|
|
||||||||
Eur J Cardiothorac Surg 2001;20:455-463
© 2001 Elsevier Science NL
a Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh and University of Edinburgh, Edinburgh, Scotland, UK
b Department of Clinical Neurosciences, Royal Infirmary of Edinburgh and University of Edinburgh, Edinburgh, Scotland, UK
c Department of Clinical and Surgical Sciences, Royal Infirmary of Edinburgh and University of Edinburgh, Edinburgh, Scotland, UK
d Department of Anaesthetics, Royal Infirmary of Edinburgh and University of Edinburgh, Edinburgh, Scotland, UK
Received 9 March 2001; received in revised form 18 April 2001; accepted 31 May 2001.
Corresponding author. Tel.: +44-131-536-4183; fax: +44-131-229-0659
e-mail: wsw{at}holyrood.ed.ac.uk
| Abstract |
|---|
|
|
|---|
Key Words: Acute phase Cytokine Minimally invasive surgery
| 1. Introduction |
|---|
|
|
|---|
Post-surgical changes in cytokine and acute phase mediators are associated with phagocyte and endothelial cell activation and increased reactive oxygen species (ROS) secretion [5,912]. There is evidence that minimally invasive abdominal surgery is less disruptive to metabolic and inflammatory responses than open laparotomy [10,12,13]. Currently, less is known about acute phase responses to minimally invasive thoracic surgery, whose pathophysiology differs in many respects from acute phase responses to abdominal surgery. Thus, for example, in cardio-thoracic surgery, phagocyte responses play a more prominent role and the acute phase immune response is closely connected with neutrophil activation [5,712,14]. The resultant acute phase reactants influence local vascular, immune and circulatory responses crucial to immediate and long-term survival, which also affect tumour growth, development and metastatic capability [69,11,1417]. Thus, acute phase responses play a prominent role in the immune, pulmonary and vascular responses to major thoracic surgery, but no prospective randomized analyses exist comparing these parameters in VATS and open thoracotomy lobectomy cases.
| 2. Patients and methods |
|---|
|
|
|---|
|
The persons involved in analyses related to the study were unaware of the operative technique used. Thus, patient details were given to those carrying out the laboratory analyses, but not the surgical technique used. This code was not supplied until the end of the study. Analyses were performed on 41 patients enrolled to the study during the allocated 18 months. Only one individual carried out each test, and therefore, the number of patient samples analyzed for acute phase reactants depended on assay availability and varied between the full cohort of 41 for C-reactive protein (CRP) and the partial cohort of 2425 for the other analyses. However, samples taken from the same day were always analyzed in full and the randomization process ensured that at least one patient from each group was analyzed on each day. Also, the mean and median tumour grades of the smaller group were not significantly different from those of the full cohort shown in Table 1 (mean grade: open group (n=12), 1.17; (n=21), 1.32; VATS group (n=12), 1.08; (n=19), 1.21; the median grade was 1 in all groups). The distribution of acute phase reactants in the larger group and the smaller group is shown for CRP in Fig. 1B and for interleukin (IL)-6 in Fig. 2B .
|
|
2.1. Sampling details
Blood samples were collected in EDTA (2 mg/ml) before operation and at 4, 24, 48, 72, 120 and 168 h post-operatively. Blood for analysis of CRP, IL-6, TNF-sR and P-selectin was stored on ice and centrifuged at 4°C within 20 min of withdrawal and stored at -70°C for 312 months before analysis. Samples taken pre-operatively and at 48 and 168 h were analyzed for T and B lymphocytes, CD4, CD8, natural killer (NK) cell populations (see [16]) and for monocyte, neutrophil and lymphocyte ROS production. These samples were analyzed within 4 h of withdrawal. Blood from healthy donors, withdrawn at the same time was used as a contemporary control.
2.2. CRP, IL-6, tumour necrosis factor, tumour necrosis factor receptor and P-selectin
These were analyzed using previously described methods [18]. Serum CRP concentration was measured by laser nephelometry (Behring, Marburg, Germany; sensitivity, 2.5 mg/l). Plasma IL-6, soluble human TNF-R type I/II (p55/p75) and P-selectin were measured using monoclonal antibodies (Monosan, Brussels, Belgium and British Biotechnology, London, respectively) and an enzyme-linked immunoassay.
