Emphysema, a form of chronic obstructive pulmonary

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1 REVIEWS Lung Volume Reduction Surgery in Emphysema: A Systematic Review George R. Stirling, FRACS, Wendy J. Babidge, PhD, Morris J. Peacock, FRACS, Julian A. Smith, FRACS, Kevin S. Matar, FRACS, Gregory I. Snell, FRACP, Deborah J. Colville, FRACS, and Guy J. Maddern, FRACS Alfred Hospital, Melbourne, Victoria; ASERNIP-S, Royal Australasian College of Surgeons, Adelaide, South Australia; Department of Surgery, University of Adelaide, The Queen Elizabeth Hospital, Adelaide, South Australia; Ladhope Chambers, Brisbane, Queensland; and Heidelberg, Victoria, Australia The aim of this study was to systematically review the literature regarding the safety and efficacy of lung volume reduction surgery (LVRS) in patients with emphysema. Studies on LVRS to August 2000 were identified using MEDLINE, Embase, Current Contents, and the Cochrane Library. Human studies of patients with upper, lower or diffuse distributions of emphysema were included. All types of bullous emphysema were excluded. A surgeon and researcher independently assessed the retrieved articles for their inclusion in the review. When LVRS was compared with medical management, at 2 years LVRS was associated with a higher FEV 1 and at least equivalent survival. The use of staple excision of selected areas of lung appeared to be more efficacious than laser ablation. There is insufficient evidence to show preference for median sternotomy or videoscopically assisted thoracotomy, as the more safe and efficacious procedure. In highly selected patients with emphysema LVRS is deemed an acceptable treatment. To fully evaluate the safety and efficacy of LVRS, outcomes beyond 2 years must be included. The results of prospective randomized trials between medical management and LVRS, now in progress, are essential before a final assessment can be made. (Ann Thorac Surg 2001;72:641 8) 2001 by The Society of Thoracic Surgeons Emphysema, a form of chronic obstructive pulmonary disease, is a condition characterized by abnormal and permanent enlargement of the air spaces distal to the terminal bronchioles and accompanied by destruction of their walls without obvious fibrosis [1]. Lung volume reduction surgery (LVRS) is a palliative operation to be considered in selected patients suffering severe dyspnea from the end stage of diffuse nonbullous emphysema, who are not responding to maximal medical management. Bullectomy has been an established technique for For editorial comments see pages 327 and 330 patients with bullous emphysema, since the work of Brantigan and Mueller 40 years ago [2]. The concept of LVRS was developed by Cooper and colleagues [3] inspired by Brantigan s earlier work. He modified the approach of Brantigan and Mueller [2] by using a median sternotomy, thus allowing access to both lungs and used a buttressed staple excision technique. The hyperinflated and relatively functionless parts of both lungs were removed and it was proposed that this would result in improvement in the function of the remaining lung, palliate the dypsnea, improve exercise ability, and provide a positive change in quality of life. A variety of different approaches to LVRS have been Address reprint requests to Professor Maddern, ASERNIP-S, PO Box 688, North Adelaide, South Australia 5006, Australia; college.asernip@surgeons.org. proposed; these include median sternotomy [3], thoracosternotomy [4] and video-assisted thoracosopic surgery (VATS) technique [5]. There are both unilateral and bilateral approaches, with significant benefits from unilateral surgery in appropriately selected patients. The areas for surgical removal are identified before surgery by computed tomography and radionuclide ventilationperfusion scanning. Methods for sealing the site of resected lung include the use of staples [6 9] or a laser (neodymium: yttrium-aluminum-garnet) [6 8]; however, prolonged air leak is a common postoperative complication. Attempts to overcome this