Patients with chronic obstructive pulmonary disease. Lung Reduction Operation and Resection of Pulmonary Nodules in Patients With Severe Emphysema

ORIGINAL ARTICLES: GENERAL THORACIC Lung Reduction Operation and Resection of Pulmonary Nodules in Patients With Severe Emphysema Joseph J. DeRose, Jr, MD, Michael Argenziano, MD, Nabeel El-Amir, MD, Patricia A. Jellen, MSN, Lyall A. Gorenstein, MD, Kenneth M. Steinglass, MD, Byron Thomashow, MD, and Mark E. Ginsburg, MD Divisions of Cardiothoracic Surgery and Pulmonary Medicine, Columbia University College of Physicians and Surgeons, Columbia-Presbyterian Medical Center, New York, New York Background. Severe pulmonary dysfunction has been considered a relative contraindication to surgical resection in patients with solitary pulmonary nodules. We report our initial experience with the combined use of lung volume reduction operation and tumor resection in this patient population. Methods and Patients. Between January 1995 and July 1996, 14 patients underwent combined lung volume reduction operation and pulmonary nodule resection. Ten (71%) patients were oxygen dependent, 5 (36%) had a room air partial pressure of carbon dioxide > 45, and 5 (36%) were steroid dependent preoperatively. Mean preoperative pulmonary function tests included a forced expiratory volume in 1 second of 680 98 ml (24% 5% predicted), forced vital capacity of 54% 5% predicted, and a forced expiratory volume in 1 second to vital capacity ratio of 37% 2% predicted. Results. Sixteen lesions were resected in the 14 patients and included 9 non-small cell s. There was one postoperative death. All other patients are alive and well through a mean follow-up of 22.6 2.3 months (12 to 35 months). At 6-month follow-up improvements were noted in dyspnea index, forced expiratory volume in 1 second forced vital capacity, and 6-minute walk distance. Mediastinal recurrence at 12-month follow-up developed in 1 patient with two separate bronchioalveolar s. Conclusions. Simultaneous lung volume reduction operation and tumor resection should be considered in patients with emphysema with marginal reserve in the hope of maximizing postoperative lung function. (Ann Thorac Surg 1998;65:314 8) 1998 by The Society of Thoracic Surgeons Patients with chronic obstructive pulmonary disease have an increased risk of the development of bronchogenic. They have common etiologic factors. It has been estimated that 90% of lung cancer patients have signs and symptoms of chronic obstructive pulmonary disease and at least 20% have severe pulmonary dysfunction [1]. Surgical resection provides the best chance for cure. However, even some patients with early stage peripheral tumors are considered inoperable because of inadequate pulmonary reserve. Lung volume reduction (LVR) has been used in the surgical treatment of severe emphysema to produce improvements in dyspnea, exercise capacity, and pulmonary function [2 8]. Patients with severe disability, hyperinflation, a heterogeneous distribution of disease, and a paucity of bronchitic symptoms appear to be the best candidates for LVR. Improvements in patient selection, anesthetic techniques, surgical instrumentation, and postoperative care have allowed for successful resections Accepted for publication July 29, 1997. Address reprint requests to Dr Ginsburg, Columbia-Presbyterian Medical Center, 161 Fort Washington Ave, Rm 310, New York, NY 10032. of emphysematous lung tissue in these select patients with multiple preoperative risk factors. By applying the rationale and techniques of LVR, it has been possible to resect pulmonary nodules and improve pulmonary function at the same operative setting. Herein we report the Columbia-Presbyterian Medical Center experience with combined LVR and pulmonary nodule resection. Material and Methods Preoperative Evaluation Between January 1995 and July 1996, 327 patients were evaluated for LVR at Columbia-Presbyterian Medical Center. Twenty-one patients (6.4%) were found to have suspicious pulmonary nodules. Routine preoperative assessment of these patients included a careful history of previous pulmonary infections, bronchitic symptoms, or thoracic operation, as well as a detailed review of old radiologic studies. Subjective evaluation of dyspnea and physical limitation was made at initial evaluation as measured by the medical research council of Great Britain dyspnea index scale. Physiologic evaluation included a room air arterial 1998 by The Society of Thoracic Surgeons 0003-4975/98/$19.00 Published by Elsevier Science Inc PII S0003-4975(97)01257-5