2.3. Leucocyte ROS
Leukocyte preparations, purified within 2 h of venepunture using hypotonic lysing solution (Ortho-lyse), were incubated for 10 min at 37°C with 5 M 2',7'-dichlorofluorescein diacetate (Kodak, Harrow, UK). The cell viability was >85% using cell permeability to ethidium homodimer [19] and was not significantly different between patient and control leukocytes. Flow cytometry of patient and control samples was carried out using an Ortho flow cytometer with Immunocount software and Ortho-count calibration (Ortho, High Wycombe, UK). ROS production was analyzed in mononuclear and polymorphonuclear phagocytes from the same individual. The rate of ROS generation was analyzed using flow cytometry in duplicate patient and control samples at 30 s intervals [9,16,19]. Oxidative activity was determined for 7 min before, then for 13 min after the addition of n-6 essential fatty acid, using arachidonic acid (AA; Sodium salt, Sigma, Poole, UK) or gamma-linolenic acid (GLA; Lithium salt, Scotia Pharmaceuticals, Stirling, UK) or saline control. Preliminary analysis indicated a normal distribution of fluorescence, and therefore, the mean fluorescence of phagocyte populations was used to estimate ROS generation. Monocytes were identified using Coulter anti-CD57 and Scottish Antibody Production Unit UCHMI antibodies, and neutrophils were routinely identified using Ortho anti-CD16 to detect the Fc
III receptor for aggregated and immune complex IgG and anti-CD65 (Coulter, High Wycombe, UK) against the granulocyte fucoganglioside antigen.
2.4. Statistical analysis
The data were analyzed using the Statistical Analysis Software (SAS Institute, Inc., North Carolina, 1991) program. The data were compared using the Student's t-test, after checking for normality of distribution, or the Wilcoxon signed rank test for non-normally distributed data. Changes within groups were analyzed using the paired t-test, pairing results from the same individual before and after surgery. Differences between groups were analyzed using the unpaired t-test. The Bonferroni correction was utilized for multiple comparisons.
| 3. Results |
|---|
|
|
|---|
The distribution of individual patient CRP values in the open surgery and the VATS groups are described in terms of the tumour stage of individual patients (Fig. 1B). In contrast to IL-6 release into the circulation after open surgery, elicited CRP concentrations appeared to be independent of stage, although there was possible evidence of an elevated pre-surgical release of these reactants in both surgical groups in the patients with higher grade tumours (grey symbols).
The response of the cytokine IL-6 to surgery also showed a lower peak concentration in the VATS group, compared with the conventional open surgery group (Fig. 2A). The mean plasma IL-6 increased rapidly in both open surgery and VATS groups 4 h after surgery (P=0.025 in the open group and P=0.002 in the VATS group, using the Wilcoxon signed rank test to compare pre-surgical and 4 h post-surgical IL-6 in the same individuals). The peak IL-6 in the VATS group appeared to occur earlier, compared with peak IL-6 in the open surgery group. The distribution of individual patient IL-6 values within each group are described in terms of the tumour stage of individual patients (Fig. 2B). This indicates that the range of IL-6 released into the circulation after open surgery is wider than that elicited in the VATS group. Comparison of post-surgical IL-6 levels released from high grade tumours (grey symbols) in the two groups raises the intriguing possibility that the exaggerated CRP response detected in high grade patients may be attenuated in patients undergoing VATS.