have been to use buttressing materials along the staple line, either bovine pericardium [6 11] or collagen [9, 11]. Lung volume reduction surgery is a procedure that requires appropriate selection of patients who have been suitably informed of the risks of this procedure. The patient selection criteria for LVRS are rigorous, involving both functional and radiological assessment. Initial selection is on clinical grounds and is confined, for the purposes of this review, to patients with nonbullous emphysema who are severely disabled by dypsnea at rest or on minimal exertion despite maximal medical treatment [12]. The number of patients who qualify for LVRS are a small percentage of those originally assessed. Patients are selected who will achieve maximal benefit with regard to safety and efficacy. Patient selection criteria have been reviewed and summarized [12, 13], and although there is consensus on some criteria, there are quite opposing views on other criteria (Table 1). Patient 2001 by The Society of Thoracic Surgeons /01/$20.00 Published by Elsevier Science Inc PII S (01)

2 642 REVIEW STIRLING ET AL Ann Thorac Surg LUNG VOLUME REDUCTION SURGERY 2001;72:641 8 Table 1. Patient Selection for Lung Volume Reduction Surgery Consensus a No Consensus b Smoking-related emphysema -1 Antitrypsin deficiency emphysema Heterogeneous emphysema with good target areas Diffuse emphysema without target areas Bilateral surgery better short-term result Role of unilateral surgery Poor general fitness/condition higher mortality Surgery in the presence of coexistent cardiac disease Upper age limit Use of V/Q vs CT to define target areas Hyperinflation Upper and lower limits of acceptability of FEV 1, DLCO, Pco 2, Pao 2, 6MW, TLC, RV, and PAP a Expert opinion as described in the literature and is generally not high level evidence nor supported by trials. b Either has not been studied or results are controversial, ie, opposing views are evident from the literature. V/Q quantitative nuclear ventilation perfusion scan; CT computed tomography; FEV 1 forced expiratory volume in 1 second; DLCO single-breath carbon dioxide diffusing capacity; Pco 2 arterial carbon dioxide tension; Pao 2 arterial oxygen tension; 6MW 6-minute walk test; TLC total lung capacity; RV residual volume; PAP pulmonary arterial pressure measurement. selection has focused on efficacy (ie, maximizing the postoperative FEV 1 ) as well as safety (ie, minimizing mortality and morbidity), although the two are not necessarily related. The reason for this review is the wide disparity in published reports of patient selection criteria and outcomes for patients submitted to LVRS. Considerable morbidity is associated with LVRS [7, 8, 14 16]. Reports indicating a low mortality [10, 17] and favorable outcomes are read alongside other reports of high mortality [9] and variable outcomes in the survivors. Data outlining success predominates over reports of failure. There seems to be a clear need for an objective systematic review, based on the hierarchy of evidence, before reaching tentative conclusions about the matter. This review is a summary of information produced during the process of assessment of LVRS for the Australian Safety and Efficacy Register of New Interventional Procedures Surgical (ASERNIP-S). The purpose of this review was to assess the outcomes of various types of LVRS, and any comparative studies of LVRS and medical management. The aim of ASERNIP-S reviews are to assess the current safety and efficacy information of a new surgical procedure, and determine whether it is appropriate for widespread use or requires further evaluation in the form of an audit or controlled clinical trial. Material and Methods ASERNIP-S Review Process A surgeon familiar with the topic of review (Protocol Surgeon) and an ASERNIP-S Researcher worked together to draft the protocol for the review and determine the studies to be included. The Review Surgeon assessed these publications and produced a narrative review. The ASERNIP-S Researcher conducted a