Ann Thorac Surg DeROSE ET AL 1998;65:314 8 LVRS AND PULMONARY NODULES 315 blood gas, standard spirometry studies, lung volume measurements by plethysmography and nitrogen washout, 6-minute walk distance, and selective use of dobutamine thallium stress test/stress echocardiogram. Radiologic studies included inspiratory and expiratory chest films, computed tomographic (CT) chest scans with cuts beyond the adrenal glands, and quantitative ventilation and perfusion scans with xenon washout. Metastatic workup included whole body bone scans and head CT scans. The inclusion and exclusion criteria for combined LVR and pulmonary resection are as follows: Inclusion criteria Severe dyspnea Localized or diffuse disease Hyperinflation with air trapping Impaired diaphragmatic excursion Regional heterogeneity of disease with appropriate target areas for resection Pulmonary nodule 3.0 cm Exclusion criteria Predominant airway disease such as asthma, bronchiectasis or chronic bronchitus with excessive purulent secretions Obliteration of pleural space by previous disease or operation Inappropriate emphysematous target areas for resection Evidence of unrespectable locoregional neoplastic disease Evidence of metastatic disease Anatomic location of tumor necessitates resection of an unacceptable amount of functional lung parenchyma Neither a minimum forced expiratory volume in 1 second (FEV 1 ) value nor pulmonary hypertension were used as exclusion criteria. Lung volume reduction was directed toward target areas of hyperinflation, and unilateral or bilateral procedures were performed based on target area distribution. Using these criteria, 14 patients were considered suitable candidates for LVR and tumor resection. All patients gave informed consent for LVR and unilateral or contralateral nodule resection. Seven additional patients with severe emphysema and pulmonary nodules evaluated at our center were deemed inappropriate candidates for LVR and pulmonary resection. Five of these patients were unsuitable candidates for LVR and 2 patients had nodules situated deep within normal lung parenchyma making safe resection impossible. Technique of Operation All patients had thoracic epidural catheters placed preoperatively. A left-sided double lumen endotracheal tube was routinely used for selective single lung ventilation. Anesthetic technique included epidural local anesthetic and strict avoidance of parenteral narcotics. Mediastinoscopy was performed only if suspicious lymph nodes ( 1 cm) were detected on chest CT. Because no patient in this series had mediastinal adenopathy on preoperative CT scanning, mediastinal node sampling was not performed before thoracotomy. Although our preferred incision for routine LVR is the bilateral anterior thoracosternotomy ( clam shell ), we tailored our surgical approach based on the anatomic distribution of the lesion in relation to the preoperative target areas when concomitant tumor resection was to be done. Eight patients underwent unilateral resections through a posterolateral thoracotomy (7) or by video-assisted thoracoscopy (1). Six patients had bilateral resections through either a median sternotomy (3) or a bilateral anterior thoracosternotomy (3). Intraoperative hilar and interlobar node sampling was not routinely performed for fear that such dissection would result in severe persistent leaks and bronchopleural fistulae. After selective one-lung ventilation, target areas for lung reduction were identified by isolating those portions of the nonventilated lung that remained distended after deflation. Resections were performed with successive firings of a linear stapling device buttressed with strips of bovine pericardium. Eleven patients underwent wide wedge resections of their pulmonary nodules. In 3 patients with marked focal bullous changes of the right upper lobe (1) or left upper lobe (2), tumor resection was accomplished with a formal lobectomy. Twelve of the pulmonary nodules were within target areas and pulmonary resection was performed as part of the nonanatomic LVRS. The remaining four pulmonary nodules were outside target areas and wedge resection of the lesion was performed in conjunction with LVR of the targeted emphysematous regions of lung. All patients were extubated in the operating room. Postoperative pain control was provided with epidural bupivicaine and intramuscular ketorolac tromethamine. Intensive chest physiotherapy was instituted immediately postoperatively, and all patients were enrolled in an inpatient physical therapy program after discharge from the thoracic