Eur J Cardiothorac Surg 2007;31:486-490. doi:10.1016/j.ejcts.2006.11.052
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved
Is there a role for therapeutic lobectomy for emphysema?
Paul Vaughan,
Inger Oey,
Apostolos Nakas,
Antonio Martin-Ucar,
John Edwards,
David Waller*
Department of Thoracic Surgery, Glenfield Hospital, Groby Road, Leicester LE3 9QP, United Kingdom
Received 15 September 2006;
received in revised form 23 November 2006;
accepted 27 November 2006.
* Corresponding author. Tel.: +44 116 2563959; fax: +44 116 2502662. (Email: david.waller{at}uhl-tr.nhs.uk).
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Abstract
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Objective: The feasibility of performing a standard lobectomy in patients with non-small cell lung cancer (NSCLC) and severe heterogeneous emphysema whose respiratory reserve is outside standard operability guidelines has been described [Edwards JG, Duthie DJR, Waller DA. Lobar volume reduction surgery: a method of increasing the lung cancer resection rate in patients with emphysema. Thorax 2001;56:791–5; Korst RJ, Ginsberg RJ, Ailawadi M, Bains MS, Downey RJ, Rusch V, Stover D. Lobectomy improves ventilatory function in selected patients with severe COPD. Ann Thorac Surg 1998;66:898–902; Carretta A, Zannini P, Puglisi A, Chiesa G, Vanzulli A, Bianchi A, Fumagalli A, Bianco S. Improvement in pulmonary function after lobectomy for non-small cell lung cancer in emphysematous patients. Eur J Cardiothorac Surg 1999;15(5):602–7]. Postoperative lung function was better than predicted, attributable to the therapeutic benefit of deflation of the hemithorax. Our aim was to determine whether the physiological benefits of this approach were superior to conventional non-anatomical lung volume reduction surgery (LVRS) in similar patients. Methods: A retrospective review of a single surgeon's experience identified 34 consecutive patients who underwent upper lobectomy for completely resected stage I–II NSCLC, and who had severe heterogeneous emphysema of apical distribution with a predicted postoperative FEV1 of less than 40%. Their perioperative characteristics, postoperative spirometry and survival of these cases were compared to 46 similar patients who underwent unilateral upper lobe LVRS during the same period. Results: Data expressed as median (range). LVRS patients were significantly younger (59 years [39–70] vs 67 years [48–79] p
< 0.001), with more severe airflow obstruction (FEV1 %pred 24 [12–60] vs 44 [17–54] p
< 0.001) and more heterogenous disease (‘Q’ score 4 [0.5–11.5] vs 7 [1–13] p
= 0.001) than the lobectomy group. No significant difference was found in median survival (88 vs 53 months, p
= 0.06). Lobectomy patients had a shorter air leak duration (5 days [2–36] vs 9 days [1–40], p
= 0.02) and hospital stay (8 days [3–63] vs 13 days [6–90] p
= 0.01). A significant correlation was found between pre-operative Q score and percentage improvement in FEV1 (r
= –0.33, p
= 0.02). Conclusions: Lobectomy for lung cancer in patients in severe heterogenous chronic obstructive pulmonary disease is associated with similar improvement in airflow obstruction as conventional LVRS, but is associated with a shorter postoperative course. Lobectomy may therefore offer a therapeutic alternative to conventional LVRS in a selected population.
Abbreviations: NSCLC = non-small cell lung cancer • LVRS = lung volume reduction surgery • COPD = chronic obstructive pulmonary disease • FEV1
= forced expiratory volume in 1 s • PpoFEV1
= percent predicted post operative FEV1 • CT = computed tomography • PET = positron emission tomography
Key Words: Lung volume reduction surgery • Non-small cell lung cancer • Thoracic surgery
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1. Introduction
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Lung volume reduction surgery (LVRS) has been described as a non-anatomical resection of peripheral lung tissue. However, the optimum amount of lung removed at the time of surgery has yet to be determined. Most centres remove 20–30% of the affected lung, after preoperative identification of ‘target areas’ [1].