methodological assessment of the literature. The protocol, review, and methodological assessment report formed the systematic review documentation, which was considered by the Review Group. The Review Group was made up of the Review and Protocol Surgeons, a Nominated Surgeon from the Division of Cardiothoracic Surgery of the Royal Australasian College of Surgeons (RACS), an Invited Physician, a surgeon from another specialty, and an ASERNIP-S Researcher. The Review Group considered the review documentation, recommendations, and ASERNIP-S classification put forward by the Review Surgeon. The Surgical Director of ASERNIP-S oversaw this process and chaired the Review Group. Consensus was reached on the recommendation and classification, which was put before the ASERNIP-S Management Committee for ratification before being considered by the RACS Council for endorsement. Search Strategy Studies on lung volume reduction surgery were identified using MEDLINE (January 1984 to August 2000), Embase (January 1974 to August 2000), Current Contents (Jaunary 1993 to Week ) and the Cochrane Library (January 1966 to Issue ). The search terms were as follows: (lung volume reduction surgery or LVRS or lung volume reduction or lung reduction surgery) and (emphyse* or COPD or chronic obstructive pulmonary disease or pneumectomy or pneumoplasty). The truncation symbol * differs in each database and allows retrieval of all possible suffix variations of a root word. There was no comparable surgical technique, so the only comparison that could be made was with medical management. Inclusion Criteria The types of study to be included in the review of LVRS included randomized controlled trials, controlled clinical trials (historical and nonrandomized), and case series. Table 2 contains the guidelines used for assessing the level of evidence of the studies [20]. Human studies of patients with any distribution of emphysema (upper, lower, and diffuse) were included, whereas all types of bullous emphysema were excluded. The surgical approach was median sternotomy, thoracotomy, or videoscopic techniques with stapled excision or laser ablation. Both bilateral and unilateral procedures were considered. Only English language articles were included for review. For inclusion, studies were required to contain data on at least one of the following outcomes: perioperative mortality; perioperative morbidities including bleeding,

3 Ann Thorac Surg REVIEW STIRLING ET AL 2001;72:641 8 LUNG VOLUME REDUCTION SURGERY 643 Table 2. Designation of Levels of Evidence a Hierarchy of Evidence I Evidence obtained from a systematic review of all relevant randomized controlled trials. II Evidence obtained from at least one properly designed, randomized controlled trial. III-1 Evidence obtained from well designed, pseudorandomized controlled trials (alternate allocation or some other method). III-2 Evidence obtained from comparative studies with concurrent controls and allocation not randomized (cohort studies), case-control studies, or interrupted time series with a control group. III-3 Evidence obtained from comparative studies with historical control, two or more single-arm studies, or interrupted time series without a parallel control group. IV Evidence obtained from case series, either posttest or pre- and posttest. a Based on Reference 20. infection, respiratory failure, sputum retention, and prolonged air leak; lung function measures such as FEV 1 ; exercise performance including 6-minute walk test; dyspnea scores; quality of life measures; length of hospital stay; need for reoperation or readmission and survival time. Particular emphasis was placed on outcomes relating to the safety and efficacy aspects of the procedures. Data Extraction Articles were assessed independently by the Protocol Surgeon and the ASERNIP-S Researcher as to their suitability for review based on the inclusion criteria specified in the protocol. Studies that clearly did not meet the inclusion criteria were marked for deletion by the ASERNIP-S