surgery service. Patients The preoperative characteristics of the 14 patients in this series are shown in Table 1 and are compared to the baseline indices of the 7 patients who were deemed inappropriate candidates for combined LVRS and pulmonary resection. In the operated group there were 8 men and 6 women, and the mean age was 69 years old (54 to 80 years). Ten patients were oxygen dependent preoperatively, 5 patients had been on chronic steroids, and 6 patients underwent preoperative rehabilitation. The mean preoperative room air partial pressure of carbon dioxide was 43 2.4 mm Hg (33 to 62 mm Hg) and 5 patients had a partial pressure of carbon dioxide of more than 45 mm Hg. The mean preoperative room air partial pressure of oxygen was 60 2 mm Hg (46 to 63 mm Hg). Before operation the mean FEV 1 was 680 98 ml (300 to 1,400 ml), 24% 5% predicted (12% to 58% predicted); the mean forced vital capacity was 54% 5% predicted (25% to 101% predicted); and the mean FEV 1 to vital

316 DeROSE ET AL Ann Thorac Surg LVRS AND PULMONARY NODULES 1998;65:314 8 Table 1. Preoperative Characteristics of Patients Undergoing Combined Lung Volume Reduction and Pulmonary Nodule Resection (operation) Compared With Those Denied Combined Tumor Resection and Lung Volume Reduction (no operation) Category Operation (n 14) No Operation (n 7) Age 69 2 70 1 Male 8 (57%) 4 (57%) Steroid dependent a 5 (36%) 2 (28%) Oxygen dependent 10 (72%) 4 (57%) Preop rehabilitation 6 (43%) 2 (28%) Room air partial pressure of 43 2 37 6 carbon dioxide (mm Hg) Room air partial pressure of 60 2 63 4 oxygen (mm Hg) Dyspnea index 3.7 0.3 4 0.6 Six-minute walk distance (ft) 816 93... Pulmonary function tests FEV 1 680 98 ml 730 206 ml 24% 5% pred 30% 11% pred FVC 54% 5% pred 54% 6% pred FEV 1 /FVC 37% 2% pred 39% 6% pred a Preoperative prednisone dose 10 mg/day. FEV 1 forced expiratory volume in 1 second; capacity; pred predicted. FVC forced vital capacity was 37% 2% predicted (30% to 47% predicted). Mean preoperative dyspnea index was 3.7 0.3 (1 to 5) and mean 6-minute walk distance was 816 93 ft (425 to 1,710 ft). All of these parameters were not statistically different from those observed in the unoperated group (Table 1). Statistical Analysis All data is expressed as the mean the standard error of the mean. The paired Student s t test was used for analyzing the relationship between preoperative and postoperative patient data. All p values are reported without corrections for multiple comparisons, and a p value less than 0.05 is considered significant. Results The preoperative lung function, surgical data, and pathology for each of the 14 patients in this series are shown in Table 2. All patients were extubated in the operating room. There was one postoperative death (Patient 5). The death occurred early in our LVR experience in a patient who had undergone ipsilateral lung operation. He died on postoperative day 18 as a result of a large bronchopleural fistula. Since this early experience we have used previous Table 2. Preoperative Pulmonary Function, Operative Data, and Pathology of 14 Patients Undergoing Combined Lung Volume Reduction and Pulmonary Nodule Resection Patient Age Sex FEV 1 (% pred) DI Tumor size (cm) Tumor Location Operation Pathology 1 80 F 37% 4 1.8 LUL MS; bilateral upper lobe LVR Squamous cell 2 67 M 49% 3 1.0, 1.0 RUL, LUL MS; bilateral upper lobe LVR Caseating granulomas 3 77 F 26% 5 1.0 RUL MS; bilateral upper lobe LVR Aspergilloma 4 65 F 21% 4 0.7 RLL Clam shell; bilateral upper lobe Hamartoma LVR, wedge resection RLL 5 73 M 35% 5 1.7 RLL Clam shell; bilateral upper lobe LVR, wedge resection RLL Bronchioalveolar 6 69 F 20% 4 2.5 RUL Right PLT; RUL and RML LVR Squamous cell 7 72 M 12% 5 2.5 LLL Clam shell; bilateral upper lobe Adeno LVR LLL wedge resection 8 61 F 6% 4 2.5 RLL Right PLT; RUL LVR; RLL wedge resection Squamous cell 9 54 M 18% 4 1.0 RUL Right PLT; right upper Hamartoma lobectomy 10 70 F 58% 2 1.6, 1.5 RUL, RLL Right PLT; RUL and superior segment RLL LVR Bronchioalveolar 11 63 M 32% 3 2.0 RLL Right PLT; RUL, RLL and RML LVR Caseating granuloma 12 66 M 23% 1 1.0 LUL Thoracoscopic LUL LVR and Aspergilloma wedge resection 13 71 M 13% 4 1.0 LUL Left PLT; left upper lobectomy Squamous cell 14 78 M 19% 3 3.0 LUL Left PLT; lingula-sparing left upper lobectomy Adeno DI dyspnea index; FEV 1 forced expiratory volume in 1 second; LLL left lower lobe; LUL left upper lobe; LVR lung volume reduction; MS median sternotomy; PLT posterolateral thoracotomy; pred predicted; RLL right lower lobe; RML right middle lobe; RUL right upper lobe.

