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J Thorac Cardiovasc Surg 2000;120:119-127
© 2000 The American Association for Thoracic Surgery
GENERAL THORACIC SURGERY |
From the Department of Cardiothoracic Surgery,a University of Vienna; the Department of Thoracic Surgery,b Center of Pulmology; and the Institute of Medical Statistics,c University of Vienna, Vienna, Austria.
Address for reprints: Adelheid End, MD, Department of Cardiothoracic Surgery, University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria (E-mail: adelheid.end{at}univie.ac.at ).
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Abstract |
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 Top Abstract IntroductionPatients and methods Results Discussion Appendix: Discussion References |
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Introduction |
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TopAbstractIntroductionPatients and methods Results Discussion Appendix: Discussion References |
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1-3 Multivariable analyses have been rarely performed. 4,5 We carried out a multivariable analysis to determine putative prognostic factors for survival. |
Patients and methods |
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TopAbstractIntroductionPatients and methods Results Discussion Appendix: Discussion References |
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Preoperative staging included chest radiography, computed tomography of the chest and upper abdomen, bronchoscopy, and upper abdominal ultrasonography; computed tomography of the cerebrum and bone scintigraphy were done in selected cases.
Operative procedure
Bronchoplastic procedures consisted of 111 lobectomies (right upper lobe, n = 69; right middle lobe, n = 1; right lower lobe, n = 4; left upper lobe, n = 26; and left lower lobe, n = 11), 17 bilobectomies (upper, n = 12; lower, n = 5), 4 right upper lobectomies with carinal resection, 8 sleeve pneumonectomies, and 4 bronchoplastic procedures without parenchymal resection (wedge resection of the apical segmental bronchus of the right lower lobe, resection of the right upper lobe bronchus, resection of the stump of the left upper lobe bronchus, and resection of the left upper lobe carina and the proximal segment of the lower lobe bronchus). The procedures were performed on the right side in 103 (72%) patients and on the left side in 41 (28%) patients. Resection of the right upper lobe was the most common procedure and was performed in 72 (63%) of 115 resections of single lobes.
Type of resection
In 116 (81%) patients a full sleeve resection was performed, and in 28 (19%) patients an incomplete sleeve or wedge bronchoplasty was performed.
Additional angioplasty was performed in 23 (16%) patients, including angioplasty of the pulmonary artery in 19 patients (7 circular resections with end-to-end anastomoses and 12 tangential resections), 3 angioplasties of the superior caval vein (1 tube graft replacement and 2 tangential resections), and 1 local resection with patch angioplasty of the aorta. Five (3.5%) patients had en bloc resection of the thoracic wall and sleeve lobectomy, and 8 (5.6%) patients had an additional wedge resection of the remaining lobe. For extended resections, cardiopulmonary bypass was used in 3 cases (right-sided pneumonectomy with resection of the carina and superior caval vein, left-sided pneumonectomy with wedge resection of the trachea and aorta, or left-sided pneumonectomy with resection of the carina and the right main bronchus).
Histology
Indications for operation were non–small cell lung cancer (NSCLC; n = 123), small cell lung cancer (n = 5), carcinoid tumor (n = 10), and metastases of extrathoracic malignant tumors (n = 6; hypernephroid carcinoma in 4 cases and breast and endometrial carcinoma in 1 case each).
Radicality of resection
Resections with completely tumor-free bronchial resection margins were defined as complete resections and were achieved in 130 (90.3%) patients. In 14 (9.7%) patients incomplete resections with histologically residual tumor were performed. No patient had visible residual tumor at the bronchial resection margins.
Staging
The TNM classification is given in Table I in accordance with the most recent International Union Against Cancer (UICC) classification. 6 Five patients with stage IV disease had cerebral metastases that had been resected before the lung operation, and 2 patients had single metastases in another lobe. One male patient had carcinoma in situ (stage 0).
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7 The risk factors, as well as their mathematical terms and coding, are listed in Table III. One of the factors investigated is tumor stage. No TNM stage is assigned to 6 patients with metastases of extrathoracic malignant disease; they are included in the multivariable analysis by means of informative imputation. These patients are assigned a TNM stage value of 6, and this group is identified by its own dichotomous variable (Table III).