Researcher. All studies were further assessed by the Review Surgeon and a decision made on the articles for inclusion. Data Analysis Three studies compared LVRS with medical management, but as outcome measures were either not given at the same time point or raw mean data not provided, a meta-analysis could not be performed. Relative risks and weighted mean differences were calculated using Rev- Man (Update Software). When the 95% confidence interval of the relative risk was less than 1 the outcome favored the LVRS treatment; otherwise the outcome was not considered different between the two groups. If the 95% confidence interval of the weighted mean difference included 0 then the comparison was considered not significant. Results Safety and Efficacy A total of 88 papers were deemed to meet the inclusion criteria for the intervention of lung volume reduction surgery. Of these, 18 were comparative studies (level II or level III evidence). There were two reports of randomized controlled trials comparing outcomes from continued medical treatment with a parallel group submitted to LVRS [21, 22]. One study [23] compared outcomes in patients who had undergone LVRS by median sternotomy with those selected, but denied the operation because of changes in the Medicare funding arrangements in the US. A description of these three studies [21 23] appears in Table 3; safety and efficacy outcomes are shown in Table 4. A comparison was made of physiologic and pulmonary function parameters in 87 patients who were selected for LVRS but in whom 22 were denied the procedure [23]. Significant improvements at both 12 and 24 months were evident in FEV 1 and oxygen requirements. Long-term follow-up (means of 976 and 867 days for LVRS and medical management, respectively) showed survival to be better in the LVRS group than those treated by medical management alone. Survival was not significantly higher in the study of Geddes and associates [22] at 12 months after LVRS, and although some pulmonary function measurements were improved, the period of benefit was varied. The study of Criner and colleagues [21] only found benefit after LVRS with regard to length of exercise time. Quality of life was improved at 3 months [21] and at 12 months [22] for those patients undergoing LVRS. All other comparative studies reviewed presented the outcomes after the use of different methods of performing LVRS. To assess the efficacy of the various techniques, a number of measures have been used. Functional status before and after surgery is assessed by the measurement of multiple parameters of pulmonary function and quality of life indicators, but the forced expiratory volume in 1 second (FEV 1 ) is most commonly used as a single indicator of functional status. Using this measure, stapling is associated with more short-term (3 to 6 months) improvement than the laser technique [6, 8]. Improvement to at least 6 months was found in another study using the laser technique [9]. With regard to buttressing of the staple line and comparisons of the type of buttressing (bovine pericardium or collagen), there have been no significant differences found with regard to efficacy [11]. Pulmonary function parameters were not significantly different between the treatments of median sternotomy and VATS [14]; however, for both methods of surgery, there was a significant improvement after operation at 6 months. Two studies [14, 24] found higher reintubation rates after median sternotomy compared with VATS. In a study assessing bilateral and unilateral surgery [16], there was a significant improvement in pulmonary function in both groups that was maintained 12 months after surgery. A study by Serna and colleagues [25] found survival at 2 years better for bilateral than unilateral VATS. Spirometry, lung volumes, and quality of life appeared to be superior for bilateral compared to unilateral VATS, although there was no significant difference in mortality between the two methods [26]. After surgery, FEV 1 was found to be significantly higher in patients treated with bilateral compared with unilateral surgery [15, 17]. One study compared outcomes for LVRS by median sternotomy with single and bilateral lung transplantation 12 months after surgery [27]. As would be expected, the degree of improvement was greater in the

