Asian Cardiovasc Thorac Ann 2004;12:33-37
© 2004 Asia Publishing EXchange Ltd
Predicting the Response to Lung Volume Reduction Surgery Using Scintigraphy
Norihisa Shigemura, MD,
Akinori Akashi, MD,
Tomoyuki Nakagiri, MD,
Mitsunori Ohta, MD1,
Hikaru Matsuda, MD1
Division of General Thoracic Surgery, Takarazuka Municipal Hospital, Hyogo, Japan
1 Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
For reprint information contact: Norihisa Shigemura, MD Tel: 81 6 6879 3152 Fax: 81 6 6879 3163 Email: n-shige{at}blue.ocn.ne.jp Department of Surgery, Osaka University Graduate School of Medicine, E1, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
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ABSTRACT
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This study was conducted to evaluate the use of quantitative scintigraphy with a newly designed marker to assess and predict the efficacy of lung volume reduction surgery in treating emphysema. In a series of 50 patients with severe emphysema who underwent the operation, ventilation/perfusion scintigraphy was performed and 2 markers of area ratio and lung uniformity were measured before and 6 months after surgery. The markers were correlated with the results of pulmonary function tests. The histopathological subtype of emphysema was also determined in the resected specimen and related to improvement in the markers. The markers were closely related to improvement in forced expiratory volume in 1 second, with the highest correlation being the marker lung uniformity measured by perfusion scintigraphy. Improvement in this marker was significantly greater in centrilobular than in panlobular emphysema. This quantitative method of scintigraphy could provide an excellent reflection of surgical efficacy as well as predict the surgical outcome. Additionally, it provides a mechanistic explanation for the differential improvement between the histopathological subtypes of emphysema following surgery.
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INTRODUCTION
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Lung volume reduction surgery (LVRS) results in objective and subjective improvement in symptom frequency and severity in patients with emphysema.1–3 However, its duration of efficacy remains a controversial issue,4,5 as emphysema and its manifestations continue to progress postoperatively.
Pulmonary function tests are the most widely used methods for assessing the response to LVRS. Forced expiratory volume in 1 second (FEV1.0), in particular, is the gold standard for the objective assessment of improvement in functional capacity. However, it does not reflect the overall status of the patient, including the quality of life, the degree of subjective dyspnea, and exercise durability.6 Radiographic techniques and nuclear medicine imaging are considered more suitable for assessing postoperative localized pulmonary function, as neither pulmonary function tests nor exercise tests can localize deficits. Reports on objective and quantitative evaluation of LVRS are rare,7 although there have been several studies that utilized radiographic methods, the majority of which involved visual assessment.8–10
This study was conducted, first, to assess the use of quantitative perfusion scintigraphy with a simple, newly designed marker in determining the response to and predicting the results of LVRS. Second, long-term follow-up examinations using the marker were carried out to decide the duration of efficacy of LVRS. Third, the results from this assessment were related to the histopathological subtypes of emphysema. This study should provide clearer insights into the indication for LVRS as well as its role and potential problems.
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PATIENTS AND METHODS
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A total of 50 consecutive patients (47 male, 3 female) with severe emphysema who underwent LVRS at our institution from April 1998 to January 2000 and were followed for at least 6 months postoperatively were included in this study. All the patients underwent a complete evaluation that included history, physical examination, complete pulmonary function testing (post-bronchodilator spirometry, static lung volumes, diffusing capacity of the lung for carbon monoxide, arterial blood gas analysis including oxygen tension or PaO2), 6-minute walk (6MW) test, chest radiography and computed tomography, pulmonary and cardiac scintigraphy, and right heart catheterization.
