- Email: [email protected]
Lobectomy for Patients With Limited Lung Function
STATE OF THE ART
Lobectomy for Patients With Limited Lung Function Sai Yendamuri, MBBS, and Todd L. Demmy, MD Increasingly, lung cancer is being diagnosed at an early stage. This trend is likely to increase with computerized tomographic screening as a result of the findings of the National Lung Screening Trial. Even in 2011, anatomical lobectomy is the gold standard for curative resection for early lung cancer. However, a significant proportion of patients with early lung cancer have limited lung function that places them at higher risk of complications from lobectomy. This article reviews the existing data for lobectomy in patients with limited lung function. Semin Thoracic Surg 23:191-195 © 2011 Elsevier Inc. All rights reserved. Keywords lung cancer, lobectomy, outcomes, pulmonary function According to the 2011 report of the American Cancer Society, ⬃221,000 new cases of lung cancer will be diagnosed in the United States alone, with 157,000 patients succumbing to the disease.1 The best chance of cure for these patients involves successful surgical resection. About 30,000 patients in the United States undergo lung resection greater than a wedge every year, ⬃95% of which are done for cancer.2 In a substantial proportion of these patients, the thoracic surgeon has to carefully judge the risk of perioperative complications versus potential benefit to the patient. Risk stratification enables informed decision-making for the surgeon and the patient. Trend studies demonstrate that the complexity of patients undergoing lung cancer resection continues to increase, making this aspect of surgical decision-making increasingly complex. A survey of the national Medicare Provider Analysis and Review (MEDPAR) files by Finks et al3 demonstrated that the proportion of patients with ⱖ3 major coexisting conditions increased from 26.6% to 36.5% from the periods 1999-2000 to 2007-2008, respectively. Although several coexisting conditions are important determinants of resectability, one of the most important variables affecting the decision to offer surgery is the adequacy of the patient’s pulmonary reserve.
Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, New York. Address reprint requests to Todd L. Demmy, MD, Department of Thoracic Surgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263. E-mail: [email protected]
1043-0679/$-see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1053/j.semtcvs.2011.09.004
WHAT CONSTITUTES LIMITED LUNG FUNCTION? Different investigators advocate different cutoffs for determination of limited lung function. One potential definition of limited lung function is the need for additional testing beyond routine spirometry (including diffusion capacity of lung for carbon monoxide [DLCO]) for risk stratification. Use of this definition leads to a cutoff of predictive postoperative forced expiratory volume in 1 second (ppoFEV1%) or a predictive postoperative DLCO (ppoDLCO%) of ⬍40%,4 according to current guidelines published by the American College of Chest Physicians. In a prospective study by Brunelli et al,5 the proportion of patients who undergo surgery that fits this criteria is 8.7% (23/263). Therefore, approximately 2600 patients in the United States have limited lung function and undergo surgical resection greater than a wedge resection for lung cancer, making this an important issue for discussion. EVALUATION OF THE PATIENT WITH LIMITED LUNG FUNCTION Patients with limited lung function should be assessed further for suitability of resection by a split lung function test and a cardiopulmonary exercise test (CPET).4,6 Split lung function testing assesses the homogeneity of lung dysfunction by using the distribution of pulmonary perfusion by using a radiotracer and enables a more accurate estimation of predicted postoperative pulmonary function. Cardiopulmonary exercise testing assesses the response of the cardiorespiratory system to stress in the form of exercise. The variable generated by CPET that has been most extensively correlated to outcome after thoracic surgery is 191
LOBECTOMY FOR PATIENTS WITH LIMITED LUNG FUNCTION Table 1. Contemporary Studies With Outcome Data for Lobectomy in Patients With Limited Lung Function Mortality Reference Thoracotomy only Brunelli et al,5 2009 Lau et al,37 2011 Bobbio et al,38 2009 VATS versus open Berry et al,36 2010 Berry et al,36 2010 Kachare et al,35 2011
N
23
Definition of Limited Function
Morbidity
Open (%)
VATS (%)
Open (%)
VATS (%)
4.7
—
22
—
35
ppoFEV1% or ppoDLCO% ⬍40% ppoFEV1% ⬍40%
14
—
85.7
—
14
VO2 max ⬍15 mL/kg/min
N/A
—
43
—
55 (open, 27; VATS, 28) ppoDLCO% ⬍45%
N/A
N/A
37
14
87 (open, 40; VATS, 47) ppoFEV1% ⬍45%
N/A
N/A
45
13
4.3
2.1
21.7
70 (open, 23; VATS, 47) ppoFEV1% ⬍40% or ppoDLCO% ⬍40%
4.3
N/A, data not available.