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2 test was used to test individual regression parameters. Ninety-five percent confidence intervals (CIs) for relative risk are given as appropriate. In addition, univariable analyses were performed to obtain survival curves according to the Kaplan-Meier estimate. 8 The log-rank test was used to assess the difference in survival curves (SAS LIFETEST). For rejection of a null hypothesis, a P value less than .05 is considered statistically significant. Baseline values are given as means ± SD. |
Results |
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TopAbstractIntroductionPatients and methods Results Discussion Appendix: Discussion References |
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Postoperative mortality and complications
Overall 30-day mortality was 8.3% (12/144). The causes of death are listed in Table IV. Five patients died within 1 week, resulting in a 7-day mortality of 3.5% (5/144). For single sleeve lobectomies, 30-day mortality was 5.4% (6/136). Including bilobectomies, 30-day mortality was 6.2% (8/128).
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Recurrence and metastases
In 52 (36%) of 144 patients, local recurrence or distant metastases occurred. Thirty-seven patients died with disease, accounting for 56% (37/66) of all deaths.
Multivariable analysis
The model selection procedure includes the variables of TNM stage, type of bronchoplastic procedure, and respiratory and cardiovascular risk factors. Table VI summarizes their estimated risk ratios (relative risks) of the Cox proportional hazard model, CIs, and P values of the Wald test. The hazard of patients with cardiovascular risk, for instance, is estimated to be 104% (CI, 22%-239%) above the hazard of patients without this risk. The hazard of patients with respiratory risk is estimated to be 126% (CI, 39%-268%) above the hazard of patients without such risk. Besides the results of multivariable analysis, Table VI gives the estimates and P values of univariable Cox regression analyses, which confirm the results of multivariable analysis.
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Discussion |
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TopAbstractIntroductionPatients and methods Results Discussion Appendix: Discussion References |
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2,8,10 Many studies deal with univariate analyses of sleeve resections in malignant and nonmalignant disease; multivariable analyses were only applied in a few studies. 4,5
We performed a multivariable analysis to determine putative prognostic factors of survival in a consecutive series of sleeve resections, including carinal resections, as did Watanabe and colleagues. 11 Like other series in the literature, this number is not very large, and therefore conclusions derived from a multivariable model must be approached with caution. From 9 investigated risk factors, 4 independent factors were entered into the analysis: TNM stage, type of surgical procedure (ie, sleeve lobectomy, sleeve bilobectomy, and sleeve pneumonectomy), and cardiovascular and respiratory risks. From a statistical point of view, this result does not mean that other factors have no influence; they may be concealed by stronger factors. It must also be taken into account that coding of the variables as done by statisticians may influence the outcome. In contrast to the long-term results of Van Schil and colleague’s multivariate analysis 4 with a minimum follow-up of 5 years for surviving patients, our results are based on a median follow-up period of 27 months for surviving patients and a median survival of 7.9 months for those who died. Thus, the number of patients at risk is small at the 3-year follow-up; we did not generally mention 5-year survivals. These small numbers might also be the reason that survival of patients with N2 disease tends to be worse but does not achieve statistical significance (3-year survival of 36% in N2 versus 63% in N0). In those series that were followed up for a longer period, however, nodal status is an important prognostic factor. 3,4 Our results correspond to the series of Rendina and colleagues, 12 who reported a 2-year survival of 72% for lung cancer (about 65% in our series) and favorable results in patients with benign lesions, with the latter being alive 8 months to 3 years after the operation. With the exception of 1 patient who died of cerebral aneurysm, all our patients with carcinoid tumors are alive.
In contrast to Van Schil and colleagues, 4 we included patients with incomplete sleeve resections, so-called wedge resections described by Khargi and colleagues, 13 and sleeve pneumonectomies to summarize our total experience with bronchoplastic procedures. Survival of total and partial bronchial resections of lobes did not significantly differ, although wedge resections tended to do better. The decision to perform a partial or total sleeve resection depended on the extent of bronchial infiltration by the tumor or lymph nodes but was also influenced by the decision of the individual surgeon. It must be considered that this 2-center study comprises the experience of a total of 8 main surgeons. The 30-day mortality of 5.4% for lobar sleeve resections lies within the range given in the literature.
In T4 tumors with carinal or tracheal invasion, however, 5-year survival may be as high as 20% but is significantly worsened by N2 disease. 14 Therefore, most authors do not advocate resection in these cases. However, we accept bronchoplasties with palliative intent in cases with N2 disease or distant metastases (eg, single brain lesions, which are amenable to surgical resection). Because the 1-year survival is as high as 25% for sleeve pneumonectomies in our series, we strongly recommend that the indication for this type of operation be established with great caution, considering the patient’s general condition and cardiorespiratory risk factors. Because some long-term survivors have been reported in literature, 5,11 operation may be considered in the individual case despite the poor prognosis. Our series of 8 sleeve pneumonectomies included a midterm survivor who was alive at 6.7 months after the operation.