Ann Thorac Surg DeROSE ET AL 1998;65:314 8 LVRS AND PULMONARY NODULES 317 Table 3. Six-Month Follow-up Functional Results Category Preop Postop Difference p Value po 2 (mm Hg) 61.1 2.3 64.6 2.7 3.5 NS PCO 2 (mm Hg) 46.8 2.9 39.6 1.7 7.0 0.016 Six-minute walk 817 100 1100 103 283 0.007 distance (ft) Dyspnea index 3.6 0.3 1.9 0.3 1.7 0.0004 FEV 1 (ml) 676 106 886 141 210 0.008 (27% 4%) (35% 5%) FVC (ml) 1947 277 2283 212 336 0.02 (54% 6%) (69% 5%) FEV 1 /FVC (%) 38 2 42 5 4% NS FEV 1 forced expiratory volume in 1 second; NS not significant; PCO 2 partial pressure of carbon dioxide; PO 2 partial pressure of oxygen. thoracic operation as an absolute contraindication to ipsilateral LVRS. Morbidity included three prolonged air leaks ( 14 days), one postoperative ileus, and one transient ischemic neurologic event. One prolonged air leak required reoperation for repair of a bronchopleural fistula. The mean length of hospital stay was 14.4 1.9 days (3 to 27 days). There were 16 nodules detected in the 14 patients. Pathologic examination determined 7 benign lesions and 9 malignant tumors. The lesions included non-small cell (9), caseating granuloma (3), hamartoma (2), and aspergilloma (2). Of the nine non-small cell s there were four squamous cell s, three bronchioalveolar s, and two adenos. One patient had two separate suspicious lesions, both of which were caseating granulomas. A second patient had two separate brochioalveolar s resected. The mean nodule size was 1.7 cm (0.7 to 3.5 cm). The anatomic distribution of the nodules was as follows: right upper lobe (5), right middle lobe (0), right lower lobe (5), left upper lobe (5), and left lower lobe (1). All patients had grossly clear surgical margins. One patient had microscopic evidence of vascular and lymphatic invasion at the resected surgical margin. All patients are alive and well through a mean follow-up period of 22.6 2.3 months (12 to 35 months). At 6-month follow-up there has been an improvement in dyspnea index (3.6 0.3 versus 1.9 0.3, p 0.0004), FEV 1 (27% 4% predicted versus 35% 5% predicted, p 0.0077), forced vital capacity (54% 6% versus 69% 5% predicted, p 0.02), and 6-minute walk distance (817 100 ft versus 1,100 308 ft, p 0.007) (Table 3). All but 1 patient has had a reduction in preoperative oxygen requirement. One patient has a suspected new primary neoplasm in unoperated lung tissue at 12 months followup. A mediastinal metastasis developed at 12 months follow-up in the patient with two separate bronchioalveolar s. The 7 patients with severe emphysema and pulmonary nodules who did not meet inclusion criteria for combined LVR and tumor resection have been followed up for a mean of 15.7 1.6 months. One patient died of progressive emphysema 7 months after initial evaluation. A second patient has metastatic disease 1 year after undergoing LVR evaluation. The other 5 patients are alive and well without evidence of worsening pulmonary function or advanced malignant disease. Comment Without therapy, lung cancer is 100% fatal. Although some investigators have found 5-year survival rates of up to 35% for patients with stage I disease who are treated with radiation therapy alone [9], overall survival rates in most series are low [10, 11]. To date, operation remains the only significant chance for cure in patients with early stage lesions. After lobectomy, patients with T1 N0 non small cell lung cancer experience up to an 80% 5-year cancer-free survival [12]. It has been difficult to assess the lower limit of tolerance for surgical resection in patients with severe emphysema. Preoperative pulmonary function testing has been used in an attempt to define postoperative morbidity and mortality after lung resection in the high-risk emphysematous patient. An FEV 1 of 800 ml or less (30% to 35% predicted), a forced vital capacity of 50% predicted or less, and a MVV of 40% predicted or less, as well as a room air partial pressure of carbon dioxide of greater than 45 mm Hg and a partial pressure of oxygen less than 50 mm Hg have all been historically associated with a marked increase in morbidity and mortality after a lung resection of any type [13 17]. In an effort to extend the criteria for operability, tests of regional lung function have been used to predict postoperative functional loss after resection [1, 18]. Gass and