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Ann Thorac Surg 2001;72:362-365
© 2001 The Society of Thoracic Surgeons


Original article: general thoracic

Pulmonary function, postoperative pain, and serum cytokine level after lobectomy: a comparison of VATS and conventional procedure

Itaru Nagahiro, MDa, Akio Andou, MDa, Motoi Aoe, MDa, Yoshifumi Sano, MDa, Hiroshi Date, MDa, Nobuyoshi Shimizu, MDa

a Department of Surgery II, Okayama University Medical School, Okayama, Japan

Accepted for publication May 1, 2001.

Address reprint requests to Dr Nagahiro, Department of Surgery II, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
e-mail: nagahiro{at}nigeka2.hospital.okayama-u.ac.jp


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Acknowledgments
 References
 
Background. Although lobectomy by the video-assisted thoracic surgical (VATS) approach is assumed to be less invasive than lobectomy by the standard posterolateral thoracotomy (PLT) approach, it has not been scientifically proven.

Methods. Twenty-two consecutive, nonrandomized patients, underwent either a VATS approach (n = 13) or a posterolateral thoracotomy approach (n = 9) to perform pulmonary lobectomy for peripheral lung cancers in clinical stage I. Pain and serum cytokines were measured until postoperative day (POD) 14. Pulmonary function tests were performed on POD 7 and POD 14.

Results. Postoperative pain was significantly less in the VATS group on PODs 0, 1, 7, and 14. Recovery of pulmonary function was statistically better in the VATS group. Negative correlations between the recovery rates of pulmonary function and postoperative pain were observed on POD 7. The serum interleukin-6 level in the PLT group was significantly elevated on POD 0 compared with the VATS group (posterolateral thoracotomy: 21.6 ± 24.3 pg/mL; VATS: 4.1 ± 7.9 pg/mL, p = 0.03).

Conclusions. Lobectomy by the VATS approach generates less pain and cytokine production, and preserves better pulmonary function in the early postoperative phase.


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Acknowledgments
 References
 
Lobectomy by the video-assisted thoracic surgical (VATS) approach is a well-established and widespread therapeutic method for treating small peripheral lung cancer [13]. In the past few years, the VATS procedure has been perceived to be less invasive than the conventional open thoracotomy with respect to less pain, better preservation of pulmonary function, and less impairment of the shoulder girdle [46]. Although there is a consensus on the benefits of the VATS procedure in general, few studies have looked at the procedure when used for lobectomy.

It is known that patients with surgical injury or infection exhibit alterations in hemodynamic, metabolic, and immune responses that are largely orchestrated by endogenous mediators referred to as cytokines [7]. Elective surgery provokes an increase in the circulating cytokine levels, especially with regard to interleukin (IL)-6, and the magnitude of the elevation is related directly to the degree of tissue injury [8]. Few studies have investigated cytokine production when comparing VATS lobectomy with conventional lobectomy.

The purpose of this study was to estimate and compare the operative stress of the VATS lobectomy and standard lobectomy through posterolateral thoracotomy (PLT), and to investigate the hypothesis that the VATS lobectomy is less invasive than the conventional PLT lobectomy.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Acknowledgments
 References
 
Patient cohorts
A series of 22 consecutive patients requiring single lobectomy for clinical stage I peripheral lung cancer between June 1999 and April 2000 were included in the study. A signed and written, informed consent was obtained from each patient, and the study was approved by the Okayama University Medical School Review Board, Okayama, Japan.

Thirteen patients whose peripheral lung cancer had a maximum diameter less than or equal to 3 cm (T1) and no hilar or mediastinal lymph node swelling (N0) on chest computed tomographic scan were operated on by VATS lobectomy. The maximum tumor dimension was more significant in predicting mediastinal lymph node metastasis than the lymph node size on computed tomographic scan [9]. At our institution, patients whose lung cancer had a diameter greater than 3 cm (T2), regardless of mediastinal lymph node status on computed tomographic scan, were normally recommended to undergo mediastinoscopy and preoperative chemoradiotherapy before lobectomy when biopsy revealed positive nodes for cancer cells. In the present study, 9 patients with peripheral lung cancer staged as T2 N0 chose not to undergo mediastinoscopy and preoperative chemoradiotherapy. There has been controversy over the adequacy of mediastinal lymph node dissection by VATS. Therefore, to accomplish more complete mediastinal lymph node dissection, conventional lobectomy with mediastinal lymph node dissection through posterolateral thoracotomy was used to treat T2 N0 disease instead of VATS lobectomy in the 9 patients, and they served as the control group.