maximal oxygen uptake (VO2 max). A small study of 22 patients in 1984 suggested a cutoff of 15 mL/kg/min as a cutoff for lobectomy.7 Although several follow-up investigations have suggested different cutoffs for anatomical resection, a fair generalization is that patients with VO2 max ⬎20 mL/kg/min are good risk candidates, and patients with VO2 max ⱕ10 mL/kg/min have a prohibitive risk. Some studies have suggested that instead of a number indexed on weight, the percentage predicted VO2 max might be a better estimate of operability.8,9 Few data are available for patients with VO2 max ⬍10 mL/kg/min; these data are limited to small case series in which mortality rate varied from 27%-50%.10-12 The rest of this review will discuss patients with limited function as defined by either ppoFEV1% or ppoDLCO% ⬍40% with VO2 max ⱖ10 mL/kg/min. RISK OF LOBECTOMY IN PATIENTS WITH LIMITED LUNG FUNCTION Most data defining the risk of patients with lobectomy with limited lung function have been in the era of thoracotomy. Table 1 summarizes data available from some studies evaluating these outcomes. For current relevance, only studies published after 2005 are included. In most instances these are subsets of patients within a larger cohort whose outcomes were being studied. As seen in Table 1, mortality and morbidity remain high when this is done by thoracotomy. Therefore, while offering lobectomy to these patients, optimization of the patient and procedure 192
is important. Evaluation and optimization of lung function perioperatively can optimize outcomes. LOBECTOMY OF THE PATIENT WITH LIMITED LUNG FUNCTION: STRATEGIES FOR OPTIMIZING OUTCOMES Combining Lung Volume Reduction With Lobectomy A number of investigators have studied the effect of lobectomy or pneumonectomy on patients with chronic obstructive pulmonary disease (COPD), with the observation that the reduction of FEV1 in patients with COPD undergoing resection is markedly less than in those without. The largest of these studies was reported by Baldi et al.13 In this study of 137 patients, the investigators measured preoperative and postoperative FEV1 in patients undergoing lobectomy and found that the mean postoperative FEV1 actually increased from 56% to 64% in those with COPD, whereas it decreased from 98% to 78% in those who did not. Similar findings were demonstrated by others.14,15 This can be explained potentially by the lung volume reduction effect that might come from lobectomy. However, enthusiasm for this is tempered by a few facts. First, postoperative FEV1 is only one spirometric parameter and does not encompass the entire physiological deficit that a lobectomy causes. For instance, a reduction in VO2 max in COPD patients after resection might be more important in determining outcome.16 Second, the lung vol-
Seminars in Thoracic and Cardiovascular Surgery ● Volume 23, Number 3
LOBECTOMY FOR PATIENTS WITH LIMITED LUNG FUNCTION ume reduction effect is more pronounced in patients having upper lobectomies and depends on the distribution of emphysema/bullous disease. Third, limited prospective data exist to support the routine application of such a strategy. Having stated this, in our practice, we are more liberal in offering lobectomy to patients with limited lung function when the lobectomy involved is an upper lobectomy. Optimizing Medical Management Although optimization of medical management of the COPD patient before surgery seems prudent, little has been published on this issue. A good resource for the standards to be adhered to for optimization is the guidelines published by Celli et al.17 Steroids should be limited, as far as possible, to ⬍20 mg/day of prednisone. Smoking Cessation Smoking is related to perioperative complications after lobectomy. A study by Bluman et al18 showed pulmonary complications rates of 22%, 12.8%, and 4.9% in current smokers, past smokers, and never smokers, respectively. Delineating the definition of past smokers is important, as demonstrated by Nakagawa et al.19 In 288 patients whose smoking history was carefully documented, smokers who quit ⬍4 weeks had more complications that those who quit more than 4 weeks or did not smoke at all. Although this might not be a reason to delay surgery by more than 4 weeks in a low-risk patient, every effort must be made in a patient with limited function to delay surgery to afford this time interval. Also, this is an opportune time to motivate the patient to quit smoking because quit rates are higher at this time. Pulmonary Rehabilitation Pulmonary rehabilitation has been demonstrated to improve exercise capacity in COPD patients generally. However, surprisingly, only a few studies have been performed to assess the benefits of a preoperative pulmonary rehabilitation program on postoperative outcomes. Most of the studies have been summarized well in a “best evidence” review by Nagarajan et al.20 Two studies looking at the effect of exercise capacity as measured by VO2 max demonstrated improvements of a mean of 2.4 mL/kg/min and 2.8 mL/kg/min,21,22 suggesting that in patients with borderline resectability, such an intervention might be useful to improve outcomes. However, a recent study published by Benzo et al23 highlighted practical problems of such an approach. The authors reported difficulty in enrolling patients to a random-
ized study involving 4 weeks of preoperative pulmonary rehabilitation because of the delay in surgery involved. Given this difficulty, a more realistic and rewarding approach might be optimization of perioperative pulmonary interventions as demonstrated by Varela et al.24 In a study comparing 119 patients with 520 historical controls, the authors demonstrated the benefits of an intensive perioperative chest physiotherapy program compared with routine incentive spirometry. Improvements in the rate of atelectasis and hospital length of stay were demonstrated. Although these data are plagued by small sample size and lack of randomization, optimization of perioperative lung function by these methods is likely to be particularly efficacious in patients with limited lung function, and every effort to incorporate these strategies should be made. Optimizing Perioperative Pain Control Postoperative pain and adverse effects arising from attempts to control it are major drivers of thoracic complications.25 Optimizing acute and chronic pain before surgery