The responses in the tumour necrosis factor (TNF) receptors and in P-selectin were smaller than those of the acute phase metabolites, CRP and IL-6. TNF-sR55 and TNF-sR75 release during cardiopulmonary procedures have been demonstrated and there is evidence that TNF-sR55 may mediate cellular responses such as neutrophil activation [8,20]. TNF-sR75 shows a distinct pattern of release and activity, but may be associated with immunoregulation rather than inflammatory activity. An increase in plasma concentrations of 12 mg/l of both TNF-R55 and TNF-R75 was observed in both patient groups 48168 h post-surgery. When plasma TNF-sR55 levels in VATS and conventional open surgery groups were directly compared, the difference between surgical groups was not significant. However, a greater post-operative increase in TNF-sR55 (compared with the pre-surgical TNF-sR55 in the same patient) was observed in the conventional open surgery group (data not shown). When the plasma TNF-R75 levels in VATS and conventional open surgery groups were compared, no significant difference between surgical groups was observed (data not shown). P-selectin in the circulation is an indicator of endothelial cellleucocyte interaction and is elevated in severe trauma. When circulating P-selectin concentrations in the two surgical groups were directly compared, no difference between VATS and open surgery groups was detected. However, when the post-surgical change within each group was monitored, a decrease in the release of P-selectin was detected in the VATS group 24 h after surgery, while the conventional open surgery group showed a more gradual, but more sustained increase in P-selectin.
3.2. Neutrophil and monocyte ROS
Both monocyte and neutrophil ROS production were stimulated by up to 40% on post-operative day 2 compared with leukocytes from healthy controls analyzed at the same time (Figs. 3 and 4) . The pre-surgical neutrophil ROS was approximately 10% above the control ROS, which may indicate local pulmonary inflammatory processes (Fig. 4). AA and GLA consistently stimulated neutrophil and monocyte ROS by up to 40% and this stimulated ROS, when compared with control stimulation, was also upregulated after surgery. Significant increases in neutrophil ROS were detected in the conventional open surgery group, but not in the VATS group (Fig. 4). Similarly, monocyte ROS increased after surgery in the conventional open surgery group compared with ROS in normal control monocytes (Fig. 3).
|
|
All patients survived and were discharged well. The duration of surgery, length of stay and pathological characteristics are listed in Table 1. These do not differ significantly, although it should be noted that, except for a few patients who lived locally in regard to the hospital, the minimum length of stay was defined by the 7 day sampling requirement. Important complications occurred in two VATS cases and four open cases. One VATS case with severe intrapleural adhesions bled from pleural adhesions and developed secondary lung collapse which required several days to reinflate; the other had very poor pre-operative respiratory function with persistent smoking and required ventilatory support for 32 h. Three of the open cases developed post-operative pulmonary infections which required minitracheostomy in two cases and suction bronchoscopy in one; the other complicated open case experienced troublesome cardiac dysrythmias.
| 4. Discussion |
|---|
|
|
|---|
In this study, we have compared pulmonary lobectomy using a VATS approach to a limited conventional open thoracotomy. It could be argued that stage I lesions are resected using either a muscle sparing or limited axillary thoracotomy in some centres, both of which might be less traumatic than our open thoracotomy model. However, the open thoracotomy approach we used is in widespread general use, provides a consistent reference point and offers good access to the chest. It would have complicated our study to have utilized an alternative type of thoracotomy which may have required conversion in some cases to a more extended procedure and might be less applicable to general thoracic surgical practice.
Our results suggest that the VATS approach was associated with less tissue and vascular trauma, and consequently, reduced the activity of acute phase associated cytokines and their receptors (IL-6, TNF-sR55) and mediators (CRP, ROS) and effector cells of cellular immunity. In the same patients, we observed less adverse immunological responses with a minimally invasive VATS approach to pulmonary resection when circulating lymphocyte numbers were analyzed [16]. The effects of surgery on acute phase responses occurred before the decrease in lymphocyte numbers and oxidative activity observed in the same patients.
Quantitatively, the greatest difference between VATS and the conventional open surgery groups were observed in CRP and IL-6 (Figs. 1 and 2). CRP and IL-6 are acute phase response markers associated with post-operative complications such as respiratory distress syndrome and multiple organ failure [21,22]. Differences between surgical groups were also observed in the kinetics of IL-6 and soluble TNF-R (p55 and p75) responses. A transient but significant increase in IL-6 was detected in the VATS group 4 h post-operatively (Fig. 2). The earlier peak in IL-6 in the VATS cases may be partly due to the earlier onset (by approximately 15 min) of pulmonary retraction and hilar dissection in this group and to the slightly longer mean operative duration (141 min VATS vs. 121 min open). This evidence of very early IL-6 responses requires further investigation using more frequent intra-operative and early post-operative sampling.