The patients’ ages ranged from 57 to 82 years (mean, 61 years), and all were previous heavy smokers. Selection criteria included severe airflow obstruction < 35% of predicted value), hyperinflation (total (FEV1.0 lung capacity > 125% of predicted value), dyspnea at rest or on minimal exertion, and smoking cessation. Principal exclusion criteria were hypercapnia (arterial carbon dioxide tension > 60 mmHg), a diffusing capacity for carbon monoxide that was less than 20% of the predicted level, significant pulmonary hypertension (mean pulmonary arterial pressure > 35 mmHg), and significant coronary artery disease. The anatomic distribution of emphysema initially was not a selection criterion. However, as various centers had reported that patients with diffuse emphysema did less well than patients with upper-lobe-predominant emphysema,6,7 the criteria were altered to include consideration of emphysema distribution. Age was not a criterion, but the patient must be able to participate in preoperative respiratory rehabilitation. In all other respects, the criteria were similar to those of other studies.1,2,5
Ventilation/perfusion scintigraphy was performed with a scintillation system (Maxxus with Starcam 4000i; GE Medical Systems, Milwaukee, WI, USA) using krypton-81m and technetium-99m macroaggregated albumin (Tc-99m MAA) for ventilation and perfusion imaging, respectively. The region of interest was set at the 10% and 50% thresholds of each maximal count density for the bipulmonary fields. The area of the 10% threshold generally corresponds to that of the whole lung, and the 50% threshold to that of the more functional lung. These cutoffs of 10% and 50% were chosen from a receiver operating characteristic curve as the most sensitive and most specific.
The ventilation and perfusion markers were defined in terms of 2 measures, which were graded for heterogeneity of disease distribution and lung ventilation/perfusion quantity: the area ratio (AR) of the 50% region to the 10% region; and lung uniformity (LU), which is the product of the mean count and the maximal count for the 50% region. These markers were automatically quantified and evaluated in the ventilation (V) and perfusion (P) scintigrams by the GE Windows Workstation (GE Medical Systems, Milwaukee, WI, USA) and were defined as V-AR, P-AR, V-LU, and P-LU (Figure 1
). After LVRS, corrections were made for regional variation in the severity of emphysema, and improvement in lung ventilation/perfusion was indicated by increases in both the mean and the maximal counts.
Bilateral stapled LVRS was performed thoracoscopically under general anesthesia supplemented by thoracic epidural anesthesia. One-lung ventilation was provided during surgery through a left-sided double-lumen endotracheal tube. The patient was placed in the decubitus position, and this position was reversed when the procedure progressed to the contralateral side.
The major focus of disease as the target area for resection in most cases was in the upper lobes; however, the region of most severe destruction in 10 patients was in the lower lobes. Although 20% to 30% of the lung was generally removed, this amount differed from patient to patient depending on the diseased area.
All patients underwent simultaneous pulmonary scintigraphy and function testing before surgery and 6 months postoperatively. Associations between changes in the markers and changes (
) in the functional parameters FEV1.0, FEV1.0%, PaO2, and 6MW at 6 months postoperatively were investigated. Additionally, using the marker that showed the highest correlation, cases were followed up for 2 to 3 years after LVRS to evaluate the duration of efficacy of the surgery.
The resected specimens were examined histologically by experienced pulmonary pathologists for emphysema subtype classification. Specimens were identified as centrilobular, focal, or panlobular type and further classified as pure or predominant.
The data are expressed as mean ± standard deviation. Pearson’s coefficients of correlation between the markers and the functional parameters were calculated. Paired two-tailed Student’s t test was computed to identify statistically significant differences ( p < 0.05) between pre- and post-operative measurements.
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RESULTS
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All patients were followed up at 6 months postoperatively, excluding 1 patient who died of duodenal ulcer hemorrhage on the 49th postoperative day. Changes in the functional parameters of the remaining 49 subjects are summarized in Table 1, and correlation between the markers and these functional parameters are shown in Table 2.
Among the parameters measured, correlated FEV1.0 and most closely with the markers, followed by PaO2 and 6MW. P-LU correlated most closely with FEV1.0 (r = 0.778, p = 0.002), and thus it would be the best predictor of surgical outcome (Figure 2).
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Figure 2. Scatter plot of improvement at 6 months after surgery over preoperative levels in forced expiratory volume in 1 second (FEV1.0) versus lung uniformity measured by perfusion scintigraphy (P-LU). The best fit has a Pearson correlation coefficient of 0.778.
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Using P-LU as the marker for long-term follow-up, 45 of the 49 patients underwent repeat scintigraphy every 6 months for more than 18 months. P-LU improved over the preoperative value (defined as 1) in the majority of the patients at all time points of follow-up until 24 months after LVRS, although it peaked at 6 months and subsequently declined over time (Figure 3). At 30 months, only 20 cases maintained a value significantly higher than that before surgery (p < 0.008). Moreover, the degree of dyspnea according to the Hugh-Jones classification in these 20 patients at 30 months was also better than before surgery.