Whenever possible, anatomical lobectomy is the procedure of choice for stage I non-small cell lung cancer (NSCLC) [2]. Available guidelines for operability in the management of these patients state that those patients with a predicted postoperative FEV1 (ppoFEV1) of less than 40% of predicted are at high risk of complications if surgical resection is undertaken [3,4]. The increasing experience with LVRS has led some authors to apply these principles to the management of NSCLC in emphysematous patients. There are limited studies however [5–7] reporting postoperative improvements in pulmonary function in emphysematous patients undergoing standard anatomical lobectomy for NSCLC.
We have previously found that in patients outside operability guidelines, postoperative lung function is significantly better than predicted values following lobectomy [5]. Encouraged by the postoperative physiological status of these ‘lobar LVRS’ patients, we hypothesise that in some patients with emphysema, lobectomy may be superior to the non-anatomical resection for emphysematous patients undergoing LVRS.
This study therefore aimed to compare the perioperative course of two theoretically similar groups of patients with COPD–those undergoing upper lobe LVRS and those undergoing ‘high-risk’ upper lobectomy for stage I–II NSCLC.
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2. Methods
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2.1 Study design
Over a 9-year-period (April 1997–July 2006), we identified 34 patients who underwent upper lobectomy with systematic lymph node dissection for stage I–II NSCLC under a single surgeons’ care. All had severe heterogenous emphysema of an upper lobe distribution with a ppoFEV1 of less than 40% using the conventional segment counting method. Their perioperative course, survival and postoperative spirometry were compared to 46 consecutive patients who underwent video-assisted thoracoscopic (VAT) unilateral upper lobe LVRS during the same period.
2.2 Patient selection
All patients were initially assessed by a multi-disciplinary team, and underwent basic spirometry, bodybox plethysmography, arterial blood gas analysis, chest radiography and computed tomography (CT). Physiological heterogeneity was assessed by radionuclide perfusion scintigraphy. This was quantified by calculating the so-called ‘Q’ score, as determined by the ratio of perfusion in the target zone to the total lung perfusion [8].
2.2.1 Lobectomy group
Resectability was defined in this study by a staging CT scan with a negative cervical mediastinoscopy if lymph nodes greater than 1 cm in their short axis were seen on CT scan, or negative mediastinal uptake on CT-PET. Only patients with completely resected NSCLC confirmed to be located within an area of emphysema in the upper lobe on pathological analysis were included.
2.2.2 LVRS group
Patients undergoing LVRS were subject to previously published selection criteria [9,10]. In summary this comprises significant dyspnoea, with evidence of hyperinflation, airway obstruction, and preserved gas transfer. Patients with target areas in their upper lobes only were included in this study. It is our policy to perform unilateral VAT LVRS upon the worst affected side first if bilateral target areas are present.
2.3 Surgical approach
All procedures were performed using double lumen endotracheal intubation and single lung ventilation. Perioperative analgesia was achieved using epidural catheterisation. LVRS was performed on the previously identified target areas, by using endoscopic stapling devices (EZ45, Ethicon and EndoGIA 60, Tyco). All staple lines were buttressed using bovine pericardium (Peri-strips, Bio-Vascular, Minnesota).
Lobectomy was performed via a standard postero-lateral thoracotomy (n
= 27), or VAT (n
= 7), with completion of the interlobar fissure using when necessary open or endoscopic linear staplers without buttressing.
In all cases one or two chest drains were left in place connected to an underwater seal system, initially with 5 kPa (38 mmHg) suction.
2.4 Postoperative management
All patients were electively extubated in the operating theatre and transferred to a high dependency unit for overnight monitoring. Similar postoperative protocols and discharge criteria were applied to all groups. Chest drains remained in-situ until there was no evidence of air leak. To encourage mobilisation, one-way flutter valves and portable bags (Portex Ltd, Hythe UK) were utilised as early as possible in the postoperative period in all groups.
All patients were reviewed in a surgical clinic at three monthly intervals. Changes in spirometry following lobectomy were compared with those at 12 months after LVRS.