probably is beneficial but might not be possible in a practical time frame. It is interesting to note that in patients with impaired pulmonary reserve, the risk of acute and chronic pain is worse. The salutary effect of video-assisted thoracoscopic surgery (VATS) on complications probably arises from reducing this pain.26 A broad-based approach is needed to avoid the amplitude and duration of the pain stimulus. This is essential to prevent the “wind-up effect” of central nervous system sensitization (without peripheral nerve injury) that is the cause of chronic pain in half of those with postthoracotomy pain syndrome.27,28 Hence, early control of pain is key,29 and combinations of the following techniques are generally regarded as useful for both thoracotomy and VATS patients: preemptive anesthesia, epidural anesthesia, patient-controlled analgesia, minimizing chest tube number/size/stiffness/duration, anxiety minimization, nonsteroidal anti-inflammatory drug analgesics, paravertebral neural blockade, avoidance of suture placement near intercostal nerves, reducing pleural inflammation, and fractured rib stabilization.30,31 Epidural anesthesia is popular for thoracotomy cases, but good pain control can be achieved without this in many VATS patients.We have shown that intrapleural anesthesia delivered to the site of chest tube stimulation is an effective adjunct for many VATS patients as well.32 Keeping the Surgery VATS Perhaps the biggest advance in the treatment of high-risk patients with lung cancer is the use of
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LOBECTOMY FOR PATIENTS WITH LIMITED LUNG FUNCTION VATS for lung resection. Although the salutary benefits of VATS have been repeatedly demonstrated in all patients,33,34 advantages of VATS are particularly obvious in patients with limited lung function. In our retrospective study of 47 patients with limited lung function undergoing VATS lobectomy, there was 1 death and 4.3% rate of pneumonia, an outcome not typically seen in such high-risk cohorts.35 Benefits of VATS can be theoretically attributed to decreased perioperative pain and less interruption of the mechanics of the thoracic musculature. However, the impact of the loss of pulmonary vascular bed is independent of the surgical approach. Therefore, an expected observation would be a relative lack of association of preoperative pulmonary function with postoperative complications in VATS patients, as seen in the recent study by Berry et al.36
1. Siegel R, Ward E, Brawley O, et al: Cancer statistics, 2011: The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 61:212236, 2011 2. Memtsoudis SG, Besculides MC, Zellos L, et al: Trends in lung surgery: United States 1988 to 2002. Chest 130:1462-1470, 2006 3. Finks JF, Osborne NH, Birkmeyer JD: Trends in hospital volume and operative mortality for high-risk surgery. N Engl J Med 364:21282137, 2011 4. Colice GL, Shafazand S, Griffin JP, et al: Physiologic evaluation of the patient with lung cancer being considered for resectional surgery: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest 132:161S177S, 2007 5. Brunelli A, Belardinelli R, Refai M, et al: Peak oxygen consumption during cardiopulmonary exercise test improves risk stratification in candidates to major lung resection. Chest 135:1260-1267, 2009 6. Brunelli A, Charloux A, Bolliger CT, et al: ERS/ ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy). Eur Respir J 34:17-41, 2009 7. Smith TP, Kinasewitz GT, Tucker WY, et al: Exercise capacity as a predictor of post-thoracotomy morbidity. Am Rev Respir Dis 129: 730-734, 1984 8. Win T, Jackson A, Sharples L, et al: Cardiopulmonary exercise tests and lung cancer surgical outcome. Chest 127:1159-1165, 2005 9. Larsen KR, Lund JO, Svendsen UG, et al: Prediction of post-operative cardiopulmonary function using perfusion scintigraphy in patients with bronchogenic carcinoma. Clin Physiol 17:257-267, 1997 10. Holden DA, Rice TW, Stelmach K, et al: Exercise testing, 6-min walk, and stair climb in the
194
11.
12.
13.
14.
15.
16.
17.
18.
However, it is important to realize that VATS resections in these patients can be technically challenging and should be attempted by experienced VATS surgeons, because conversion to an open procedure has a bigger consequence on the outcome of these patients compared with the average-risk patient. CONCLUSIONS There is a paucity of outcome data for lobectomy in patients with limited lung function. In this highrisk cohort, factors that have a modest effect on outcome in the average-risk patient are likely to have a greater impact and so must be optimized. Use of a thoracoscopic approach has the potential to improve outcomes of this fragile group of patients and should be evaluated systematically.
evaluation of patients at high risk for pulmonary resection. Chest 102:1774-1779, 1992 Olsen GN, Weiman DS, Bolton JW, et al: Submaximal invasive exercise testing and quantitative lung scanning in the evaluation for tolerance of lung resection. Chest 95:267-273, 1989 Bechard D, Wetstein L: Assessment of exercise oxygen consumption as preoperative criterion for lung resection. Ann Thorac Surg 44:344349, 1987 Baldi S, Ruffini E, Harari S, et al: Does lobectomy for lung cancer in patients with chronic obstructive pulmonary disease affect lung function? A multicenter national study. J Thorac Cardiovasc Surg 130:1616-1622, 2005 Kushibe K, Kawaguchi T, Kimura M, et al: Changes in ventilatory capacity, exercise capacity, and pulmonary blood flow after lobectomy in patients with lung cancer: Which lobectomy has the most loss in exercise capacity? Interact Cardiovasc Thorac Surg 7:1011-1014, 2008 Subotic DR, Mandaric DV, Eminovic TM, et al: Influence of chronic obstructive pulmonary disease on postoperative lung function and complications in patients undergoing operations for primary non-small cell lung cancer. J Thorac Cardiovasc Surg 134:1292-1299, 2007 Bobbio A, Chetta A, Carbognani P, et al: Changes in pulmonary function test and cardio-pulmonary exercise capacity in COPD patients after lobar pulmonary resection. Eur J Cardiothorac Surg 28:754-758, 2005 Celli BR, MacNee W, ATS/ERS Task Force: Standards for the diagnosis and treatment of patients with COPD: A summary of the ATS/ ERS position paper. Eur Respir J 23:932-946, 2004 Bluman LG, Mosca L, Newman N, et al: Preoperative smoking habits and postoperative
19.
