the

few randomized studies that have been reported, open

fundoplication was compared with medical therapy

using histamine-2 antagonist (H2A) in a multicenter

Veteran’s Administration (VA) setting [45]. Patients

in this study maintained a diary of symptoms to

construct a gastroesophageal reflux disease activity

index (GRACI). In the initial report from this study

with 2-year follow-up, the mean activity index and

grade of esophagitis were better in the surgical group.

A follow-up study on these patients was published

recently [46]. The median follow-up period was

7.3 years for the medical group and 6.3 years for the

surgical group, with follow-up available in 91 medical

and 38 surgical patients. Follow-up included use of

the SF36 and the GRACI. A large number of the

surgical patients (62%) required antireflux medica-

tions; however, this number was still significantly

lower than the proportion of medical patients requir-

ing antireflux medications (92%). GRACI scores and

SF36 bodily pain scores were significantly better in

the surgical group. Another randomized study from

Sweden compared open fundoplication to PPI with

5 years of follow-up [47]. In this study the PGWB

(generic instrument) and the GSRS (disease-specific)

were used. QOL scores were found to be similar

between the groups. There were more treatment fail-

ures in the medical group, although when higher-dose

omeprazole was used this difference did not reach

statistical significance.

The authors’ group compared patients undergoing

medical therapy to patients undergoing laparoscopic

antireflux operations [20]. The study population in-

cluded all patients presenting with a primary diagno-

sis of reflux to the gastroenterology or surgical clinic

during a 1-year period. Despite the surgical group

demonstrating more severe reflux (based on greater

usage of PPI and propulsid) before therapy, results

were better in the surgical cohort. Reflux severity

using the HRQOL was 4 in the surgical group versus

21 in the medical group. SF36 scores were signifi-

cantly better in six of the eight domains of QOL in

the surgical group.

Summary

QOL measurement is being reported with increas-

ing frequency in the surgical literature. The authors

and others have found that the use of a generic

instrument such as the SF36 used in combination

with a disease-specific instrument will provide the

most comprehensive information. GERD is a signifi-

cant health problem that primarily affects the QOL

of a large segment of the population. New therapies

for GERD continue to be developed and introduced

into clinical practice. QOL assessment should be an

important part of the evaluation of these new thera-

pies. Similarly, the management of esophageal cancer

and high-grade dysplasia is also controversial. QOL

assessment should be a crucial factor in determining

which surgical or nonoperative approach is used for

these patients

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Quality of life after lung volume reduction surgery

Douglas E. Wood, MD

Section of General Thoracic Surgery, Lung Cancer Research, University of Washington, Box 356310, 1959 NE Pacific,

AA-115, Seattle, WA 98195-6310, USA

Chronic obstructive pulmonary disease (COPD) therapies for emphysema, the most recent of which

is a heterogeneous disease manifested by airflow

obstruction and hyperinflation. Patients with emphy-

sema compose a subset of COPD patients in which

loss of elastic retraction on the terminal bronchioles

results in abnormal permanent enlargement of the

airspaces and destruction of the alveolar walls. The

resulting airflow obstruction and hyperinflation re-

sult in increased work of breathing and inefficient

use of respiratory muscles. There is a simultaneous

loss of the alveolar capillary membrane, decreasing

the area of gas exchange. These physiologic changes

all can be quantified by various measures of pulmo-

nary function. Patients typically have a marked de-

crease in expiratory flow volumes and diffusing

capacity, combined with overinflation of the lung

volumes measured by plethysmography. These

physiologic changes are reflected in a diminishing

functional capacity of the emphysema patient, most

commonly measured by the 6-minute walk test or

exercise studies. These commonly measured variables

of pulmonary function and exercise capacity act only

as easily measurable surrogates for quality of life

(QOL), however.

In general, patients remain asymptomatic until

fairly profound decreases occur in pulmonary func-

tion. Despite medical therapy, in patients with ad-

vanced disease, function deteriorates episodically but

relentlessly. The increased work of breathing leads

to progressive dyspnea, which subsequently leads to

progressive inactivity and physical deconditioning. A

vicious cycle ensues with patients disabled by breath-

lessness, fatigue, irritability, and depression. It is this

spectrum of symptoms that are the target of palliative


doi:10.1016/S1547-4127(04)00029-5


is lung volume reduction surgery (LVRS).

The modern era of LVRS was initiated in the early

1990s by Cooper et al [1] at Washington University.

Using a median sternotomy to perform bilateral sta-

pled wedge resections on patients with heterogeneous

emphysema and hyperinflation resulted in an objec-

tive improvement in forced expiratory volume in

1 second (FEV1) of 82%. This improvement led to a

rapid dissemination of LVRS with initial publications

confirming objective improvement in FEV1 and the

6-minute walk test. These initial results have been

refined and confirmed by additional case-control

series [2–5], randomized studies [6–11], and the

multi-institutional prospective randomized National

Emphysema Treatment Trial (NETT) [12]. Cooper

et al [1] correctly identified health-related quality of

life (HRQOL) as the most important outcome af-

fected by LVRS and examined QOL measures pro-

spectively in patients undergoing LVRS at

Washington University. Other authors have variably

examined HRQOL after lung reduction surgery, more

commonly reporting the more easily measured objec-

tive variables of pulmonary function and exercise

capacity. A variety of disease-specific and generic

instruments for measurement of QOL have been used

and increasingly reported as the most important

clinical outcome after LVRS.

Because the relationship between spirometric and

exercise measures and QOL are indirect and nonlin-

ear, it is important to examine HRQOL as a primary

outcome measure after LVRS. Although patients with

more severe spirometric limitations might be expected

to have the most dyspnea, patients with similar FEV1

values may have different degrees of symptoms [13].

Similarly the relationship between exercise measure-

ments and QOL is inconsistent [13,14]. Dyspnea is

s reserved.

D.E. Wood / Thorac Surg Clin 14 (2004) 375–383376

important, but it is only a single symptom affecting

QOL, and no physiologic or functional variable can

summarize adequately the impact of emphysema on

symptoms and HRQOL. A measurement of HRQOL

provides the best estimate of treatment effect for

LVRS rather than any of the commonly measured

physiologic outcomes.

Quality-of-life instruments

A variety of disease-specific and general instru-

ments for measuring HRQOL have been used by

authors evaluating LVRS outcomes (Box 1). Disease-

specific instruments focus on specific symptoms

within the disease category, such as shortness of

Box 1. Instruments used to measurehealth-related quality of life in lung volumereduction surgery patients

Disease specific

St. George’s Respiratory Questionnaire(SGRQ)

Chronic Respiratory Questionnaire(CRQ)

Transitional Dyspnea Index (TDI)Modified Medical Research Council

Dyspnea Index (MRC)Borg ScaleUniversity of California San Diego

(UCSD) Shortness of BreathQuestionnaire

Mahler Baseline Dyspnea Index

General

Medical Outcomes Study Short-FormHealth Survey (SF-36)

Sickness Impact Profile (SIP)Nottingham Health Profile (NHP)

Preference based

Standard GambleTime Trade-offWillingness to PayQuality of Well-Being Questionnaire

(QWB)Health Utility IndexEuropean Quality of Life tools (EuroQol)

breath in a patient with emphysema. These disease-

specific measures are likely to be more sensitive

because their content is directly related to the disease

in question. Disease-specific measures are more likely

to be sensitive to small but clinically important

changes in health status compared with general in-

struments for measuring HRQOL. The commonly

used lung disease–specific measures include the

Transitional Dyspnea Index, modified Medical Re-

search Council dyspnea index (MRC dyspnea index),

St. George’s Respiratory Questionnaire (SGRQ),

Chronic Respiratory Questionnaire (CRQ), Borg

Scale, and University of California San Diego

(UCSD) Shortness of Breath Questionnaire.

General HRQOL instruments have the advantage

of a comprehensive evaluation, including the ability

to compare QOL across diseases. General HRQOL

instruments may be less sensitive in detecting subtle

differences of symptoms within the disease category

but may be more relevant to overall assessment of

HRQOL. These general instruments look at the to-

tal impact of disease on a patient’s QOL independent

from disease-specific symptoms. General HRQOL

instruments frequently used in evaluating LVRS out-

comes include the Medical Outcome Study Short-

Form Health Survey (SF-36), the Sickness Impact

Profile (SIP) and the Nottingham Health Profile.

An additional complexity in QOL studies is that

disease-specific or general instruments that assess

only functional status miss other important aspects

of HRQOL. Patients with a similar functional impair-

ment may experience a different impact on their

QOL. Decisions about an invasive procedure such

as LVRS depend not only on the expected improve-

ment in QOL, but also on the potential morbidity and

mortality of the procedure. Most HRQOL question-

naires do not account for this difference in perception

of functional status and the patient’s willingness to

accept risk. Preference-basedHRQOLmeasures evalu-

ate the degree of impairment, the impact of the

impairment on the patient, and the willingness of

the patient to undergo risk to improve QOL. These

preference-based HRQOL measures provide an im-

portant means for measuring the impact of an inter-

vention such as LVRS [15]. Instruments of preference

assessment include the Standard Gamble, Time Trade-

off, and Willingness to Pay and the standardized

instruments of the Quality of Well-Being Question-

naire (QWB), the Health Utility Index, and the

European Quality of Life tools [15].

Instruments for measuring HRQOL are well vali-

dated and reliable, although they are less familiar to

clinicians caring for emphysema patients than spiro-

metric and functional studies. Because of this lack of

D.E. Wood / Thorac Surg Clin 14 (2004) 375–383 377

familiarity among pulmonary physicians and thoracic

surgeons treating emphysema patients with LVRS,

measures of HRQOL are employed sporadically

and unevenly in the evaluation of LVRS outcomes.

Many LVRS publications have attempted to evaluate

HRQOL as a primary outcome, however, and the best

have used a battery of assessments that include

disease-specific, general, and preference-based

HRQOL instruments. This combination of studies

allows the benefit of sensitivity in disease-specific

instruments, combined with a generalized applicabil-

ity and utility defined by the general and preference-

based instruments. The preference-based utility data

also provide the necessary data to allow estimation of

cost-effectiveness as measured in quality-adjusted

life-years.

Quality of life after lung volume reduction surgery

Case-control series

Cooper and the Washington University group have

been leaders in the development and investigation of

LVRS, and these authors recognized from the outset

the importance of QOL assessments to validate out-

comes of LVRS. Cooper et al [1] performed the first

prospective study to assess HRQOL formally in

patients undergoing LVRS in their initial cohort of

20 patients published in 1995 (Table 1). This was a

short-term study with an average follow-up of

Table 1

Studies reporting health-related quality-of-life assessments before

Author Year Study type N

Cooper et al [1] 1995 Case-controlled 20

Brenner et al [21] 1997 Case-controlled 145

Anderson [26] 1999 Case-controlled 20

Moy et al [22] 1999 Case-controlled 19

Criner et al [6] 1999 Randomized 37

Lofdahl et al [10] 2000 Randomized 38

Pompeo et al [7] 2000 Randomized 60

Geddes et al [8] 2000 Randomized 48

Hamacher et al [23] 2002 Case-controlled 39

Appleton et al [5] 2003 Case-controlled 29

Ciccone et al [19] 2003 Case-controlled 250

Goldstein et al [11] 2003 Randomized 55

NETT [12] 2003 Randomized 1218

Abbreviations: National Emphysemia Treatment Trial Research Gr

6 months. They recognized the importance of sepa-

rating HRQOL effects of pulmonary rehabilitation

from those of LVRS, however. Preoperative HRQOL

scores were obtained after completion of a formal

pulmonary rehabilitation program to provide baseline

scores for each patient, which were then compared

with the postoperative outcomes. This group used the

disease-specific instrument of the modified MRC

dyspnea scale, which scores patients from 0 to 4, with

4 representing the most severe dyspnea. MRC scores

in this cohort of 20 patients improved from a mean of

2.9 after rehabilitation to a mean of 0.8 after LVRS.

This study also used the generic QOL instruments of

the SF-36 and the Nottingham Health Profile. Patients

experienced large improvements in both of these

general measures of HRQOL after LVRS, but it was

noted that measurements of physiologic variables did

not correlate well with the HRQOL at baseline or

HRQOL improvements [16].

After their initial report of 20 patients undergoing

LVRS, Cooper et al [17–19] published analyses of

150 patients, 200 patients, and 250 patients. The most

recent of these studies included long-term results in

the initial 250 consecutive patients undergoing LVRS

at Barnes Jewish Hospital in St. Louis. The inves-

tigators were able to achieve a high degree of patient

follow-up after LVRS (range 1.8–9.1 years; median

4.4 years) [19]. The MRC dyspnea scale showed a

significant reduction in dyspnea at 6 months, with

88% of patients reporting improvement. This im-

provement deteriorated gradually over time, however,

and after lung volume reduction surgery

Follow-up (mo) Instruments Outcomes

6 MRC Improved

SF-36/NHP Improved

6 MRC Improved

12 QOLS Improved

6 SF-36 Improved

3 SIP Improved

12 SGRQ Improved

6 MRC Improved

12 SF-36 Improved

24 MRC Improved

SF-36 Improved

51 MRC Improved

52 MRC Improved

SF-36 Improved

12 CRQ Improved

29 UCSD SOB Improved

SGRQ Improved

QWB Improved

oup.

Fig. 1. Long-term improvements in modified Medical Research Council Dyspnea Scale after lung volume reduction surgery.

White represents improved, gray shows no change, and black indicates worse. (From Ciccone AM, Meyers BF, Guthrie TJ, et al.

Long-term outcome of bilateral lung volume reduction in 250 consecutive patients with emphysema. J Thorac Cardiovasc Surg

2003;125:513–25; with permission.)


with a percentage of patients continuing to report an

improved dyspnea scale decreasing to 60% at 3 years

and 45% at 5 years (Fig. 1) [19]. The SF-36 also

showed marked improvement compared with base-

line after pulmonary rehabilitation. With follow-up

successful in greater than 90% of patients at 1, 3, and

5 years, 96% of patients reported a substantial im-

provement at 6 months postoperatively. Although this

improvement also slowly deteriorated over time, at

5 years after LVRS (n = 100), 79% of patients

remained improved in their general QOL score com-

pared with preoperatively (Fig. 2) [19].

These data from the Washington University group

sound compelling regarding the improvement in the

disease-specific and generic QOL in patients after

Fig. 2. SF-36 physical functioning scores from before lung volume

AM, Meyers BF, Guthrie TJ, et al. Long-term outcome of bilate

emphysema. J Thorac Cardiovasc Surg 2003;125:513–25; with pe

LVRS, even with long-term follow-up. These data

are strengthened by the prospective evaluation of pa-

tients and by a high rate of follow-up compliance.

These data also are limited, however, by the progres-

sive censoring of dying patients and patients under-

going lung transplantation, both expected to represent

poor performing patients or patients with worse out-

comes. Of the initial 250 patients, 96 (38%) had died

at the time of the report, and an additional 7% of

patients had undergone lung transplantation [19].

Combined, 45% of patients, representing the patients

with the worst outcomes, were excluded from follow-

up analysis. This survivorship bias could result in

an overly optimistic view of long-term outcomes

after LVRS. Other case-control series are often limited

reduction surgery (baseline) and after surgery. (From Ciccone

ral lung volume reduction in 250 consecutive patients with

rmission.)


by the similar effect of a follow-up bias, with poor-

performing patients failing to return for follow-up and

positively skewing postoperative analysis [20].

Brenner et al [21] used the MRC dyspnea scale to

compare dyspnea before and after LVRS in 145 pa-

tients. In this series, the MRC dyspnea scale improved

by at least 1 point in nearly 90% of patients with fol-

low-up greater than 6 months. Approximately 60% of

patients had 6-month improvement in the MRC scale

of 2 or greater. Neither baseline FEV1 nor change in

FEV1 correlated well with dyspnea, confirming the

importance of HRQOL outcomes over physiologic

outcomes for validating efficacy of LVRS.

Because LVRS has been combined most frequently

with an intensive pulmonary rehabilitation program,

each of these interventions may have a cumulative

effect on HRQOL. Some studies, such as those de-

scribed earlier from the Washington University group,

have tried to distinguish between improvements due

to rehabilitation versus improvements due to LVRS by

defining the postrehabilitation assessments as the

patient’s baseline. Other studies have not clearly

defined whether QOL assessments were performed

before or after pulmonary rehabilitation or whether a

routine pulmonary rehabilitation was used before

LVRS. Moy et al [22] specifically assessed HRQOL

by the generic instrument SF-36 before pulmonary

rehabilitation, after pulmonary rehabilitation, and

again 6 months after LVRS. Although this analysis

of 19 patients was small, it allowed the direct analysis

of the impact of pulmonary rehabilitation, the impact

of LVRS, and the cumulative impact of both inter-

ventions on HRQOL. These authors found no signifi-

cant change in any of the domains of the SF-36 after

pulmonary rehabilitation compared with baseline

measures [22]. Patients experienced significant im-

provement in only one domain, vitality, at 6 months

after LVRS compared with scores after pulmonary

rehabilitation. When comparing the combined effects

of pulmonary rehabilitation and LVRS, however,

patients experienced significant improvements from

baseline (prerehabilitation) in four of the eight do-

mains of the SF-36, including physical functioning,

role limitations due to physical problems, social func-

tioning, and vitality [22]. The combination of pulmo-

nary rehabilitation and LVRS resulted in significant

improvements in HRQOL, but each intervention con-

tributed in a distinct way. Pulmonary rehabilitation

accounted for more than 90% of the improvements

in role limitations due to physical problems, whereas

LVRS accounted for nearly all the improvements in

physical functioning and vitality [22].

Hamacher et al [23] from Zurich specifically

investigated disease-specific and general QOL out-

comes 2 years after LVRS in 39 patients prospec-

tively assessed before LVRS with the MRC dyspnea

scale and the SF-36. Marked improvements were

seen in the dyspnea scale with patients having a

mean preoperative score of 3.9 (maximum dyspnea

= 4), which decreased 3 months postoperatively to a

mean score of 1.5. This improvement was largely

sustained throughout the follow-up period, slightly

deteriorating 2 years after LVRS to a mean score of 2

[23]. In the general measure of HRQOL, the SF-36

showed significant improvement in six of eight

domains at 3, 6, 12, and 18 months after LVRS.

Improvements occurred in the domains of physical

functioning, role physical, general health, vitality,

social functioning, and mental health, with no signifi-

cant improvements in the domains of bodily pain and

role emotional. Although there was some deteriora-

tion at 24 months, improvements continued to be

statistically significant in five of the six improved

domains, only returning to baseline in the domain of

general health [23]. The strength of this European

study lies in its prospective analysis and the exami-

nation of longer term outcomes measured at 2 years

after LVRS. Because patients did not routinely un-

dergo pulmonary rehabilitation, it would seem that

the study would be less confounded by the additional

impact of pulmonary rehabilitation on LVRS and that

the benefits would be related purely to the surgical

intervention. The additional medical attention paid to

the preoperative and postoperative LVRS patient is

likely to contribute additional health benefits func-

tionally beyond that conferred by the surgery alone,

however, and paradoxically may make it harder to

separate LVRS outcomes from preoperative medical

management. A series that specifically conducts pul-

monary rehabilitation and measures HRQOL after a

course of pulmonary rehabilitation partially controls

for the increased medical attention provided to the

LVRS patient and the benefit, independent from

surgery, that may result. The Hamacher study is

limited further by the fact that more than half of the

patients undergoing LVRS surgery in this center were

censored as a result of patient mortality, loss of

follow-up, intervening lung transplantation, poor

comprehension of the German language, or short

follow-up. These patients lost for evaluation had the

potential to confound the results, most likely skewing

the reported results in a favorable direction for the

reasons of follow-up and survivorship bias as de-

scribed earlier.

A series from Australia published by Appleton

et al [5] further examined long-term outcomes in

HRQOL after LVRS. This retrospective analysis of

29 survivors of 54 patients undergoing LVRS exam-


ined patients from 3 to 5.5 years after surgery (mean

51 months) and found a significant and sustained

improvement in the modified MRC dyspnea scores.