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Figure 3. Improvement in lung uniformity measured by perfusion scintigraphy (P-LU) at 6-month intervals after surgery compared with preoperative values.
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Postoperative histopathological analysis revealed 30 centrilobular, 16 panlobular, and 4 focal emphysema cases. Among these 3 groups, significantly greater improvement in P-LU was noted in the centrilobular than in the panlobular group (p < 0.05). Additionally, 19 of the 20 cases in which P-LU was higher at 30 months postoperatively than before surgery were of the centrilobular type.
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DISCUSSION
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LVRS is recognized as an effective treatment for emphysema, especially when there is appropriate patient selection. Consequently, a variety of screening tests based on radiographic techniques have been developed for patient selection. In addition, a study has demonstrated that radiographic findings may predict the response to LVRS.11 However, these methods are limited in the assessment of regional lung function and small airway function, being based on visual evaluation of radiographic data. Relatively few studies used objective and quantitative means of assessment.9,10,12–14
The present study utilized ventilation–perfusion scintigraphy for quantitative evaluation of the functional response to LVRS, a method already in use in various institutions for preoperative screening for LVRS.1,2,5 The rationale behind this scintigraphic method is that LVRS is performed for the purpose of remodeling the ventilation/perfusion distribution. We showed a close correlation of the ventilation and perfusion markers with conventional measures of functional capacity, thus lending support to the validity of pre- and post-LVRS scintigraphic findings. The markers correlated most closely with FEV1.0. This is particularly significant, as previous studies have demonstrated a strong correlation and the prognosis of patients with chronic between FEV1.0 obstructive pulmonary disease.15
In the present study, P-LU was used as a marker of perfusion to assess clinical changes following LVRS. Consistent with previous reports,10 our study demonstrated that perfusion scintigraphy is more useful than ventilation scintigraphy for identifying patients with favorable postoperative results. Pulmonary perfusion scintigraphy is useful for identifying areas of vascular insufficiency to be targeted for resection in LVRS. The additional use of ventilation scintigraphy may be beneficial for identifying areas that are prone to hypoxemic pulmonary vasoconstriction and subsequent pulmonary hypertension, but the drawback is that it may complicate the screening process. Considering that clinical usefulness declines as the method of analysis becomes more complicated in the pursuit of accuracy, we have striven for the development of a simple method for the therapeutic evaluation of LVRS.
Besides serving as an index of quantitative and spatial perfusion distribution and providing a good reflection of the functional response to LVRS, P-LU improved to markedly different degrees in the distinct histopathological subtypes of emphysema. Vascular destruction is more severe and perfusion remodeling more difficult in panlobular than in centrilobular emphysema. A study reported that improvement in elastic recoil after LVRS resulted in increased pulmonary function and that elastic recoil loss was more severe in panlobular than in centrilobular emphysema.16 The close relation between P-LU changes and the histopathological emphysema types suggests that perfusion remodeling might underlie improvement in functional capacity after LVRS. Further, differences in P-LU might provide a mechanistic explanation for the differences in outcome between the histopathological types. This relationship between LVRS results and the histopathological patterns of emphysema should improve objectivity and consistency in, and could help standardize, the preoperative imaging evaluation of candidates for LVRS, especially with more advanced imaging technology that may reveal even the most minute structure of the lung.
Long-term follow-up revealed that only 20 out of 45 cases had a P-LU value at 30 months that was higher than the preoperative level. P-LU began to decline after peaking at 6 months. This may reflect a natural course toward homogeneous destruction of the pulmonary vascular beds. Surgical outcomes are affected by postoperative complications and the effectiveness of medical treatment in addition to the surgical technique. The patients in this study had an uneventful postoperative course with no complications and received aggressive medical management. Thus, the results suggest that the duration of efficacy of LVRS may not exceed 30 months.
In conclusion, the markers are good predictors of the functional response to LVRS and provide a mechanistic explanation for the differential responses of the emphysema subtypes. Since LVRS is not effective for every patient, preoperative selection is critical. The scintigraphic method employed in this study, combined with conventional clinical evaluation, is thus expected to be a valuable evaluation tool for LVRS.