20.
21.
22.
23.
24.
25.
26.
pulmonary complications. Chest 113:883889, 1998 Nakagawa M, Tanaka H, Tsukuma H, et al: Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery. Chest 120:705-710, 2001 Nagarajan K, Bennett A, Agostini P, et al: Is preoperative physiotherapy/pulmonary rehabilitation beneficial in lung resection patients? Interact Cardiovasc Thorac Surg 13:300-302, 2011 Jones LW, Peddle CJ, Eves ND, et al: Effects of presurgical exercise training on cardiorespiratory fitness among patients undergoing thoracic surgery for malignant lung lesions. Cancer 110:590-598, 2007 Bobbio A, Chetta A, Ampollini L, et al: Preoperative pulmonary rehabilitation in patients undergoing lung resection for non-small cell lung cancer. Eur J Cardiothorac Surg 33:9598, 2008 Benzo R, Wigle D, Novotny P, et al: Preoperative pulmonary rehabilitation before lung cancer resection: Results from two randomized studies. Lung Cancer 2011 Jun 8 (Epub ahead of print) Varela G, Ballesteros E, Jiménez MF, et al: Cost-effectiveness analysis of prophylactic respiratory physiotherapy in pulmonary lobectomy. Eur J Cardiothorac Surg 29:216-220, 2006 Handy JR Jr, Asaph JW, Skokan L, et al: What happens to patients undergoing lung cancer surgery? Outcomes and quality of life before and after surgery. Chest 122:21-30, 2002 Handy JR Jr, Asaph JW, Douville EC, et al: Does video-assisted thoracoscopic lobectomy for lung cancer provide improved functional outcomes compared with open lobectomy? Eur J Cardiothorac Surg 37: 451-455, 2010
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LOBECTOMY FOR PATIENTS WITH LIMITED LUNG FUNCTION 27. Steegers MA, Snik DM, Verhagen AF, et al: Only half of the chronic pain after thoracic surgery shows a neuropathic component. J Pain 9:955-961, 2008 28. Woolf CJ: Central sensitization: Uncovering the relation between pain and plasticity. Anesthesiology 106:864-867, 2007 29. Katz J, Jackson M, Kavanagh BP, et al: Acute pain after thoracic surgery predicts long-term post-thoracotomy pain. Clin J Pain 12:50-55, 1996 30. Alex J, Ansari J, Bahalkar P, et al: Comparison of the immediate postoperative outcome of using the conventional two drains versus a single drain after lobectomy. Ann Thorac Surg 76: 1046-1049, 2003 31. Joshi GP, Bonnet F, Shah R, et al: A systematic review of randomized trials evaluating regional techniques for postthoracotomy analgesia. Anesth Analg 107:1026-1040, 2008
32. Demmy TL, Nwogu C, Solan P, et al: Chest tube-delivered bupivacaine improves pain and decreases opioid use after thoracoscopy. Ann Thorac Surg 87:1040-1046, 2009, discussion 1046-1047 33. Scott WJ, Allen MS, Darling G, et al: Videoassisted thoracic surgery versus open lobectomy for lung cancer: A secondary analysis of data from the American College of Surgeons Oncology Group Z0030 randomized clinical trial. J Thorac Cardiovasc Surg 139:976-981, 2010, discussion 981-983 34. Paul S, Altorki NK, Sheng S, et al: Thoracoscopic lobectomy is associated with lower morbidity than open lobectomy: A propensity-matched analysis from the STS database. J Thorac Cardiovasc Surg 139:366378, 2010
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35. Kachare S, Dexter EU, Nwogu C, et al: Perioperative outcomes of thoracoscopic anatomic resections in patients with limited pulmonary reserve. J Thorac Cardiovasc Surg 141:459462, 2011 36. Berry MF, Villamizar-Ortiz NR, Tong BC, et al: Pulmonary function tests do not predict pulmonary complications after thoracoscopic lobectomy. Ann Thorac Surg 89:1044-1051, discussion 1051-1052, 2010 37. Lau KK, Martin-Ucar AE, Nakas A, et al: Lung cancer surgery in the breathless patient—the benefits of avoiding the gold standard. Eur J Cardiothorac Surg 38:6-13, 2010 38. Bobbio A, Chetta A, Internullo E, et al: Exercise capacity assessment in patients undergoing lung resection. Eur J Cardiothorac Surg 35:419-422, 2009