Although the Dartmouth Primary Care Cooperative

Quality of Life Questionnaire was used to assess

general HRQOL, this was assessed only postopera-

tively and so was not able to be assessed prospec-

tively related to patient function before LVRS. These

outcomes, including examination of the Care Giver

Burden Scale, simply revealed that recipients of

LVRS have similar QOL and burden to caregivers

as other individuals with chronic illnesses [5]. The

major limitation of this study is that it was conducted

retrospectively. The lack of prospective assessments

substantially limits the credibility and reliability of

the findings because they rely on patient recollection

several years after surgery.

Many additional case-control series of LVRS

have used some element of QOL assessment and have

been summarized in two reviews of LVRS [2,15].

Cordova et al [24] used the SIP before and after

LVRS and showed significant improvements in phys-

ical and psychosocial scores and overall scores 3 to

12 months after LVRS. This study confirmed the

cumulative benefits of pulmonary rehabilitation and

LVRS, showing a sustainable improvement after

8 weeks of pulmonary rehabilitation with additional

improvement occurring after LVRS. Few centers have

reported HRQOL using respiratory disease–specific

instruments. Bagley et al [25] used the Chronic Res-

piratory Questionnaire (CRQ), a disease-specific ques-

tionnaire developed for use in patients with COPD.

Short-term follow-up in this study noted improve-

ments in dyspnea, fatigue, emotional function, and

mastery. The SGRQ also has been used in LVRS

studies as a disease-specific HRQOL instrument;

this instrument is discussed later in a review of

the NETT.

Overall QOL was prospectively assessed in 20 pa-

tients before and after LVRS by the researchers at

the University of Washington. This study used the

Quality of Life Scale and showed significant improve-

ment in Quality of Life Scale at 3, 6, and 12 months

after surgery correlating with similar improvements

in FEV1 and exercise capacity [26].

Although many studies failed to identify a direct

or linear relationship between physiologic or func-

tional outcomes with the outcomes of HRQOL,

researchers at Temple University specifically exam-

ined these correlations [27]. QOL was assessed by the

SIP and correlated to changes in FEV1 and exercise

capacity before and after LVRS. Although there was

no significant correlation between changes in SIP

scores and routine measures of lung function, exer-

cise capacity, or gas exchange, changes in SIP did

correlate to the change in oxygen cost of breathing

(volume of oxygen use-to-respiratory minute volume

ratio), reduction in residual volume-to-total lung ca-

pacity ratio, and the subjective assessment of post-

operative steroid and oxygen requirements [27].

Randomized studies

Seven randomized trials of LVRS have been

published, and six of these provide an assessment

of HRQOL [6–8,10–12]. The first was performed

by Criner et al [6] at Temple University and random-

ized 37 patients to undergo pulmonary rehabilitation

versus pulmonary rehabilitation followed by LVRS.

The SIP was significantly improved after 8 weeks

of rehabilitation, and this was maintained during

3 months of additional rehabilitation. Further im-

provement in the SIP was noted 3 months after

LVRS, however, compared with the initial improve-

ment gained after rehabilitation.

Lofdahl et al [10] from Sweden randomized

38 patients to rehabilitation versus rehabilitation fol-

lowed by LVRS and followed these patients using

preoperative and postoperative QOL as measured by

the SGRQ. Although published only in abstract form,

this study showed impressive improvement in the

total SGRQ and the domains of symptoms, activity,

and impact.

Pompeo et al [7] published the largest single-

institution randomized series, evaluating 60 patients

who were randomized to pulmonary rehabilitation ver-

sus LVRS. The surgical patients in this series did not

undergo preoperative or postoperative pulmonary

rehabilitation, so these patients did not benefit from

the cumulative impact of rehabilitation plus LVRS.

This group evaluated only the MRC dyspnea index

as a disease-specific measure of HRQOL along with

several other physiologic and functional outcomes.

This group identified significant improvement in the

dyspnea index, in the medically randomized arm

6 months after pulmonary rehabilitation. There was

a further significant improvement of the dyspnea

index, however, in the surgically randomized patients

compared with medical patients [7].

Until the publication of the NETT, the British trial

published by Geddes et al [8] received the most

attention. This trial randomized 48 patients to a

6-week program of outpatient rehabilitation followed

by randomization to either continued rehabilitation or

LVRS. The QOL was assessed with SF-36 before ran-

domization and at follow-up 3, 6, 12, and 24 months

after randomization. Although scores in the SF-36

tended to decline over time in the medically random-


ized group, scores in the surgically treated group were

significantly improved over baseline and over the

medical cohort at 6 and 12 months (Fig. 3) [8]. This

study showed the benefit of comparing surgically

treated patients with a randomized medical cohort

rather than with their baseline characteristics because

the 1-year follow-up revealed a progressive decline in

spirometry, exercise, and QOL in the medically

treated patients compared with a sustained improve-

ment in the surgical patients.

Goldstein et al from the University of Toronto

[11] reported a single-institution randomized study of

LVRS. In this study, all patients were enrolled in a

6-week program of pulmonary rehabilitation before

Fig. 3. Changes in exercise capacity and quality of life measure

patients randomized to lung volume reduction surgery. (From Ged

reduction surgery in patients with severe emphysema. N Engl J M

being randomized to surgery versus continued medi-

cal therapy. Patients were followed at 3-month

intervals with assessments out to 1 year after ran-

domization. This study is unique in that it chose a

primary outcome of disease-specific HRQOL as mea-

sured by the CRQ. A significant treatment effect in

favor of LVRS was found in each of the CRQ domains

of dyspnea, fatigue, emotional function, and mastery.

The magnitude of this effect also was greater than the

minimally clinically important difference, defined as

an improvement of 0.5 point in all domains at each

time point. Surgical treatment also had a large and

significant effect in preventing treatment failure over

12 months, with failure defined as death, missing data,

d by SF-36 in patients randomized to medical therapy and

des D, Davies M, Koyama H, et al. Effect of lung-volume-

ed 2000;343:239–45; with permission.)


treatment complications, or consistent decrease in at

least two domains of the CRQ. Although limited by a

small sample size (n = 55) and only 1-year follow-up,

this study did take into account dead and missing

patients, which are censored from data analysis in

most other studies [11].

National Emphysema Treatment Trial

The NETT is the first published multi-institutional

randomized trial on LVRS [12]. This trial has several

strengths over previously reported trials. The first is

the aspect of randomization after a period of formally

prescribed pulmonary rehabilitation, which provides

a common baseline formedically and surgically treated

patients and eliminates rehabilitation as a confound-

ing outcome variable. The second is its conduct as a

multi-institutional trial to minimize the outcomes that

may be specific or unique to a single center and less

applicable to practice across a broad spectrum of

academic or community centers. The third advantage

of the NETT was its size, with 1218 patients random-

ized, over an order of magnitude larger than any of

the other randomized studies of LVRS. Fourth, the

NETT used disease-specific and preference-based

instruments for measurement of HRQOL for a thor-

ough examination of the impact of LVRS in symp-

toms and overall QOL. Fifth, the NETT chose

outcomes at 2 years to examine durability of benefits

achieved by LVRS and did not allow crossover in the

study. Finally, similar to the Toronto study by Gold-

stein et al [11], the NETT included all patients in its

analysis, including patients who had died or were

missing data points, to avoid any skewing of out-

comes by follow-up or survivorship bias.

The NETT evaluated the symptom of dyspnea via

the UCSD Shortness of Breath Questionnaire, exam-

ined disease-specific HRQOL via the SGRQ, and

evaluated general QOL via the preference-based

QWB. Dyspnea was significantly improved in surgi-

cally randomized patients at 6, 12, and 24 months

compared with baseline and compared with progres-

sive worsening of symptoms in the medically ran-

domized patients [12]. With a threshold of 8 units of

improvement in SGRQ defined as significant, the

overall surgical cohort was much more likely to see

a significant improvement in SGRQ than medically

randomized patients (33% versus 9%). Upper lobe

emphysema versus non–upper lobe emphysema and

high exercise capacity versus low exercise capacity

were found to be important preoperative variables

predicting differential outcomes between medically

treated patients and patients undergoing LVRS. Of

the four subgroups identified in the NETT, three had

an improved opportunity for substantial benefit in the

SGRQ. These included all upper lobe–predominant

emphysema patients and patients with non–upper

lobe emphysema but low baseline exercise capacity

after a course of pulmonary rehabilitation. When

high-risk patients were excluded from the analysis

[28], the QWB was statistically improved in surgi-

cally treated patients compared with medical patients

at 6, 12, and 24 months [12].

The results from the NETT have provided rein-

forcement and validation of the data provided in

previous case-control or small randomized series

despite a conservative statistical analysis. Although

a randomized study, the NETT analysis compared

patients with their baseline, similar to the case control

series, to provide data regarding the changes to be

anticipated after LVRS. When surgically treated

patients were compared with the progressive decline

in function of medically treated patients, however,

these differences between groups seem even more

profound. A companion study about the cost-effec-

tiveness of LVRS also was performed alongside the

clinical NETT trial [29]. This study was able to take

advantage of the preference-based utility score,

QWB, to assess the cost-effectiveness ratio for LVRS

compared with medical therapy. These data are pro-

vided in another article in this issue.

Summary

The common physiologic and functional variables

that quantify limitation in emphysema patients have

been the most common outcomes measured after

LVRS. Spirometric values and exercise capacity are

merely surrogates, however, for their impact on

symptoms and QOL in patients with severe emphy-

sema. Because LVRS has been developed as a surgery

to palliate disabling symptoms of emphysema, many

studies now have included HRQOL outcomes along

with the commonly measured physiologic and func-

tional outcomes. Some studies have centered on the

QOL as the primary outcome instead of physiologic

variables. Many symptom scales and disease-specific

and general instruments of HRQOL have been used

for evaluating emphysema patients before and after

LVRS. Case-control studies and randomized studies

have shown a consistent improvement in symptoms

related to emphysema and general QOL. These studies

validate the use of LVRS as a palliative therapy for se-

lected patients with emphysema. The NETT suggests

that this benefit is applicable primarily to patients

with an upper lobe–predominant pattern of emphy-

sema or patients with low exercise capacity. Valida-


tion or refinement of these criteria depends on the

continued contributions of the many investigators

performing LVRS.

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Quality of life after lung transplantation

Cliff K. Choong, MBBS, FRACS, Bryan F. Meyers, MD*

Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, Suite 3108,

Queeny Tower, One Barnes–Jewish Hospital Plaza, St. Louis, MO 63110, USA

Lung transplantation is now an accepted form of lung transplantation. Survival alone is not a compre-

treatment for many end-stage lung diseases. After the

report of the first clinically successful lung transplan-

tation in 1983, the number of lung transplantations

and lung transplant centers increased substantially.

Between 1985 and 2001, 14,586 lung transplanta-

tions had been performed and registered with the

International Society of Heart and Lung Trans-

plantation. Numerous studies have reported the im-

provements in pulmonary function and exercise

performance after lung transplantation. The survival

of lung transplant recipients also has improved as a

result of improved patient selection, perioperative

care, surgical techniques, and immunosuppression

regimens. Although some studies also have shown a

survival benefit after lung transplantation for patients

with specific diagnoses, the survival benefit of trans-

plant in many diseases remains debatable [1].

Importance of quality-of-life measurements in

lung transplantation

Traditionally the outcome of lung transplantation

has been measured by graft function and patient

survival. When lung transplantation first became

feasible, the criteria for listing a patient for transplant

included the stipulation that life expectancy be less

than 1 year in the absence of the transplant. As

survival expectations and organ waiting times have

increased, so too have the life expectancies of pa-

tients referred for transplant. Quality-of-life (QOL)

measurement now is increasingly recognized as an

important tool of health care assessment and is

especially appropriate for evaluating the effects of


doi:10.1016/S1547-4127(04)00025-8


E-mail address: [email protected] (B.F. Meyers).

hensive way to summarize the existence of survivors

of lung transplantation or that of patients with chronic

lung disease managed without transplantation. Some

transplant recipients experience dramatic relief of

symptoms and a clear prolongation of life, whereas

other recipients may experience posttransplant com-

plications, such as bronchiolitis obliterans syndrome

(BOS), and remain in a disabling state of disease. The

pretransplant existence may be of such poor quality

that many potential recipients would accept any risks

for an opportunity at improved health and function,

even if it meant shortening their life to do so. A

careful evaluation in the improvement in QOL before

and after lung transplantation is important and forms

a necessary outcome measure to be viewed alongside

statistics for overall survival and graft function.

QOL studies also allow the direct comparison of

lung transplantation with other specific treatments for

end-stage lung diseases. These therapies include

prostaglandin infusion pumps for primary pulmonary

hypertension or lung volume reduction surgery for

severe emphysema. It is difficult to compare distinctly

different therapies based on duration of survival alone

when one therapy carries a higher early mortality risk

in exchange for a chance at greatly improved func-

tional status and improved longevity among the

survivors. This information is important and useful

as a resource for potential recipients considering lung

transplantation and for physicians considering referral

of their patients for lung transplantation.

Finally, QOL assessment facilitates the measure-

ment of efficiency of medical and surgical therapies.

The surgical treatment of end-stage lung disease with

lung transplantation and subsequent postoperative

management are expensive. QOL measurement

allows for the estimation of utility and allows valua-

tion and comparison of competing therapeutic options

s reserved.

Box 2. Quality-adjusted life-years

Quality-adjusted life-years (QALY) =health utility score � survival or lifeexpectancy in years.

Examples

Medical group before transplantation

Health utility score: 0.31Life expectancy: 2.7 years

C.K. Choong, B.F. Meyers / Thorac Surg Clin 14 (2004) 385–407386

in cost-utility analyses. The combination of duration

of life and QOL after lung transplantation must be

quantified to justify the high costs of transplantation

in the current era of cost containment in medical

expenditures. Quantifying QOL after lung transplan-

tation and comparing it with the QOL after other

medical therapies allows calculation and comparison

of quality-adjusted life expectancy and makes possi-

ble the economic evaluation of these disparate treat-

ments. Sensitivity analyses of the resulting cost-utility

estimates would point practitioners to the problem

areas that act as barriers to improved efficiency.
QALY = 0.31 � 2.7 = 0.84
Bilateral lung transplant recipient group

Health utility score: 0.82Life expectancy: 5 years

General strategies in assessing quality of life for

lung transplant candidates and recipients

A wide variety of instruments and indices have

been used in QOL studies performed in lung trans-

Box 1. Classification of quality-of-lifeinstruments

Global

Look at overall life satisfaction

Generic

Allow assessment of basic valuesthat are relevant for everyone’shealth status

Allow assessment to be performedacross all types of patientpopulations regardless of underlyingdiagnosis or treatment regimen

Allow for comparisons between oramong disparate diseases

Lack focus on disease-specific issues,such as a dyspnea index

Limited sensitivity to changes indisease condition

Disease specific

Limited to a specific patientpopulation with that particulardisease condition

Provide better sensitivity to diseasechanges

QALY = 0.82 � 5 = 4.1

QALY gained of bilateral lung recipientgroup over medical group= 4.1� 0.84=3.3 life-years gained.

plantation [2–33]. In general, they can be classified

as global, generic, or disease specific (Box 1). Global

instruments assess the overall well-being of the

patient, whereas generic instruments evaluate one

or more areas of QOL in such a way that is applica-

ble across a wide variety of disease diagnoses and

population groups. Unidimensional generic question-

naires focus on a single area or domain, such as

physical functioning, whereas multidimensional ques-

tionnaires evaluate several domains, such as psycho-

logical, social, and physical areas. Disease-specific

questionnaires are used for particular conditions, such

as the dyspnea index for patients with lung diseases,

to provide better sensitivity to changes caused by

therapy or passage of time. In addition to the generic

instruments, some studies have applied a utility

estimation generic tool, such as the European Quality

of Life tools (EuroQol) EQ5D, Quality of Well-Being

(QWB) scale, Standard Gamble, and Time Trade Off

to assess QOL [4,9,12,33]. These instruments allow a

utility value, usually a value in the range of 0 (worst

health) to 1 (best health), to be attached to the health-

related QOL evaluation. The utility value allows

direct measurement of QOL as an outcome and

enables adjustment of survival times to produce

quality-adjusted survival (Box 2).

C.K. Choong, B.F. Meyers / Thorac Surg Clin 14 (2004) 385–407 387

Quality-of-life instruments used in lung

transplantation studies

Table 1 provides a brief description of the various

QOL instruments. Most studies have used a multi-

dimensional generic instrument, such as the Notting-

ham Health Profile (NHP), the EuroQol, the Medical

Outcome Study 36-Item Short Form (MOS-SF36),

the QWB, and the Quality of Life Index (QLI)

to evaluate the QOL in candidates and recipients

(Table 2) [2–4,6,9,10]. Most of these instruments

consist of simple, self-administered questionnaires

and are chosen for simplicity, the ease in application

and analyses, and the cost savings that result from

self-administered questionnaires. These instruments

have the advantage of being validated across a wide

variety of diseases and patient populations. Most

of the published studies in the lung transplant litera-

ture have combined a multidimensional generic in-

strument with a single-dimension instrument such,

as the State-Trait Anxiety Inventory (STAI) or the

Zung Self-Rating Depression Scale (Z-SDS) [15,17].

Studies from the United Kingdom and the Netherlands

frequently have used either the Nottingham Health

Profile or the EuroQoL (see Table 2) [34–40]. Studies

from Canada and United States typically have used

instruments that originated from North America, such

as the MOS-SF36 [5,21,24,31,41,42].

The EuroQol, Standard Gamble, and Time Trade

Off are generic instruments or techniques that provide

a utility estimation tool [4,12,33]. The EuroQol

EQ5D is a simple generic instrument that evaluates

five dimensions of QOL (see Table 1). In each

dimension, a respondent can indicate one of three

categories: no problem, moderate problem, or severe

problems. Combinations of these categories result in

243 permutations of health states. A regression equa-

tion defines a utility value for these health states. The

possible health utility value ranges from �0.59 (se-

vere problems in all five dimensions) to 1 (no

problem in all dimensions) and is translated onto a

scale of 0 representing death to 1 representing best

possible health state. An individual’s EQ5D utility

value is based on the absence or presence of moderate

or severe problems in the five dimensions. The

EuroQol has the advantage of being a simple self-

administered questionnaire requiring about 1 minute

for completion with a track record of reliable use in

many studies. The Time Trade Off and Standard

Gamble techniques allow participants to evaluate

the impact of the disease or intervention on their

QOL. The values indicated by the study subjects

provide preference-weighted measures of utility esti-

mation. A scenario reflecting the health state of

interest is developed, then utility weights are derived

from the individual subject’s evaluation responses.

Such utility estimation tools were used in several of

the reviewed studies [36,43,44].

The strategy of any study is based on the goal of

the study and the availability of patients for study.

Some authors have employed cross-sectional studies

to evaluate QOL before and after transplantation.

These studies are easier to perform compared with

longitudinal evaluation. The advantages are that the

study can be performed relatively faster and cheaper

in that they can be applied to all patients awaiting

transplant or in the posttransplant period. Cross-

sectional studies are less valuable in drawing com-

parisons across time because the variability among

subjects is inherently greater than variability over

time in a given subject. The cross-sectional studies

tend to be observational and descriptive without any

specific hypothesis testing involved. Longitudinal

studies are more useful because they account for

intersubject variability with repeated measures of

the same subjects. These studies take longer to

complete, require a larger population of patients,

and are generally more expensive to execute.

Descriptive studies

Cross-sectional studies

Busschbach et al [36] evaluated the feasibility of

applying QOL instruments on lung transplant patients

before and after transplantation. Three patients each

were studied before and after bilateral lung transplan-

tation, all of whom had cystic fibrosis. The authors

reported that the methodology was feasible, and the

preliminary results suggested that the improvement

in QOL after bilateral lung transplantation was com-

parable to that seen after heart transplantation. Cohen

et al [45] assessed the degree to which pretransplant

psychological measures were associated with physi-

cal health, QOL, and overall adjustment after trans-

plantation. The study compared 17 pretransplant

candidates with 60 recipients and found associations

between QOL and adjustment in recipients. Lanuza

et al [46] reported on the QOL, symptom experiences,

and work status of single-lung and bilateral lung

transplant recipients. There was no pretransplant

comparative group in this observational descriptive

study. The 48 respondents represented a response

rate of 87% and were 1.5 F 0.7 years posttransplant.