Olsen [19] suggest that a predicted postoperative FEV 1 of 30% to 35% is an acceptable value for operation. Other researchers have used exercise testing and measurements of oxygen consumption to determine risk. Walsh and colleagues [20] have reported a 0% 30-day operative mortality in high-risk patients who have a preoperative exercise oxygen consumption of 15 ml kg 1 min 1. With the advent of LVR, many of the classic criteria for determining operability in lung cancer must be reassessed. McKenna and colleagues [21] recently reported their experience with resection of 51 lung masses in 325 patients undergoing LVR. Only 11 of the lesions in their series were non-small cell and follow-up was short. Nonetheless, an acceptable mortality of 3.5% was achieved and no evidence of recurrent or metastatic disease was detected through a mean follow-up of 9 months. As in our series, a significant improvement in pulmonary function was observed in all patients undergoing combined LVR and tumor resection. McKenna and colleagues [21] concluded that LVR allowed operation for lung cancer in patients who otherwise would be considered to have physiologically inoperable disease. All of the patients in the present series would be considered high risk by present preoperative indices. Nonetheless, morbidity and mortality were acceptable after combined LVR and tumor resection. Most important, resection was accompanied by an improvement in

318 DeROSE ET AL Ann Thorac Surg LVRS AND PULMONARY NODULES 1998;65:314 8 pulmonary performance. Of all 13 surviving patients, none had a deterioration in pulmonary function, oxygen requirement, or degree of dyspnea. Furthermore, improvements in exercise tolerance and dyspnea after combined LVR and pulmonary nodule resection can improve quality of life. Eleven of the resections in this series were wide wedge resections with only three formal lobectomies. The Lung Cancer Study Group study has shown lobectomy to be superior to wedge resection in terms of early locoregional recurrence without a significant difference in overall survival for stage I lung cancer [13]. Although lobectomy is our preferred cancer operation for stage I and II lesions, the heterogeneous distribution of emphysematous changes frequently results in the removal of a large portion of functional lung tissue with such a resection. When very focal target areas of emphysema exist isolated to the upper lobe, formal lobectomy may be acceptable. However, it should be noted that the behavior of a lung cancer arising in emphysematous lung tissue with severely damaged regional lymphatic channels is not entirely known. In these select patients, wide wedge resection may provide adequate excision of both the primary lesion and the poorly preserved surrounding lymphatic basin. Long-term follow-up of combined wedge resection and LVR will be needed to determine whether adequate local control and survival advantage is conferred by this operation. All lesions in this series were highly suspicious for malignancy based on CT scan criteria before resection. Invasive preoperative evaluation of these lesions by transthoracic needle biopsy was believed to be contraindicated because of severe emphysema. Given the peripheral location of the lesions, bronchoscopy was deferred until the time of operation. Although 7 of the 16 resected nodules were benign, potentially life-saving information was frequently gleaned from pathologic examination. In five of the seven benign nodules (caseating granuloma and aspergilloma) resected in this series, appropriate pharmacologic therapy was instituted based on the pathologic findings. Combining tumor resection with LVR allows definitive diagnosis as well as treatment of the benign or infectious nodule. In the hope of better defining the preoperative nature of solitary lung lesions in severely emphysematous patients, we recently have instituted a pilot study using positron emission scanning. In conclusion, with the techniques of LVR surgery, emphysematous patients with suspicious pulmonary nodules and severe pulmonary dysfunction can be offered resection aimed at both cure of tumor and improvement in quality of life. The currently used predictors of perioperative risk in lung resection do not accurately apply to LVR candidates. 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