4 644 REVIEW STIRLING ET AL Ann Thorac Surg LUNG VOLUME REDUCTION SURGERY 2001;72:641 8 Table 3. Description of Controlled Trials of Lung Volume Reduction Surgery Versus Medical Management Authors, Year, Ref. Level of Evidence Comparison Participants % Follow-up [Months] Criner et al, 1999 [21] Geddes et al, 2000 [22] II LVRS (median sternotomy-bilateral, staple) vs medical management II LVRS (median sternotomy bilateral, staple bovine epicardium) vs medical management 19 LVRS (mean age 59 y, 13 female) LVRS Medical management 18 medical management (mean age 57 y, 10 15/19 (79%) [3] 15/18 (83%) [3] female) Inclusion criteria New York Heart Association Class III IV Evidence of airflow obstruction and hyperinflation by pulmonary function studies (FEV 1 30% predicted, postbronchodillator administration, FRC or TLC 120% of predicted) Hyperinflation (by chest x-ray), diffuse bullous emphysema (by high resolution CT scan) Decreased/absent perfusion in planned resected lung tissue by V/Q scan Exclusion criteria Severe and refractory hypoxemia (Pao 2 /FIO 2 ratio 150) Severe hypercapnic respiratory failure requiring mechanical ventilation Presence of significant cardiovascular disease Presence of severe pulmonary hypertension (Mean pulmonary artery pressure 35 mm Hg) Severe debilitated state with total body weight 70% ideal Presence of significant extrapulmonary endorgan dysfunction expected to limit survival Psychologic dysfunction Continued smoking 24 LVRS (median age 62 y) LVRS Medical management 24 medical management (median age 60 y) Inclusion criteria Severe emphysema on CT scan (no restriction on pattern or distribution) 19/24 (79%) [3] 23/24 (96%) [3] Age 75 y 19/24 (79%) [6] 23/24 (96%) [6] FEV L 13/24 (54%) [12] 19/24 (79%) [12] O 2 use 18 h/day Steroid use 10 mg/day Pco 2 45 mm Hg Exclusion criteria Asthma Previous thoracic surgery Other serious medical condition

5 Ann Thorac Surg REVIEW STIRLING ET AL 2001;72:641 8 LUNG VOLUME REDUCTION SURGERY LVRS (mean age 66 y) LVRS Medical management 22 medical management (mean age 65 y) Inclusion criteria Emphysema with hyperinflation and target areas 51/65 (79%) [12] 22/22 (100%) [12] Marked physiologic impairment (FEV 1 35%) 45/65 (69%) [24] 17/22 (77%) [24] Marked restriction in activity despite maximal 37/65 (57%) [36] 5/22 (23%) [36] medical therapy Age 75 y Body weight % of ideal Ability to participate in vigorous pulmonary rehabilitation program No coexisting major medical problems Willing to undertake risk of morbidity and mortality Abstinence from cigarette smoking Exclusion criteria Large emphysematous bullae 1-antitrypsin deficiency III-2 LVRS (median sternotomy, bilateral, staple bovine pericardium) vs medical management Meyers et al, 1998 [23] CT computed tomography; FEV 1 forced expiratory volume in 1 second; FRC functional residual capacity; LVRS lung volume reduction surgery; Pao 2 /Fl O 2 ratio of arterial oxygen tension to fraction of inspired oxygen; Pco 2 arterial carbon dioxide tension; TLC total lung capacity; V/Q scan quantitative ventilation perfusion scan. lung transplant groups; however, an acceptable increase was evident in the LVRS group. Lung volume reduction surgery was considered a satisfactory treatment option for some patients with end-stage emphysema, whereas avoiding transplant-specific complications and providing an early option (or maybe, the only option) in certain cases. Assessment of the safety and efficacy in these comparative studies of LVRS has been performed by determining the types and proportions of adverse outcomes. Postoperative mortality was extremely varied, between 0% and 28% with an average of about 9%. In comparing the laser to the staple technique [6 9], mortality was higher in the laser group in three studies [6 