Approximately 90% of the respondents were very

satisfied with their QOL. No associations were found

Table 1

Quality-of-life instruments used in lung transplantation studies

Name of instrument Type No. questions Domains assessed

Nottingham Health

Profile (NHP) [2]

Generic Part I

38 yes/no items

Part II

7 yes/no items

Part I and II take only several

minutes to complete

Part I evaluates 6 specific domains:

1. Physical mobility (8 items)

2. Pain (8 items)

3. Energy (3 items)

4. Sleep (5 items)

5. Social isolation (5 items)

6. Emotional reaction (9 items)

Part II evaluates 7 areas of task performance

most affected by health

1. Occupation

2. Ability to perform jobs around the home

3. Social life

4. Sexual life

5. Home life

6. Hobbies

7. Holidays

EuroQol – EQ5D [3,4] Generic Respondent indicates 1 of

3 categories for each domain:

No problem

Moderate problem

Severe problem

5 specific domains:

1. Mobility

2. Self-care

3. Usual activities

4. Pain and discomfort

5. Anxiety or depression

EuroQol – Visual

Analogue Scale [3,4]

Global Single question: scale of 0

(worst) to 100 (best possible

health)

Subjective overall assessment of health

by respondent

Overall QOL visual

analog scale

(OQOLVAS) [5]

Global Visual analogue scale of 0

(worst possible QOL) to 100

(best possible QOL)

Subjective global assessment of QOL

Medical Outcomes Study

Short Form–20

(MOS SF-20) [6,62]

Generic 20-item questionnaire assessing

6 dimensions. Each dimension

is scored as a summated rating

scale and adjusted so that

scores range from 0 (worst) to

100 (best)

Evaluates 6 dimensions of ‘‘core health

concepts’’

1. Limitations in physical activities because of

health problems

2. Limitations in social activities because of

physical or emotional problems

3. Limitations in usual role activities because

of physical health problems

4. Bodily pain

5. General mental health

6. General health perceptions

Medical Outcome Study

Short Form–36

(MOS SF-36) [6,62]

Generic 36-item questionnaire Assesses 8 health concepts

1. Limitations in physical activities

because of health problems

2. Limitations in social activities because of

physical or emotional problems


of physical health problems

4. Bodily pain

5. General mental health


of emotional problems

7. Energy and fatigue (vitality)

8. General health perceptions



Table 1 (continued)


General Health/QOL

Rating Scale

(GHQOLRS) [7]

Generic 5-item questionnaire using

6-point scale

Assesses subject’s overall satisfaction in the

following areas

1. QOL

2. Current health

3. Psychological/emotional strength

4. Physical strength

5. Satisfaction with the outcome of treatment

General health

questionnaire

(GHQ) [8]

Generic 60-item questionnaire Was developed to help primary care physicians

screen for nonpsychotic psychiatric disorders

and consists of 4 subscales

1. Somatic symptom

2. Anxiety and insomnia

3. Social dysfuction

4. Depression

Quality of Well-Being

scale (QWB) [9]

Generic

preference

weighted

Has 3 scales of function;

each step on these

scale has its own associated

preference weight

Also has 23 symptom/problem

complexes for the subject to

indicate the presence or

absence of each complex

on a given day

Measures 3 aspects of function

1. Mobility

2. Physical activity

3. Social activity

In addition, each patient is classified according

to the symptom or problems that bothered him

or her most. Observed function and symptomatic

complaints are then weighted by preference and

integrated in a manner that places the individual

on a continuum between death (0) and optimal

function (1) for any point in time. Provides

a utility-based outcome measure with a score

on a continuum ranging from 0 (dead) to 1

(optimal function)

Quality of Life

Index (QLI) [10]

Generic 32-item questionnaire and

subject respond to each item

on a 6-point Likert-type scale

ranging from ‘‘very satisfied’’

to ‘‘very dissatisfied’’

The instruments consists of 2 sections: one

measures satisfaction with various domains of

life, and the other measures the importance of

the domain to the subject. The satisfaction and

importance sections have 32 items that assess

the following areas: health care, physical

health and functioning, marriage, family,

friends, stress, standard of living, occupation,

education, leisure, future retirement, peace of

mind, personal faith, life goals, personal

appearance, self-acceptance, general

happiness, and general satisfaction

Index of Well

Being (IWB) [11]

Standard Gamble

(SG) [33]

Generic

Generic

preference

weighted

Requires an interview that

follows a structured

questionnaire. Interview

averages about 75 min

Interview is conducted and

requires 15 – 30 min.

Subject is offered 2 alternatives.

Alternative 1 is a treatment

with 2 possible outcomes:

either the patient returns to

normal health and lives for

an additional t years

(probability P), or the

patient dies immediately

Respondents are asked to describe and assess

their experience in 15 separate domains of life

and to respond to more general measures

regarding their lives as a whole

The interview is to assist patient in assigning

a utility score in the range of 0 (death) to 1

(perfect health). Patients are asked to choose

between living with the disease or having a

risky operation that could result in either

complete cure or immediate death. The main

principle is that patients are willing to accept

a higher risk of death if their health state is

worse than if their health is relatively good.

The amount of risk the patient is willing



Table 1 (continued)


(probability 1-P). Alternative 2

has the certain outcome of

chronic state i for t years.

Probability P is varied

until the respondent is

indifferent between 2

alternatives, at which point

the required preference

value for state i is P

to take reveals information about the QOL of

the health states

Time Trade-Off

(TTO) [12]

Generic

preference

weighted

2 alternatives are offered.

Alternative 1 is state i for time

t followed by death; alternative

2 is full (or normal) health for

time x. Time is varied until the

respondent is indifferent

between 2 alternatives, at

which point the required

preference value for state

i is given by hi = x/t.

The technique was derived from Standard

Gamble that avoids the difficult risk factor.

Patients are asked to indicate the maximal

number of years they are willing to give up to

avoid a poor state of health: ‘‘. . ..if there was

a medicine that could change your present

health state, but it would decrease your life by

10 years, would you take that medicine. . ..?’’

Patients in extremely poor health state tend

to accept a substantial decrease in their life span.

The number of years of life that patients are

willing to give up gives an indication of the

quality of life in that particular health state

Sickness Impact

Profile (SIP) [13]

Generic 136-item questionnaire;

it can be administered by

an interviewer in

20–30 min or can be

self-administered

SIP scores are reported for the total tool, for

physical and psychological dimensions, and

for 12 functional categories

1. Sleep and rest

2. Emotion

3. Body care

4. Home management

5. Mobility

6. Social interaction

7. Ambulation

8. Alertness

9. Communication

10. Recreation

11. Eating

12. Work

Hospital Anxiety and

Depression Scale

(HADS) [14]

Generic 14-item questionnaire Assessment of depression and anxiety in

physically ill patients

State-Trait Anxiety

Inventory (STAI) [15]

Domain

specific

20-item questionnaire Anxiety

Beck Depression

Inventory (BDI) [16]

Domain

specific

21-item self-report depression

inventory

Measurement of patient depressive symptoms

Zung Self-rating

Depression Scale

(Z-SDS) [17]

Symptom Checklist-90

(SCL-90) [18]

Domain

specific

Generic

20-item questionnaire

Items are rated on a 5-point

scale

Assesses depressive symptoms

Assesses various types of symptoms including

anxiety, depression and anger-hostility

Brief Symptom

Inventory (BSI) [19]

Generic 53-item multidimensional,

psychological symptom

inventory. Each item has a

5-point scale ranging from

0 to 4

Includes 3 global indexes

1. Global Severity Index

2. Positive Symptom Total

3. Positive Symptom Distress Index



Table 1 (continued)


and 9 primary symptom dimensions

1. Somatization

2. Obsessive-compulsive

3. Interpersonal sensitivity

4. Depression

5. Anxiety

6. Hostility

7. Phobic anxiety

8. Paranoid ideation

9. Psychosis

Symptom Frequency/

Symptom Distress Scale

(SFSD) [20]

Generic A list of 27 symptoms Assesses the frequency of symptoms and the

distress caused by these symptoms

Transplant Symptom

Frequency and Distress

Scale (TSFQ) [21]

Generic 29-item questionnaire Assesses 29 symptoms commonly experienced

secondary to chronic illness and

immunosuppression

Karnofsky Performance

Status (KPS) [22]

Generic A list of 11 states of health

and for each state, an index

may be assigned ranging

from 0 (death) to 100

(health state

without problems)

Measure of patient functioning in day-to-day

activity. Evaluates intensity of treatment and

ability to take care of oneself

UCLA Loneliness

Scale–Revised [23]

Generic 20-item questionnaire Assesses the quality of relationship with

others. It consists of 2 subscales — loneliness

and companionship—and has a total

loneliness score

Difficulty with Adherence

(DWA) [24]

Generic 8-item questionnaire with a

4-point rating scale

Patients are asked to rate the degree of difficulty

in following posttransplant medical regimes in

the areas of

1. Taking medications regularly

2. Coming in for clinic regularly

3. Undergoing biopsies when necessary

4. Undergoing other invasive procedures

5. Abstaining from smoking

6. Abstaining from alcohol

7. Staying in shape

8. Keeping weight down

Sleep Disturbance

(SD) [24]

Generic 7-item questionnaire Measures the amount of sleep disturbance

experienced by patients during the previous 2 wk

Illness Intrusive

Rating Scale

(IIRS) [25]

Generic 13-item questionnaire Assesses patients’ perceptions of the degree

to which their transplant and the associated

posttransplant medical regimen interferes with

13 life domains, including work, active

recreation, passive recreation, financial situation,

relationship with spouse, sex life, family relations,

other social relations, self-expression and

self-improvement, religious expression, and

community and civic involvement

Body Cathexis

Scale (BC) [26]

Generic 46-item questionnaire Assesses the degree of a person’s satisfaction

with various parts or processes of the body

Derogatis Sexual

Functioning Inventory

(DSFI) [27]

Generic Self-report test of

sexual functioning

Assesses and quantifies nature of current sexual

functioning and comprises 10 subtests, including

information, experience, drive, attitude, psychologi-

cal symptoms, affects, gender role definition,

fantasy, body image, and sexual satisfaction



Table 1 (continued)


Rosenberg Self-Esteem

Scale (RSES) [28]

Generic Composed of 10 items (5 are

positive and 5 negative).

Participants indicate the extent

to which they agree with each

statement on a scale of 1,

‘‘strongly agree,’’ to 4,

‘‘strongly disagree.’’ Higher

scores indicate lower

self-esteem

Measure of general self-esteem

Basic Personality

Inventory (BPI) [29]

Generic 240-item true/false

self-report inventory

Assesses 12 domains of psychopathology

Campbell Sense of

Well-Being Scale

(CSWBS) [30]

Generic 8 7-point semantic differential

scales of polarized adjectives

Assesses overall life quality

Perceived Social Support

Related to Transplantation

(PSS) [31]

Disease

specific

10-item questionnaire on a

4-point Likert-type

response scale

Assesses the extent to which individuals feel

supported by the people in their lives (ie, family,

friends, transplant team members)

Pulmonary-specific QOL

Scale (PQLS) [32]

Disease

specific

25-item questionnaire on a

5-point Likert-type

response scale

Assesses the effects of pulmonary disease on

7 areas

1. Physical functioning

2. Psychological/emotional status

3. Functional status/activities of daily living

4. Social activities

5. Intimacy/relationship/sexuality

6. Occupational functioning

7. View of self

Abbreviation: QOL, quality of life.


between QOL and variables such as diagnosis, gen-

der, and transplant type (ie, single versus bilateral).

Stilley et al [47] examined depression, anxiety,

anger-hostility, and overall quality of life in 36 lung

and 14 heart-lung transplant recipients. The mean

anxiety symptoms were elevated over normative

levels, and nearly half of the subjects showed clini-

cally significant distress in one or more areas. The

findings suggested that anxiety symptoms, relatively

common in patients with chronic lung disease, remain

relatively common after lung transplantation. The

pretransplant psychiatric history, educational level,

posttransplant caregiver support, and health concerns

were important independent predictors of the recipi-

ent psychological outcome. The study did not find

any significant differences between lung and heart-

lung recipients, but it lacked statistical power to

exclude such differences.

Anyanwu et al [40] used the EuroQol instru-

ment to compare 87 pretransplant candidates with

225 transplant recipients in four transplant units.

Health status of the pretransplant group was evaluated

over 3 months in two hospitals. There were 28 patients

listed for single-lung transplantation, 24 for bilateral

lung transplantation, and 34 for heart-lung transplan-

tation. Of the posttransplant respondents, 106 had

received single-lung transplants, 79 had received

bilateral lung transplants and 70 had received heart-

lung transplants. The analysis of the EuroQol ques-

tionnaires was divided into four epochs: 0 to 6 months,

7 to 18 months, 19 to 36 months, and more than

36 months, with 41, 43, 61, and 110 patients in each

epoch. QOL in all five EuroQol domains was better in

the transplanted group than in the waiting list group.

Sixty-one percent Of the wait-list patients, 61% ex-

perienced extreme problems in one or more of the five

EuroQol domains. One year after transplantation, 20%

of the single-lung transplant recipients and none of the

bilateral or heart-lung transplant recipients reported

extreme problems in one or more of the five domains.

The mean utility value of the waiting list group was

0.31 versus 0.61 for single-lung transplant, 0.82 for

bilateral transplant, and 0.87 for heart-lung transplant

recipients 3 years posttransplantation.

The utility values reported in the Anyanwu study

[40] were in agreement with other earlier published

reports [34,36,37,48,49]. The study explored other

utility measures by recording self-rated health status

using the visual analogue scale, which ranged from

0 (worst health) to 100 (best health). The pretrans-

Table 2

Quality-of-life studies in lung transplantation

Author journal,

year, study country Type of study Instruments

Type of

transplant

(no. patients)

Disease diagnosis

(no. of patients)

No. candidate

patients

No. recipient

patients Overall results

O’Brien et al [35],

J Epidemiol

Community Health,

1988, UK

Prospective

longitudinal

NHP HLT Not mentioned 48 28 at 3 mo

24 at 6 mo

13 at 12 mo

Recipients reported

significant improvement

in QOL at 3 mo

after transplant

Improvements sustained

at 6 and 12 mo

after transplant

NHP was found to be

easy to use as an

interview or postal

follow-up

Caine et al [34]

Transplant Proc,

1991, UK

Prospective

longitudinal

NHP HLT CF 54 13 out of 24 at

interval of 3–6 mo

after transplant

Recipients who

responded reported

marked improvement in

QOL after transplantation

Busschbach et al

[36], Chest, 1994,

Netherlands

Manzetti et al [56],

Heart Lung

Transplant,

1994, US

Cross-sectional

pilot study

Comparative

(comparison of

education versus

education plus

exercise on the

effects of QOL)

SG

TTO

KPS

EuroQol VAS

NHP

QWB

QLI

SFSD

BLT

NA

CF

Emphysema (1);

bronchiectasis (2);

CF (2); pulmonary

fibrosis (2);

sarcoidosis (2)

3

9 total; education

group (4);

education plus exercise

group (5)

3 (12, 14, and

16 mo after

transplant)

NA

Feasible to measure QOL

with SG, TTO, and

EuroQol-VAS

Patients do not experience

high levels of stress when

interviewer chooses

appropriate interviewing

settings

Lung transplantation

results in improvement

in QOL similar to that

after heart transplantation

QWB scores and 6-min

walk distance improved

over time in both groups

Similar improvement in

QOL and symptom

experiences between


C.K.Choong,B.F.Meyers

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Table 2 (continued)

Author journal,


Type of

transplant

(no. patients)

Disease diagnosis

(no. of patients)

No. candidate

patients

No. recipient


2 groups

Education plus exercise

conferred no benefit

beyond those achieved by

education alone

Gross et al [41];

Chest, 1995 US

Ramsey et al [44],

J Heart Lung

Transplant,

1995, US

Cross-sectional

longitudinal study

(5 before and after

transplant and

18 after transplant

at 2 time period)

Cross-sectional

MOS 20

KPS

IWB

SIP

SG

SLT (34)

BLT (7)

HLT (13)

SLT

BLT

COPD

A1AD

PPH

Others

Emphysema

CF

A1AD

IPF

PPH

Others

44

21

54 total

(16 at 6–18 mo

17 at 19–34 mo

21 at >35 mo

after transplant)

18 at 2 time points

18 months apart

23

Dramatic improvements

in health status and QOL

occurred after successful

lung transplant and remain

stable over time

Recipients reported

significantly higher level

of happiness, satisfaction

with life and health than

candidates

Recipients reported better

function on Karnofsky

Index and in every MOS

20 dimension except pain


in QOL between recipients

from 3 different time

periods suggesting that

the improvement remained

stable with time BOS

adversely affected quality

of life

Overall QOL improved

significantly after

transplantation

Most functional disabilities

improve after transplant

Significant improvement

in utility scores

in recipients

QOL gains may


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394

not be equal for all

pretransplant conditions

Squier et al [50],

Am J Respir

Crit Care Med,

1995, US

Longitudinal

(evaluation of

whether baseline

QOL values

were predictive

of survival)

QWB

BDI

Not

mentioned

CF

COPD

Restrictive PVD

74 49 Pretransplant QWB

was the most significant

predictor of survival

Depression scores

were not predictive

of survival

Littlefield et al

[24], Gen Hosp

Psychiatry,

1996, Canada

Limbos et al

[42], Chest, 1997,

Canada and US

Comparison of QOL

between lung, heart,

and liver recipients

Cross-sectional

Female

patients only

MOS SF-36

MHI

STAI

UCLALSR

DWA

SD

IIRS

MOS SF-36

RSES

HADS

DSFI

BC

2 open-ended

questions

Lung, heart,

and liver

Not

mentioned

Not mentioned

Emphysema

CF

PPH

IPF

Congenital bronchiectasis

NA

7

263 recipients

(representing

a response

rate of 83%)

59 lung

55 heart

149 liver

Median time since

transplantation

was 26 mo

34 (representing

a response rate

of 63%)

Lung transplant

recipients reported

better functioning in

the domains of

physical, psychological

and social functioning

and less difficulty

complying with

medical regimens

than did heart and

liver recipients

Lung patients’ level

of functioning was

equivalent to or better

than published norms

for SF-36

Recipients reported

a higher level of

physical and

general health

No significant

difference in anxiety

Body satisfaction and

sexual functioning

were negatively

correlated with age

and depression

Body satisfaction

remained a concern

for 42% of recipients

No significant



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395

Table 2 (continued)

Author journal,


Type of

transplant

(no. patients)

Disease diagnosis

(no. of patients)

No. candidate

patients

No. recipient


difference in sexual

functioning between

the groups and

negatively associated

with anxiety

Sexual functioning in

both groups was

lower compared with

published normal values

Lanuaza et al

[46] Circulation,

1997, US

Cross-sectional QLI SLT

BLT

Not mentioned NA 48 (representing

a response rate

of 85.7%)

90% of respondents

were generally

satisfied with their QOL

TenVergert et al

[37], Chest,

1998, Netherlands

Longitudinal NHP

STAI

Z-SDS

Karnofsky

IWB

ADL

Dyspneic

SLT (1)

BLT (23)

Emphysema

(13)

CF (7)

Bronchiectasis (2)

PF (1)

PH (1)

37 24 Recipients reported


in mobility, energy,

sleep, level of

dependency on others

Recipients experienced

less dyspnea

question Improvements after

transplant were sustained

over 15 mo BOS adversely

affected quality of life

McNaughton

et al [21],

Clin Transpl,

1998, US

Cohen et al [45],

Chest, 1998,

Canada and US

Longitudinal

Cross-sectional

longitudinal

MOS SF-36

TSFQ

BPI

BDI

STAI

SLT (14)

BLT (3)

