Video-Assisted Thoracic Surgery Pulmonary Resection for Lung Cancer in Patients with Poor Lung Function

GENERAL THORACIC Video-Assisted Thoracic Surgery Pulmonary Resection for Lung Cancer in Patients with Poor Lung Function Juan C. Garzon, MD, Calvin S. H. Ng, MBBS, Alan D. L. Sihoe, MBBChir, Anthony V. Manlulu, MD, Randolph H. L. Wong, MBChB, Tak Wai Lee, MBChB, and Anthony P. C. Yim, MD, FRCS Division of Cardiothoracic Surgery, Chinese University of Hong Kong and Minimally Invasive Surgery Center, Union Hospital, Hong Kong, China Background. The aim of this study is to evaluate the early outcome of patients with poor lung function who underwent video-assisted thoracic surgery (VATS) pulmonary resection for primary non-small cell lung carcinoma. Methods. We reviewed retrospectively the records of patients with lung cancer undergoing VATS lung resection over a period of 5 years. Twenty-five patients with preoperative poor lung function defined as forced expiratory volume in 1 second less than 0.8 L or the percentage predicted value for forced expiratory volume in 1 second less than 50% were identified. Thirteen patients underwent VATS lobectomies and 12 VATS wedge resections. Data were analyzed with respect to demographics, risk factors, and early postoperative outcome and survival. Results. There were 8 cases of morbidities (29%) and no surgical mortality. Five of these 8 patients had respiratory-related complications after surgery. A deterioration in pulmonary performance as indicated by the Eastern Cooperative Oncology Group (ECOG) score was seen in 7 patients (28%), with only 1 patient having an ECOG score greater than 2. No patient required home oxygen supplementation beyond the third month postoperatively. After a median follow-up period of 15.1 months (range, 1 to 24), 5 patients died. Only 1 patient (4%) died of a respiratory complication (pneumonia 6 weeks after surgery). The other 4 deaths were due to recurrent or metastatic disease. The actuarial survival rates at 1 and 2 years were 80% and 69%, respectively. Conclusions. Video-assisted thoracic surgery pulmonary resection for cancer in patients with poor lung function can achieve acceptable functional and oncologic outcome. (Ann Thorac Surg 2006;81:1996 2003) 2006 by The Society of Thoracic Surgeons Despite progress in chemotherapy and radiotherapy, surgery remains an important therapeutic approach for patients with resectable non-small cell lung cancer (NSCLC) [1]. However, many lung cancer patients are also smokers who have associated cardiorespiratory comorbidities that increase perioperative and long-term pulmonary morbidity as well as mortality. Attempts have been made to define the physiologic limits for safe lung resection [2 5], but application of such limits may have hitherto excluded a significant number of patients from curative surgery. Some investigators have found that operative risk is related to the absolute value of the predicted postoperative forced expiratory volume in 1 second (ppofev 1 ) [6], with a forced expiratory volume in 1 second (FEV 1 ) of less than 0.8L conventionally used as the cut-off for surgery. Others have found the percentage of the predicted FEV 1 based on sex, age, height, and body weight (FEV 1 %) to be Accepted for publication Jan 5, 2006. Address correspondence to Dr Yim, Division of Cardiothoracic Surgery, Chinese University of Hong Kong, Prince of Wales Hospital, Minimally Invasive Center, Union Hospital, Shatin, NT, Hong Kong SAR, China; e-mail: yimap@cuhk.edu.hk. more useful. A preoperative FEV 1 % of greater than 50%, or a predicted postoperative value (ppofev 1 %) of greater than 40% has been recommended for patients receiving lung resection [3, 7]. However, in patients with a preoperative FEV 1 % of less than 70%, the ppofev 1 may be an unreliable predictor of postoperative morbidity [8]. Another predictor of the likelihood of pulmonary complications after major lung resection is the preoperative diffuse capacity for carbon monoxide, although its routine use for preoperative assessment and ability to predict surgical outcome remains controversial, and it is not often performed [5]. Measuring oxygen uptake has evolved as a useful objective tool in the evaluation of patients with poor pulmonary function, but again is not always readily available in many centers. However, with modern advances in surgery, anesthesia, and perioperative care, the definitions of prohibitive risk based on these tests may have to be revised [3, 4, 9, 10]. Recently, for example, it has been suggested that patients with FEV 1 % values considerably lower than the currently accepted level of greater than 50% can receive surgical intervention for lung cancer without significantly increased mortality [10]. 2006 by The Society of Thoracic Surgeons 0003-4975/06/$32.00 Published by Elsevier Inc doi:10.1016/j.athoracsur.2006.01.038