Smaller differences were observed when post-surgical changes in soluble TNF-R (p55 and p75) were monitored. TNF-sR55 and TNF-sR75 are released in a wide range of immune responses and TNF-sR55 was associated with mortality in patients undergoing cardiopulmonary bypass [8]. An increase in the plasma concentrations of TNF-sR55 and TNF-sR75 was observed in both patient groups 48168 h post-surgery. The difference between surgical groups was not, overall, significant, but in the open surgery group, the increase in TNF-sR55 was approximately 20% greater than in the conventional open surgery group.
There is evidence in patients undergoing cardio-thoracic surgery that, although certain cytokine responses result in homeostasis, the catabolic state elicited by acute phase mediators may be serious or fatal [21,22]. Therefore, the duration, as well as the extent of cytokine and ROS release during the post-surgical period may be critical to organ function and anti-tumour responses. This study is consistent with reports that minimally invasive abdominal surgery is associated with an attenuation of acute phase and phagocyte responses [12,13]. Currently, less is known about acute phase responses to minimally invasive thoracic surgery, whose pathophysiology differs in many respects from responses to abdominal surgery. Thus, for example, in cardio-thoracic surgery, the acute phase immune response is closely connected with neutrophil activation. The resultant acute phase reactants influence local immune and circulatory responses crucial to the immediate and long-term survival, which also affect tumour growth, development and metastatic capability.
A neutrophil leukocytosis is common in the post-operative period. The production of ROS by phagocytes is upregulated by intrinsic and extrinsic stimuli [5,20,23]. These stimuli may be generated during invasive procedures, as humoral factors released during dialysis have been reported to stimulate monocyte and neutrophil ROS using the same assay used to detect ROS in the current study [23]. We detected upregulation of phagocyte ROS after pulmonary resection, but, in common with other acute phase responses, the mean increase in ROS was lower in the VATS group (Figs. 3 and 4). This has functional implications, as it has been reported that the neutrophil population circulating after surgery may function inadequately in antibacterial defence [5,12]. Defects in neutrophil chemotaxis, phagocytosis, lysosomal enzyme content and antibacterial defence processes have also been identified in patients following surgery [5,9]. There is evidence that minimally invasive surgery may affect phagocyte responsiveness less than conventional open surgery [10,12,14]. This is consistent with the results of this study, which detected upregulation in phagocyte activity after pulmonary resection, and an associated decline in the ability of phagocytes to undergo an oxidative burst stimulated by the intracellular signalling molecule, arachidonic acid. A previous analysis of mononuclear and polymorphonuclear phagocyte activation by arachidonic acid in vitro also indicated a lower response to arachidonic acid after surgery [9].
The interaction between phagocytes and tumour cells and their products are complex. However, phagocyte infiltration and activation may limit tumour growth [24]. ROS are involved in cytotoxic reactions involving phagocytes, and we have also demonstrated tumour-associated ROS activity stimulated by arachidonic acid which may be involved in tumour apoptosis [25]. In summary, therefore, major surgery is associated with abnormalities of phagocyte function and our results are consistent with reports of a decreased effect of minimally invasive surgery on phagocyte activation.
The release of P-selectin, which is expressed in the effector phase of leukocyte recruitment, was used to monitor endothelial cell activation and tissue damage, as elevated selectin levels have been reported in organ dysfunction, including pulmonary trauma [11]. No significant differences in P-selectin between surgical groups were detected after surgery, but, when post-surgical changes within individuals were compared, an gradual increase in P-selectin was detected in the open surgery group. Thus, greater release of the cytokine, IL-6, and the acute phase reactants, CRP and phagocyte ROS, in the open surgery group was followed by evidence of greater endothelial cellleukocyte interaction detected using P-selectin.