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Lobectomy for Patients With Limited Lung Function Sai Yendamuri, MBBS, and Todd L. Demmy, MD Increasingly, lung cancer is being diagnosed at an early stage. This trend is likely to increase with computerized tomographic screening as a result of the findings of the National Lung Screening Trial. Even in 2011, anatomical lobectomy is the gold standard for curative resection for early lung cancer. However, a significant proportion of patients with early lung cancer have limited lung function that places them at higher risk of complications from lobectomy. This article reviews the existing data for lobectomy in patients with limited lung function. Semin Thoracic Surg 23:191-195 © 2011 Elsevier Inc. All rights reserved. Keywords lung cancer, lobectomy, outcomes, pulmonary function According to the 2011 report of the American Cancer Society, ⬃221,000 new cases of lung cancer will be diagnosed in the United States alone, with 157,000 patients succumbing to the disease.1 The best chance of cure for these patients involves successful surgical resection. About 30,000 patients in the United States undergo lung resection greater than a wedge every year, ⬃95% of which are done for cancer.2 In a substantial proportion of these patients, the thoracic surgeon has to carefully judge the risk of perioperative complications versus potential benefit to the patient. Risk stratification enables informed decision-making for the surgeon and the patient. Trend studies demonstrate that the complexity of patients undergoing lung cancer resection continues to increase, making this aspect of surgical decision-making increasingly complex. A survey of the national Medicare Provider Analysis and Review (MEDPAR) files by Finks et al3 demonstrated that the proportion of patients with ⱖ3 major coexisting conditions increased from 26.6% to 36.5% from the periods 1999-2000 to 2007-2008, respectively. Although several coexisting conditions are important determinants of resectability, one of the most important variables affecting the decision to offer surgery is the adequacy of the patient’s pulmonary reserve.
Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, New York. Address reprint requests to Todd L. Demmy, MD, Department of Thoracic Surgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263. E-mail: [email protected]
1043-0679/$-see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1053/j.semtcvs.2011.09.004
WHAT CONSTITUTES LIMITED LUNG FUNCTION? Different investigators advocate different cutoffs for determination of limited lung function. One potential definition of limited lung function is the need for additional testing beyond routine spirometry (including diffusion capacity of lung for carbon monoxide [DLCO]) for risk stratification. Use of this definition leads to a cutoff of predictive postoperative forced expiratory volume in 1 second (ppoFEV1%) or a predictive postoperative DLCO (ppoDLCO%) of ⬍40%,4 according to current guidelines published by the American College of Chest Physicians. In a prospective study by Brunelli et al,5 the proportion of patients who undergo surgery that fits this criteria is 8.7% (23/263). Therefore, approximately 2600 patients in the United States have limited lung function and undergo surgical resection greater than a wedge resection for lung cancer, making this an important issue for discussion. EVALUATION OF THE PATIENT WITH LIMITED LUNG FUNCTION Patients with limited lung function should be assessed further for suitability of resection by a split lung function test and a cardiopulmonary exercise test (CPET).4,6 Split lung function testing assesses the homogeneity of lung dysfunction by using the distribution of pulmonary perfusion by using a radiotracer and enables a more accurate estimation of predicted postoperative pulmonary function. Cardiopulmonary exercise testing assesses the response of the cardiorespiratory system to stress in the form of exercise. The variable generated by CPET that has been most extensively correlated to outcome after thoracic surgery is 191
LOBECTOMY FOR PATIENTS WITH LIMITED LUNG FUNCTION Table 1. Contemporary Studies With Outcome Data for Lobectomy in Patients With Limited Lung Function Mortality Reference Thoracotomy only Brunelli et al,5 2009 Lau et al,37 2011 Bobbio et al,38 2009 VATS versus open Berry et al,36 2010 Berry et al,36 2010 Kachare et al,35 2011
N
23
Definition of Limited Function
Morbidity
Open (%)
VATS (%)
Open (%)
VATS (%)
4.7
—
22
—
35
ppoFEV1% or ppoDLCO% ⬍40% ppoFEV1% ⬍40%
14
—
85.7
—
14
VO2 max ⬍15 mL/kg/min
N/A
—
43
—
55 (open, 27; VATS, 28) ppoDLCO% ⬍45%
N/A
N/A
37
14
87 (open, 40; VATS, 47) ppoFEV1% ⬍45%
N/A
N/A
45
13
4.3
2.1
21.7
70 (open, 23; VATS, 47) ppoFEV1% ⬍40% or ppoDLCO% ⬍40%
4.3
N/A, data not available.