Ann Thorac Surg GARZON ET AL 2006;81:1996 2003 VATS FOR LUNG CANCER WITH POOR LUNG FUNCTION Experience from lung volume reduction surgery, for example, has shown that some patients with poor lung function due to emphysematous change can safely undergo concurrent lung resection for both their lung cancer and lung volume reduction surgery within the same procedure at an acceptable level of risk, and even with improvement of their pulmonary status [11, 12]. Postoperatively, advances in pain management, the increasing early use of minitracheostomy for airway secretions, and incentive spirometry have aided the reduction in respiratory complications. The addition of structured postoperative pulmonary rehabilitation by specialist units has been responsible for shifting many patients from the physiologically unresectable category to the resectable [12]. The development of video-assisted thoracic surgery (VATS) has proven to be an attractive alternative approach for selected patients with normal or near-normal lung function, offering reduced pain and morbidity compared with open surgery [13]. By minimizing chest wall trauma and the potentially consequent effects on postoperative pulmonary impairment, VATS may even allow patients with very poor lung function to be surgical candidates. However, data regarding outcome in terms of postoperative complications, recurrence, survival, and quality or life are limited in such patients with poor lung function undergoing VATS for lung cancer. We retrospectively review our experience of VATS lung resection for poor lung function patients with NSCLC over a 5-year period. Material and Methods We reviewed retrospectively the records of our patients with NSCLC operated on in two University-affiliated teaching hospitals under one surgical team from January 2000 to January 2005. Ethical approval was given by the Research Ethics Committee of the Chinese University of Hong Kong, and informed consents for the study were obtained from the patients. Of 626 major pulmonary resections performed for lung cancer during this time, we identified 25 patients (4%) with poor lung function who underwent VATS pulmonary resection. Video-assisted thoracic surgery is the standard approach for resection of lung cancer in our institute. Tumors larger than 5 cm are usually resected by open thoracotomy, and distance of tumor from the pleura (unless there is suspicion of chest wall involvement) is not contraindication for VATS in this center. Bronchoplastic procedures are performed by the open approach. Inclusion criteria included diagnosis of NSCLC, VATS lung resection, and patients with poor lung function preoperatively. Poor lung function was defined as a forced expiratory volume in 1 second (FEV 1 ) less than 0.8 L or the percentage of the predicted value for FEV 1 less than 50%. Predicted postoperative FEV 1 (ppofev 1 ) values were calculated by multiplying preoperative FEV 1 by number of segments remaining divided by total number of segments. The wedge resections are considered to be equivalent to 1.5 segments and the ppofev 1 calculated 1997 accordingly. The location of tumor, degree of upper dominance emphysema, and degree of restrictive lung disease are not absolute determinants for operability in this group of patients. The choice between lobectomy and wedge resection depends on a number of factors. We aim for VATS lobectomy in all our poor lung function cancer patients. However, in general, those with exercise tolerance of one flight of stairs or less will undergo VATS wedge resection. An additional consideration is that the location and size of tumor should allow wedge resection to be performed without resecting more than 1.5 pulmonary segments. Furthermore, the patient s general health, cardiac reserve, as well as available family and social support, are also considered. In our experience, exercise tolerance in terms of flights of stairs is more important. Patients with CO 2 retention (PaCO 2 6 kpa) or known pulmonary hypertension (although we do not routinely perform a preoperative