2.5 Statistical analysis
The data is presented as median (range) unless otherwise stated. Univariate analysis was performed using the Mann–Whitney U-test for quantitative data and the 
2 test for qualitative data. Postoperative survival was plotted according to the Kaplan–Meier method and any difference in survival between the groups evaluated with the log-rank test. Statistical significance was defined by p values <0.05 throughout the study.
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3. Results
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Lobectomy was performed upon 34 patients (27 with pathological stage I and 7 with stage II disease) and LVRS upon 46 patients. LVRS patients were found to be significantly younger than those undergoing lobectomy, with significantly more severe airways obstruction, more hyperinflation, poorer gas transfer and a more heterogenous distribution of reduced perfusion (See Table 1
).
Perioperatively, patients undergoing lobectomy had a significantly shorter duration of air leak (5 days [2–36] vs 9 days [1–40], p
= 0.03) and in-hospital stay (8 days [3–63] vs 13 days [6–90], p
= 0.001). A significant correlation was found between heterogeneity as measured by the Q score and duration of air leak (r
= 0.27, p
= 0.04, see Fig. 1
).
The differences seen between side of operation and use of VATS are a reflection of practice at our institution. There were only three in-hospital deaths (3/80, 4%) within 90 days of their procedure. All three patients died of respiratory failure secondary to Methycillin Resistant Staphylococcus Aureus pneumonia at 14, 26, and 90 days postoperatively (Table 2
).
LVRS patients appear to live longer after their procedure than patients undergoing lobectomy (88 months ± 11 vs 53 months ± 16, p
= 0.06). See Table 3
and Fig. 2
. However when they are stratified according to age, there is no significant survival difference (71 months ± 6 vs 54 months ± 32, p
= 0.36, respectively). See Table 4
and Fig. 3
.
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Table 3 Postoperative characteristics between the two groups expressed as median (range) or median (±standard error) according to Kaplan–Meier
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Fig. 2. Survival according to the Kaplan–Meier method, of LVRS group versus lobectomy group (log-rank). p
= 0.06.
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Table 4 Survival according to the Kaplan–Meier method of the LVRS group versus lobectomy group (log-rank) when stratified according to age
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Fig. 3. Survival according to the Kaplan–Meier method of the LVRS group versus lobectomy group when stratified according to age (p
= 0.36).
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As expected LVRS patients have significant improvement in their FEV1 at 1 year (21% [–30 to +71%]). Patients in the lobectomy group did not show any significant improvement in FEV1 (0% [–52 to +63]), however the actual FEV1 post operatively was significantly higher than their ppoFEV1 (36% [18–70] vs 35% [14–40], p
= 0.008).
For the entire study population, there was a significant correlation between preoperative Q score, and the percentage improvement in FEV1 (r
= –0.33, p
= 0.02). See Fig. 3.
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4. Discussion
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In recent years, we have achieved a better understanding of the consequences of surgery for end-stage emphysema and the management of its complications. Our understanding of the beneficial mechanisms of LVRS has led to authors aiming to extend the indications for surgery for NSCLC to patients previously deemed unfit due to concomitant severe emphysema [6,7,11]. The experience in our institution with ‘Lobar LVRS’ [5] for NSCLC, has suggested we could extend the extent of resection in LVRS.
Since the re-introduction of LVRS by Cooper and colleagues [12] however, there has been surprisingly little work investigating the optimum quantity of lung to be removed. The technique of LVRS was initially described as multiple wedge excisions or plications [13], and has since developed into an oblique/inverted U-shaped excision over the apex [12] or a horseshoe encompassing the horizontal fissure/free edge of the upper lobe [1]. One would expect that within limits, the amount of lung resected would positively correlate with improvement in spirometry postoperatively. Outside these limits, then either too little is removed therefore not achieving deflation, or too much is resected, which may result in impairment of gas exchange. Despite finding a correlation between weight of lung resected at bilateral VAT LVRS and change in FEV1, Brenner et al. [14] did not find any relationship with survival.