In the VATS lobectomy, a 7-cm long skin incision was made at the fourth intercostal space in the anterior axillary line as a minithoracotomy. Two other 2- to 3-cm long incisions for ports were made at the sixth intercostal space in the posterior axillary line and at the seventh intercostal space in the midaxillary line. No ribs were resected. A metal chest retractor was not used in the minithoracotomy, but instead, a silicon rubber instrument usually used in laparoscopic surgery (Lap Protector, Hakko Co, Ltd, Tokyo, Japan) was applied to open the wound and prevent chest wall closure. In the conventional PLT approach, an incision approximately 20-cm long was made, the latissimus dorsi muscle and the serratus anterior muscle were divided, and a thoracotomy was performed at the fourth or fifth intercostal space. One or two ribs adjacent to the thoracotomy were resected at the posterior segment. A metal chest retractor was used to open the wound and spread the intercostal space.

All patients in both groups received epidural tube insertion just before the operation, and were then intubated with a double lumen tracheal tube for anesthesia. All patients received epidural administration of 0.125% bupivacaine during the operations. Continuous epidural infusion of 0.125% bupivacaine (4 mL/hr) was used postoperatively until chest drainage tubes were removed. Diclofenac suppository was predominantly used for postoperative pain control in addition to the epidural anesthesia, and intramuscular administration of pentazocine was used if the pain was uncontrollable by suppository.

Measurements
Pain was quantitated by an 11-point pain scale (0 = no pain, 10 = maximal imaginable pain) [10] on PODs 0, 1, 2, 4, 7, and 14. Blood samples were drawn preoperatively and on the same PODs as the pain measurement, centrifuged at 3000 G for 5 minutes, and then stored in deep refrigeration at –70°C until serum cytokines measurements were performed. Serum cytokines consisting of IL-6, -8, -10, and tumor necrosis factor-{alpha} (TNF-{alpha}) were measured using ELISA. Chest tubes were removed by POD 7 in all patients, and pulmonary function tests were performed in the usual manner on PODs 7 and 14 by portable spirometer (Autospiro AS-303, Minato Medical Science Co Ltd, Osaka, Japan). Recovery rates of forced vital capacity (FVC), vital capacity, and forced expiratory volume in one second (FEV1) were expressed by the percent of predicted values that were calculated by numbers of resected pulmonary segments: Predicted value (mL) = preoperative value (mL) x (19 - the number of resected segment)/19. The number of segments in each lobe was defined as follows: right upper lobe: 3, right middle lobe: 2, right lower lobe: 5, left upper lobe: 5, left lower lobe: 4.

Statistics
The {chi}2 test, Mann-Whitney U test, and Student’s t test were used to compare the characteristics of both groups and paired data. Analysis of variance was used for continuous data. Probability of less than 0.05 was considered significant. All data were expressed as mean ± the standard deviation of the mean.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Acknowledgments
 References
 
Patient characteristics and anatomic distribution of the primary lung cancers (ie, lobectomies performed) are shown in Tables 1 and 2. Gender, age, histologic type of tumor, operation time, amount of intraoperative bleeding, duration of chest drainage, duration of epidural anesthesia, pulmonary function, and method of lobectomy performed were not different between the groups. All tumors in the VATS group were pathologic stage I, but one tumor was stage II for hilar lymph node metastasis, and two tumors were stage IIIA for mediastinal lymph node metastasis in the PLT group.


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Table 1. Characteristics of the VATS Lobectomy and Standard Lobectomy Groups

 

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Table 2. Anatomic Distribution of the Primary Lung Cancers and Lobectomies Performed

 
The amounts of postoperative analgesics (except for epidural administration) used by POD 14 were compared, and the patients in the PLT group needed significantly larger amounts of analgesics postoperatively (Diclofenac suppository; PLT: 406 ± 212 mg, VATS: 202 ± 238 mg, p = 0.034, Pentazocine; PLT: 13.1 ± 16.9 mg, VATS: 1.4 ± 4.5 mg, p = 0.042). The postoperative pain measurements in the VATS group were significantly less than in the PLT group (Fig 1). Serum IL-6 level, a pro-inflammatory cytokine, was significantly higher in the PLT group on POD 0 than in the VATS group (Fig 2). Other serum cytokine levels did not differ between the groups during the postoperative period. When the correlation between pain and serum cytokine level was examined in all cases, a significant correlation was observed in IL-10 levels (r = 0.245, p = 0.003). The recovery rates of FVC, FEV1, and vital capacity were significantly better and faster in the VATS group (FVC on POD7: PLT 71.4% ± 15.8% vs VATS 87.4% ± 11.7%, p = 0.011; FVC on POD14: PLT 76.5% ± 15.6% vs VATS 97.3% ± 13.8%, p = 0.005; FEV1 on POD14: PLT 80.6% ± 13.7% vs VATS 95.4% ± 15.7%, p = 0.039; vital capacity on POD7: PLT 67.7% ± 21.8% vs VATS 86.8% ± 13.6%, p = 0.019). When the correlation between pain and pulmonary function was examined in all cases, a significant correlation was observed on POD 7 (Fig 3). However, the correlation no longer existed on POD 14.