maximal oxygen uptake (VO2 max). A small study of 22 patients in 1984 suggested a cutoff of 15 mL/kg/min as a cutoff for lobectomy.7 Although several follow-up investigations have suggested different cutoffs for anatomical resection, a fair generalization is that patients with VO2 max ⬎20 mL/kg/min are good risk candidates, and patients with VO2 max ⱕ10 mL/kg/min have a prohibitive risk. Some studies have suggested that instead of a number indexed on weight, the percentage predicted VO2 max might be a better estimate of operability.8,9 Few data are available for patients with VO2 max ⬍10 mL/kg/min; these data are limited to small case series in which mortality rate varied from 27%-50%.10-12 The rest of this review will discuss patients with limited function as defined by either ppoFEV1% or ppoDLCO% ⬍40% with VO2 max ⱖ10 mL/kg/min. RISK OF LOBECTOMY IN PATIENTS WITH LIMITED LUNG FUNCTION Most data defining the risk of patients with lobectomy with limited lung function have been in the era of thoracotomy. Table 1 summarizes data available from some studies evaluating these outcomes. For current relevance, only studies published after 2005 are included. In most instances these are subsets of patients within a larger cohort whose outcomes were being studied. As seen in Table 1, mortality and morbidity remain high when this is done by thoracotomy. Therefore, while offering lobectomy to these patients, optimization of the patient and procedure 192
is important. Evaluation and optimization of lung function perioperatively can optimize outcomes. LOBECTOMY OF THE PATIENT WITH LIMITED LUNG FUNCTION: STRATEGIES FOR OPTIMIZING OUTCOMES Combining Lung Volume Reduction With Lobectomy A number of investigators have studied the effect of lobectomy or pneumonectomy on patients with chronic obstructive pulmonary disease (COPD), with the observation that the reduction of FEV1 in patients with COPD undergoing resection is markedly less than in those without. The largest of these studies was reported by Baldi et al.13 In this study of 137 patients, the investigators measured preoperative and postoperative FEV1 in patients undergoing lobectomy and found that the mean postoperative FEV1 actually increased from 56% to 64% in those with COPD, whereas it decreased from 98% to 78% in those who did not. Similar findings were demonstrated by others.14,15 This can be explained potentially by the lung volume reduction effect that might come from lobectomy. However, enthusiasm for this is tempered by a few facts. First, postoperative FEV1 is only one spirometric parameter and does not encompass the entire physiological deficit that a lobectomy causes. For instance, a reduction in VO2 max in COPD patients after resection might be more important in determining outcome.16 Second, the lung vol-
Seminars in Thoracic and Cardiovascular Surgery ● Volume 23, Number 3
LOBECTOMY FOR PATIENTS WITH LIMITED LUNG FUNCTION ume reduction effect is more pronounced in patients having upper lobectomies and depends on the distribution of emphysema/bullous disease. Third, limited prospective data exist to support the routine application of such a strategy. Having stated this, in our practice, we are more liberal in offering lobectomy to patients with limited lung function when the lobectomy involved is an upper lobectomy. Optimizing Medical Management Although optimization of medical management of the COPD patient before surgery seems prudent, little has been published on this issue. A good resource for the standards to be adhered to for optimization is the guidelines published by Celli et al.17 Steroids should be limited, as far as possible, to ⬍20 mg/day of prednisone. Smoking Cessation Smoking is related to perioperative complications after lobectomy. A study by Bluman et al18 showed pulmonary complications rates of 22%, 12.8%, and 4.9% in current smokers, past smokers, and never smokers, respectively. Delineating the definition of past smokers is important, as demonstrated by Nakagawa et al.19 In 288 patients whose smoking history was carefully documented, smokers who quit ⬍4 weeks had more complications that those who quit more than 4 weeks or did not smoke at all. Although this might not be a reason to delay surgery by more than 4 weeks in a low-risk patient, every effort must be made in a patient with limited function to delay surgery to afford this time interval. Also, this is an opportune time to motivate the patient to quit smoking because quit rates are higher at this time. Pulmonary Rehabilitation Pulmonary rehabilitation has been demonstrated to improve exercise capacity in COPD patients generally. However, surprisingly, only a few studies have been performed to assess the benefits of a preoperative pulmonary rehabilitation program on postoperative outcomes. Most of the studies have been summarized well in a “best evidence” review by Nagarajan et al.20 Two studies looking at the effect of exercise capacity as measured by VO2 max demonstrated improvements of a mean of 2.4 mL/kg/min and 2.8 mL/kg/min,21,22 suggesting that in patients with borderline resectability, such an intervention might be useful to improve outcomes. However, a recent study published by Benzo et al23 highlighted practical problems of such an approach. The authors reported difficulty in enrolling patients to a random-
ized study involving 4 weeks of preoperative pulmonary rehabilitation because of the delay in surgery involved. Given this difficulty, a more realistic and rewarding approach might be optimization of perioperative pulmonary interventions as demonstrated by Varela et al.24 In a study comparing 119 patients with 520 historical controls, the authors demonstrated the benefits of an intensive perioperative chest physiotherapy program compared with routine incentive spirometry. Improvements in the rate of atelectasis and hospital length of stay were demonstrated. Although these data are plagued by small sample size and lack of randomization, optimization of perioperative lung function by these methods is likely to be particularly efficacious in patients with limited lung function, and every effort to incorporate these strategies should be made. Optimizing Perioperative Pain Control Postoperative pain and adverse effects arising from attempts to control it are major drivers of thoracic complications.25 Optimizing acute and chronic pain before surgery probably is beneficial but might not be possible in a practical time frame. It is interesting to note that in patients with impaired pulmonary reserve, the risk of acute and chronic pain is worse. The salutary effect of video-assisted thoracoscopic surgery (VATS) on complications probably arises from reducing this pain.26 A broad-based approach is needed to avoid the amplitude and duration of the pain stimulus. This is essential to prevent the “wind-up effect” of central nervous system sensitization (without peripheral nerve injury) that is the cause of chronic pain in half of those with postthoracotomy pain syndrome.27,28 Hence, early control of pain is key,29 and combinations of the following techniques are generally regarded as useful for both thoracotomy and VATS patients: preemptive anesthesia, epidural anesthesia, patient-controlled analgesia, minimizing chest tube number/size/stiffness/duration, anxiety minimization, nonsteroidal anti-inflammatory drug analgesics, paravertebral neural blockade, avoidance of suture placement near intercostal nerves, reducing pleural inflammation, and fractured rib stabilization.30,31 Epidural anesthesia is popular for thoracotomy cases, but good pain control can be achieved without this in many VATS patients.We have shown that intrapleural anesthesia delivered to the site of chest tube stimulation is an effective adjunct for many VATS patients as well.32 Keeping the Surgery VATS Perhaps the biggest advance in the treatment of high-risk patients with lung cancer is the use of
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LOBECTOMY FOR PATIENTS WITH LIMITED LUNG FUNCTION VATS for lung resection. Although the salutary benefits of VATS have been repeatedly demonstrated in all patients,33,34 advantages of VATS are particularly obvious in patients with limited lung function. In our retrospective study of 47 patients with limited lung function undergoing VATS lobectomy, there was 1 death and 4.3% rate of pneumonia, an outcome not typically seen in such high-risk cohorts.35 Benefits of VATS can be theoretically attributed to decreased perioperative pain and less interruption of the mechanics of the thoracic musculature. However, the impact of the loss of pulmonary vascular bed is independent of the surgical approach. Therefore, an expected observation would be a relative lack of association of preoperative pulmonary function with postoperative complications in VATS patients, as seen in the recent study by Berry et al.36
1. Siegel R, Ward E, Brawley O, et al: Cancer statistics, 2011: The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 61:212236, 2011 2. Memtsoudis SG, Besculides MC, Zellos L, et al: Trends in lung surgery: United States 1988 to 2002. Chest 130:1462-1470, 2006 3. Finks JF, Osborne NH, Birkmeyer JD: Trends in hospital volume and operative mortality for high-risk surgery. N Engl J Med 364:21282137, 2011 4. Colice GL, Shafazand S, Griffin JP, et al: Physiologic evaluation of the patient with lung cancer being considered for resectional surgery: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest 132:161S177S, 2007 5. Brunelli A, Belardinelli R, Refai M, et al: Peak oxygen consumption during cardiopulmonary exercise test improves risk stratification in candidates to major lung resection. Chest 135:1260-1267, 2009 6. Brunelli A, Charloux A, Bolliger CT, et al: ERS/ ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy). Eur Respir J 34:17-41, 2009 7. Smith TP, Kinasewitz GT, Tucker WY, et al: Exercise capacity as a predictor of post-thoracotomy morbidity. Am Rev Respir Dis 129: 730-734, 1984 8. Win T, Jackson A, Sharples L, et al: Cardiopulmonary exercise tests and lung cancer surgical outcome. Chest 127:1159-1165, 2005 9. Larsen KR, Lund JO, Svendsen UG, et al: Prediction of post-operative cardiopulmonary function using perfusion scintigraphy in patients with bronchogenic carcinoma. Clin Physiol 17:257-267, 1997 10. Holden DA, Rice TW, Stelmach K, et al: Exercise testing, 6-min walk, and stair climb in the
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However, it is important to realize that VATS resections in these patients can be technically challenging and should be attempted by experienced VATS surgeons, because conversion to an open procedure has a bigger consequence on the outcome of these patients compared with the average-risk patient. CONCLUSIONS There is a paucity of outcome data for lobectomy in patients with limited lung function. In this highrisk cohort, factors that have a modest effect on outcome in the average-risk patient are likely to have a greater impact and so must be optimized. Use of a thoracoscopic approach has the potential to improve outcomes of this fragile group of patients and should be evaluated systematically.
evaluation of patients at high risk for pulmonary resection. Chest 102:1774-1779, 1992 Olsen GN, Weiman DS, Bolton JW, et al: Submaximal invasive exercise testing and quantitative lung scanning in the evaluation for tolerance of lung resection. Chest 95:267-273, 1989 Bechard D, Wetstein L: Assessment of exercise oxygen consumption as preoperative criterion for lung resection. Ann Thorac Surg 44:344349, 1987 Baldi S, Ruffini E, Harari S, et al: Does lobectomy for lung cancer in patients with chronic obstructive pulmonary disease affect lung function? A multicenter national study. J Thorac Cardiovasc Surg 130:1616-1622, 2005 Kushibe K, Kawaguchi T, Kimura M, et al: Changes in ventilatory capacity, exercise capacity, and pulmonary blood flow after lobectomy in patients with lung cancer: Which lobectomy has the most loss in exercise capacity? Interact Cardiovasc Thorac Surg 7:1011-1014, 2008 Subotic DR, Mandaric DV, Eminovic TM, et al: Influence of chronic obstructive pulmonary disease on postoperative lung function and complications in patients undergoing operations for primary non-small cell lung cancer. J Thorac Cardiovasc Surg 134:1292-1299, 2007 Bobbio A, Chetta A, Carbognani P, et al: Changes in pulmonary function test and cardio-pulmonary exercise capacity in COPD patients after lobar pulmonary resection. Eur J Cardiothorac Surg 28:754-758, 2005 Celli BR, MacNee W, ATS/ERS Task Force: Standards for the diagnosis and treatment of patients with COPD: A summary of the ATS/ ERS position paper. Eur Respir J 23:932-946, 2004 Bluman LG, Mosca L, Newman N, et al: Preoperative smoking habits and postoperative
19.
20.
21.
22.
23.
24.
25.
26.
pulmonary complications. Chest 113:883889, 1998 Nakagawa M, Tanaka H, Tsukuma H, et al: Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery. Chest 120:705-710, 2001 Nagarajan K, Bennett A, Agostini P, et al: Is preoperative physiotherapy/pulmonary rehabilitation beneficial in lung resection patients? Interact Cardiovasc Thorac Surg 13:300-302, 2011 Jones LW, Peddle CJ, Eves ND, et al: Effects of presurgical exercise training on cardiorespiratory fitness among patients undergoing thoracic surgery for malignant lung lesions. Cancer 110:590-598, 2007 Bobbio A, Chetta A, Ampollini L, et al: Preoperative pulmonary rehabilitation in patients undergoing lung resection for non-small cell lung cancer. Eur J Cardiothorac Surg 33:9598, 2008 Benzo R, Wigle D, Novotny P, et al: Preoperative pulmonary rehabilitation before lung cancer resection: Results from two randomized studies. Lung Cancer 2011 Jun 8 (Epub ahead of print) Varela G, Ballesteros E, Jiménez MF, et al: Cost-effectiveness analysis of prophylactic respiratory physiotherapy in pulmonary lobectomy. Eur J Cardiothorac Surg 29:216-220, 2006 Handy JR Jr, Asaph JW, Skokan L, et al: What happens to patients undergoing lung cancer surgery? Outcomes and quality of life before and after surgery. Chest 122:21-30, 2002 Handy JR Jr, Asaph JW, Douville EC, et al: Does video-assisted thoracoscopic lobectomy for lung cancer provide improved functional outcomes compared with open lobectomy? Eur J Cardiothorac Surg 37: 451-455, 2010
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LOBECTOMY FOR PATIENTS WITH LIMITED LUNG FUNCTION 27. Steegers MA, Snik DM, Verhagen AF, et al: Only half of the chronic pain after thoracic surgery shows a neuropathic component. J Pain 9:955-961, 2008 28. Woolf CJ: Central sensitization: Uncovering the relation between pain and plasticity. Anesthesiology 106:864-867, 2007 29. Katz J, Jackson M, Kavanagh BP, et al: Acute pain after thoracic surgery predicts long-term post-thoracotomy pain. Clin J Pain 12:50-55, 1996 30. Alex J, Ansari J, Bahalkar P, et al: Comparison of the immediate postoperative outcome of using the conventional two drains versus a single drain after lobectomy. Ann Thorac Surg 76: 1046-1049, 2003 31. Joshi GP, Bonnet F, Shah R, et al: A systematic review of randomized trials evaluating regional techniques for postthoracotomy analgesia. Anesth Analg 107:1026-1040, 2008
32. Demmy TL, Nwogu C, Solan P, et al: Chest tube-delivered bupivacaine improves pain and decreases opioid use after thoracoscopy. Ann Thorac Surg 87:1040-1046, 2009, discussion 1046-1047 33. Scott WJ, Allen MS, Darling G, et al: Videoassisted thoracic surgery versus open lobectomy for lung cancer: A secondary analysis of data from the American College of Surgeons Oncology Group Z0030 randomized clinical trial. J Thorac Cardiovasc Surg 139:976-981, 2010, discussion 981-983 34. Paul S, Altorki NK, Sheng S, et al: Thoracoscopic lobectomy is associated with lower morbidity than open lobectomy: A propensity-matched analysis from the STS database. J Thorac Cardiovasc Surg 139:366378, 2010
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35. Kachare S, Dexter EU, Nwogu C, et al: Perioperative outcomes of thoracoscopic anatomic resections in patients with limited pulmonary reserve. J Thorac Cardiovasc Surg 141:459462, 2011 36. Berry MF, Villamizar-Ortiz NR, Tong BC, et al: Pulmonary function tests do not predict pulmonary complications after thoracoscopic lobectomy. Ann Thorac Surg 89:1044-1051, discussion 1051-1052, 2010 37. Lau KK, Martin-Ucar AE, Nakas A, et al: Lung cancer surgery in the breathless patient—the benefits of avoiding the gold standard. Eur J Cardiothorac Surg 38:6-13, 2010 38. Bobbio A, Chetta A, Internullo E, et al: Exercise capacity assessment in patients undergoing lung resection. Eur J Cardiothorac Surg 35:419-422, 2009
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