Because comorbidity has significant influence on survival, patients chosen to undergo bronchoplastic operations should be selected with caution. This concurs with the conclusions of Tedder and colleagues 9 on the basis of a review of 1915 patients with bronchoplastic resections. Especially patients with cardiovascular risk factors, as well as those with impaired pulmonary function, require a careful preoperative evaluation. In these patients mediastinoscopy is strongly indicated to exclude those with mediastinal disease.
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Appendix: Discussion |
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TopAbstractIntroductionPatients and methods Results Discussion Appendix: Discussion References |
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The first issue, of course, is survival. Two articles have appeared within the last couple of years concerning the survival of patients with bronchogenic carcinoma after sleeve resections. I want to draw your attention to the fact that survival is related to nodal status, which is not surprising at all. Yet in the authors’ article today, survival did not appear to be related to nodal status, and I would like you to comment as to why you think that might be the case. Your first slide did say that there were some 31 patients with N2 disease. Therefore, I am surprised that survival was not related to N2 disease.
I think the bigger issue in this article is the mortality, which you reported as 8%. However, your abstract also says that 4 deaths occurred beyond the 30-day limit as a result of anastomotic problems. If I add those in, I get a mortality of 11% and not 8%. However, even 8% is still high. Indeed, the highest mortality, 5%, is the one from my own center reported in 1979 by Dr Weisel. Why was the mortality in your series so high? Weisel’s article pointed out that there were several ways that we could stratify the type of patients coming to operation. Indeed, it was 5% for those patients in whom the sleeve lobectomy was undertaken because the surgeon believed it was the best operation for that patient. However, in a separate group of patients in that article, in whom sleeve lobectomy was done as a compromise procedure because of concern that the patient would not tolerate a pneumonectomy even though a pneumonectomy was thought to be indicated, the mortality was actually 22%.
As I look through your article, I note that 21 patients had an angioplasty, 31 patients had N2 disease, and 5 patients had chest wall resections. Therefore, I have to wonder whether the mortalities were related to compromised cardiopulmonary function or to the presence of N2 disease. With N2 disease, of course, you may be devascularizing a portion of the bronchus as you do your complete nodal dissection. Therefore, my question for you is simply this: How many of those 16 deaths were in the group of patients who had compromised cardiopulmonary function or who had N2 disease?
Dr Wolner. I apologize that you did not get the manuscript.
The overall mortality of the whole group, including this fatal second operation, was 8%. Of the 8 patients in the sleeve lobectomy group, 2 underwent pulmonary embolism and 1 underwent myocardial infarction. Perhaps a larger series will then bring other results, but what is true is this 5.8% mortality among patients with the sleeve lobectomy. I think that we had with this 60% cardiovascular risk and 60% respiratory risk a group of patients with a higher risk generally in pulmonary resection, and this could be my explanation.
Also surprising for us was the fact that these patients with N2 disease were not so very different from the patients with N0 or N1 disease. Perhaps this has something to do with the low number of these patients after 5 years. It has also something to do, I hope, with the extended lymph node dissection and all of the radiotherapy and chemotherapy after the operation. That would be my explanation for this unexpected result of our multivariate and univariate analysis.
Dr Todd. Do you know what the mortality was within the group of 21 patients who had angioplasty as well as sleeve resection?
Dr Wolner. No. However, in the long-term survival, angioplasty has no influence. Therefore, I must speculate that there was no difference.
Dr Steven J. Mentzer (Boston, Mass). Did you have any data on local recurrence, that is, on the pattern of failure? In addition, the abstract mentions dehiscence after 30 days. This seems like a long time after the initial reconstruction. What were the causes of the dehiscence?
Dr Wolner. No, we have no dehiscence.
Dr Mentzer. Did you have any local recurrences?
Dr Wolner. Yes. Of the 50 patients who died, 60% died of local or distant disease, and 40% died of different reasons.
Dr Douglas E. Wood (Seattle, Wash). I agree with Dr Todd’s points about the relationship to nodal disease and angioplastic procedures, which is contradictory to several other articles regarding sleeve resections. However, I am going to restrict my questions and comments to the carinal pneumonectomies. This is clearly a very difficult group of patients, and in very experienced hands they have a mortality of approximately 15%, ranging up to 30% at best. In your series I believe it was 50%, which I think gives us all just about when to consider carinal pneumonectomy as an extended resection for NSCLC.