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Fig 1. Operative approach for lobectomy and postoperative pain measured by eleven-point pain scale. Data are shown as mean ± standard deviation of the mean. *p less than 0.05; **p less than 0.01. (POD = postoperative day; VATS = video-assisted thoracic surgery.)

 


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Fig 2. Operative approach for lobectomy and interleukin-6 levels. Data are shown as mean ± standard deviation of the mean. (IL-6 = interleukin-6; POD = postoperative day; VATS = video-assisted thoracic surgery.)

 


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Fig 3. Correlation between postoperative pain and pulmonary function recovery rate. Pain was measured by an 11-point pain scale. (FEV1.0 = forced expiratory volume in one second; FVC = forced vital capacity; VATS = video-assisted thoracic surgery; VC = vital capacity.)

 

    Comment
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Acknowledgments
 References
 
As we expected, postoperative pain and recovery of pulmonary function were both superior in the VATS group for 2 weeks postoperatively in this study. Giudicelli and colleagues [11] compared lobectomy by the VATS approach and muscle-sparing thoracotomy without rib resection, and they found that there was no difference in FVC and FEV1 between the groups, and the difference in pain lasted for only 4 days postoperatively. In the present study, one or two ribs were resected posteriorly and a metal chest retractor was used to spread the intercostal space in the PLT group, while no ribs were resected and no rib spread technique was used in the VATS group. This may have enhanced the differences between the groups, resulting in a long-lasting difference in pain and a more obvious difference in pulmonary function. This may indicate the benefits of both the VATS procedure and muscle-sparing thoracotomy because these muscles and ribs are preserved.

An interesting finding in this study was the correlation between pain and pulmonary function recovery. The correlation was easily anticipated; however, it existed only in the early postoperative phase and disappeared after a week. This might indicate that adequate analgesia is necessary to reach sufficient pulmonary function recovery in the first postoperative week. To elicit better pulmonary function recovery in the early postoperative period, VATS lobectomy is advantageous because of the decreased postoperative pain. On the other hand, although the differences between the groups in postoperative pain, FVC, and FEV1 still remained on POD 14, the correlation between pain and pulmonary function no longer existed in this study. These differences in pulmonary function on POD 14 would have been caused mainly by the impairment of respiratory muscles, including serratus anterior, latissimus dorsi, and rib cage in the PLT group, not by the pain.

The IL-6 response to injury was uniquely consistent and was also related to the magnitude of the insult [8]. In the present study, the IL-6 levels in the PLT group on POD 0 were significantly higher than in the VATS group. This objectively supports the hypothesis that the operative insults of the VATS lobectomy are less than the PLT lobectomy. In addition, serum IL-10 level and postoperative pain had a significant correlation in this study. The correlation between pain and cytokines was also recently studied. A number of cytokines are released from a variety of immune cells and can induce powerful hyperalgesia [12]. Although, so far, there is no evidence that cytokines directly affect the excitability of sensory fibers, it is clear that messages can be relayed to the brain through activation of vagal afferents, and cutaneous nerves can be activated by cytokines [13]. Whether these afferent pathways will create hyperalgesia through common central neurocircuitries and neurochemistries remains to be explained.

It is important that a patient who has undergone pulmonary resection coughs vigorously to discharge more sputum in the early postoperative phase. This is advantageous in avoiding postoperative pneumonia, which is sometimes fatal for elderly patients or patients with poor pulmonary function. In this respect, the VATS lobectomy is advantageous for such patients with respect to minimizing postoperative pain and increasing preservation of pulmonary function in the early postoperative phase. Although lobectomy by the VATS procedure has been controversial because the adequacy of cancer excision by VATS has been questioned [14], some reports have shown that the survival of patients undergoing VATS lobectomy with mediastinal lymph node dissection was comparable to or better than the survival expected for lung cancer patients undergoing thoracotomy [13]. Therefore, the VATS lobectomy would be a better choice for high-risk patients with small peripheral lung cancer.