Not

mentioned

Emphysema

A1AD

COPD

PF

Not mentioned

17

17 QOL

evaluation;

107 psychological

17

32

Recipients reported


in general health,

physical functioning,

vitality, and

social functioning

Recipients reported

a marked decrease

in breathing difficulties


significantly better

QOL and mental


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396

MHI

MHLC

assessment health status

Anxiety levels

decreased significantly

after transplantation

Stilley et al [47],

Psychosomatics,

1999, US

Cross sectional SCL-90

CSWBS

Lung (36)

HLT (14)

Not specified NA 50 total

36 Lung recipients

14 HLT

Recipients’ mean

anxiety symptoms

were elevated over

normative levels

Nearly half of the

subjects showed

clinical significant

distress in �1 of

the 3 symptom areas

Van den Berg et al

[38] Am J

Resp Crit Care

Med, 2000,

Netherlands

Lanuza et al [7],

Chest, 2000 US

Cross-sectional

longitudinal

Longitudinal

NHP

STAI

Z-SRD

IWB

SIP

BSI

GHQOLRS

Open-ended

questions

SLT (22)

BLT (93)

HLT (1)

SLT (2)

BLT (8)

6 groups

COPD (5)

CF (4)

IPF (1)

Cross-sectional (64)

longitudinal (22)

10

Cross-sectional (52)

Longitudinal (22)

10

BOS resulted in

significant decrease

in energy and

physical mobility

Anxiety levels

increased significantly

after onset of BOS

BOS was associated

with increased

depressive symptoms

in cross-sectional

evaluation

Significant improvement

in overall function


Perceived improvement

in physical function


was accompanied by

increased satisfaction

with physical strength,

current health, and QOL

90% were very satisfied

with transplant decision

Limbos et al [5],

Chest, 2000,

Cross-sectional MOS SF-36

OQOLVAS

Not

mentioned

COPD

CF

36 73 Recipients had

significantly better scores



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Table 2 (continued)

Author journal,


Type of

transplant

(no. patients)

Disease diagnosis

(no. of patients)

No. candidate

patients

No. recipient


Canada BSI

DSFI

HADS

RSES

BC

PPH

IPF

Others

in the measures of MOS

SF-36 total, physical

health, role limitations due

to physical health, general

health, vitality, and social

functioning subscale

MOS SF-36 emotional

health and role limitations

were similar in candidate

and recipient groups

and lower than

published norms

Significant proportion of

patients in both groups

had borderline or clinical

levels of anxiety

The RSES and DSFI

mean scores were lower

than published norms in

both groups

TenVergert et al

[39], Psychol

Rep, 2001,

Netherlands

Longitudinal

comparative

(QOL in patients

with emphysema

versus other

indications)

NHP

STAI

Z-SRDS

IWB

KPS

RSQ

Not

mentioned

Emphysema (23)

Others (19)

(CF 8, PH 4, PF 2,

bronchiectasis 5)

Emphysema (23)

Other (19)

4, 7, 13, and

25 months after

transplantation

No significant

differences in

QOL between

emphysema and other

indications either before

or after transplantation

Before transplantation,

both groups reported

major restrictions on the

dimension of energy and

mobility of NHP, low

experienced well-being,

depressive symptoms, and

high dyspnea

About 4 mo after

transplantation,


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398

most health-related

QOL measures

improved significantly

The improvements

noted after transplant

maintained in the

following 21 mo

Anyanwu et al [40],

Thorax, 2001, UK

Cross sectional

(before and after

transplant)

Comparative

(SLT versus BLT

& HLT)

EuroQol SLT

BLT

HLT

Not mentioned 87 (28 listed for

SLT, 24 for BLT,

34 for HLT)

225 (106 had

received SLT,

79 BLT

and 70 HLT)


significantly better QOL

BLT and HLT recipient

groups reported better

QOL than SLT

recipient group

Napolitano et al [31],

Chest, 2002, US

Comparative

(comparison

of telephone-based

psychosocial

intervention versus

none on the

effects of QOL

in candidates)

MOS SF-36

GHQ

PQLS

PSS

PSRT

NA COPD (25)

CF (9)

PPH (10)

Others (27)

Intervention (36)

Control (35)

NA Intervention group

reported greater

general well-being,

better general QOL,

better disease-specific

QOL, and higher level

of social support than

the control group

Abbreviations: ADL, Activities of daily living; A1AD, a1 antitrypsin deficiency; BC, Body Cathexis Scale; BDI, Beck depression inventory; BLT, bilateral lung transplant; BOS,

bronchiolitis obliterans syndrome; BPI, Basic Personality Inventory; BSI, Brief Symptom Inventory; CF, cystic fibrosis; COPD, chronic obstructive pulmonary disease; CSWBS, Campbell

Sense of Well-Being Scale; DSFI, Derogatis Sexual Functioning Inventory; DWA, difficulties with adherence; GHQ, general health questionnaire; GHQOLRS, General Health/QOL Rating

Scale; HADS, Hospital anxiety and depression scale; HLT, Heart-lung transplant; IWB, Index of Well-Being; KPS, Karnofsky performance status; MHI, Mental Health Inventory; MHLC,

Multidimensional Health Locus of Control Scales; MOS, Medical Outcome study; NA, not applicable; NHP, Nottingham Health Profile; OQOLVAS, Overall quality of life visual analogue

scale; PF, pulmonary fibrosis; PH, pulmonary hypertension; PPH, primary pulmonary hypertension; PQLS, pulmonary-specific quality-of-life scale; PSRT, perceived stress related to

transplantation; PSS, perceived social support related to transplantation; PVR, pulmonary vascular disease; QLI, Quality of Life Index; QOL, quality of life; QWB, Quality of Well-being

scale; RSES, Rosenberg Self-Esteem Scale; RSQ, respiratory-specific questions; SCL-90, Symptom Checklist-90; SD, sleep disturbance; SFSD, Symptom Frequency/Symptom Distress

scale; SG, Standard Gamble; SIP, Sickness Impact profile; SLT, single lung transplant; SRS, Satisfaction rating scale; STAI, State-Trait Anxiety Inventory; TSFQ, Transplant symptom

frequency and distress scale; TTO, Time Trade-Off; UCLALSR, UCLA Loneliness Scale-Revised; VAS, Visual Analogue Scale; Z-SDS, Zung-Self-rating Depression Scale.


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plant group had a mean score of 35 F 19 (FSD),

whereas the posttransplant groups had mean scores of

60 F 19 for single-lung transplant, 77 F 18 for

bilateral lung transplant, and 79 F 19 for heart-lung

transplant recipients at 3 years. The limitations in the

study included the assumptions that the health status

of the pretransplant group was constant and the

changes of the response variable were a reflection

of individual variations in health status rather than

factors related to the preoperative diagnosis or dura-

tion on the waiting list. The study did not take into

consideration that ill patients are more likely to be

nonparticipants and these same patients would have a

poor QOL. There was an additional selection bias in

that the sickest patients and the patients who died

either on the waiting list or early after lung trans-

plantation were excluded from the evaluation.

Longitudinal studies

Some studies evaluated QOL in a longitudinal

fashion, comparing the QOL differences with time

progression in the same group of patients. These

studies are more powerful in detecting differences

over time between groups of patients because the

use of sequential measurements in the same patients

reduces the variance and enhances statistical power.

Two early studies from the United Kingdom evaluated

QOL in the same patients before and after heart-lung

transplantation. In a prospective study, O’Brien et al

[35] used the Nottingham Health Profile in 48 candi-

dates and followed the patients after heart-lung trans-

plantation. Posttransplant evaluation was performed

in 28 recipients at 3 months, with the numbers

declining to 24 at 6 months and 13 at 12 months.

The study found a significant improvement in the

QOL at 3, 6, and 12 months posttransplantation. Caine

et al [34] evaluated the QOL of 54 candidates with

cystic fibrosis. Twenty-four patients underwent heart-

lung transplantation, and 13 of the 24 completed the

questionnaires 3 to 6 months posttransplantation. A

marked improvement in QOL was found among the

respondents after transplantation. Similar observa-

tional work has been reported by Gross et al [41].

Squier et al [50] investigated the association

between quality of well-being and survival in lung

transplant candidates. Predictors of survival were

evaluated for 74 transplant candidates. Each patient

completed the QWB, a utility-based outcome mea-

sure that gives a score on a continuum ranging from 0

(dead) to 1 (optimal function), and a measure of

depressive symptoms (Beck Depression Inventory).

During the study, 24 patients died, including 13 of 49

transplant recipients and 11 of 25 of the transplanted

patients. The most significant predictor of survival

was the QWB score. The study concluded that health-

related QOL was an important predictor of survival

for patients with serious lung diseases.

TenVergert et al [37] conducted a longitudinal

study on 24 Dutch lung transplant candidates and

followed them up at several intervals after lung

transplantation. Various generic QOL instruments

were used as outlined in Table 2. Disease-specific

questionnaires on severity of dyspnea also were

evaluated. The study enrolled 37 transplant recipi-

ents, 10 patients died during the study, and 3 other

patients were unable to complete questionnaires be-

cause of poor health. Although the study has a small

sample size of 24 responding patients, it allowed an

accurate evaluation in change in the QOL in the same

group of patients over time. Transplant candidates

reported major restrictions on mobility and energy in

the NHP. Also reported were low levels of well-

being, frequent depressive symptoms, difficulty in

performing activities of daily living, and low ability

for self-care. Improvements were recorded in mobil-

ity, energy, sleep, freedom from dependency on

others, and dyspnea 4 months posttransplantation.

These improvements were maintained in the follow-

ing 15 months.

Cohen et al [45] examined the predictors of QOL

posttransplantation by evaluating archival data for

107 transplant candidates with pretransplant psy-

chological assessments and posttransplant physical

health status data. Pretransplant anxiety, depression,

and personality inventory scores were not associated

with posttransplant physical health. Of the 107 can-

didates, 32 later completed adjustment and QOL

questionnaires after their transplantation. Signifi-

cantly improved QOL and mental health status were

found in the 32 patients posttransplantation. In

13 patients with data before and after transplantation,

anxiety levels decreased significantly after the opera-

tion. Pretransplant anxiety and psychopathology were

associated strongly with posttransplant adjustment

and QOL. Patients with posttransplant sleep distur-

bances had poorer adjustment and QOL.

Sustained improvement in QOL after lung trans-

plantation was found in several other longitudinal

studies [35,37,40,51]. These findings suggest that the

improved QOL among living and responding recipi-

ents remains. It is widely acknowledged, however,

that these findings of sustained improvement during

the follow-up period posttransplantation may be due

to selection bias because stable and healthy patients

were most likely to participate. Similarly the small

sample sizes may have had insufficient power to


detect statistical differences, or the length of time

between data collection intervals was too short.

Comparative studies

Quality-of-life differences between single-lung versus

bilateral lung recipients

Anyanwu et al [40] found that single-lung trans-

plant recipients reported more problems in all five

domains compared with bilateral lung transplant

recipients and heart-lung transplant recipients. The

health profiles and utility scores were consistently

better in bilateral lung transplant and heart-lung

transplant groups compared wth the single-lung trans-

plant group. These results also correlated with the

self-rated visual analogue scale scores. Apart from

Anyanwu’s study, few other studies specifically com-

pared the QOL of single-lung versus bilateral lung

recipients. Some studies indirectly support these

findings of better QOL in bilateral lung transplant

recipients versus single-lung transplant recipients

[52,53]. Gartner et al [52] assessed the health utility

of 16 single-lung transplant recipients and 4 bilateral

lung transplant recipients using a generic instrument

and reported a mean utility score of 0.60. A higher

utility score of 0.8 was reported by van Enckevort

et al [53] from the Dutch lung transplantation pro-

gram, in which most recipients had received bilateral

lung transplants (43 of 57). Physiologic differences

between single-lung and bilateral lung transplants

may provide additional explanations for the differ-

ences in observed posttransplant QOL [54]. Single-

lung transplant recipients have less improvement in

forced vital capacity and forced expiratory volume in

1 second (FEV1). Most recipients of two lungs

achieve their predicted total lung capacity within

1 year; however, similar improvements do not occur

with single-lung transplant recipients. In addition, the

presence of native disease in the contralateral non-

transplanted lung can cause physiologic and patho-

logic changes. Bavaria et al [55] reported results in

comparison of single-lung versus bilateral lung trans-

plantation in patients with emphysema and found

superiority in the FEV1, 6-minute walk test, and other

clinical indices in recipients of bilateral lungs com-

pared with patients who received a single lung. The

authors suggested that bilateral lung transplantation

provided better symptomatic improvement than sin-

gle-lung transplantation in patients with emphysema.

These physiologic differences may account for much

of the difference in QOL between the two operations.

Pretransplant differences between patients may play a

role as well. In the report from the United Kingdom,

single-lung transplantations were reserved primarily

for selected cases of emphysema and pulmonary

fibrosis [40]. Patients undergoing single-lung trans-

plantation are often older emphysema patients,

whereas bilateral lung transplant recipients are youn-

ger patients with cystic fibrosis. Native disease and

age of the patient may contribute further to the

differences in the posttransplant QOL observed be-

tween single-lung transplant and bilateral lung trans-

plant recipients.

Quality of life with emphysema versus other

indications

TenVergert et al [39] evaluated health-related

QOL before and after lung transplantation in patients

with emphysema and compared the results with other

end-stage lung disease diagnostic groups. Twenty-

three emphysema patients and 19 patients with other

indications completed self-administered question-

naires before lung transplantation and at intervals

after transplantation between 1992 and 1999. The

mean age in the emphysema group was 49.3 years,

and in all others it was 33.4 years (range 20 to

50 years). Male patients composed approximately

61% in the emphysema group and 42% in the other

group. The questionnaire included the NHP, the

STAI, the Z-SDS, the Index of Well-Being, the self-

report Karnofsky Index, and four respiratory-specific

questions. No significant differences were found

between the two diagnostic groups on most dimen-

sions of health-related QOL before or after transplan-

tation. Before transplantation, both groups reported

major restrictions on the dimensions of energy and

mobility of the NHP, low levels of well-being, de-

pressive symptoms, and high levels of dyspnea. Four

months after transplantation, most health-related

QOL measures improved significantly in both groups,

and these improvements were maintained in the fol-

lowing 21 months.

Influence of exercise and education on quality of

life in lung transplant candidates

Manzetti et al [56] evaluated the impact of an

exercise program on QOL in patients awaiting lung

transplantation. This pilot study served as an initial

step toward evaluating outcomes of a health mainte-

nance program on exercise tolerance and QOL. Nine

lung transplant candidates were randomized to par-

ticipate in a 6-week health maintenance program


consisting of education alone or education plus exer-

cise. The subjects completed cardiopulmonary exer-

cise testing, a 6-minute walk test, the QWB, Quality

of Life Index, and Symptom Frequency/Symptom

Distress scale before and after completion of the

program. QWB scores and 6-minute walk distance

improved over time in both groups. The study did not

find differences between the two groups. Candidates

awaiting lung transplantation perceived an improved

quality of well-being and increased walk distance

after participation in a health maintenance program,

but the addition of exercise did not confer any

additional benefits beyond the benefits achieved

by education.

Impact of bronchiolitis obliterans on quality of life

Few studies have evaluated the effect of BOS on

QOL. Gross and Raghu [48] reported on five recipi-

ents who developed BOS and found decrements in

their health-related QOL particularly in the dimen-

sions of physical functioning, social functioning, and

bodily pain. In a longitudinal study by TenVergert

et al [37], 6 of the 24 patients developed BOS within

19 months posttransplantation. Physical functioning

was significantly lower in these 6 patients compared

with the remaining 18 patients without BOS. The

study found no differences in the areas of social and

psychological functioning between the two groups. In

a cross-sectional evaluation by Van den Berg et al

[38], the QOL of 64 recipients without BOS was

compared with 52 recipients with BOS. Patients

with BOS reported more restrictions of energy and

physical mobility as captured by the NHP. The

domains of pain, sleep, social interaction, and emo-

tional reactions were not affected. Patients with

BOS also reported more depressive symptoms and

anxiety after transplantation. The study also per-

formed a longitudinal analysis on 22 recipients who

completed QOL questionnaires before and after the

development of BOS. The findings were similar to

the findings of the cross-sectional evaluation except

that no change in depressive symptoms could be

found after the onset of BOS. The authors’ explana-

tion for the decreased energy and physical mobility

in recipients with BOS was that it was due to a

decrease in lung function.

Employment

It seems logical that the ability to pursue active

employment would be associated strongly with QOL

and utility. Various studies have evaluated the QOL

and employment status in lung transplantation candi-

dates and recipients [35–37,39,44–46]. O’Brien et al

[35] reported that health-related employment prob-

lems decreased from a prevalence of 77% pretrans-

plantation to 15% posttransplantation. Other studies

have agreed that a large percentage of candidates

awaiting lung transplantation were not employed,

although improvements in QOL posttransplantation

have not reliably resulted in an improvement in

employment status. Gross et al [41] found no signifi-

cant change in the employment status between the

candidates and the transplant recipients. In their

study, 24% of the transplant candidates and 16% of

the recipients were employed part-time or full-time.

In the Dutch study, 25% of the patients were working

at a median duration of 20 hours a week before

transplantation [37]. Of the transplant candidates,

60% reported inability to work for pay as a result

of lung disease. Nineteen months after transplanta-

tion, 33% of the patients had returned to work part-

time with a median duration of 18 hours a week.

None of the patients had returned to paid employment

full-time. Cohen et al [45] also found that despite

the reported improvement in QOL, functioning, and

satisfaction after lung transplantation, there was

little change in employment patterns posttransplanta-

tion. The 1997 United Network for Organ Sharing

(UNOS) Registry Report for Heart and Lung Trans-

plantation [57] stated that although most lung trans-

plant patients have no limitations that should exclude

them from working, approximately 40%, not includ-

ing patients who are retired, are not working. It seems

that improvements in QOL do not correlate with

improvement in employment status.

Economic evaluations and cost-effectiveness

Despite the importance placed on cost analysis in

the current climate of escalating health care costs, few

studies have evaluated the cost-effectiveness of lung

transplantation. Ramsey et al [43] performed a pilot

study in the United States comparing the costs and

outcomes of the first 25 patients who received lung

transplantation at the University of Washington with

24 patients who were on the lung transplant waiting

list. The study calculated inpatient and outpatient

charges from hospital billing services and home

health agencies. Quality-adjusted life-year calcula-

tions as shown in Box 2 earlier were incorporated

into the study. The quality adjustments were derived

from utility scores obtained through Standard Gamble

interviews and survival data from the International


Lung Registry and published studies on lung trans-

plant waiting lists. Transplantation charges were

found to average $164,989 (median $152,071). The

average monthly posttransplant charges were calcu-

lated to be $11,917 in year 1 and $4525 for subse-

quent years, whereas the pretransplant monthly costs

for recipients were $3395. The QOL utility scores

were 0.80 in recipients and 0.68 in pretransplant

candidates. The calculated life expectancy was sim-

ilar between the two groups: The recipient group was

estimated at 5.89 years, and the candidate group

was estimated at 5.32 years. The incremental cost

per quality-adjusted life-year gained for lung trans-

plant patients was calculated to be $176,817. The

study concluded that lung transplantation can im-

prove quality of life substantially, but it is an expen-

sive treatment. The high costs of postrecovery care

and lower than expected life gains in life were the

principal barriers to cost-effectiveness. One might

question the representativeness of the cost data,

given the fact that the data were obtained in the

earliest period of lung transplant experience for the

reporting center.

Reports from the Netherlands suggest that lung

transplantation extends life expectancy approximately

4.5 years, whereas Dutch programs for heart and liver

transplantation showed extensions of life expectancy

by 9 to 15 years [53,58,59]. The average costs per life-

year gained for lung, heart, and liver transplantation

were 76,120 Euros, 32,840 Euros, and 26,870 Euros.

The study concluded that lung transplantation was an

expensive surgical treatment modality, and the cost-

effectiveness was unfavorable compared with other

solid-organ transplant programs due to the associated

substantial morbidity and mortality and the smaller

gain in survival [53,60]. Quality adjustment of the

survival is important because patients with emphy-

sema, the most common indication for lung trans-

plantation, may continue to live for many years on the

waiting list. This durability on the wait-list may result

in a limited calculated survival benefit for these

patients [1].