8], whereas air leak of more than 7 days occurred in a high percentage of cases in both the laser and staple groups [7, 8]. For all techniques, air leak of more than 7 days was the most common complication, occurring on average in about 50% of cases [7, 8, 16]. Other common postoperative complications included pneumonia, delayed pneumothorax, respiratory failure, wound infection, and reintubation and reoperation for various complications. Roberts and colleagues [24] reported that colonic and gastroduodenal perforation had contributed significantly to mortality in their experience. Cetindag and colleagues [28] confirmed this. It is generally agreed that the maximum increase in FEV 1 is evident at 6 months after LVRS but steadily diminishes after that time. Kesten and colleagues [29], in a study of 54 patients who had had bilateral LVRS by median sternotomy, noted a wide variation in responses measured by FEV 1. Approximately one half of the cohort had an increase of FEV 1 greater than 10% with a mean of 18%, whereas the rest of the cohort had an increase of less than 10% with a mean of 2.2%. In the first group, 17 of the 26 patients were restudied over a period of 15 to 23 months. Six of these patients showed an accelerated decline in FEV 1. The authors noted that the accelerated decline occurred in patients who had had a better than average early increase in FEV 1. Brenner and colleagues [9] report similar data. Fessler and Wise [30] also confirm the observation and provide a good review of the growing literature on the matter. Whereas long-term outcomes are crucial, short-term outcomes are equally important. In their opinion, 20% to 50% of patients may achieve little or no benefit from current techniques of LVRS. This is very relevant to the question of informing the patient adequately before gaining consent for operation. Many of their patients voiced the view that they were prepared to accept a considerable risk of death to achieve relief from severe dyspnea. Patients should also be informed that, at least in a significant minority of patients who survive operation, there will be no relief of dyspnea. An excellent systematic review of the subject of expected outcomes after LVRS has been carried out by Young and colleagues [31]. Their analysis was handicapped by the paucity of significant data; from 75 potentially relevant studies only 19 satisfied their inclusion criteria. A major difficulty in comparing results lies in the

6 646 REVIEW STIRLING ET AL Ann Thorac Surg LUNG VOLUME REDUCTION SURGERY 2001;72:641 8 Table 4. Safety and Efficacy Outcomes After LVRS Compared With Medical Management Criner et al, 1999 [21] a Geddes et al, 2000 [22] b Meyer et al, 1998 [23] Adverse Outcome, Complication or Outcome Variable Follow-up (months) LVRS/Medical Management Weighted Mean Difference (95% CI) LVRS/Medical Management p Value LVRS/Medical Management Relative Risk (95% CI) Safety Actuarial survival 12 89%/100% e 24 85%/80% 36 83%/64% e Absolute survival 82%/64% f Mortality (total) 3 17%/? 12 21%/12% 0.43 Efficacy FEV 1, L / ( 0.27, 0.33) 0.91/ FEV / /0.52 c FEV /0.57 d O 2 rest, % use 24 27/ (0.18, 0.51) O 2 exercise, % use 24 67/ (0.54, 0.82) Steroid, % use 24 15/ (0.26, 3.02) FVC, L / ( 0.26, 0.68) 2.84/ FVC / TLC, L / ( 1.24, 0.56) 119/ TLC / RV, L 3 3.7/ ( 1.31, 0.17) 169/ RV / pco 2, mm Hg 3 43/ ( 6.35, 2.35) 38/ pco / MW (m) 3 321/ ( 54.48, 90.48) 260/ MW / Exercise time, min 3 9.1/7 2.1 (0.91, 3.29) Quality of life SIP score 3 Decrease/Increase SF / SF / a Cross-over patients not included. b Median values. c p d p e No significant difference by Mantel test. f Mean follow-up of 976 and 867 days, respectively. CI confidence interval; Decrease decreased at 3 months; FEV 1 forced expiratory volume in 1 second; FVC forced vital capacity; Increase increased at 3 months; LVRS lung volume reduction surgery; Pco 2 arterial carbon dioxide tension; RV residual volume; SF-36 - short form 36; SIP sickness impact profile; TLC total lung capacity; 6MW 6-minute walk test;? not reported.