Our work suggests that lobectomy may have a therapeutic role in the surgical treatment of pulmonary emphysema. The length of hospital stay and duration of air leak are both significantly shorter in patients undergoing anatomical lobectomy, than non-anatomical LVRS. This is presumably due to the more favourable nature and the smaller amount lung parenchyma required to be divided in the former. Hospital mortality is also not statistically different between the two groups however this is almost certainly due to the low numbers in our study (1 vs 2 patients).
Our study does however suffer a number of problems. Firstly the retrospective nature of the data collection for the lobectomy group has resulted in a wide variation of times from operation to spirometry (median 12 months, range 2–66 months). It is entirely possible that progression of the COPD has resulted in worse spirometry among this group, than would have been noted if all patients had undergone pulmonary function testing within one year of their procedure. Other sources of bias are, that overall the lobectomy group although older had significantly less airflow obstruction, less hyperinflation and more homogenous disease than the LVRS group.
Although superficially it appears that patients undergoing non-anatomical LVRS live longer than those undergoing Lobectomy, when the two groups are stratified according to age, there was no significant difference in survival. It is interesting to note that early mortality (i.e. within the first 12 months) affects the Lobectomy group more than the non-anatomical LVRS. It is unclear if this is related to recurrent disease or the intensity of follow up for the LVRS patients.
A therapeutic lobectomy for emphysema is an attractive solution to the current morbidity associated with air leakage following non-anatomical LVRS. Certainly in the largest series of LVRS worldwide [1], 19/250 (8%) of LVRS procedures have been anatomical lobectomy, usually for a completely destroyed lobe, although a small number were performed due to early stage NSCLC. A balance must be struck however between the negative effects of removing functioning lung tissue and the positive effects of deflation. We feel that perfusion radionuclide scintigraphy is critical to the selection process. This is demonstrated in our study by the correlations with heterogeneity, duration of intercostal drainage and spirometric outcome. The correlation between air leak duration and heterogeneity can be explained by the extent of parenchymal destruction at the site of resection. A similar correlation was found between Q score and percentage change in FEV1, with increased heterogeneity being associated with a better spirometric outcome as shown in Fig. 4
.
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Fig. 4. Correlation between preoperative Q score and percentage improvement in FEV1 (r
= –0.33, p
= 0.02).
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In summary, our study demonstrates that there may be a role for therapeutic lobectomy for emphysema, even if this is only to reduce the in-patient morbidity and length of stay. In order to derive maximal benefit from ‘Lobar LVRS’, our study suggests that only those patients with the most heterogenous disease should undergo the procedure.
The amount of lung resected seems to be only one facet of the pre and perioperative factors that affect outcome after LVRS. Future work is being directed towards prospective accumulation of data from patients undergoing lobectomy for LVRS, as well as the influence of the length of staple lines upon air leak duration. A prospective randomised controlled trial comparing anatomical versus non-anatomical resection for emphysema, however, would provide the best evidence of the effectiveness of this technique.
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Appendix A
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Conference discussion
Dr H. Batirel (Istanbul, Turkey): What is your opinion about the development of pulmonary hypertension in long-term if you do an anatomic lobectomy in a patient with end-stage emphysema?
Dr Vaughan: Certainly none of those patients had evidence of pulmonary hypertension clinically preoperatively. In terms of postoperatively, it's an area of interest. I think it's something that could be looked into.
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Footnotes
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\#9734; Presented at the joint 20th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 14th Annual Meeting of the European Society of Thoracic Surgeons, Stockholm, Sweden, September 10–13, 2006.
\#9734;\#9734; Nominated for the Brompton Prize.
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References
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- Ginsberg RJ, Rubinstein LV. Randomised trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg 1995;60(3):615-622Discussion 622–3.[Abstract/Free Full Text]
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- Korst RJ, Ginsberg RJ, Ailawadi M, Bains MS, Downey RJ, Rusch V, Stover D. Lobectomy improves ventilatory function in selected patients with severe COPD. Ann Thorac Surg 1998;66:898-902.[Abstract/Free Full Text]
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Abstract
1. Introduction