Anyanwu et al [61] performed an economic eval-

uation of lung transplantation in the United Kingdom,

analyzing and comparing the cost-effectiveness of

single-lung transplant, bilateral lung transplant, and

heart-lung transplant. The study evaluated a 4-year

cohort of patients involving 1030 patients on the

waiting list: 260 single-lung transplant, 199 bilateral

lung transplant, and 218 heart-lung transplant recipi-

ents. The 4-year national survival data were extrapo-

lated to 15 years by means of parametric techniques.

The EuroQol utility scores (scale 0 to 1) for this study

were obtained from a cross-section of patients in a

parallel study evaluating QOL in lung transplantation

[40]. The mean expected survival during the 15-year

period was 2.7 years in the medical group, 4.7 years

in the single-lung transplant group, 5 years in the

bilateral lung transplant group, and 5.2 in the heart-

lung transplant group. The EuroQol utility score was

0.31 in the medical group, whereas the recipient

groups had a better utility score of greater than

0.6 (range 0.61 to 0.87) during the each of 4 separate

postoperative QOL evaluation. The resultant quality-

adjusted life expectancies were 0.8 for the medical

group, 3.0 for the single-lung transplant group, 4.1

for the bilateral lung transplant group, and 4.4 for the

heart-lung transplant group, resulting in quality-ad-

justed life-year gains of 2.1 for single-lung transplant,

2.4 for bilateral lung transplant, and 2.5 for heart-lung

transplant groups. The mean cost of medical treat-

ment only in US dollars, was estimated at $73,564.

Costs for single-lung transplant were $176,640,

whereas cost estimates for bilateral lung transplant

and heart-lung transplant were $180,528 and

$178,387. The costs per quality-adjusted life-year

gained were $48,241 for single-lung transplant,

$32,803 for bilateral lung transplant, and $29,285

for heart-lung transplant. The sensitivity analysis

reported that the principal determinants of cost-

effectiveness were QOL and maintenance costs

after transplantation. The authors concluded that

although lung transplantation results in survival and

QOL gains, it was expensive, with cost-effectiveness

limited by substantial morbidity and mortality and

high maintenance costs.

Limitations and barriers to quality-of-life

assessment in lung transplantation clinical

practice

Although QOL now is recognized as an important

outcome measure in clinical practice, few institutions

have used it for lung transplantation. The major

barriers to routine QOL measurement seems to be

the complexity of some measurements requiring the

use of detailed questionnaires or interviews. These

techniques may require considerable time by the

patient and researcher. The lack of experience with

QOL measurements, the shortage of health care

personnel to coordinate and analyze the measure-

ments, and budget limitation further contribute to its

barriers in clinical practice.

Many limitations have been pointed out for each

of the QOL studies involving lung transplantation

and are outlined in Table 3. Most of the reports

evaluating QOL in lung transplantation have consid-

Table 3

Study limitations

Author, journal, year Limitations

O’Brien et al [35],

J Epidemiol Community Health, 1988

<50% of recipients completed questionnaires 12 mo

after transplant

No reasons stated for decrease in posttransplant response

Small no. of posttransplant respondents

The much less common practice of heart-lung transplantation

these days makes the results and generalizations of the

findings limited

Caine et al [34], Transplant Proc, 1991 Only 13 out of 25 recipients completed questionnaires

Small no. of posttransplant respondents

The much less common practice of heart-lung transplantation

these days makes the results and generalizations of the

findings limited

Busschbach et al [36], Chest, 1994 Small no. of patients in the cross-sectional study (3 candidates

and 3 recipient patients)

No indication of how comparable the cohort groups were

Some patients had problem associated with long-term

memory recall

Manzetti et al [56], Heart Lung

Transplant, 1994

Small sample size of 9 patients

Limited duration of follow-up

Gross et al [41], Chest, 1995 Small no. of patients in 3 separate recipient groups

Ramsey et al [44], J Heart Lung

Transplant, 1995

Cross-sectional study

Small sample size

Squier et al [50], Am J Respir

Crit Care Med, 1995

Small no. of subjects

Heterogeneity of sample

Limited long-term follow up

QWB scores accounted for a small but significant portion

of survival variance

Littlefield et al [24], Gen Hosp

Psychiatry, 1996

Mean age of lung transplant group was younger than that of

heart transplant group

Limbos et al [42], Chest, 1997 Exclusion of men limit ability to make generalization about

the findings

Small no. of subjects in candidate cohort

Large amount of missing data

20% of sample group did not complete the entire sexual

functioning tool, which meant that findings regarding sexual

tool may not be representative of the sample

Lanuaza et al [46], Circulation, 1997 Lack a pretransplant group for comparison

Small sample size for subgroup comparisons

TenVergert et al [37], Chest, 1998 13 patients did not complete posttransplant questionnaires

Small sample size

McNaughton et al [21], Clin

Transpl, 1998

Small sample size

Cohen et al [45], Chest, 1998 Cross-sectional study

Small no. of patients in longitudinal arm

Stilley et al [47], Psychosomatics, 1999 No pretransplant group for comparison

Small no. of patients in the 2 separate recipient groups

Van den Berg et al [38], Am J Resp

Crit Care Med, 2000

Cross-sectional study

Small no. of patients in longitudinal analysis

Less than half of patients with BOS (22 of 52) were involved

in the longitudinal analysis

Lanuza et al [7], Chest, 2000 Small sample size of 10 patients

Short posttransplant follow-up of 3 mo



Table 3 (continued)

Author, journal, year Limitations

Anyanwu et al [40], Thorax, 2001 Cross-sectional study

Preoperative diagnosis, duration on the waiting list, and type of

lung transplant proposed were not taken into consideration

No mention of no. of patients who declined participation

Abbreviations: BOS, bronchiolitis obliterans syndrome; QWB, Quality of Well-being scale.


ered all lung transplant candidates and recipients as a

single homogeneous group. Lung transplant candi-

dates and recipients are a heterogeneous group of

patients, however. Patients on the transplant waiting

list have end-stage pulmonary disease that is the

result of one of many underlying diseases, including

emphysema, cystic fibrosis, pulmonary fibrosis, pul-

monary hypertension, and other causes. Most of the

studies on QOL in lung transplantation were not

controlled for the many important covariates that

might help explain QOL differences, such as gender,

age, comorbidities, and severity of lung disease.

While these variables are known to affect survival,

they also affect QOL and therefore must be adjusted

for [1]. Physiologic variables, such as FEV1, often

were not taken into consideration in most studies. The

influence of these variables on QOL is understudied

in lung transplantation. Despite the fact that gender

has been shown to influence risk of mortality in lung

transplantation, only a few studies have incorporated

gender as a study variable. Age may vary greatly

across lung transplant candidates due to different

diagnostic groups, such as younger age in patients

with cystic fibrosis and older age in patients with

chronic obstructive airway disease. Only a few

reports included type of transplant procedure as a

study variable, and the symptom experiences of lung

transplant patients were examined in only a few

studies [21,40,46,56]. In some studies in which

cohorts were considered similar for comparison, the

studies did not show or address the similarity in terms

of demographic data [34,36].

Various types of lung transplant procedures (sin-

gle-lung, bilateral, or heart-lung) are performed and

are determined by the patient’s underlying diagnosis,

institutional surgical practice, availability of organs,

and other factors. Earlier reports from the late 1980s

and early 1990s included many heart-lung and bilat-

eral lung transplant procedures [34,35]. The peak of

these procedures was reached around 1989, and since

then the most common procedures performed have

been single-lung and bilateral lung transplants. The

effects of these various procedures often were not

taken into consideration in the evaluation of QOL

after lung transplantation.

Most of the studies performed have been retro-

spective or cross-sectional in nature (see Table 2).

Cross-sectional studies may be useful in describing

QOL at a particular time but may not be accurate in

assessing changes over time because the cohorts of

patients before and after transplantation are different.

Only a few studies have been performed as a longi-

tudinal design evaluating prospective pretransplant-

to-posttransplant changes in the same group of

patients (Table 2). Some studies had only a few

patients in their study population, and some studies

did not describe methods in patient sampling [21,56].

Because many different QOL instruments were

used in different studies and in different countries,

interpretations in the comparisons of QOL results

across the various studies can be difficult, making

generalizations difficult. Some studies also did not

report the reliability and validity of the QOL instru-

ments used [5,7,21,24,31].

Summary

Despite the potential differences in patient char-

acteristics, study designs, and types of instruments

used, this review of the literature showed several

common findings. Important improvements in QOL

are reported after lung transplantation. These im-

provements were observed when cross-sectional

comparisons were made across the cohort of candi-

dates and recipients and during longitudinal follow-

up of patients at pretransplant and posttransplant

time points. The improvements in QOL after trans-

plantation seem to be sustained for at least 1 to

3 years after transplant. Lung transplant recipients

generally were satisfied with their decision to have

undergone transplantation.

Many issues require further clarification. Variables

that may influence QOL before and after lung trans-


plantation, such as age, sex, pretransplant diagnosis,

and type of procedure performed, should be consid-

ered carefully as study variables. Carefully designed,

prospective longitudinal studies with many patients

would result in stronger conclusions regarding the

importance of QOL assessment in lung transplanta-

tion. It would be useful for a few QOL measurement

tools to emerge as standard instruments so that many

centers and investigators could adopt them to use

independently. Standard instruments would allow

comparison of outcomes between centers and would

allow meta-analyses of multiple studies using the

same methodology. Interpretation of the studies

would be improved because there would be improved

familiarity with a few tools, rather than vague recog-

nition of a large variety of tools.

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Return to work after thoracic surgery: an overlooked

outcome measure in quality-of-life studies

Chuong D. Hoang, MDa, Marc C. Osborne, BSa,Michael A. Maddaus, MDa,b,*

aSection of General Thoracic Surgery, Division of Cardiovascular and Thoracic Surgery,

University of Minnesota Medical School, 420 Delaware Street S.E., MMC 207, Minneapolis, MN 55455, USAbCenter for Minimally Invasive Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA

A report from the National Center for Health Sta- Numerous studies have investigated thoroughly

tistics in 2000 (http://www.cdc.gov/nchs/fastats/

insurg.htm) showed that every year in the United

States, nearly 1 million thoracic procedures are per-

formed to treat patients with malignant and nonma-

lignant pathology—a number almost twice that for

coronary artery bypass graft surgery [1]. Tradition-

ally, open thoracotomy has been the technique of

choice. The usual patient rehabilitation period has

been prolonged, requiring 6 to 8 weeks. During this

period, the patient is not likely to resume normal

activity or be able to return to work. Increasingly,

chest physicians are beginning to recognize that

optimization of the number of thoracic surgery

patients who return to work must be considered an

important outcome measure and rehabilitation aim.

Multiple series (discussed subsequently) from the

minimally invasive thoracic surgery literature suggest

that earlier return to work can be achieved and is

likely more desirable for patients and cost-effective

for health care systems. In a public survey of patients

undergoing a chest organ transplant, 72% of respon-

dents agreed that the recipient’s return to work or

ability for other regular activity was second in im-

portance only to survival [2,3].


doi:10.1016/S1547-4127(04)00026-X

* Corresponding author. Section of General Thoracic

Surgery Division of Cardiovascular and Thoracic Surgery,

University of Minnesota Medical School, 420 Delaware

Street S.E., MMC 207, Minneapolis, MN 55455.


(M.A. Maddaus).

the return-to-work rate and factors that influence it in

patients undergoing surgical procedures such as

inguinal hernia repair [4], coronary artery bypass

graft surgery [5], and kidney transplants [6]. Similar

studies have not been published, however, to the best

of the authors’ knowledge, that directly pertain to

thoracic surgical procedures involving the lung or

esophagus. Data on this topic are currently available,

in general, only as related components of a limited

number of quality-of-life (QOL) studies dealing with

thoracic cancer resection and less so with benign

thoracic pathologies. The authors reviewed selected

studies that investigated QOL after thoracic surgery

and included at least partial return-to-work data. To

underscore the broad implications of an improved

understanding of return to work after thoracic sur-

gery, first the general concepts of worker absenteeism

are discussed. By identifying the deficiencies in the

literature, the authors hope to help inspire a logical

series of much-needed clinical studies to bring clari-

fication to this important topic.

Worker absenteeism for surgical procedures

In analyzing the costs of illness among their

employees, American businesses generally classify

the costs into two groups: direct and indirect costs

[7]. Direct costs are costs that can be measured or

calculated easily, such as payments for medical goods

and services to health maintenance organizations or

insurance companies. Indirect costs are a broad cate-

s reserved.

http:\\www.cdc.gov\nchs\fastats\insurg.htm

C.D. Hoang et al / Thorac Surg Clin 14 (2004) 409–416410

gory of expenses incurred secondary to an employ-

ee’s illness, including costs of recruitment, training,

and other accommodations to temporary, long-term

absence or to permanent loss of a skilled worker.

Worker absenteeism serves as a proxy for these

indirect costs of illness; often, absenteeism is meant

to measure worker ‘‘productivity.’’ Calculating indi-

rect costs of illness by using worker absenteeism rates

is not straightforward, however.

In 1989, one review estimated that American

businesses spend about $37 billion per year because

of employees’ absence from work [8]. In addition to

the significant societal costs, employees incur sizable

personal costs that are more difficult to quantitate di-

rectly. A sense of the magnitude of these costs may be

inferred from Department of Labor statistics (2003)

indicating that although most (79%) employees in

private industry earn some paid time off, relatively

few carry either short-term (37%) or long-term (28%)

disability insurance that would cover their lost wages

in the event of an extended absence [9]. A significant

percentage of workdays lost are the result of surgical

procedures to correct common health problems. The

Department of Labor includes surgical procedures

such as aortocoronary artery bypass, cholecystecto-

my, appendectomy, abdominal hysterectomy, and

mastectomy, but makes little or no mention of tho-

racic surgical procedures. Nevertheless, it is likely

safe to infer that the costs of thoracic surgery would

be considerable.

Return to work as a valid outcome measure

The ability to resume normal work activity

(ie, return to work) is the equivalent clinical assess-

ment of health-related worker absenteeism, a con-

struct more often used by economists and public

health experts. An operational definition of return

to work is the time elapsed between undergoing a

surgical procedure and returning to normal daily

activities. Although return to work can be measured,

there are large overall variations in reported rates,

even among closely related studies [10,11]. Return to

work after a particular type of surgical procedure is

poorly understood and vaguely defined.

Jones et al [4] conducted a prospective study in

inguinal hernia repair patients to characterize better

the confounding variables that may affect return to

work after surgery. Bivariate analysis showed that

nonsurgical factors, such as age, education level,

income level, and type of occupation, significantly

influenced the actual return-to-work rate postopera-

tively. Mittag et al [5] reached similar conclusions

in a comparative analysis of return to work after cor-

onary artery bypass graft surgery, which represents

a much more complicated disease and a much more

invasive procedure (compared with inguinal her-

nia epair).

Those two studies, taken together, suggest that

(1) return to work is a complex concept, influenced

not only by the type of surgical procedure, but also by

a multitude of other variables; (2) the issue of return

to work after many types of surgical procedures

warrants further investigation; and (3) return to work

is a highly desirable outcome measure as perceived

by patients and increasingly by the health care in-

dustry. The central importance and validity of return

to work after thoracic surgical procedures are likely to

be high.

Return to work after thoracic surgery

The authors identified potentially relevant articles

in the National Library of Medicine PubMed database

(1966–2003) by computerized methods in two inde-

pendent searches (C.D.H and M.C.O). The following

key words were used (combined with the Boolean

operators ‘‘OR’’): return to work, RTW, quality of life,

QOL, thoracic, lung, esophagus, surgery, video-

assisted thoracoscopic, and VATS. These two

searches provided the initial database of articles for

review. Additional possible articles were found by

manual searches. There were no specific criteria for

inclusion of articles, but articles were excluded if

they were not in the English language. A total of

69 journal articles were reviewed.

Specific studies aimed at investigating the impact

of thoracic surgery on return-to-work or on inability-

to-work rates remain to be published. Preoperative

employment status and return to work were men-

tioned briefly in a few studies, although rarely dis-

cussed in depth (Table 1). In general, those two

variables were documented as part of a global effort

to study QOL issues resulting from thoracic surgery

for a variety of pathologic processes, such as lung

cancer, esophageal cancer, and other nonmalignant

diseases (eg, spontaneous pneumothorax).

Lung cancer

Lung cancer is among the most common of ma-

lignancies in the United States, accounting for 14%

of all malignancies [12]. Most lung cancer patients

have non– small cell lung carcinoma (NSCLC).

NSCLC accounts for more cancer-related deaths

Table 1

Selected thoracic surgery studies with return-to-work results

Study Design Surgical intervention

Instrument used

or end point RTW results

Lung cancer Dales et al [18]

(1994)

Prospective

cohort

Open thoracotomy QL Index Work-related activity impairment levels were:

24% preoperative, increased to 52% at 1 mo

postoperative, and returned to baseline at 6 mo

(27%) and 9 mo (17%). Extent of resection

correlated with worsening QOL

Zieren et al [20]

(1996)

Prospective

cohort

Open thoracotomy Self-developed

questionnaire

Preoperative, 50% of patients were employed

full-time and 25% were retired due to

disease-induced limitations. At 5 mo

postoperative, 60% returned to full-time

employment, 40% of patients retired permanently

Demmy et al [21]

(1999)

Case-control VATS versus

thoracotomy

Average time to

return of full activity

Survivors in the VATS group returned to full

activity on average at 2.2 mo postoperative

versus 3.6 mo for thoracotomy. At 3 mo

postoperative 31% of VATS patients had limited

activity versus 44% of thoracotomy patients

Sugiura et al [22]

(1999)

Prospective

cohort

VATS versus

thoracotomy

Average time to

resume normal

activity; self-developed

questionnaire

VATS patients resumed normal activity at 2.5 mo

postoperative versus 7.8 mo for thoracotomy patients

Esophageal cancer Zieren et al [31]

(1996)

Prospective

cohort

Transthoracic

or transhiatal

Self-developed

questionnaire

Postoperative, 30% of patients remained employed

full-time; no preoperative data presented.

McLarty et al [28]

(1997)

Prospective

cohort

Transthoracic Medical Outcomes

Study Short Form-36

at 5 y postoperative

No significant difference in RTW in patients

undergoing esophageal resection compared with a

cancer-free matched population

Benign thoracic

pathology

Paris et al [35]

(1998)

Prospective

cohort

Bilateral or

single-lung

transplantation

Self-developed

questionnaire

Preoperative, 50% of patients were employed and

44% were medically disabled. At median follow-up

of 25 mo postoperative, 22% were employed, 38%

were unemployed but medically fit to work, and

29% were disabled

Stammberger et al

[34] (2000)

Prospective

cohort

VATS (PTX,

SPN, pleura, or

interstitial lung)

Self-developed

questionnaire

Of 140 patients employed preoperative, 89%

returned to work within 2 wk and 99% returned

within 12 wk

Abbreviations: PTX, pneumothorax; QL or QOL, quality of life; RTW, return to work; SPN, solitary pulmonary nodule; VATS, video-assisted thoracoscopic surgery.

C.D.Hoanget

al/ThoracSurg

Clin

14(2004)409–416

411


than the next three most common malignancies

(breast, prostate, and colon) combined [12].

For the estimated 9 million US cancer survivors,

self-reported multidimensional health-related QOL

descriptions of physical and social well-being (among

other parameters) after their diagnosis and treatment

have been increasing steadily [13,14]. Information on

lung cancer survivors in general remains sparse,

however. QOL end points have become important

benchmarks for evaluating short-term and long-term

results for lung cancer survival [15]. Detailed infor-

mation on return-to-work rates after lung cancer

thoracotomy to treat cancer remains elusive.

Open surgical series

Schag et al [16] were among the first researchers

to comment specifically on return to work after

thoracic surgery in a cross-sectional QOL study of

lung, prostate, and colon cancer survivors who were

now disease-free. In their report on a sample of

57 lung cancer patients, the specific type of surgical

procedure was not made available. Overall, the lung

cancer group had more problems at short-term, inter-

mediate-term, and long-term time points (compared

with the other cancer groups). Exact figures were

unavailable, but the lung cancer group had more

difficulty in the postoperative period with return to

work and with the ability to function at near their

preoperative capacity. The Schag study revealed

many deficiencies with regard to return to work,

which the authors likely never intended to address

directly. This theme persists in other, more recent

studies on QOL after lung cancer thoracotomy.

Handy et al [17], in their prospective study of

131 patients, documented QOL as a function of lung

cancer surgical resection but failed to report all of

their available data pertaining to return to work. Their

outcomes questionnaire included employment status;

however, only the preoperative employment figure

(32.4%) was mentioned in their results.

In contrast, Dales et al [18] prospectively enrolled

117 patients who underwent thoracotomy with a

certain or presumptive diagnosis of lung cancer. Their

study documented multiple QOL variables, including

work activity, at four separate postoperative time

points up to 9 months. They compared patients with

proven NSCLC (n = 91) with patients without ma-

lignancy (n = 26). Work-related activity was assessed

by using the QL-index [19]; scores were arbitrarily

dichotomized into ‘‘better’’ (not defined by the

authors) and ‘‘poor’’ (defined as requiring major

assistance or reduction in work, not working/study-

ing, or not managing a household) scores. Work-

related activity already was impaired in 26% (n = 24)

of NSCLC patients preoperatively, a percentage that

increased to 52% (n = 47, P < .005) at 1 month post-

operatively. The impairment in work-related activity

returned to preoperative baseline at 6 (27%, n = 25)

and 9 (19%, n = 17) months in survivors. The reason

for curtailed work (or home) activities preoperatively

and at 9 months postoperatively was due to dyspnea,

as measured by the Clinical Dyspnea Index. The

extent of surgical resection negatively correlated with

global QOL scores, but it was not possible to deter-

mine, from the data as presented, whether or not this

observation held true for return-to-work rates.

Similarly, Zieren et al [20] addressed the return-

to-work issue in two groups of patients with bron-

chogenic NSCLC who underwent open thoracotomy.

Employment status was assessed directly in 52 ‘‘post-

operative’’ patients and in another 20 ‘‘follow-up’’

patients. The postoperative group comprised patients

who had a curative resection and completed a QOL

analysis at 1 year after surgery; the follow-up group

comprised disease-free survivors who completed

QOL assessments preoperatively and postoperatively

(at a total of six time points) 1 year after surgery.

Only 50% (n = 10) of the follow-up patients were

employed full-time preoperatively; another 25%

(n = 5) of follow-up patients reported that they retired

preoperatively due to disease-induced job limitations.

After a median of 5 months postoperatively, 60%

(n = 6) of follow-up patients returned to full-time

employment; the other patients in this group retired

permanently. Some follow-up patients underwent

postoperative radiotherapy for N2 disease, but Zieren

et al [20] were not able to determine any significant

return-to-work differences in radiotherapy patients

versus patients receiving only surgery. The return-

to-work information in the postoperative group was

less complete, with no preoperative employment sta-

tus given. At 1 year postoperatively, 63% (n = 33)

of the postoperative patients had retired perma-

nently, and only 12% (n = 6) of patients were em-

ployed full-time.

Minimally invasive surgical series

Return-to-work rates have been cited more fre-

quently in minimally invasive thoracic surgery stud-

ies to support the argument that this surgical approach

is more beneficial to patients. Overall the available

literature suggests that return-to-work ability is likely

to be better preserved with minimally invasive tech-

niques (compared with traditional open thoracotomy).

This conclusion is based on only a few studies that

present partial data on postoperative ability to resume

normal activity—not on direct effects related to return

to work.

C.D. Hoang et al / Thorac Surg Clin 14 (2004) 409–416 413

Demmy and Curtis [21] compared 38 patients

who required lung resection for bronchogenic malig-

nancy in a case-control study design. Nineteen

patients with a high preoperative risk underwent

video-assisted thoracoscopic surgery (VATS). Their

functional outcomes were compared with outcomes

of 19 patients who underwent thoracotomy. Survivors

in the VATS group were able to return to ‘‘full

activity’’ at an average of 2.2 months, whereas the

thoracotomy group required a significantly longer

average of 3.6 months (P < .001). The authors

presume that the term full activity encompassed, in

part, return to work ability, albeit not directly

assessed. At 3 months postoperatively, only 31%

(n = 5) of VATS patients had limited activity versus

44% (n = 8) of thoracotomy patients (P < .01).

Logistic regression analyses did not show post-

operative reduced activity levels to be an indepen-

dent risk factor for morbidity and mortality.

Similarly, Sugiura et al [22] compared long-term

QOL using a self-developed questionnaire in patients

with stage I NSCLC who underwent lobectomy by

VATS (n = 22) versus by thoracotomy (n = 22). The

VATS patients resumed ‘‘normal activity’’ within an

average of 2.5 months, which was significantly

shorter than the average of 7.8 months required by

the thoracotomy patients (P < .03). Return to work

was not directly assessed, and the term normal

activity was never defined or discussed in detail.

Lewis et al [23] also made oblique reference to return

to work rates in a study of 250 VATS patients, stating

that most resumed preoperative activity within 7 to

10 days, and some returned to work in that period;

specific figures from this large cohort were not

presented, however.

Esophageal cancer

Most patients with esophageal cancer present with

advanced disease; overall 5-year survival rates are

poor. Early detection and surgical resection provide

the best chance for cure. Survival at 5 years for

patients with resected stage I esophageal carcinoma

is estimated at 50% to 85%; with resected stage II

carcinoma, survival is 20% to 50% [24–26]. World-

wide, most patients with esophageal cancer have the

squamous type. The incidence of adenocarcinoma

of the esophagus and the gastroesophageal junction

has risen fourfold, however, since the 1970s—the

most rapid increase of any type of cancer. Esophageal

adenocarcinoma now accounts for greater than 50%

of all cases of esophageal cancer in the United

States, causing about 10,000 deaths per year [27].

Compared with lung cancer, esophageal cancer has

been the focus of even fewer QOL studies performed

to evaluate the effect of surgical resection. Conse-

quently, information on return to work after esoph-

ageal resection that includes a thoracic incision

is incomplete.

McLarty et al [28] reported on long-term QOL in

64 patients who underwent esophageal resection (an

Ivor Lewis esophagogastrectomy for most) who were

disease-free at 5 years. The return-to-work ability

postoperatively was assessed with the Medical Out-

comes Study 36-Item Short-Form Health Survey;

the esophagectomy group was compared with the

national norm (a cancer-free matched patient popula-

tion). McLarty et al [28] found no significant differ-

ence in return to work, although detailed preoperative

and postoperative data were not available.

Branicki et al [29] observed at 1 month after

esophagectomy for cancer that few patients had

returned to full-time or part-time work and that most

were retired. Additional details were not available,

including the specific type of surgical procedure

performed. It is difficult to discern whether these

return-to-work results may be a consequence of a

thoracic incision. This same concern applies to pre-

operative work status figures reported by Blazeby et al

[30]: They did not mention the specific type of

surgical resection. In their study of QOL after esoph-

ageal cancer in a large cohort, only 28% (n = 74) of

patients were able to work full-time preoperatively;

they did not present postoperative data.

The study by Zieren et al [31], which assessed

employment status as part of a QOL study in two

patient groups who underwent esophageal surgery,

had similar shortcomings. A group (postoperative)

comprised 119 patients who completed a QOL ques-

tionnaire at 12 months postoperatively, and a second

group (follow-up) comprised 30 patients who com-

pleted QOL questionnaires preoperatively and post-

operatively at six time points up to 1 year. In the

postoperative group, only 30% (n = 36) of patients

remained in full-time employment. No preoperative

work data were presented. In the follow-up group,

50% (n = 15) of patients worked full-time, but the

effect of surgery on return to work could not be

discerned because postoperative work data were not

provided. These data should be interpreted with

caution because only 15% of all patients were ap-

proached via a transthoracic route; most patients had

an abdominal incision and transhiatal approach.

Benign thoracic pathology

The published reports on nonmalignant thoracic

conditions mention only briefly return-to-work issues


related to the surgical procedure. Bousamra et al [32]

conducted a small (n = 17) study to compare out-

comes for patients who underwent VATS versus

thoracotomy for resection of benign neurogenic me-

diastinal tumors. On average, return to work required

less time for the VATS group (4.3 weeks) versus the

thoracotomy group (7.7 weeks), although the differ-

ence was not statistically significant. Bertrand et al

[33] also cited earlier ‘‘return to occupational activ-

ity’’ (42 F 34 days) in 163 young adults who

underwent VATS for spontaneous pneumothorax.

This interval was significantly (P < 0.001) shorter

compared with a matched group of 87 patients who

underwent lateral limited thoracotomy for the same

disease in a separate study, but required 74F 60 days

before their return to work. Both groups required

relatively lengthy periods before their return to work,

which was attributed to prevailing cultural attitudes

of the French population under study.

Stammberger et al [34] presented more complete

data regarding return-to-work issues in relation to

VATS for patients with pneumothorax (n = 70),

pulmonary nodules (n = 44), interstitial lung disease

(n = 20), pleural effusion (n = 20), and empyema

(n = 19). Of the 140 patients employed preoperatively,

125 (89%) were able to return to work within 2 weeks.

The other 15 patients, for a postoperative interval

of 3 to 16 weeks, were unable to return to work

(14 because of chest pain, 1 because of shoulder

pain). At 12 weeks postoperatively, a total of 139

(99%) of the patients who were employed preopera-

tively were able to return to work; 1 patient experi-

enced disabling shoulder pain. These impressive data

should be interpreted with caution, however, because

the study was retrospectively performed with an

unvalidated, self-reported questionnaire. The lack of

a control group of patients who underwent open

thoracotomy is another serious limitation.

Lung transplantation is the only subfield of gen-

eral adult thoracic surgery in which detailed and

complete data regarding return-to-work rates are

available, but from only one study. Multiple studies

have reported on the impact that a solid organ

transplant in general likely exerts on return to work,

but, to the authors’ knowledge, only one such study

[35] focused on the lung. In that study, Paris et al [35]

evaluated data from 99 lung transplant recipients

(43 single, 56 bilateral) from two centers by a

stepwise discriminant analysis to identify factors

influencing return to work posttransplant. Preopera-

tively, 50% (n = 50) of the patients were employed,

and 44% (n = 44) were medically disabled; postop-

eratively, after a median follow-up of 25 months,

22% (n = 22) were employed, 38% (n = 38) were

unemployed but medically fit to work, and 29%

(n = 29) were disabled. The adjusted (for subjects

physically able to work) return-to-work rate of 37%

(22 of 60 patients) was similar to other types of organ

transplant recipients.

In the Paris et al [35] study, lung transplant

recipients were less likely to be employed if they

were older or had a lower educational level. The rate

of spousal employment decreased regardless of the

recipient’s employment status (P < .01) and resulted

in a decreased mean family income. Significant

factors that fostered return to work included pretrans-

plant employment, self-reported ability to work, and

objectively measured improvement in functional sta-

tus. Certain social barriers to employment posttrans-

plant included changes in lifestyle priorities, the

restrictive cost or unavailability of health insurance,

and hiring discrimination. The type of surgical trans-

plant (single or bilateral) did not affect return to work

in these patients.

Unanswered questions and the need for future

studies

From the few pertinent articles reviewed here

(see Table 1), it is evident that the large gaps of

knowledge about return to work after thoracic surgery

may not be addressed in the near future. Multiple

reasons contribute to this situation. First, chest sur-

geons generally do not recognize that return to work

is a highly important outcome variable after thoracic

procedures. Consequently, they likely are not inter-

ested in characterizing return-to-work issues related

to thoracic surgery. Compounding this problem is the

fact that the term return to work remains poorly

defined and inconsistently used. None of the studies

cited except that by Paris et al [35] explicitly defined

return to work, and none of the studies reported

return-to-work results in a standard fashion.

The available data on return to work after thoracic

surgery are conflicting, with no clear patterns. Reas-

ons include limited sample sizes, heterogeneous

patient populations, and different experimental study

designs used by the investigators. Initial clinical

investigations aimed at addressing these deficiencies

are warranted, to establish a foundation for future,

larger trials (multi-institutional, prospective, random-

ized, and appropriately controlled). Likely what will

be revealed about return to work related to thoracic

surgery is that there are a host of complex, influen-

tial factors, some of which are controllable and

others uncontrollable.

C.D. Hoang et al / Thorac Surg Clin 14 (2004) 409–416 415

Summary

In the literature on thoracic surgery, return to work

has received little attention in QOL investigations. At

present, it is difficult to appreciate clinically mean-

ingful trends in return to work after thoracic surgery,

even within a specialized area, such as lung cancer

resection. It is evident, however, that return to work is

not a simple variable, easily measured; rather, it is a

complex construct that is influenced by a multitude

of personal and societal factors. Focusing only on

disease-related or treatment-related symptoms renders

QOL studies limited in scope and perhaps in useful-

ness. Return to work is not a trivial component of

global postsurgical QOL; it should be recognized as a

major factor. Patients have indicated that maintaining

return-to-work ability is as highly valued as their

overall health. Surgical societies should design, vali-

date, and implement a simple data collection instru-

ment to characterize better return to work after

thoracic surgery.

Acknowledgment

The authors are grateful to Dr. Mary Knatterud for

expert editorial assistance.

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Chronic respiratory failure after lung resection: the role of

pulmonary rehabilitation

Bartolome R. Celli, MDa,b,*

aDivision of Pulmonary and Critical Care Medicine, Caritas St. Elizabeth’s Medical Center, Seton 3 Pulmonary,

736 Cambridge Street, Brighton, MA 02135, USAbDepartment of Medicine, Tufts University, Boston, MA, USA

Patients with advanced chronic respiratory dis- Definition and goals

ease frequently have distressing symptoms, limita-

tions in exercise ability, and reductions in health and

functional status that persist despite optimal pharma-

cologic management. Pulmonary rehabilitation com-

plements standard medical therapy and can provide

additional, clinically meaningful benefit in these

areas. Pulmonary rehabilitation has become the stan-

dard of care for patients who are motivated to par-

ticipate in such programs. Patients improve their

exercise and functional capacity, decrease their dysp-

nea, improve their health status, and perhaps postpone

premature morbidity and mortality. Although pulmo-

nary rehabilitation was designed and is applied pri-

marily to symptomatic patients who are limited due

to chronic obstructive pulmonary disease (COPD), the

same fundamental principles seem to be applicable to

other disease states leading to disability. Pulmonary

rehabilitation has become an essential component in

the optimization of therapy in patients considered for

lung volume reduction surgery and an absolute requi-

site for patients undergoing lung transplant. Pulmo-

nary rehabilitation has a major role in the prevention

of complications.


doi:10.1016/S1547-4127(04)00017-9

* Caritas St. Elizabeth’s Medical Center, Seton 3

Pulmonary, 736 Cambridge Street, Brighton, MA 02135.


Rehabilitation attempts to restore the individ-

ual to the fullest medical, mental, emotional, social,

and vocational potential to which he or she is capable.

Based on this basic concept, pulmonary rehabilita-

tion has been defined as ‘‘a multidisciplinary program

of care for patients with chronic respiratory impair-

ment that is individually tailored and designed to

optimize physical and social performance and auton-

omy.’’ [1] From this definition, it follows that pul-

monary rehabilitation has three major goals:

1. To control, alleviate, and, as much as possible,

reverse the symptoms and pathophysiologic

processes leading to respiratory impairment

2. To improve functional status and participation

in daily activities

3. To enhance health-related quality of life and

attempt to prolong the patient’s life

The concept of pulmonary rehabilitation has two

other important elements: its use of a wide array of

disciplines to achieve these goals and its recognition

that the patient has unique medical problems and

needs that require an individualized approach. In the

case of surgery, pulmonary rehabilitation includes the

psychological support required during the stressful

period before and after the operation and the appro-

priate timing to optimize results.

Pulmonary rehabilitation and its components have

been recognized by clinicians as an effective inter-

vention since at least the middle of the 20th century

s reserved.

B.R. Celli / Thorac Surg Clin 14 (2004) 417–428418

[2–4]. Since the 1980s, pulmonary rehabilitation has

risen to prominence as a state-of-the-art, scientifically

proven intervention for patients with chronic lung

disease. Its current importance as a therapeutic option

is underscored by the following three events:

1. Its incorporation as the ‘‘best therapy’’ with

which lung volume reduction surgery was

compared in the National Emphysema Treat-

ment Trial [5]

2. A Cochrane report showing the effectiveness of

pulmonary rehabilitation in meta-analyses [6]

3. Its endorsement by the Global Initiative for

Obstructive Lung Disease and its prominent

position in their treatment algorithm for

COPD [7]

Over time, what previously was considered a form

of therapy reserved only for the most severe patients

now is recommended for patients with symptoms that

limit their performance, usually with moderate sever-

ity of disease. Several studies influential in the

development of pulmonary rehabilitation are listed

in Table 1 [8–10,12–14,]. These studies show the

science behind pulmonary rehabilitation and the ef-

fectiveness of this form of treatment.

Before 1991, much of the literature supporting

pulmonary rehabilitation consisted of descriptions

of comprehensive pulmonary rehabilitation and pre-

sentations of uncontrolled, preintervention and postin-

tervention studies showing its effectiveness primarily

in reducing hospital use. In 1991, Casaburi et al [8]

reported on a study of 19 COPD patients who were

randomized to either higher or lower levels of exer-

cise training on a cycle ergometer, 5 days per week

for 8 weeks. The patients who trained at lower levels

exercised longer so that the total amount of work was

roughly equivalent in both groups. Low levels of

Table 1

Selected studies in the development of pulmonary rehabilitation

Year First author Importance i

1991 Casaburi [8] Shows a dos

1994 Goldstein [9] First of man

of pulmonar

1994 Reardon [10] First study to

1995 Ries [12] A landmark

in multiple o

1996 Maltais [13] Shows the im

COPD and t

2000 Griffiths [14] This large ra

substantial re

Abbreviation: COPD, chronic obstructive pulmonary disease.

exercise resulted in lactic acid production, indicating

a low aerobic capacity at baseline. Both levels of

training led to significant physiologic benefits, mani-

fest by a reduced lactic acidosis and ventilatory re-

quirement at the same work rate. Patients who trained

at higher intensity had more physiologic benefit,

however, than patients who trained at lower intensity.

Subsequently, Goldstein et al [9] reported a prospec-

tive, randomized, controlled trial of pulmonary reha-

bilitation in which 89 patients were randomized to

either pulmonary rehabilitation, initially given in an

inpatient setting, or conventional medical care. The

group that participated in pulmonary rehabilitation

had significantly greater increases in the 6-minute

walk distance, submaximal cycle endurance time, and

health status compared with the group that received

standard medical care. This was the first of several

randomized, controlled trials of pulmonary rehabili-

tation that unequivocally established the effectiveness

of pulmonary rehabilitation as a treatment option for

chronic lung disease.

Reardon et al [10] reported on 20 COPD patients

who were randomized to either comprehensive out-

patient pulmonary rehabilitation or a waiting period,

during which they were given conventional medical

care. Rehabilitation led to significant improvement in

exertional dyspnea, measured during incremental

treadmill exercise testing, and overall, question-

naire-rated dyspnea with daily activities. This was

the first study to show the effectiveness of pulmonary

rehabilitation on dyspnea, the most important symp-

tom in advanced lung disease. Subsequent studies

by O’Donnell et al showed that the reduction in

post–exercise training dyspnea was associated with

decreased ventilatory demand, probably owing to

improved exercise efficiency [11].

Ries et al [12] reported on 119 patients with COPD

who were randomized to either comprehensive out-

n pulmonary rehabilitation

e-dependent physiologic benefit from exercise training

y randomized controlled trials establishing the effectiveness

y rehabilitation

prove that pulmonary rehabilitation relieves dyspnea

study showing the effectiveness of pulmonary rehabilitation

utcome areas

portance of biochemical abnormalities in the muscles of

heir improvement with pulmonary rehabilitation

ndomized trial showed, among other positive outcomes, a

duction in health care use after pulmonary rehabilitation

B.R. Celli / Thorac Surg Clin 14 (2004) 417–428 419

patient pulmonary rehabilitation or education alone.

Compared with education alone, rehabilitation led to

significant improvement in dyspnea, maximal exer-

cise capacity, exercise endurance, and self-efficacy

for walking. The last-mentioned refers to the patient’s

confidence in successfully managing respiratory

symptoms associated with walking. Positive results

declined over time, approaching those of the control

group by 18 to 24 months. The decline in gains made

over time underscored the importance of strategies to

improve long-term adherence with rehabilitation.

This concept has led to the current concept that

patients considered for lung transplantation must

continue the gains obtained from rehabilitation

through maintenance of the exercise program [15].

Maltais et al [13] reported on 11 patients with

COPD who were evaluated before and after 36 ses-

sions of high-intensity endurance training. In addition

to the expected physiologic training effect (including

reduced exercise-induced lactic acidosis), exercise

training led to increased levels of oxidative enzymes

in muscle biopsy specimens. The improvement in

biochemical markers correlated with reduced lactic

acid production during exercise. Along with other

work, this study proves that exercise training improves

skeletal muscle oxidative capacity in COPD patients,

and this improvement has clinical importance.

Griffiths et al [14] presented data on 200 patients

with chronic lung disease who were randomized to

either 6 weeks of multidisciplinary pulmonary reha-

bilitation or standard medical management. In addi-

tion to showing substantial improvements in exercise

performance and health-related quality of life, the

pulmonary rehabilitation intervention led to fewer

days in the hospital and fewer primary care home

visits in the 1-year follow-up period. A subsequent

study from this group [16] provided evidence support-

ing the cost-effectiveness of pulmonary rehabilitation.

Rationale for pulmonary rehabilitation

Pulmonary rehabilitation has a minimal, if any,

effect on the abnormal lung function of individuals

with chronic lung disease. Despite this minimal ef-

fect, rehabilitation usually results in clinically signifi-

cant improvement in multiple outcome areas of

considerable importance to the patient, including re-

duction in exertional dyspnea and dyspnea associated

with daily activities, improvement in exercise perfor-

mance and in health status, and reduction in health

care use.

The apparent paradox whereby functional capac-

ity can improve without major change in pulmonary

function is explained by the fact that a considerable

portion of the dyspnea and functional status and

health status limitations from chronic lung disease

results from extrapulmonary effects of the disease,

which do respond to treatment. Some of the associ-

ated systemic manifestations include nutritional de-

pletion [17,18], decrease in lower extremity muscle

mass and peripheral muscle weakness and fatigability

[19,20], alterations in peripheral muscle fiber type,

and reduction in peripheral muscle oxidative en-

zymes. These manifestations, in addition to the clas-

sic changes of cardiovascular deconditioning, poor

pacing techniques, maladaptive coping skills, and

fear and anxiety for dyspnea-producing activities,

result in a vicious cycle of ever further decondition-

ing and debilitation. The accumulated evidence indi-

cates that pulmonary rehabilitation is highly effective

in improving and in some instances reverting many of

these systemic abnormalities.

Indications for pulmonary rehabilitation

Pulmonary rehabilitation is indicated for patients

with chronic respiratory disease who have persistent

symptoms or disability despite standard medical

therapy. Fig. 1 depicts the course of patients with

lung function limitation over time and the role of

pulmonary rehabilitation. Although all patients with

chronic respiratory disease are eligible for considera-

tion for pulmonary rehabilitation, to date, COPD is

the most common disease for which patients are re-

ferred, often from one or more of the following

symptoms or conditions:

1. Severe dyspnea or fatigue

2. Decreased exercise ability

3. Interference with performing activities of

daily living

4. Impaired health status

5. Decreased occupational performance

6. Nutritional depletion

7. Increased medical resource consumption

Persistent symptoms and limitation in these clini-

cal areas—not just the specific physiologic impair-

ment of the lungs (eg, a low forced expiratory volume

over time or hypoxemia)—dictate the need for this

intervention. Symptoms, exercise performance, func-

tional status, and health status individually correlate

relatively poorly with pulmonary function abnormali-

ties. There are no specific threshold pulmonary func-

tion inclusion criteria for pulmonary rehabilitation.

0102030405060708090

100

5 10 20 30 40 50 60 70 80

Age in years

FE

V1

(% p

redi

cted

at a

ge 2

5)

Symptoms

Disability

DeathSmoking

Pulmonary Rehabilitation

Fig. 1. Change in forced expiratory volume over time (FEV1) in persons susceptible to the effect of cigarette smoking and

who develop chronic obstructive pulmonary disease. The progressive decline results in functional limitation, poor health status,

and eventual death.


Often the referral to pulmonary rehabilitation has

been reserved for patients with advanced lung dis-

ease. Although patients in this category benefit from

the intervention [21], a referral at an earlier stage

allows for more emphasis on preventive strategies,

such as smoking cessation and exercise training at a

higher level of intensity.

Traditionally, pulmonary rehabilitation has dealt

primarily with COPD, and its effectiveness for other

pulmonary conditions has received less attention [22].

Patients with chronic asthma with airways remodel-

ing, bronchiectasis, cystic fibrosis, chest wall disease,

or interstitial lung disease may be appropriate candi-

dates. Pulmonary rehabilitation is the standard of care

before and after lung transplantation and lung volume

reduction surgery (Fig. 2) [23–27]. Based on these

accepted indications, pulmonary rehabilitation also

should be useful to recondition patients for other

major surgical procedures.

Disease progression

Lung function

Symptoms

Indication for PR

Medical therapy

Fig. 2. Pulmonary rehabilitation (PR) is an appropriate ther-

apy in respiratory disease when, after usual medical ther-

apy, physiologic impairment is associated with significant

symptoms and functional status limitation.

There are two primary exclusion criteria for pul-

monary rehabilitation:

1. An associated condition that might interfere

with the rehabilitative process. Examples in-

clude disabling arthritis or severe neurologic,

cognitive, or psychiatric disease. These patients

are unlikely candidates for any major surgery.

2. A comorbid condition that might place the

patient at undue risk during exercise training.

Examples include severe pulmonary hyperten-

sion and unstable cardiovascular disease.

Poor motivation is a relative contraindication

to pulmonary rehabilitation. The level of motivation

might change during therapy, however, especially

if patients perceive demonstrable benefit from

the sessions.

Smoking cessation

Cigarette smoking is the cause of COPD in more

than 90% of affected patients. There is no doubt that

smoking cessation is the most important therapy that

can retard the progression of airflow limitation and

influence survival positively. The various pharmaco-

logic and behavior modification techniques that are

available to assist persons to stop smoking are not

reviewed here. Although controversy still exists,

active cigarette smokers are reasonable candidates for

pulmonary rehabilitation, provided that smoking ces-

sation interventions become an important component

of the process. Frequent contact and reinforcement

during the rehabilitation program can influence a

patient into adopting a proactive role in cessation.


The inclusion of a smoking patient in a rehabilitation

program may help achieve cessation and help the

patient qualify for surgery.

Components of a comprehensive pulmonary

rehabilitation program

Exercise training

Comprehensive exercise training, including upper

and lower extremity endurance training and strength

training, is an essential component of comprehensive

pulmonary rehabilitation. Inclusion of exercise train-

ing follows the current knowledge that the peripheral

muscles in chronic lung disease not only are wasted,

but also appear to have alterations in fiber-type

distribution and decreased metabolic capacity. Exer-

cise training improves endurance, increases level of

functioning, aids in performance of activities of daily

living, helps reduce systemic blood pressure, im-

proves lipid profiles, tends to counteract depression,

reduces anxiety associated with dyspnea-producing

activities, and facilitates sleep.

Exercise training for patients with chronic lung

disease—similar to healthy individuals—is based on

general principles of intensity (higher levels of train-

ing produce more results), specificity (only muscles

that are trained show an effect), and reversibility

(cessation of regular exercise training leads to loss

of training effect) [28]. Many patients also are limited

by peripheral muscle and cardiovascular decondi-

tioning, with an early onset of anaerobic metabolism

and lactic acidosis during exercise. This decondition-

ing is responsive to exercise training. Additionally,

many respiratory disease patients often are capable of

exercising for prolonged periods at levels close to

their peak exercise capacity. Higher levels of exercise

training such as this result in greater improvement in

exercise performance [29]. The demonstrated reduc-

tion in ventilation and lactate levels at identical

submaximal work after high-intensity exercise train-

ing strongly suggests that a training effect is attain-

able in many patients with advanced lung disease. A

dose-related increase in oxidative enzymes in the

peripheral muscles accompanies these physiologic

adaptations to training [19]. A reduction in lactic

acid production has been shown to be associated with

improvement in oxidative capacity of the peripheral

muscles [30].

Most pulmonary rehabilitation programs empha-

size endurance training of the lower extremities, often

advocating sustained exercise for about 20 to 30 min-

utes, two to five times a week. This training may

include pedaling on a stationary cycle ergometer,

walking on a motorized treadmill, climbing stairs,

or walking on a flat surface such as a corridor or

auditorium. Training usually is performed at levels

equal to or greater than 50% or 60% of the maximal

work rate. For patients unable to maintain this inten-

sity for the recommended duration, interval training,

consisting of 2 to 3 minutes of high-intensity (60% to

80% maximal exercise capacity) training alternating

with equal periods of rest, has similar results with less

dyspnea [31].

The total duration of exercise training depends on

the individual pulmonary rehabilitation program but

should reflect the patient’s underlying respiratory

disease, his or her level of physical and cardiovascu-

lar conditioning, and the progress made during the

exercise training sessions. COPD guidelines (Global

Initiative for Obstructive Lung Disease) recommend

at least 8 weeks of exercise training as part of a

pulmonary rehabilitation program [7]. When patients

are considered for surgical procedures that may

require less waiting time, however, the programs

can be compressed to 3 weeks with daily sessions.

This approach should provide enough training to

obtain benefits and avoid the waiting periods that

often generate anxiety in the patient.

Although the strength of the upper extremity mus-

cles is relatively preserved compared with that of the

lower extremities in COPD [20,32], use of these

muscles is associated with considerable dyspnea.

Endurance training of the upper extremities is impor-

tant [33] because the arms are used in many activities

of daily living, and the arm muscles are accessory

muscles of respiration. Training can be accomplished

using supported arm exercises, such as arm ergometry,

or unsupported arm exercises, such as lifting free

weights or dowels or stretching elastic bands.

Because peripheral muscle weakness or depletion

contributes to exercise limitation in patients with lung

disease [34], strength training is a rational component

of exercise training during pulmonary rehabilitation.

Weight-lifting training alone involving the upper and

lower extremities increases muscle strength and en-

durance performance on a cycle ergometer [35]. The

current practice of pulmonary rehabilitation usually

adds strength training to standard aerobic training.

This combination increases muscle strength and

mass, but its additive effect on health status has not

been proved [36].

Inspiratory muscle training increases strength and

endurance of the inspiratory muscles [37,38]. Most

studies have not established a link, however, between

improvements in respiratory muscle strength or en-


durance and dyspnea, exercise performance, or health

status [39]. Newer approaches emphasizing endur-

ance training of the respiratory muscles at more

precise percentages of maximal capacity are promis-

ing, although not yet proved.

Education

Education is an integral component of virtually all

comprehensive pulmonary rehabilitation programs.

Besides providing the patient and the family impor-

tant information on the disease process, its comor-

bidity, and its treatment, education encourages active

participation in health care, promoting adherence and

self-management skills [40]. Additionally, education

helps the patient and family find ways to cope better

with the illness. Important components of the educa-

tional process are encouraging a healthy lifestyle,

incorporating adaptive techniques learned in rehabili-

tation into the home setting, and promoting long-term

adherence with the rehabilitative instructions.

Education usually is provided in small group

settings and a one-to-one format. Educational needs

are determined as part of the initial evaluation, then

are reassessed during the course of the program.

Box 1. Educational elements of acomprehensive pulmonary rehabilitationprogram

Normal pulmonary anatomy andphysiology

Pathophysiology of lung diseaseDescription and interpretation of

medical testsBreathing retrainingBronchial hygieneMedicationsExercise principlesActivities of daily living and energy

conservationRespiratory modalitiesSelf-assessment and symptom

managementNutritionPsychosocial issuesEthical issuesAdvance directives

Advance directive discussions are an important com-

ponent of pulmonary rehabilitation [41]. Generally,

many standard topics are addressed in the educational

sessions (Box 1).

Education is a component of virtually all pul-

monary rehabilitation programs. Consequently, few

studies evaluate the effectiveness of this single com-

ponent as isolated therapy. A study evaluating self-

management strategies (which are prominent in

comprehensive pulmonary rehabilitation) applied to

the home setting showed this form of therapy to be

effective, however, in improving health status and

reducing use of medical resources. Although no

studies have evaluated the role of education in the

rehabilitation of patients considered for surgery, it is

believed that instruction of patients in the prevention

of pulmonary complications is crucial to better out-

comes [42–45].

Psychosocial training and support

Psychosocial problems (eg, anxiety, depression,

deficiencies with coping, and decreased self-efficacy)

contribute to the burden of advanced respiratory

disease [46]. Psychosocial and behavioral interven-

tions vary widely among comprehensive pulmonary

rehabilitation programs but often involve educational

sessions or support groups, focusing on areas such as

coping strategies or stress management techniques.

Techniques of progressive muscle relaxation, stress

reduction, and panic control may reduce not only

anxiety, but also dyspnea [47]. Educational efforts

also may improve coping skills. Participation by

family members or friends in pulmonary rehabilitation

support groups is encouraged. Informal discussions

of symptoms frequently present in chronic lung dis-

ease and common concerns may provide emotional

support to patients and their families. Individuals

with substantial psychiatric disease should be re-

ferred for appropriate professional care outside of

the program.

Few studies have evaluated the effect of pul-

monary rehabilitation on psychological outcomes. A

randomized, controlled trial of comprehensive pul-

monary rehabilitation failed to show a significant

effect on depression. In one noncontrolled study of

pulmonary rehabilitation, depression and anxiety lev-

els decreased, however, after 1 month of pulmonary

rehabilitation. This program included psychological

counseling and stress management sessions twice

weekly in addition to standard exercise training and

educational topics [48].


Nutritional support

Nutritional depletion, including decreased weight

and abnormalities in body composition, such as de-

creased lean body mass, is present in 20% to 35% of

patients with stable COPD [49,50]. This depletion

undoubtedly contributes to the morbidity of COPD.

Nutritional depletion is associated with reductions in

respiratory muscle strength [51], handgrip strength,

exercise tolerance [52], and health status [53]. Nutri-

tional depletion and alteration in body composition

also are significant predictors of mortality of COPD,

independent of forced expiratory volume over time

[54,55]. For all the aforementioned reasons, nutri-

tional optimization is a recommended component of

comprehensive pulmonary rehabilitation.

The benefit from simple nutritional supplementa-

tion to underweight patients with chronic lung disease

has not been substantial, with one meta-analysis of

nutritional intervention for COPD reporting only a

1.65-kg increase in weight after intervention [56].

Further studies are needed to determine the optimal

approach to treatment of nutritional depletion in

chronic lung disease.

Physical modalities of ventilatory therapy

Physical modalities of ventilatory therapy have

been part of the armamentarium of pulmonary reha-

bilitation over the years, but conclusive evidence

supporting their effectiveness in pulmonary rehabili-

tation is lacking. These modalities comprise two

categories: controlled breathing techniques (diaphrag-

matic breathing exercise, pursed-lip breathing, and

bending forward) and chest physical therapy (postural

drainage and chest percussion and vibration position).

Controlled breathing techniques are aimed at decreas-

ing dyspnea, and chest physical therapy is aimed at

enhancing drainage of secretions. Reputed benefits of

these modalities include less dyspnea, a decrement in

anxiety and panic attacks, and improvement in sen-

sation of well-being. These modalities require careful

instruction by persons familiar with the techniques. It

often is necessary to involve relatives because many

of these modalities require the help of another person

(eg, chest percussion).

Breathing training is aimed at controlling the

respiratory rate and breathing pattern, possibly result-

ing in decreased air trapping. It also may decrease the

work of breathing by improving the position and

function of the respiratory muscles [57]. The easiest

of these maneuvers is pursed-lip breathing: Patients

inhale through the nose and exhale over 4 to 6 sec-

onds through lips pursed in a whistling or kissing

position. The exact mechanism by which pursed-lip

breathing decreases dyspnea is unknown. It does not

seem to change functional residual capacity or oxygen

uptake, but it does decrease respiratory frequency,

increase tidal volume, and improve blood gases.

Bending forward posture has been shown to result

in a decrease in dyspnea in some patients with severe

COPD at rest and during exercise. The best explana-

tion for this improvement is through improved dia-

phragmatic function, as the increased gastric pressure

in these positions places the diaphragm in a better

contracting position.

Diaphragmatic breathing is a technique aimed at

changing the breathing pattern from one in which the

ribcage muscles are the predominant pressure genera-

tors to a more normal one in which the pressures are

generated with the diaphragm. It usually is practiced

for at least 20 minutes two to three times daily. The

patient should start the training in the supine position

and when familiar with it perform breathing in the

upright posture. The patient is instructed to breathe in

trying to displace outwardly the hand that is placed

on the abdomen. The patient exhales with pursed lips

while encouraged to use the abdominal muscles in an

attempt to return the diaphragm to a more lengthened

resting position. Although most patients report im-

provement in dyspnea, this technique results in mini-

mal, if any, changes in oxygen uptake and resting

lung volume. Similar to pursed lip breathing, there is

usually a decrease in respiratory rate, minute venti-

lation, and increased tidal volume.

Chest physical therapy is used to attempt to

remove airways secretions. The different techniques

include postural drainage, chest percussion, vibration,

and directed cough. Postural drainage uses gravity to

help drain the individual lung segments. Chest per-

cussion should be performed with care in patients

with osteoporosis or bone problems. Cough also is an

effective technique for removing excess mucus from

the larger airways. Patients with COPD have im-

paired cough mechanisms (maximal expiratory flow

is reduced, ciliary beat is impaired), and the mucus

itself has altered viscoelastic properties.

Because cough spasms may lead to dyspnea,

fatigue, and worsened obstruction, directed cough

might be helpful by modulating the beneficial effect

and preventing the untoward effects. With controlled

coughs, patients are instructed to inhale deeply, hold

their breath for a few seconds, then cough two or three

times with the mouth open. Patients also are instructed

to compress the upper abdomen to assist in the cough.

Pulmonary functions do not improve with any of

these techniques. A combination of postural drain-


age, percussion, vibration, and cough increases the

clearance of inhaled radiotracers and increases spu-

tum volume and weight. The most important crite-

rion for chest physical therapy is the presence of

sputum production.

The use of one or more of these modalities during

the perioperative period is the routine in high-risk

surgery, including lung-volume reduction surgery

and transplantation. An adequate preparation of

the patient makes him or her more capable of man-

aging the postoperative period with more knowledge

and confidence.

Vaccination

The causes of exacerbations of COPD are poorly

understood and probably are multifactorial. Influenza

virus and Streptococcus pneumoniae may play a role,

and when either of these infections occurs, patients

with chronic lung disease have an increased incidence

of serious complications, including death [58]. One of

the national health objectives in the United States for

2000 was to increase influenza and pneumococcal

vaccination levels to greater than 60% among persons

at high risk for complications and all persons 65 years

old or older; this includes all patients with COPD and

other forms of chronic lung disease, regardless of age.

Because the influenza vaccine is type specific and

serotypes are constantly changing, vaccination must

be repeated every year, preferably at the beginning of

the season in the fall. The pneumococcal vaccine is

polyvalent, and its benefits should last a lifetime [59].

One of the responsibilities of a rehabilitation program

is to educate enrollees about the importance of

vaccination against influenza and pneumococcal

infections and to ensure that it is performed and, for

influenza, repeated annually. Although not specific

for surgery, it is recommended that attention be paid

to these details because a healthier individual is more

likely to have a better outcome.

Long-term adherence to pulmonary rehabilitation

Although the short-term effects of pulmonary

rehabilitation in multiple outcome areas are firmly

established, the long-term effectiveness of this ther-

apy often is disappointing. In controlled trials of

pulmonary rehabilitation, gains in exercise perfor-

mance and health status obtained after 6 to 8 weeks

of therapy essentially disappear by 18 to 24 months

[60,61]. It seems illogical, however, to expect that a

therapy that is applied only for 6 to 8 weeks could

modify the natural course of the disease substanti-

ally. The decline in function probably is greater than

what would be expected from progression of the

underlying disease process. In all likelihood, two

factors are mainly responsible for this drop-off in

effectiveness: (1) exacerbations of underlying lung

disease, leading to prolonged symptoms and a reas-

sumption of a more sedentary lifestyle, and (2) a

gradual decline in adherence to the postrehabilitation

exercise prescription.

The pulmonary rehabilitation program designed

for patients undergoing lung reduction surgery or

lung transplant must include strategies to promote

long-term adherence. One approach would be to

incorporate more actively the principles of pulmonary

rehabilitation (including exercise training) into the

home setting. This approach is supported by studies

of home-based programs, which suggest that gains

made in this setting may be longer lasting [62] than

the gains of hospital-based programs. Additionally,

giving a ‘‘booster shot’’ of pulmonary rehabilitation

after an exacerbation, emphasizing short periods of

supervised exercise training to return the patient to

baseline performance, would seem to be a reasonable

intervention in selected cases.

Program organization

The pulmonary rehabilitation program needs a

coordinator to organize the different components into

a functioning unit. The coordinator develops the

integrated program and monitors its progress and

function. The program should have resources avail-

able to teach and supervise respiratory therapy tech-

niques (eg, oxygen, use of inhalers, nebulizers),

physical therapy (breathing techniques, chest physical

therapy, postural drainage), exercise conditioning

(upper and lower extremity), and activities of daily

living (work simplification, energy conservation).

Also desirable are services to evaluate and advise

on nutritional needs, psychological evaluation, and

support of vocational counseling [63].

The decision whether to have an inpatient or an

outpatient program depends on the methods of reim-

bursement, patient population, available personnel,

and institutional policy. The ideal system is one that

provides an in-hospital component for patients who

may benefit from the program while recovering from

acute exacerbations and an outpatient component

(including home therapy) that could complete the

program started in the hospital. This system ensures

good continuity of care.


Outcomes and pulmonary rehabilitation

Outcome analysis can be defined as the assess-

ment of the ‘‘consequences’’ of an intervention.

Pulmonary rehabilitation does not affect the degree

of respiratory impairment as measured by tests of

physiologic pulmonary function. Exercise training

in rehabilitation increases the content of oxidative

enzymes in the trained muscles, however, and this

is accompanied by a beneficial delay in the gen-

eration of lactate (a marker of muscle performance).

This delay results in improved exercise performance

and dyspnea and may be responsible, at least in

part, for the improved functional capacity of these

patients. Although pulmonary rehabilitation does

not change the impairment (lung function), it has a

profound impact on the disability and handicap of

the patient.

Outcome assessment for pulmonary rehabilitation

encompasses three different areas: (1) a generalized

audit of the effectiveness of the global pulmonary

rehabilitation program and its components; (2) evalua-

tion of individual patient response to the interven-

tion; and (3) assessment of the effect of pulmonary

rehabilitation on society, especially with respect to

its effect on health care use and its cost-effective-

ness. Commonly used outcome measures are listed

in Table 2.

Evaluating the effectiveness of the pulmonary

rehabilitation program is important in continuous

quality assessment. Testing can be made in several

areas, especially in the measurement of dyspnea,

exercise performance, and health status. Dyspnea

evaluation falls into two categories: measurement of

exertional dyspnea during standardized exercise test-

Table 2

Examples of outcome assessment for pulmonary rehabilitation

Exertional dyspnea Borg scale or visual anal

Dyspnea with daily activities Modified Medical Resea

Dyspnea Indexes (BDI/T

Functional exercise capacity 6-min walk test, increme

Laboratory measures of exercise

performance

Incremental cardiopulmo

work rate

Health status Chronic Respiratory Dise

Questionnaire (SGRQ), M

Functional performance Pulmonary Functional St

Dyspnea Questionnaire (

Nutritional status/body composition Body mass index, body c

x-ray absorption

Psychological variables Measurement of anxiety

(HAD) questionnaire

ing, and questionnaire-measurement of breathless-

ness. Exertional dyspnea usually is rated using a

Borg scale or visual analogue scale [63]. Question-

naire-measurement of dyspnea usually assesses dysp-

nea associated with daily activities or the effect of

exertional dyspnea in limiting activities [64].

Exercise performance can be measured in the

laboratory, using protocols involving incremental

treadmill or stationary bicycle exercise. Field tests

of exercise performance, such as the 6-minute walk

test or the shuttle walk test, are performed more com-

monly. The 6-minute walk test is easy to perform,

relates well to functional status, and is responsive to

the pulmonary rehabilitation intervention. For the

shuttle walk test [65], the patient is instructed to

walk around a 10-m course at gradually increasing

speeds. Speed is determined by an auditory beeping

signal that sets the pace. The test is terminated when

the patient cannot complete the course in time,

usually because of breathlessness. Total distance

traveled is the variable assessed. Fig. 3 shows the

increase in the 6-minute walk distance of 26 patients

who underwent lung reduction surgery at St. Eliz-

abeth’s Medical Center.

Health status often is assessed using respiratory-

specific questionnaires, such as the Chronic Respira-

tory Disease Questionnaire (CRQ) or the St. George’s

Respiratory Questionnaire (SGRQ) [66,67]. Some

pulmonary rehabilitation programs also may use a

generic instrument, such as the Medical Outcomes

Study Short Form 36 (SF-36) [25], to complement

information from the respiratory-specific question-

naires. Using these tools, it has been shown that lung

surgery does result in significant improvement in

these outcomes [5,25,68–70]. Assessment in the

ogue scale during exercise testing

rch Council (MRC) questionnaire, Baseline and Transitional

DI), San Diego Shortness of Breath Questionnaire

ntal and endurance shuttle walk tests

nary exercise testing, endurance testing at constant

ase Questionnaire (CRQ), St. George’s Respiratory

edical Outcomes Study Short Form 36 (SF-36)

atus Scale (PFSS), Pulmonary Function Status and

PFSDQ)

omposition using bioelectrical impedance or dual-energy

and depression using the Hospital Anxiety and Depression

100

150

200

250

300

350

Baseline 2 weeks 4 weeks 6 weeks 8 weeks

6 M

WD

(met

ers)

Fig. 3. The 6-minute walk distance (6MWD) of patients

completing a comprehensive pulmonary rehabilitation

program at St. Elizabeth’s Medical Center increased 22%

after 8 weeks of training.


areas of nutrition and body composition, educational

goal achievement, and psychosocial variables (eg,

anxiety, depression, or coping skills) also is possible.

Despite the short time that has elapsed since the

introduction of outcome studies, there is evidence

that pulmonary rehabilitation results in significant

improvement in many outcomes, all of which are im-

portant to patients. These outcomes include reduced

exertional dyspnea, decreased dyspnea with daily

activities, increased exercise performance of the

lower and upper extremities, increased peripheral

muscle strength, increased strength and endurance of

respiratory muscles, increased self-efficacy for walk-

ing, improved health status, and reduced health care

use and increased cost-effectiveness.

Summary

Pulmonary rehabilitation gradually has become

the gold standard treatment for patients with severe

lung disease, especially COPD. By definition, reha-

bilitation services are provided to patients with symp-

toms, most of whom have moderate-to-advanced lung

disease. Because new therapeutic strategies, such as

lung volume-reduction surgery and lung transplanta-

tion, require well-conditioned patients, pulmonary

rehabilitation is becoming a crucial component of

the overall treating strategy of many patients who

heretofore were deemed untreatable. The positive

results in several randomized trials have documented

the effectiveness of pulmonary rehabilitation. Cur-

rently, pulmonary rehabilitation should be made

available to all patients with symptomatic respiratory

disease and be an integral part of any program

considering high-risk surgery.

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Index

Note: Page numbers of article titles are in boldface type.

A

Acute right heart failure, after lung surgery, 329–330

Amiodarone, for arrhythmias, after lung surgery, 327

Arrhythmias, after lung surgery, 325–327

Aspirin, for myocardial infarction, after lung

surgery, 327

Atrial tachyarrhythmias, after lung surgery, 325–327

B

b-Blockers, for myocardial infarction, after lung

surgery, 328

Breathing training, in pulmonary rehabilitation, after

lung resection, 423

Bronchiolitis obliterans, and quality of life, 402

Bronchoscopy, to predict postoperative pulmonary

function, 319

C

Cardiac herniation, after lung surgery, 325

Cardiopulmonary function, after lung surgery,

325–330

acute right heart failure and, 329–330

arrhythmias and, 325–327

cardiac herniation and, 325

chronic heart failure and, 328–329

hypertension and, 328

myocardial infarction and, 327–328

to predict postoperative pulmonary function, 318

Chemotherapy, and preoperative pulmonary

function, 299

Chest physical therapy, in pulmonary rehabilitation,

after lung resection, 423

Chronic heart failure, after lung surgery, 328–329

Chronic obstructive pulmonary disease, lung

resection for, pulmonary rehabilitation after.

See Pulmonary rehabilitation.

lung volume reduction surgery for, quality of life

after. See Quality of life.

pulmonary function in, preoperative optimization

of. See Pulmonary function.

Computed tomography, to predict postoperative

pulmonary function, 319

D

Diaphragmatic breathing, in pulmonary

rehabilitation, after lung resection, 423

Directed cough, in pulmonary rehabilitation, after

lung resection, 423

DLCO, to predict postoperative pulmonary

function, 318

E

Emphysema, lung transplantation for, quality of life

after, 401

Epidural anesthesia, thoracic, and postthoracotomy

pain syndrome, 348

Esophageal surgery, quality of life after. See Quality

of life.

return to work after, 413

Exercise tests, and preoperative pulmonary function,

297, 299

Exercise training, in pulmonary rehabilitation, after

lung resection, 421–422

F

Fundoplication, for gastroesophageal reflux disease,

quality of life after, 371

1547-4127/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved.

doi:10.1016/S1547-4127(04)00101-X


G

Gastroesophageal reflux disease, surgery for,

quality of life after. See Quality of life, after

esophageal surgery.

Glycoprotein IIb/IIIa inhibitors, for myocardial

infarction, after lung surgery, 327–328

H

Heart failure, after lung surgery, 328–330

Heparin, for myocardial infarction, after lung

surgery, 327

Hypertension, after lung surgery, 328

pulmonary, and preoperative pulmonary

function, 299

I

Inspiratory muscle training, and preoperative


L

Laparoscopic fundoplication, for gastroesophageal

reflux disease, quality of life after, 371

Long thoracic nerve, injury of, thoracic surgery

and, 334

Low-molecular-weight heparin, for myocardial

infarction, after lung surgery, 327

Lung surgery, cardiovascular function after.

See Cardiopulmonary function.

pulmonary function after.

See Pulmonary function.

pulmonary function optimization before.

See Pulmonary function.

quality of life after. See Quality of life.

return to work after. See Thoracic surgery, return

to work after.

risk acceptance and risk aversion in, 287–293

decision making in, 290–292

numeracy in, 287–288

patient preferences in, 288–290

Lung transplantation, quality of life after.

See Quality of life.

return to work after, 414

Lung volume reduction surgery, quality of life after.

See Quality of life.

M

Magnetic resonance imaging, to predict postoperative


Median sternotomy, pulmonary function after,

319–320

Minimally invasive thoracic surgery. See Video-

assisted thoracoscopic surgery.

Muscle-sparing thoracotomy, shoulder disorders

after, 333–335, 340

Myocardial infarction, after lung surgery, 327–328

Myofascial pain, in postthoracotomy pain

syndrome, 347

N

Neurogenic tumors, video-assisted thoracoscopic

surgery for, return to work after, 414

Neurohumoral paradigm, for chronic heart

failure, 329

Neuropathic pain, in postthoracotomy pain

syndrome, 347

Nutritional status, and preoperative pulmonary

function, 299, 300

Nutritional support, in pulmonary rehabilitation, after

lung resection, 423

P

Pain control, postoperative, and postthoracotomy

pain syndrome, 347–348

and reduced pulmonary function, 320

and shoulder disorders, 334–335

Postthoracotomy pain syndrome, 345–352

and quality of life, 349–350

etiology of, 346–347

incidence of, 345

management of, 350–351

myofascial pain in, 347

neuropathic pain in, 347

pain characteristics in, 345–346

pain control and, 347–348

pathogenesis of, 346–347

posterolateral thoracotomy and, 348

predictors of, 347

rib resection and, 349

surgical technique and, 348–349

thoracic epidural anesthesia and, 348

video-assisted thoracoscopic surgery and, 349

Index / Thorac Surg Clin 14 (2004) 429–433430

Procainamide, for arrhythmias, after lung

surgery, 327

Pulmonary function, postoperative, 317–323

degree of resection and, 320

long-term changes in, 320–321

pain control and, 320

preoperative assessment for, 317–319

bronchoscopy in, 319

cardiopulmonary function in, 318

computed tomography in, 319

DLCO in, 318

magnetic resonance imaging in, 319

spirometry in, 317–318

surgical approach and, 319–320

median sternotomy, 319–320

thoracotomy, 319

video-assisted thoracoscopic surgery, 319

preoperative optimization of, 295–304

age in, 299

future research on, 301

gender in, 299

in chronic obstructive pulmonary disease, 295,

297, 299

exercise tests in, 297, 299

prediction of, 295, 297

pulmonary function tests in, 297

scoring systems in, 299

inspiratory muscle training in, 300

nutritional status in, 299, 300

patient selection in, 300–301

preoperative chemotherapy and radiation

therapy in, 299

pulmonary function tests in, 300–301

pulmonary hypertension in, 299

smoking cessation in, 300

Pulmonary function tests, and preoperative

pulmonary function, 297, 300–301

Pulmonary hypertension, and preoperative


Pulmonary rehabilitation, after lung resection,

417–428

definitions and goals of, 417–419

education in, 422

exercise training in, 421–422

indications for, 419–420

long-term adherence to, 424

nutritional support in, 423

outcomes of, 425–426

program organization in, 424

psychosocial training and support in, 422

rationale for, 419

smoking cessation in, 420–421

vaccination in, 424

ventilatory therapy in, 423–424

Q

Quality of life, after esophageal surgery, 367–374

instruments for, 367–369

after laparoscopic fundoplication, 371

after minimally invasive esophagectomy,

370–371

after open esophagectomy, 369–370

after open fundoplication, 371

disease-specific, 368–369

EORTC questionnaires, 369, 370

Gastroesophageal Reflux Disease–Health

Related Quality of Life Scale, 369

Gastrointestinal Symptom Rating Scale,

368–369

generic, 368

in esophageal cancer, 369

in gastroesophageal reflux disease,

371–372

Psychological General Well-Being

Index, 368

SF-36, 368

Spitzer Quality of Life Index, 370

versus medical therapy, 372

after lung resection, 305–315

clinical studies on, 356–362

comparison of results in, 310–311

data analysis in, 311–314

evaluation criteria in, 309

imputation methods in, 307–308

instruments for, 354, 356

EORTC Quality of Life Questionnaires,

355, 356, 357, 358, 360, 362

Ferrans and Powers Quality of Life

Index, 355

Functional Assessment of Cancer

Therapy, 355

Functional Living Index-Cancer, 355

Lung Cancer Symptom Scale, 355

Nottingham Health Profile, 355

Rotterdam Symptom Checklist, 355

SF-36, 355, 357, 358, 359

Sickness Impact Profile, 355, 356, 358

Spitzer Quality of Life Index, 356,

357, 358

WHO Quality of Life Instrument, 355

long-term, 361

measurement of, 354

simulation study in, 308–309

symptom assessment in, 306–307

Index / Thorac Surg Clin 14 (2004) 429–433 431

versus health-related quality of life, 353–356

with video-assisted thoracoscopic surgery, 362

after lung transplantation, 385–407

bronchiolitis obliterans and, 402

comparative studies on, 401

cross-sectional studies on, 387, 392, 400

economic evaluation and cost-effectiveness in,

402–403

employment and, 402

exercise and education in, 401–402

for emphysema, 401


Basic Personality Inventory, 392

Beck Depression Inventory, 390

Body Cathexis Scale, 391

Brief Symptom Inventory, 390–391

Campbell Sense of Well-Being Scale, 392

Derogatis Sexual Functioning

Inventory, 391

Difficulty with Adherence, 391

EuroQol, 387, 388, 392

General Health/QOL Rating Scale, 389

general health questionnaire, 389

Hospital Anxiety and Depression

Scale, 390

Illness Intrusive Rating Scale, 391

Index of Well Being, 389

Karnofsky Performance Status, 391

Nottingham Health Profile, 388

Overall QOL visual analog scale, 388

Perceived Social Support Related to

Transplantation, 392

Pulmonary-specific QOL Scale, 392

Quality of Life Index, 389

Quality of Well-Being scale, 389

Rosenberg Self-Esteem Scale, 392

SF-20, 388

SF-36, 388

Sickness Impact Profile, 390

Sleep Disturbance, 391

Standard Gamble, 387, 389–390

State-Trait Anxiety Inventory, 390

Symptom Checklist-90, 390

Symptom Frequency/Symptom Distress

Scale, 391

Time Trade Off, 387, 390

Transplant Symptom Frequency and

Distress Scale, 391

UCLA Loneliness Scale-Revised, 391

Zung Self-rating Depression Scale, 390

limitations in, 403–405

longitudinal studies on, 400–401

significance of, 385–386

after lung volume reduction surgery, 375–383

case-control series of, 377–380


National Emphysema Treatment Trial on, 382

randomized studies of, 380–382

R

Radiation therapy, and preoperative pulmonary

function, 299

Respiratory failure, after lung resection, pulmonary

rehabilitation for. See Pulmonary rehabilitation.

Rib resection, and postthoracotomy pain

syndrome, 349

S

Shoulder disorders, after thoracic surgery, 331–343

etiology of, 331–335

muscle division, 332–334

patient positioning, 332

postoperative pain, 334–335

long thoracic nerve injury, 334

posterolateral versus muscle-sparing

thoracotomy, 335, 340

rehabilitation for, 340

video-assisted thoracoscopic surgery, 334, 340

Smoking cessation, and preoperative pulmonary

function, 300

in pulmonary rehabilitation, after lung resection,

420–421

Spirometry, to predict postoperative pulmonary

function, 317–318

T

Tachyarrhythmias, atrial, after lung surgery, 325–327

Thoracic epidural anesthesia, and postthoracotomy

pain syndrome, 348

Thoracic surgery, return to work after, 409–416

as outcome measure, 410

costs of absenteeism, 409–410

for benign thoracic pathology, 413–414

for esophageal cancer, 413

for lung cancer, 410, 412–413

open surgery, 412

video-assisted thoracoscopic surgery,

412–414

future research on, 414

shoulder disorders after. See Shoulder disorders.

Index / Thorac Surg Clin 14 (2004) 429–433432

Thoracotomy, pain after. See Postthoracotomy

pain syndrome.

pulmonary function after, 319

return to work after, 412, 414

shoulder disorders after. See Shoulder disorders,

after thoracic surgery.

V

Vaccination, in pulmonary rehabilitation, after lung

resection, 424

Ventilatory therapy, in pulmonary rehabilitation, after

lung resection, 423

Video-assisted thoracoscopic surgery, and

postthoracotomy pain syndrome, 349

pulmonary function after, 319

quality of life after, 362

return to work after, 412–414

shoulder disorders after, 334, 340

Index / Thorac Surg Clin 14 (2004) 429–433 433

Documents

Quality of life after thoracic surgery