I want to go back to your point that 2 of your patients required cardiopulmonary bypass. My adage that I give to the residents is that in bronchoplastic procedures, including carinal pneumonectomies, most of them are straightforward enough that they do not require cardiopulmonary bypass, and if they are enormously complicated, then cardiopulmonary bypass is contraindicated. Therefore, we always come up with some routine to manage to do the operations off-pump. Did the 2 patients who had cardiopulmonary bypass undergo carinal resections, and did they die in the postoperative period? I think that would be useful to know and potentially provide experience in favor of or against cardiopulmonary bypass to support of bronchoplastic procedures.
Dr Wolner. First, let me start my answer by saying that we are a department of cardiothoracic surgery and we do about 1300 heart operations per year besides these 700 different general thoracic procedures. Therefore, in general I am sure we are more liberal in using cardiopulmonary bypass if it seems to be necessary. However, these patients are not among those who died. One patient who died had an infiltration in the aorta and a piece of the aorta was replaced. The other patients were in severe trouble on admission because of bleeding at the junction of the superior vena cava and the innominate vein. Fortunately, this situation is rare in cardiac operations, but it is very difficult to treat. This was the second case with the heart-lung machine. Therefore, cardiopulmonary bypass was used in 2 of these 3 patients because of catastrophic vascular problems during the operation.
Dr Wood. Neither one died?
Dr Wolner. No.
Dr David J. Sugarbaker (Boston, Mass). I have two comments. At the Brigham Hospital, any patient who would be considered for carinal pneumonectomy would undergo a mediastinoscopy, and if N2 disease was determined to be present, that patient would be ruled out for routine carinal pneumonectomy outside of some specific protocol or clinical trial. My first question to you is this: Because in your particular abstract N2 disease was indeed a poor predictor of survival, what is the role of mediastinoscopy for any patient whom one might consider for carinal pneumonectomy? Second, what is your technique in terms of using a parathymic-pericardial fat pad or other buttress of your bronchoplastic suture line?
Dr Wolner. With regard to the first question, usually we try to obtain complete staging of the disease in all of our patients. As you know, in the last year there has been some change in staging with the computed tomographic scan, but I cannot tell you what the percentage is or how many mediastinoscopies were done. In general, when we have a suspicion that there is N2 disease on the basis of the computed tomographic scan, the x-ray film, and so on, a mediastinoscopy or a thoracoscopy will be performed.
To answer the second question, we use polydioxanone sutures (PDS-40; Ethicon, Inc, Somerville, NJ) and in some cases, but not all, we use intercostal flaps or pericardial flaps and fibrin glue.
Dr Douglas J. Mathisen (Boston, Mass). Could you please describe the technique you use to do bronchoplasty? Is it open, interrupted, or running?
Second, a number of your patients had bilobectomies and bronchoplastic procedures. In that group did you notice any size discrepancy, and if you did find size discrepancy, could you share with us how you dealt with that problem?
Dr Wolner. This is from two hospitals, and the majority of the anastomoses were done with a polydioxanone running suture, but I cannot tell you how many. There were some with a single-stitch technique. If there is a size discrepancy, we use the usual technique with a longitudinal incision, which I use in vascular operations, to bring together the two stumps.
Dr L. Penfield Faber (Chicago, Ill). Quoting from the abstract, "The presence of cardiac risk factors, chronic obstructive disease, N2 disease, R1 resection, performance of sleeve pneumonectomy with a 50% mortality had an adverse influence on survival." With these points in mind, I would appreciate your telling us what your absolute contraindications are for bronchoplastic procedures.
Dr Wolner. That is a very good question. I would say my personal feeling is that if you have a patient who is under 70 years with a bronchial carcinoma and no distant metastases who seems, from your staging, to be a candidate for resection, then I am more in favor of resection. Also, there was this discussion before of brain metastasis and N1 disease and whether we should resect. My personal attitude for many years in such cases is to be more on the side of the operation. It is clear that if you have distant metastases, pleural involvement, or diseased lymph nodes outside of the mediastinum (contralateral), then you have contraindications. Those are the typical indications for chemotherapy and radiotherapy.
Dr Todd. I will just make one other technical comment. Somebody did bring up the role of mediastinoscopy before doing sleeve pneumonectomy. Coming from a place where mediastinoscopy is really quite routine, the one lesson we have learned is that if we are contemplating from the endobronchial appearance that we are going to need to do a sleeve pneumonectomy, that is the one time when I really do want to do the mediastinoscopy at the same time as the procedure. If you do it before the procedure and then go back, it is a little harder to pull that trachea down to get your anastomosis done without tension.
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Acknowledgments |
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Footnotes |
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References |
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TopAbstractIntroductionPatients and methods Results Discussion Appendix: Discussion References |
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