echocardiogram) are usually excluded. Preoperative staging included chest reontgenogram, thoracic and abdominal computed tomography (CT) scan, flexible bronchoscopy, and positron emission tomography (PET)-CT scan when suspicious images of mediastinal lymph node enlargement were seen in thoracic CT scan. Our technique of VATS pulmonary resection for lung cancer has been previously described [13]. Sampling of the hilar, subcarinal, paratracheal, prevascular, aortopulmonary, and paraesophageal mediastinal lymph nodes was routinely performed. Demographics, risk factors, smoking history, pulmonary function tests, and clinical course including respiratory and nonrespiratory complications were documented. In an attempt to quantify more objectively from the patients perspective their pulmonary performance after pulmonary resection, we evaluated the pulmonary changes using the Eastern Cooperative Oncology Group (ECOG) score [5] (Appendix) at 1 month postoperatively, which was done by the hospital occupational therapist, as well as record the oxygen requirements during the postoperative period [14]. Follow-up data including respiratory status, recurrence, and survival data were recorded in outpatient clinic follow-up and by telephone contact. Full follow-up data were obtained from all patients. Patents with stage IB or above tumors receive an oncology consultation postoperatively based on recommendations from the Southwest Oncology Group JBR10 and Cancer and Leukemia Group B 9633 trials. Nevertheless, for this poor risk group of patients, only 2 patients received adjuvant chemotherapy after balancing the pros and cons. Statistical analysis using the two-sided 2 test and Fisher s exact test was performed to determine association between respiratory complications and each independent variable when appropriate. The log-rank test was used to identify significant risk factors affecting survival at 2-year follow-up. Data analysis was performed using SPSS Version 11.5 (SPSS, Chicago, Illinois). A two sided p value of less than 0.05 was considered significant. GENERAL THORACIC

GENERAL THORACIC 1998 GARZON ET AL Ann Thorac Surg VATS FOR LUNG CANCER WITH POOR LUNG FUNCTION 2006;81:1996 2003 Results Demographic and Clinical Data A total of 25 patients during the study period fit the inclusion criteria for this retrospective review. Based on the exclusion criteria, 11 patients were not suitable for the study. The ages of the patients ranged from 69 to 80 years, with a mean of 75 years. Seventeen (68%) were male and 8 (32%) were female. Seventeen patients (68%) were smokers, and Brinkman s index among smokers ranged between 10 and 50 pack-years, with a mean of 33 packyears. Seventeen (68%) had FEV 1 less than 0.8 L, 21 (84%) had FEV 1 % less than 50% predicted, and 13 (52%) had both. Surgical procedures were 13 lobectomies (52% [right upper lobe 3, right middle lobe 1, right lower lobe 5, left upper lobe 2, left lower lobe 2]) and 12 limited (wedge) resections (48%). Four of the 5 upper lobectomy patients have chronic obstructive pulmonary disease. Mean operative time was 2 hours and 3 minutes (range, 45 to 220 minutes). None of the patients required conversion from VATS to thoracotomy. All surgical margins were clear, and the most frequent histological subtype was adenocarcinoma seen in 19 patients (76%). The patients with clinical stage IIIa (T3N1) disease preoperatively had local invasion of pericardium and diaphragm. The additional patient with stage IIIa postoperatively had pathologic N2 disease found after surgery. The stage IIIB patient diagnosed after surgery was found to have metastasis within the same resected lobe (T4). The preoperative and pathologic TNM stage was given according to the criteria of the American Joint Committee on Cancer (Table 1). Smoking history was present in 17 of 25 patients (68%). Chronic obstructive pulmonary disease was diagnosed in 20 patients (80%). According to the American Thoracic Society classification, of these 20 patients, 7 were classified as moderate and 13 as severe chronic obstructive pulmonary disease [15]. From these 12 risk factors included in the database format, chronic obstructive pulmonary disease was the most frequently found (80%). In general, all the patients had associated risk factors, with a mean of 2.8 (Table 2). Table 1. Demographics and Clinical Data Variable Value Demographics Age, years 75 (range, 69 80) Male : female 17:08 Preoperative lung function FEV 1 