The results obtained in this study suggest that VATS pulmonary lobectomy, when compared with a limited conventional open thoracotomy, was associated with less traumatic insult to the patient, and consequently, reduced the activity of the acute phase cytokine IL-6 and mediators (CRP, ROS) and effector cells of cellular immunity. We have also demonstrated in this patient group that VATS was associated with less effect on circulating T (CD4) cells at 2 days after surgery and on NK lymphocytes at 7 days after surgery [16]. Thus, in this patient group, there is evidence that elements of both specific anti-tumour immunity (T and NK cells) and non-specific secondary immunity (phagocyte responses) were less affected in the VATS group. These data suggest that, during surgery, the degree of procedural invasiveness may influence the extent of immunosuppression in patients undergoing lobectomy for pulmonary neoplasm. The specific molecular and cellular interactions which underlie these phenomena remain to be determined, but, from a clinical perspective, it is apparent that the choice of an open or VATS operative strategy may have implications for tumour recurrence and long-term survival in lung cancer patients.
| Acknowledgments |
|---|
| References |
|---|
|
|
|---|
induced activation of neutrophil respiratory burst on biological surfaces is mediated by the p55 TNF receptor. Blood 1994;84:287-293.This article has been cited by other articles:
![]() |
C. S. Ng, I. Y. Wan, and A. P. Yim Impact of Video-Assisted Thoracoscopic Major Lung Resection on Immune Function Asian Cardiovasc Thorac Ann, August 1, 2009; 17(4): 426 - 432. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. M. Flores, B. J. Park, J. Dycoco, A. Aronova, Y. Hirth, N. P. Rizk, M. Bains, R. J. Downey, and V. W. Rusch Lobectomy by video-assisted thoracic surgery (VATS) versus thoracotomy for lung cancer J. Thorac. Cardiovasc. Surg., July 1, 2009; 138(1): 11 - 18. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. W. Seder, K. Hanna, V. Lucia, J. Boura, S. W. Kim, R. J. Welsh, and G. W. Chmielewski The safe transition from open to thoracoscopic lobectomy: a 5-year experience. Ann. Thorac. Surg., July 1, 2009; 88(1): 216 - 226. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Loscertales, R. Jimenez-Merchan, M. Congregado, F. J. Ayarra, G. Gallardo, and A. Trivino Video-Assisted Surgery for Lung Cancer. State of the Art and Personal Experience Asian Cardiovasc Thorac Ann, June 1, 2009; 17(3): 313 - 326. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. D. Yan, D. Black, P. G. Bannon, and B. C. McCaughan Systematic Review and Meta-Analysis of Randomized and Nonrandomized Trials on Safety and Efficacy of Video-Assisted Thoracic Surgery Lobectomy for Early-Stage Non-Small-Cell Lung Cancer J. Clin. Oncol., May 20, 2009; 27(15): 2553 - 2562. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Tajima, M. Kohno, M. Watanabe, Y. Izumi, S. Tasaka, I. Maruyama, T. Miyasho, and K. Kobayashi Occult injury in the residual lung after pneumonectomy in mice Interactive CardioVascular and Thoracic Surgery, December 1, 2008; 7(6): 1114 - 1120. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. O. Jones, G. Casali, and W. S. Walker Does Failed Video-Assisted Lobectomy for Lung Cancer Prejudice Immediate and Long-Term Outcomes? Ann. Thorac. Surg., July 1, 2008; 86(1): 235 - 239. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. G. Nicastri, J. P. Wisnivesky, V. R. Litle, J. Yun, C. Chin, F. R. Dembitzer, and S. J. Swanson Thoracoscopic lobectomy: Report on safety, discharge independence, pain, and chemotherapy tolerance J. Thorac. Cardiovasc. Surg., March 1, 2008; 135(3): 642 - 647. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. M. Flores and N. Alam Video-Assisted Thoracic Surgery Lobectomy (VATS), Open Thoracotomy, and the Robot for Lung Cancer Ann. Thorac. Surg., February 1, 2008; 85(2): S710 - S715. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. L. Demmy and C. Nwogu Is Video-Assisted Thoracic Surgery Lobectomy Better? Quality of Life Considerations Ann. Thorac. Surg., February 1, 2008; 85(2): S719 - S728. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. J. Szczesny, R. Slotwinski, B. Szczygiel, A. Stankiewicz, M. Zaleska, M. Kopacz, and A. Olesinska-Grodz Systematic mediastinal lymphadenectomy does not increase postoperative immune response after major lung resections Eur. J. Cardiothorac. Surg., December 1, 2007; 32(6): 868 - 872. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. Swanson, J. E. Herndon II, T. A. D'Amico, T. L. Demmy, R. J. McKenna Jr, M. R. Green, and D. J. Sugarbaker Video-Assisted Thoracic Surgery Lobectomy: Report of CALGB 39802 A Prospective, Multi-Institution Feasibility Study J. Clin. Oncol., November 1, 2007; 25(31): 4993 - 4997. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Solli and L. Spaggiari Indications and Developments of Video-Assisted Thoracic Surgery in the Treatment of Lung Cancer Oncologist, October 1, 2007; 12(10): 1205 - 1214. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Schilling, A. Kozian, M. Kretzschmar, C. Huth, T. Welte, F. Buhling, G. Hedenstierna, and T. Hachenberg Effects of propofol and desflurane anaesthesia on the alveolar inflammatory response to one-lung ventilation Br. J. Anaesth., September 1, 2007; 99(3): 368 - 375. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. J. Szczesny, R. Slotwinski, A. Stankiewicz, B. Szczygiel, M. Zaleska, and M. Kopacz Interleukin 6 and interleukin 1 receptor antagonist as early markers of complications after lung cancer surgery Eur. J. Cardiothorac. Surg., April 1, 2007; 31(4): 719 - 724. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. West, S. Rashid, and J. Dunning Does video-assisted thoracoscopic lobectomy produce equal cancer clearance compared to open lobectomy for non-small cell carcinoma of the lung? Interactive CardioVascular and Thoracic Surgery, February 1, 2007; 6(1): 110 - 116. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. E. Friscia, J. Zhu, J. W. Kolff, Z. Chen, L. R. Kaiser, C. S. Deutschman, and J. B. Shrager Cytokine Response is Lower After Lung Volume Reduction Through Bilateral Thoracoscopy Versus Sternotomy Ann. Thorac. Surg., January 1, 2007; 83(1): 252 - 256. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Amar, A. Goenka, H. Zhang, B. Park, and H. T. Thaler Leukocytosis and increased risk of atrial fibrillation after general thoracic surgery. Ann. Thorac. Surg., September 1, 2006; 82(3): 1057 - 1061. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. E. Froudarakis, M. Klimathianaki, and M. Pougounias Systemic inflammatory reaction after thoracoscopic talc poudrage. Chest, February 1, 2006; 129(2): 356 - 361. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Jinbo, K. Ueda, Y. Kaneda, M. Sudo, T.-S. Li, and K. Hamano Video-assisted transcatheter lung perfusion regional chemotherapy Eur. J. Cardiothorac. Surg., June 1, 2005; 27(6): 1079 - 1082. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. P. Grichnik and T. A. D'Amico Acute Lung Injury and Acute Respiratory Distress Syndrome After Pulmonary Resection Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2004; 8(4): 317 - 334. [Abstract] [PDF] |
||||
![]() |
A. Sedrakyan, J. van der Meulen, J. Lewsey, and T. Treasure Video assisted thoracic surgery for treatment of pneumothorax and lung resections: systematic review of randomised clinical trials BMJ, October 30, 2004; 329(7473): 1008. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Endo, Y. Sato, T. Hasegawa, K. Tetsuka, S. Otani, N. Saito, Y. Tezuka, and Y. Sohara Preoperative chemotherapy increases cytokine production after lung cancer surgery Eur. J. Cardiothorac. Surg., October 1, 2004; 26(4): 787 - 791. [Abstract] [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
P. Thomas, C. Doddoli, S. Yena, X. Thirion, F. Sebag, P. Fuentes, and R. Giudicelli VATS is an adequate oncological operation for stage I non-small cell lung cancer Eur. J. Cardiothorac. Surg., June 1, 2002; 21(6): 1094 - 1099. [Abstract] [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |