Summary of Key Points
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Predicted postoperative forced expiratory volume in 1 second (ppoFEV 1 ) has been shown to be inaccurate in predicting actual postoperative FEV 1 in patients with chronic obstructive pulmonary disease (COPD). It should not be used alone to select patients for surgery.
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FEV 1 and carbon monoxide lung diffusion capacity (DLCO) and their derivate ppoFEV 1 and predicted postoperative DLCO (ppoDLCO) should be measured and calculated in all candidates for lung resection by estimating the number of functioning segments to be removed during an operation.
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ppoDLCO has been shown to be a reliable predictor of pulmonary morbidity and mortality in both patients with and patients without COPD.
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Low-technology exercise tests (i.e., Shuttle Walk Test and Stair-Climbing Test) may be used to screen patients before surgery. However, poor performance at these tests (i.e., <25 shuttles or 400 m at Shuttle Walk Test or <22 m at Stair-Climbing Test) indicates functional limitation. These patients should be referred to cardiopulmonary exercise test (CPET).
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CPET assesses the global fitness of the patient expressed as the rate of maximum oxygen (VO 2peak ) consumption and several other direct and derivate measures, which can be used to identify the limiting factor in the oxygen transport system.
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A VO 2peak less than 10 mL/kg/min or over 35% of the predicted value indicates high risk for anatomic lung resection.
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Cardiac risk stratification should be performed in all candidates for lung resection. The use of a risk score, such as thoracic Revised Cardiac Risk Index (ThRCRI), is a simple and reliable means to refer patients to noninvasive cardiac evaluation (i.e., ThRCRI >1.5).
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Appropriately aggressive cardiac interventions should be instituted before surgery only for patients who would need such interventions irrespective of the planned surgery. However, prophylactic coronary revascularization before surgery in patients who otherwise do not need such a procedure does not appear to reduce perioperative risk.
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Minimally invasive thoracic surgery (video-assisted thoracoscopic surgery) has been shown to be associated with reduced risk of morbidity and mortality, particularly in high-risk patients.
For stage I and II nonsmall cell lung cancer, resection is the best validated treatment option with the aim of cure. In order for this aim to be achieved, not only should the tumor be resectable, but also the patient should be operable (i.e., fit enough to undergo the resection as well as to have satisfactory postoperative quality of life). Deciding on resectability typically is a team effort and depends on staging based on adequate imaging of the tumor and its potentially metastatic sites, both locoregional and systemic. Operability is based first on the risk of immediate perioperative and postoperative complications and second on the risk of long-term disability after resection of parts of the affected lung (or lungs). Consequently, the decision to proceed with curative-intent surgery should take into account both aspects of operability. This decision is becoming increasingly critical as alternative strategies for resection are gaining ground and outcomes are promising, particularly for patients with smaller (stage 1A) tumors, despite the fact that many patients who are judged to be inoperable receive stereotactic radiotherapy and are not selected for inclusion in phase II studies.
Many patients with lung cancer have been smokers and have comorbidities resulting from damage to sensitive organs and organ systems. Damage to lung tissue resulting in COPD with reduced pulmonary function and atherosclerotic cardiovascular disease are the most common findings in these patients. The presence of such comorbidities makes it critical to evaluate the possibly increased risks of both long-term disability and possible perioperative complications. Preoperative physiologic assessment aims to quantify the magnitude of this risk.
Furthermore, lung cancer is a disease of elderly people and logically many of these patients may have comorbid conditions such as diabetes or renal disease.
Evaluation of Comorbidity
Comorbid conditions are best evaluated with use of the Charlson Comorbidity Index ( Table 26.1 ), which has been shown to be an independent predictor of surgical mortality as well as long-term survival. A subset of 1844 patients with lung cancer who had had surgical resection in Norway from 1993 to the end of 2005 was evaluated according to the Charlson Comorbidity Index, and potential factors influencing 30-day mortality were analyzed. The overall mortality rate within 30 days postoperatively was 4.4%. Male gender (odds ratio, 1.76), older age (odds ratio, 3.38 for an age between 70 and 79 years), right-sided tumors (odds ratio, 1.73), and extensive procedures (odds ratio, 4.54 for pneumonectomy) were identified as risk factors for postoperative mortality in multivariate analysis. The Charlson Comorbidity Index was identified as an independent risk factor for postoperative mortality ( p = 0.017).
| Score | Condition |
|---|---|
| 1 | Coronary artery disease Congestive heart failure Chronic pulmonary disease Peptic ulcer disease Peripheral vascular disease Mild liver disease Cerebrovascular disease Connective tissues disease Diabetes Dementia |
| 2 | Hemiplegia Moderate-to-severe renal disease Diabetes with end-organ damage Any prior tumor (within 5 y of diagnosis) Leukemia Lymphoma |
| 3 | Moderate-to-severe liver disease |
| 6 | Metastatic solid tumor AIDS (not only HIV positive) |
In a study of 433 consecutive patients (340 men and 93 women) who underwent curative resection for the treatment of nonsmall cell lung cancer, the Charlson Comorbidity Index was used to estimate the risk of mortality. The overall 5-year survival rate was 52% among patients with a Charlson Comorbidity Index of 0, 48% among those with an index of 1 or 2, and 28% among those with an index of 3 or more. Multivariate analysis showed that age; a Charlson comorbidity grade of 1 or 2; a Charlson comorbidity grade of 3 or more; bilobectomy; pneumonectomy; and pathologic stages IB, IIB, IIIA, IIIB, and IV were associated with impaired survival.
Combining the score with physiologic parameters should therefore help in deciding whether a patient may be a candidate for surgery.
Estimation of Cardiac Risk
The risk of major cardiac events, defined as the occurrence of ventricular fibrillation, pulmonary edema, complete heart block, cardiac arrest, or cardiac death, during admission has been reported to be approximately 3% after major anatomic lung resection. Typical candidates for pulmonary surgery for the management of lung cancer usually have both pulmonary and cardiac diseases as a result of cigarette smoking and are potentially at increased risk for perioperative cardiovascular complications. Unfortunately, the available literature specific to cardiac risk in patients undergoing surgery for the management of lung cancer is minimal, and most of what can currently be recommended must be extrapolated from literature on intraabdominal surgery and suprainguinal vascular surgery, both of which, like lung resection, are regarded as high-risk procedures from a cardiac standpoint.
A recent study using Surveillance, Epidemiology, and End Results Medicare data on patients undergoing resection for the management of lung cancer within 1 year after coronary stenting showed that patients who had been treated with stenting had higher rates of major cardiovascular events and mortality (9.3% and 7.7%, respectively) in comparison with those who had not (4.9% and 4.6%, respectively; p < 0.0001 for both comparisons).
Two organizations have produced guidelines on the evaluation and treatment of cardiac risk factors in candidates for lung resection: (1) the European Respiratory Society/European Society of Thoracic Surgeons (ERS/ESTS) joint task force and (2) the American College of Chest Physicians (ACCP).
In general, a detailed evaluation for coronary heart disease is not recommended for patients who have an acceptable exercise tolerance or a Revised Cardiac Risk Index (RCRI) of less than 2.5.
The RCRI, as originally described by Lee et al., is a four-class cardiac risk score with six factors, including a history of coronary artery disease, cerebrovascular accident, insulin-dependent diabetes, congestive heart failure, a serum creatinine level of greater than 2 mg/dL, and high-risk surgery. All factors are equally weighted, and one point is assigned for the presence of each factor.
Although the RCRI was cited as the preferred cardiac risk score in the recently published American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology/European Society of Anaesthesiology guidelines as well as by the joint ERS/ESTS task force on fitness for radical treatment of patients with lung cancer, this score originally was developed from a generic surgical population that included only a small group of thoracic patients. Brunelli et al. recently recalibrated the RCRI in a study involving a large population of candidates for major anatomic lung resection to obtain a more specific tool for our setting. In that study, only four of the original six factors were found to be reliably associated with major cardiac morbidity and these four factors were assigned different weights (history of coronary artery disease, 1.5 points; cerebrovascular disease, 1.5 points; serum creatinine level of greater than 2 mg/dL, 1 point; and pneumonectomy, 1.5 points). The resulting aggregate score, ranging from 0 to 5.5 points and named the ThRCRI, was found to be more accurate than the traditional score in this population (c index, 0.72 compared with 0.62; p = 0.004). The risk of major cardiac events was 23% for patients with an aggregate score of more than 2.5 (class D), compared with 1.5% for those with a score of 0 (class A).
The ThRCRI was subsequently validated in a number of studies. Most recently, the score was tested and validated in a large population of patients who were included in the Society of Thoracic Surgeons (STS) database. Major cardiovascular complications were reported in 4.3% of more than 26,000 patients who underwent pulmonary anatomic resection. The average ThRCRI score for patients without major cardiovascular complications was half of that for patients with complications (0.6 compared with 1.1; p < 0.0001). Incremental differences in the risk of major cardiovascular complications were noted among the score categories (grade A, 2.9%; grade B, 5.8%; grade C, 11.9%; grade D, 11.1%; p < 0.0001). On the basis of this recent evidence, the ACCP guidelines included this parameter in their updated cardiac algorithm.
According to the ACC/AHA guidelines, noninvasive cardiac evaluation is recommended for patients with limited capacity for exercise, those with a ThRCRI of more than 1.5, and those with a known or newly suspected cardiac condition to identify the relatively small proportion of patients who need intensified intervention to control heart failure or arrhythmias or to treat underlying myocardial ischemia.
Appropriately aggressive cardiac interventions should be instituted before surgery only for patients who would need such interventions irrespective of the planned surgery. However, prophylactic coronary revascularization before surgery in patients who otherwise do not need such a procedure does not appear to reduce perioperative risk. McFalls et al. recently demonstrated that, in a population of patients undergoing major elective vascular surgery who had concomitant stenosis of more than 70% in one or more coronary vessels, prophylactic percutaneous coronary intervention or coronary artery bypass grafting did not change the risk of 30-day mortality, postoperative myocardial ischemia, or long-term survival.
Recent data from the Perioperative Ischemic Evaluation study group indicated that although commonly used regimens of perioperative beta-blockers reduced the risk of cardiovascular death and nonfatal myocardial ischemia (hazard ratio, 0.84), they actually increased the risk of stroke (hazard ratio, 2.17) and overall mortality (hazard ratio, 1.33), perhaps by interfering with stress responses in critically ill patients. Therefore, the new institution of a beta-blocker therapy is not recommended for patients with ischemic heart disease who are not already taking them.
Finally, CPET has been shown to be a useful tool for detecting both overt and occult exercise-induced myocardial ischemia with a diagnostic accuracy similar to single-photon emission computed tomographic myocardial perfusion testing and superior to standard electrocardiographic stress testing. For this reason, CPET can be proposed as a noninvasive test for detecting and quantifying myocardial perfusion defects in patients who are at increased risk for coronary artery disease.
Predicted Postoperative Forced Expiratory Volume in 1 Second
ppoFEV 1 , which is estimated on the basis of the number of functioning, nonobstructed segments to be removed during an operation, traditionally has been used to stratify respiratory risk in candidates for lung resection. The following equations can be applied to estimate the residual lung function.
For candidates for pneumonectomy, the perfusion method is used with the following formula:
ppoFEV 1 = preoperative FEV 1 × ( 1 − fraction of total perfusion for the resected lung )
A quantitative radionuclide perfusion scan is performed to measure the fraction of total perfusion for the resected lung. For candidates for lobectomy, the anatomic method is used with the following formula:
ppoFEV 1 = preoperative FEV 1 × ( 1 – a / b )
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