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REFERENCES
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- Cooper JD, Patterson GA, Sundaresan RS, Trulock EP, Yusen RD, Pohl MS, et al. Results of 150 consecutive bilateral lung volume reduction procedures in patients with severe emphysema. J Thorac Cardiovasc Surg
1996;112:1319–29.[Abstract/Free Full Text]
- Miller JI Jr, Lee RB, Mansour KA. Lung volume reduction surgery: lessons learned. Ann Thorac Surg
1996;61:1464–8.[Abstract/Free Full Text]
- Keenan RJ, Landreneau RJ, Sciurba FC, Ferson PF, Holbert JM, Brown ML, et al. Unilateral thoracoscopic surgical approach for diffuse emphysema. J Thorac Cardiovasc Surg
1996;111:308–15.[Abstract/Free Full Text]
- Make BJ, Fein AM. Is volume reduction surgery appropriate in the treatment of emphysema? No. Am J Respir Crit Care Med
1996;153(Pt 1):1205–7.[Medline]
- Tonelli MR, Benditt JO, Albert RK. Clinical experimentation. Lessons from lung volume reduction surgery. Chest
1996;110:230–8.[Abstract/Free Full Text]
- National Emphysema Treatment Trial Research Group. Rationale and design of the National Emphysema Treatment Trial (NETT): a prospective randomized trial of lung volume reduction surgery. J Thorac Cardiovasc Surg
1999;118:518–28.[Free Full Text]
- Wang SC, Fischer KC, Slone RM, Gierada DS, Yusen RD, Lefrak SS, et al. Perfusion scintigraphy in the evaluation for lung volume reduction surgery: correlation with clinical outcome. Radiology
1997;205:243–8.[Abstract/Free Full Text]
- Jamadar DA, Kazerooni EA, Martinez FJ, Wahl RL. Semiquantitative ventilation/perfusion scintigraphy and single-photon emission tomography for evaluation of lung volume reduction surgery candidates: description and prediction of clinical outcome. Eur J Nucl Med
1999;26:734–42.[Medline]
- Sugi K, Matsuoka T, Tanaka T, Sakano H, Nawata K, Ueda K, et al. Lung volume reduction surgery for pulmonary emphysema using dynamic xenon-133 and Tc-99m-MAA SPECT images. Ann Thorac Surg
1998;4:149–53.
- Gierada DS, Slone RM, Bae KT, Yusen RD, Lefrak SS, Cooper JD. Pulmonary emphysema: comparison of preoperative quantitative CT and physiologic index values with clinical outcome after lung-volume reduction surgery. Radiology
1997;205:235–42.[Abstract/Free Full Text]
- Yusen RD, Lefrak SS. Evaluation of patients with emphysema for lung volume reduction surgery. Semin Thorac Cardiovasc Surg
1996;8:83–93.[Medline]
- Gierada DS, Yusen RD, Villanueva IA, Pilgram TK, Slone RM, Lefrak SS, et al. Patient selection for lung volume reduction surgery: an objective model based on prior clinical decisions and quantitative CT analysis. Chest
2000;117:991–8.[Abstract/Free Full Text]
- Flaherty KR, Kazerooni EA, Curtis JL, Iannettoni M, Lange L, Schork MA, et al. Short-term and long-term outcomes after bilateral lung volume reduction surgery: prediction by quantitative CT. Chest
2001;119:1337–46.[Abstract/Free Full Text]
- Cederlund K, Tylen U, Jorfeldt L, Aspelin P. Classification of emphysema in candidates for lung volume reduction surgery: a new objective and surgically oriented model for describing CT severity and heterogeneity. Chest
2002;122:590–6.[Abstract/Free Full Text]
- Anthonisen NR, Wright EC, Hodgkin JE. Prognosis in chronic obstructive pulmonary disease. Am Rev Respir Dis
1986;133:14–20.[Medline]
- Sciurba FC, Rogers RM, Keenan RJ, Slivka WA, Gorcsan J III, Ferson PF, et al. Improvement in pulmonary function and elastic recoil after lung-reduction surgery for diffuse emphysema. N Engl J Med
1996;334:1095–9.[Abstract/Free Full Text]
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ABSTRACT
INTRODUCTION