0.8 liters 17 (68%) FEV 1 50% predicted 21 (84%) Both 13 (52%) FEV 1 /FVC mean 57.1 VATS operations Lobectomy 13 (52%) Right upper lobe 3 Right middle lobe 1 Right lower lobe 5 Left upper lobe 2 Left lower lobe 2 Wedge resection 12 (48%) Mean operative time, 123 (range, 45 220) minutes Histology Adenocarcinoma 19 (76%) Squamous cell 2 (8%) carcinoma Sarcomatoid 1 (4%) carcinoma Poorly differentiated 3 (12%) NSCLC Pathologic staging Preoperative Postoperative Ia 6 (24%) 5 (20%) Ib 15 (60%) 12 (48%) II 1 (4%) 1 (4%) IIIa 3 (12%) 4 (16%) IIIb 1 (4%) IV 2 (8%) Characteristics of the data were presented either in mean and SD or median and inter-quartile range. For categorical data, frequencies and percentages were summarized. FEV 1 forced expiratory volume in 1 second; FVC forced vital capacity; NSCLC nonsmall-cell lung cancer; VATS videoassisted thoracic surgery. Perioperative Morbidity There was no perioperative (30-day) mortality. Complications occurred in 7 patients (28%) of whom 5 (20%) had respiratory complications. Two patients had prolonged air leakage for more than 7 days, 2 had atelectasis, and 1 had pneumonia. The complications are summarized in Table 3, and grades given according to National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Despite the complications, the mean duration of postoperative in-hospital stay for these patients was 7.4 days (range, 2 to 26). Follow-up data were available for all 25 patients at 1 month after surgery, and for 18 patients at 6 months after surgery. Deterioration in postoperative pulmonary functional status as indicated by the ECOG score was seen in 7 patients (28%) and 2 patients (11%), respectively, at these time points. Nevertheless, most of these patients had only mild functional impairment, and only 1 had ECOG score greater than 2 at 1 and 2 months after surgery, indicating significant impairment. Two patients (8%) required home oxygen after discharge. Both were smokers with severe chronic obstructive pulmonary disease, and both died before the third postoperative month. One died of disease progression, and the other died of pneumonia 6 weeks after surgery. The latter case was the only patient (4%) who died of respiratory complications in this study. Statistical analysis revealed no association between any of the risk factors (including FEV 1 ) and occurrence of postoperative morbidity (Table 2).

Ann Thorac Surg GARZON ET AL 2006;81:1996 2003 VATS FOR LUNG CANCER WITH POOR LUNG FUNCTION Table 2. Some Risk Factors for Postoperative Morbidity Variable n (%) PLF (n 25) p Values a p Values b Respiratory Complications (n 5) 4 Patients 1999 Survival at 2 years (5 Deaths) GENERAL THORACIC Female 8 (32) 0.27 0.11 Smoker 17 (68) 0.27 0.13 Age in years, median (IQR) 75 (69 80) Risk factors Risk factors, median (IQR) 2 (2 4) Chronic obstructive pulmonary disease 20 (80) 0.54 0.24 Hypertension 15 (60) 0.27 0.06 Steroids 1 (4) 0.16 0.57 Cerebrovascular disease 2 (8) 1 0.43 Tuberculosis 3 (12) 0.42 0.45 Chronic heart failure 10 (40) 0.63 0.39 Peripheral vascular disease 0 (0) Coronary artery disease 8 (32) 1 0.06 Diabetes mellitus 4 (16) 1 0.3 Renal failure 5 (20) 0.55 0.78 Neoadjuvant chemotherapy 4 (16) 0.53 0.4 Neoadjuvant radiotherapy 1 (4) 1 0.002 c Pulmonary function tests FEV 1 mean (SD) 0.82 (0.19) FEV 1 0.7 16 FEV 1 0.7 9 1 0.27 FEV 1 % mean (SD) 45.8 (10.9) FEV 1 % 45% 10 FEV 1 % 45% 15 1 0.07 FEV 1 /FVC mean (SD) 57.2 (18.8) ppofev 1 mean (SD) 0.66 (0.16) ppofev 1 % mean (SD) [range] 36.4 (8.8) [13 55] 0.8 0.09 Type of resection Curative intention (lobectomy) 13 (52) Limited resection (wedge) 12 (48) 1 0.010 c a By Fisher s exact test. Values are presented in n (%). b By log-rank test. c p Value 0.05. FEV 1 forced expiratory volume in 1 second; FVC forced vital capacity; IQR interquartile range; ppofev 1 predictive postoperative FEV 1. Survival on Midterm Follow-Up After a median follow-up time of 15.1 months (range, 1 to 24), 5 patients had died. Follow-up at 1 and 2 years was complete for 20 and 16 patients, respectively. Actuarial survival rates were 80% at 1 year after surgery and 69% at 2 years. Four deaths were related to lung cancer. Two patients had local disease progression within 6 months of surgery and died 3 and 4 months, respectively, after discovery of recurrence. Another 2 patients were found to have distant metastasis within 1 year of surgery (1 patient with brain metastases and 1 patient with both hepatic and bone metastases), and they died at 6 and 18 months after surgery, respectively. These 4 patients all received limited resections. Statistical analysis of all demographic and clinical factors revealed that limited resection was the only one significantly associated with poorer survival after 2 years of follow-up (p 0.01; Tables 2 and 4). The fifth death was the patient who died of pneumonia at 6 weeks after surgery. There were no other deaths or long-term complications attributable to poor lung function after surgery in any patient. Comment Poor preoperative pulmonary function is a wellrecognized predictor for morbidity and mortality after lung cancer surgery [3, 16]. However, with advancements in surgical technology and strategies, the guidelines for offering surgery to patients with poor lung function have evolved accordingly, allowing curative resection to be offered to many patients who would have been previously considered inoperable [7]. In particular, the minimally invasive nature of VATS may broaden the applicability of lung resection surgery for lung cancer patients with poor lung function [17]. For early-stage lung cancer

GENERAL THORACIC 2000 GARZON ET AL Ann Thorac Surg VATS FOR LUNG CANCER WITH POOR LUNG FUNCTION 2006;81:1996 2003 Table 3. Complications Patient Smoker Preop FEV 1 Preop %FEV 1 VATS Operation Complication (NCI CTCAE v3.0 Grade) Occurrence Length of Hospital Stay 1 Yes 1.1 46 R. upper lobe wedge Atelectasis & bronchoscopy toileting required (3) Immediate postoperative time 2 Yes 0.4 18 R. lower lobe wedge Pneumonia (2) 5 days postop 24 days 3 Yes 0.7 44 L. lower lobe lobectomy Atrial fibrillation (2) 1 day postop 3 days 4 Yes 0.7 38 R. upper lobe lobectomy Wound infection (3) 2 days postop 26 days 5 Yes 0.9 42 R. lower lobe lobectomy Air leak for more than 7 days (3) 6 Yes 1.2 43 R. upper lobe lobectomy 7 Yes 1.1 42 L. lower lobe lobectomy Air leak for more than 7 days (3) Atelectasis & bronchoscopy toileting required (3) Immediate postoperative time 2 days 18 days Atrial fibrillation (2) 2 days postop 7 days Immediate postoperative time 2 days postop 25 days FEV 1 forced expiratory volume in 1 second; L left; NCI CTCAE National Cancer Institute Common Terminology Criteria; postop postoperative; Preop preoperative; R right; VATS video-assisted thoracic surgery. resection, this approach is now widely accepted, and its advantages in terms of reduced postoperative morbidity, shorter hospital stays, and reduced functional and immunologic impairment have been demonstrated by many groups as well as the adequacy of resection, which has also been recently addressed [18 21]. In this study, we have demonstrated that the perioperative morbidity and mortality for patients with poor lung function undergoing VATS lung resection for lung cancer is very acceptable. Our patients had no surgical mortality and an overall morbidity rate of 29%. These figures are comparable with open major lung resection surgery [9, 12, 22 25] (Table 5). In one study, Cerfolio and colleagues [22] reported mortality of 2.4% and morbidity of 49% in 85 patients with poor lung function defined as FEV 1 less than 1.2 L. Another more recent study by Magdeleinat and colleagues [23], reported high operative morbidity (70%) and mortality (8.5%) seen in a group of 106 patients with poor lung function who underwent open lung resection; however, long-term survival and respiratory function were acceptable. In particular, VATS causes less postoperative pain and may offer faster recovery for the frail or high-risk patient with poor lung function [17]. Table 4. Lobectomy Versus Limited Resection Group Poor Lung Function Limited Resection Lobectomy Variable (n 25) (n 12) (n 13) p Value Pulmonary function tests FEV 1 0.82 0.75 0.86 FEV 1 % 45.8 42.1 49.2 Complications a Yes 8 (32%) 2 (16.7) 6 (46.2%) 0.378 Complications (pulmonary) a Yes 5 (20%) 2 (16.7) 2 (15.4) 1 ECOG 1 st month (change) b 2 (16.6) 1 (7.6) 0.574 Oxygen requirement 1 st month b 2 (16.6) 1 (7.6) 0.689 Hospital stay 7.4 6.5 8.3 Recurrence c 1 1(6 months) 0 0.241 Metastasis c 2 2(1 month/1 year) 0 0.127 Overall mortality c 0.010 d 1 month 0% n 25 0% n 12 0% n 13 3 months 2 (9.0%) n 22 2 (20%) n 10 0% n 12 1 year 4 (20%) n 20 4 (40%) n 10 0% n 10 2 years 5 (31.2) n 16 5 (55.5%) n 9 0% n 7 a By Fisher s exact test. Values are presented in n (%). b By Mann-Whitney U test. c By log rank test. d p Value 0.05. ECOG European Cooperative Oncology Group; FEV 1 forced expiratory volume in 1 second.

Table 5. Lung Resection in Poor Pulmonary Function Reference No. of Patients Pulmonary Function Tests Approach Hospital Stay Magdeleinat et al 2005 [24] Martin U et al 2005 [26] Shennib et al 2005 [25] 106 Pred FEV% 50% r(23% 50%) 34 ppofev 1 % 40% Pred FEV 1 % m 43.7%. Two matched groups of 17 patients. 65 FEV 1 40%. Diffuse capacity for carbon monoxide 50%. Win et al 2005 [9] 110 Borderline lung function 29% (n 32) FEV 1 1.5 L for lobectomy. Choong et al 2003 [11] Cerfolio et al 1996 [23] 21 Lung volume reduction surgery lung cancer resection m(fev 1 0.7 L); (PredFEV 1 % 29%). 85 FEV 1.2L m 1.44L r(0.5 1.2) Present study 25 FEV 1 0.8 or predicted FEV 1 % 50% Open 20 days Complicated Mortality 30 Days % Morbidity 30 Days Respiratory Complications (Pulmonary and Pleural) and Remarks 8.50% 70% (n 74) 45 27 pneumonia, 16 atelectasis, 1 bronchitis, 1 NIRF Open/VATS 7 days r(3 31) 11.6% (n 2) 36% (n 10) 7 3 pneumonia, 3 air leak, 1 empyema VATS 4% 10% air leak 6% pneumonia 4% respiratory failure Open 3% 22% (n 24) 11 respiratory failure, 21 pneumonia Open 9 days r(5 24) 0% (n 19) 13 2 respiratory failure, 11 air leak, minitracheostomy in 7 patients Open 15 days r(5 66) 2.40% 49% (n 42) 29 18 prolonged air leak, 6 pulmonary failure, 3 pneumonia, 2 empyema VATS 7.4 days r(2 26) 0% 29% 5 2 prolonged air leak, 2 atelectasis and 1 pneumonia FEV forced expiratory volume; NIRF noninfectious respiratory failure; ppofev1 predicted postoperative percentage of FEV 1 ; Pred predicted; VATS video-assisted thoracic surgery. Ann Thorac Surg GARZON ET AL 2006;81:1996 2003 VATS FOR LUNG CANCER WITH POOR LUNG FUNCTION 2001 GENERAL THORACIC

GENERAL THORACIC 2002 GARZON ET AL Ann Thorac Surg VATS FOR LUNG CANCER WITH POOR LUNG FUNCTION 2006;81:1996 2003 Upon follow-up for as long as 2 years, the observed actuarial survival rates of our patients were 80% at 1 year and 69% at 2 years. Even though our cohort included patients with different stages (I, II, and IIIa surgically resectable), and some who received only limited (sublobectomy) resections, these figures are comparable with those reported for patients with normal lung function receiving curative lung cancer resections [13], including those undergoing open surgery [26]. It should be noted that the advanced stage in some of our patients undergoing resection may have influenced the outcome more than the poor lung function. Statistical analysis revealed that the only preoperative demographic or clinical factor associated with improved survival at 2 years was anatomical resection (lobectomy) with curative intention (p 0.01). This conclusion has been reached by several other studies [24, 25]. However, selection bias may have accounted for survival differences between the wedge and lobectomy patients. The survival data should also be interpreted with caution because of the modest patient numbers and short followup, and hence limited power of the current study. Nevertheless, our results suggest that VATS lobectomy can be performed in patients with poor lung function, achieving satisfactory outcomes in terms of survival at 2 years. Limited resection for lung cancer is also an acceptable option for selected patients. Our data confirmed that limited resection using VATS in patients with very poor lung function results in acceptably low rate of surgeryrelated respiratory complications. Some studies have found that surgical morbidity may be associated with ppofev 1 less than 40% [3, 6, 7], preoperative FEV 1 of less than 0.8 L, and FEV 1 % of less than 50% [3, 7]. However, it should be noted that the ppofev 1 becomes less reliable as a predictor of postoperative morbidity when the patient s preoperative FEV 1 % is less than 70% [8]. We found that the ppofev 1 (mean ppofev 1 % 36.4%) in our poor lung function patients undergoing VATS major lung resection did not significantly predict morbidity or survival at 2 years, which is concurrent with recent large series [5]. The preoperative functional status of the patient may be a more important predictor [5]. Of course, failure to show ppofev 1 % is associated with outcome is by no means the same as establishing that it is not associated with outcome. Postoperative functional status of the patients, rather than survival per se, has become an increasingly important issue in assessing the benefits of lung surgery [16, 27]. Palliation of tumor-related symptoms needs to be carefully balanced against the morbidity caused by surgery. Prospective studies analyzing long-term quality of life after lung resection surgery are not available, but retrospective data from previous studies suggest that long-term survivors after lung cancer surgery enjoy good quality of life [16]. The postoperative functional status (as assessed by the ECOG score) and the requirement for postoperative oxygen have given us some indication of the pulmonary status in the postoperative period. Although 28% of the patients noted an elevation in their ECOG scores at 1 month, only 1 patient had ECOG score greater than 2. Patients with persistent functional deficit appear to drop rapidly, to just 11% after 6 months. Furthermore, only 2 patients required home oxygen supplements on discharge after surgery, including 1 who had pneumonia that would subsequently prove fatal. The limitation of using ECOG in patients after major lung resection is that pain and psychological effects may be additional factors affecting this performance. Future prospective studies assessing the postoperative functional status may be improved by using European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 and LC-13, which would have been difficult to complete in the present retrospective study. In this study, we have not identified any preoperative demographic or clinical factors that are significantly related to postoperative respiratory morbidity in these patients. Nevertheless, we would advice that potential surgical candidates be meticulously prepared for surgery, with preoperative chest physiotherapy, strict smoking cessation, and optimization of medical therapy for preexisting pulmonary and airways diseases. Postoperatively, these patients should undergo vigorous chest physiotherapy and early mobilization. A formal postoperative rehabilitation program should be available for select patients with especially poor pulmonary function after surgery. Early and aggressive intervention for chest infections, including bronchoscopic toileting and minitracheostomy for suctioning, may be required to avoid pneumonia, which can be fatal in these patients. We conclude that VATS pulmonary resection for lung cancer in patients with poor lung function can achieve morbidity and survival rates comparable to those of patients with adequate pulmonary function without resulting in long-term respiratory impairment. In addition to other nonsurgical factors, the benefits of a minimal access technique may play a role in improving outcomes in this high-risk group. The authors would like to thank Tse Yee-Kit of the Centre of Epidemiology and Biostatistics, the Chinese University of Hong Kong, for his kind assistance with the statistical analysis. References 1. Reif MS, Socinski MA, Rivera MP. Evidence-based medicine in the treatment of non-small-cell lung cancer. Clin Chest Med 2000;21:107 20. 2. Robles AM, Shure D. Optimization of lung function before pulmonary resection: pulmonologists perspectives. Thorac Surg Clin 2004;14:295 304. 3. Markos J, Mullan BP, Hillman DR, et al. Preoperative assessment as a predictor of mortality and morbidity after lung resection. Am Rev Respir Dis 1989;139:902 10. 4. Kaza AK, Mitchell JD. Preoperative pulmonary evaluation of the thoracic surgical patient. Thorac Surg Clin 2005;15:297 304. 5. Berrisford R, Brunelli A, Rocco G, Treasure T, Utley M, on behalf of the Audit and Guidelines Committee of the European Society of Thoracic Surgeons and the European Association of Cardiothoracic Surgeons. The European Thoracic