7 Ann Thorac Surg REVIEW STIRLING ET AL 2001;72:641 8 LUNG VOLUME REDUCTION SURGERY 647 different criteria that have been used in selection for medical or surgical treatment. A definite decision about the course of treatment to follow in long-term management should be delayed until the maximum response has been achieved by intensive medical treatment and rehabilitation. Objective evaluation also should be carried out after the maximum response to medical treatment has been achieved. Standardization and refinement of the techniques of physiologic measurement is vital, particularly with regard to maximizing the bronchodilator response before measuring FEV 1, residual volume, and total lung capacity. Unless there is rigor in this matter it is impossible to separate the changes from medical treatment alone from those due to surgery, as all patients continue on intensive medical treatment. Neglect of these criteria in the selection process has been a major defect in many studies reviewed. A Cochrane review by Hensley and colleagues [32], which was updated to June 1999, identified only one RCT [8] of LVRS for diffuse emphysema. This study compared stapled unilateral thoracoscopic lung reduction coupled with bovine pericardium reinforcement with a unilateral neodymium: yttrium-aluminum-garnet laser contact reduction. The review concluded that there was insufficient evidence to support the use of LVRS for treatment of severe diffuse emphysema, outside of the large RCTs underway in Europe and the US comparing LVRS to optimal medical therapy. Another difficulty is evident in reporting mortality in the surgical series. Some authors report hospital mortality, others operative or perioperative mortality, and others 30-day mortality. Because significant mortality occurs between 30 and 90 days, it is considered that 90-day mortality is the most useful indicator to be accepted [30]. Finally, it should be stated that in a formal prospective study, assessment of late follow-up status by independent and expert professionals is the ideal. As of August 2000, no significant data from randomized prospective controlled trials is available from the US, Canadian, or United Kingdom trials. The first Australian operation of LVRS was carried out in September Since that time a sustained effort has been made to encourage surgeons and physicians involved with LVRS to submit their results to a database for all patients operated on in Australia and New Zealand. The fifth report of the Australia and New Zealand LVRS Database [33], records in October 1999 that 309 patients from 10 centers had undergone LVRS. This may be the only national database in the world at this time. Detailed adequate data were available from 235 cases (76%) and form the basis of the report. The remainder of cases were recently operated upon and had inadequate data for inclusion or had no data at that time. The potential database for later study should contain 92% to 100% of cases in this time frame. The largest series consisted of 108 patients operated on by the median sternotomy approach, with a 90-day mortality of 10.8%. Porter and colleagues [34] have presented their results in 55 patients using the VATS approach. The present position of LVRS in Australia and New Zealand is described by Snell and associates [35]. Comment This review of the techniques and outcomes of LVRS has led to the following opinions. Lung volume reduction surgery using the stapling excision technique and the median sternotomy approach, in highly selected cases, has proved to be a safe and reasonably efficacious procedure in the treatment of diffuse nonbullous emphysema according to Cooper and colleagues [19]. These results have been shown to be reproducible by other workers [36 40]. The notion of efficacy has to be qualified by two factors, the first being that there is clear evidence that although quality of life and pulmonary function improve to a maximal level by 6 months, there is then a variable and expected deterioration in these quantifiers of improvement in the next 2 years. Although significant improvement is demonstrable at 2 years on the basis of reasonable published data, the evidence concerning 3-year results is scanty and based on a few papers, the most significant of which are those of Cooper and Lefrak [41] and Brenner and colleagues [18]. The second qualification of this opinion on efficacy, therefore, is that there is inadequate data about outcomes beyond 2 years. Two studies by Gelb and colleagues [42] and Cassina and associates [43] draw attention to the disappointing results achieved in patients with diffuse emphysema due to -1 antitrypsin deficiency. Reports by McKenna and colleagues [16] on LVRS by VATS, using a similar stapling excision technique, record results strikingly similar to those achieved by median sternotomy; and again, the results have been reproduced by other workers [14, 44, 45]. Review of the results of laser ablation of emphysema by VATS, though producing encouraging results in bullous emphysema, has resulted in a higher 1-year mortality, frequent late pneumothorax, and less measurable improvement in function than that for staple excision [8]. There is insufficient evidence at this time to recommend laser ablation as a safe and efficacious treatment for diffuse emphysema. This systematic review complements that of Young and colleagues [31]. Such methodologically directed reviews are critical for the assessment of new surgical procedures such as LVRS. However, higher-level evidence is required in the form of randomized controlled trials comparing LVRS with medical management to establish the worth of this technique in clinical practice. We acknowledge the Australian Commonwealth Department of Health and Family Services for their support of the ASERNIP-S project. References 1. American Thoracic Society. American Thoracic Society: chronic bronchitis, asthma and pulmonary emphysema: a statement by the committee on diagnostic standards for non-tuberculous respiratory diseases. Am Rev Resp Dis 1962;85: Brantigan O, Mueller E. Surgical treatment of pulmonary emphysema. Am Surg 1957;23:

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