    Acknowledgments
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Acknowledgments
 References
 
We are indebted to Satsuki Kametaka and the resident surgeons in our department for their conscientious contribution to this study. We also thank Dawn Schuessler for secretarial support.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Lewis R.J., Caccavale R.J., Bocage J.P., Widmann M.D. Video-assisted thoracic surgical non-rib spreading simultaneously stapled lobectomy. Chest 1999;116:1119-1124.[Abstract/Free Full Text]
  2. McKenna R.J., Wolf R.K., Brenner M., Fischel R.J., Wurnig P. Is lobectomy by video-assisted thoracic surgery an adequate cancer operation?. Ann Thorac Surg 1998;66:1903-1908.[Abstract/Free Full Text]
  3. Kaseda S., Aoki T., Hangai N., Shimizu K. Better pulmonary function and prognosis with video-assisted thoracic surgery than with thoracotomy. Ann Thorac Surg 2000;70:1644-1646.[Abstract/Free Full Text]
  4. Landreneau R.J., Hazelrigg S.R., Mack M.J., et al. Postoperative pain-related morbidity: video-assisted thoracic surgery versus thoracotomy. Ann Thorac Surg 1993;56:1285-1289.[Abstract]
  5. Tschernko E.M., Hofer S., Bieglmayer C., Wisser W., Haider W. Early postoperative stress. Video-assisted wedge resection/lobectomy vs conventional axillary thoracotomy. Chest 1996;109:1636-1642.[Abstract/Free Full Text]
  6. Demmy T., Curtis J. Minimally invasive lobectomy directed toward frail and high-risk patients: a case-control study. Ann Thorac Surg 1999;68:194-200.[Abstract/Free Full Text]
  7. Lin E., Calvano S.E., Lowry S.F. Inflammatory cytokines and cell response in surgery. Surgery 2000;127:117-126.[Medline]
  8. Biffl W.L., Moore E.E., Moore F.A., Peterson V.M. Interleukin-6 in the injured patient. Marker of injury or mediator of inflammation?. Ann Surg 1996;224:647-664.[Medline]
  9. Takamochi K., Nagai K., Suzuki K., Yoshida J., Ohde Y., Nishiwaki Y. Clinical predictors of N2 disease in non-small cell lung cancer. Chest 2000;117:1577-1582.[Abstract/Free Full Text]
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  11. Giudicelli R., Thomas P., Lonjon T., et al. Video-assisted minithoracotomy versus muscle-sparing thoracotomy for performing lobectomy. Ann Thorac Surg 1994;58:712-718.[Abstract]
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Ann. Surg. Oncol.Home page
P. P. B. Massone, C. Lequaglie, B. Magnani, F. Ferro, and I. Cataldo
The Real Impact and Usefulness of Video-Assisted Thoracoscopic Surgery in the Diagnosis and Therapy of Clinical Lymphadenopathies of the Mediastinum
Ann. Surg. Oncol., December 1, 2003; 10(10): 1197 - 1202.
[Abstract] [Full Text] [PDF]


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Ann. Thorac. Surg.Home page
F. Gharagozloo, B. Tempesta, M. Margolis, and E. P. Alexander
Video-assisted thoracic surgery lobectomy for Stage I lung cancer
Ann. Thorac. Surg., October 1, 2003; 76(4): 1009 - 1015.
[Abstract] [Full Text] [PDF]


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ThoraxHome page
R Booton, M Jones, and N Thatcher
Lung cancer * 7: Management of lung cancer in elderly patients
Thorax, August 1, 2003; 58(8): 711 - 720.
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Ann. Thorac. Surg.Home page
G. M. Wright, C.P. Clarke, and J. M. Paiva
Hand-assisted thoracoscopic surgery
Ann. Thorac. Surg., May 1, 2003; 75(5): 1665 - 1667.
[Abstract] [Full Text] [PDF]


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Ann. Thorac. Surg.Home page
R. G. Soto and E. S. Fu
Acute pain management for patients undergoing thoracotomy
Ann. Thorac. Surg., April 1, 2003; 75(4): 1349 - 1357.
[Abstract] [Full Text] [PDF]


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Eur. J. Cardiothorac. Surg.Home page
W. W.L. Li, R. L.M. Lee, T.W. Lee, C. S.H. Ng, A. D.L. Sihoe, I. Y.P. Wan, A. A. Arifi, and A. P.C. Yim
The impact of thoracic surgical access on early shoulder function: video-assisted thoracic surgery versus posterolateral thoracotomy
Eur. J. Cardiothorac. Surg., March 1, 2003; 23(3): 390 - 396.
[Abstract] [Full Text] [PDF]


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Eur. J. Cardiothorac. Surg.Home page
W. S. Walker, M. Codispoti, S. Y. Soon, S. Stamenkovic, F. Carnochan, and G. Pugh
Long-term outcomes following VATS lobectomy for non-small cell bronchogenic carcinoma
Eur. J. Cardiothorac. Surg., March 1, 2003; 23(3): 397 - 402.
[Abstract] [Full Text] [PDF]


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Ann. Thorac. Surg.Home page
A. P.C. Yim
VATS major pulmonary resection revisited--controversies, techniques, and results
Ann. Thorac. Surg., August 1, 2002; 74(2): 615 - 623.
[Abstract] [Full Text] [PDF]


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Eur. J. Cardiothorac. Surg.Home page