Ann Thorac Surg GARZON ET AL 2006;81:1996 2003 VATS FOR LUNG CANCER WITH POOR LUNG FUNCTION Surgery Database project: modeling the risk of in-hospital death following lung resection. Eur J Cardiothorac Surg. 2005;28:306 311. 6. Kearney DJ, Lee TH, Reilly JJ, DeCamp MM, Sugarbaker DJ. Assessment of operative risk in patients undergoing lung resection. Importance of predicted pulmonary function. Chest 1994;105: 753 9. 7. British Thoracic Society. Society of Cardiothoracic Surgeons of Great Britain, Ireland Working Party. Guidelines on the selection of patients with lung cancer for surgery. Thorax 2001;56:89 108. 8. Brunelli A, Al Refai M, Monteverde M, et al. Predictors of early morbidity after major lung resection in patients with and without airflow limitation. Ann Thorac Surg 2002;74:999 1003. 9. Varela G, Novoa N, Jimenez MF. Influence of age and predicted forced expiratory volume in 1 s on prognosis following complete resection for non-small cell lung carcinoma. Eur J Cardiothorac Surg 2000;18:2 6. 10. Win T, Jackson A, Sharples L, et al. Relationship between pulmonary function and lung cancer surgical outcome. Eur Respir J 2005;25:594 9. 11. Martin J. Lung resection in the pulmonary-compromised patient. Thorac Surg Clin 2004;14:157 62. 12. Choong CK, Meyers BF, Battafarano RJ, et al. Lung cancer resection combined with lung volume reduction in patients with severe emphysema. J Thorac Cardiovasc Surg 2004;127: 1323 31. 13. Yim AP. VATS major pulmonary resection revisited controversies, techniques, and results. Ann Thorac Surg 2002;74:615 23. 14. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649 55. 15. Celli BR, MacNee W, for the 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 2004;23:932 46. 16. Iizasa T, Suzuki M, Yasufuku K, et al. Preoperative pulmonary function as a prognostic factor for stage I non small cell lung carcinoma. Ann Thorac Surg 2004;77:1896 903. 17. Demmy TL, Curtis JJ. Minimally invasive lobectomy directed toward frail and high-risk patients: a case-control study. Ann Thorac Surg 1999;68:194 200. 18. Iwasaki A, Shirakusa T, Shiraishi T, Yamamoto S. Results of video-assisted thoracic surgery for stage I/II non-small cell lung cancer. Eur J Cardiothorac Surg 2004;26:158 64. 19. Demmy TL, Plante AJ, Nwogu CE, Takita H, Anderson TM. Discharge independence with minimally invasive lobectomy. Am J Surg 2004;188:698 702. 20. Yim AP, Wan S, Lee TW, Arifi AA. VATS lobectomy reduces cytokine responses compared with conventional surgery. Ann Thorac Surg 2000;70:243 7. 21. Ng CSH, Lee TW, Wan S, et al. Thoracotomy is associated with significantly more profound suppression in lymphocytes and natural killer cells than video-assisted thoracic surgery following major lung resections for Cancer. J Invest Surg 2005;18:81 8. 22. Cerfolio SJ, Allen MS, Trastek VF, et al. Lung resection in patients with compromised pulmonary function. Ann Thorac Surg 1996;62:348 51. 23. Magdeleinat P, Seguin A, Alifano M, et al. Early and longterm results of lung resection for non-small-cell lung cancer in patients with severe ventilatory impairment. Eur J Cardiothoracic Surg 2005;27:1099 105. 24. Shennib H, Bogart J, Herdon JE II, et al. Video-assisted wedge resection and local radiotherapy for peripheral lung cancer in high risk patients: the Cancer and Leukemia Group B (CALGB) 9335, a phase II, multi-institutional cooperative group study. J Thorac Cardiovasc Surg 2005;129: 813 8. 25. Martin AE, Nakas A, Pilling JE, et al. A case-matched study of anatomical segmentectomy versus lobectomy for stage I lung cancer in high-risk patients. Eur J Cardiothorac Surg 2005;27:675 9. 26. Roviaro G, Varoli F, Vergani C, Nucca O, Maciocco M, Grignani F. Long-term survival after videothoracoscopic lobectomy for stage I lung cancer. Chest 2004;126:725 32. Appendix Eastern Cooperative Oncology Group Score (ECOG) Grade ECOG Performance Status 2003 0 Fully active, able to carry on all pre-disease performance without restriction. 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light house work, office work. 2 Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3 Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours. 4 Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair. 5 Dead. Reprinted from Oken MM, et al, Toxicity and response criteria of the Eastern Cooperative Oncology Group, Am J Clin Oncol 1982;5:649 55 [14], with permission. GENERAL THORACIC