Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Iterative surgical resections for local recurrent and second primary bronchogenic carcinoma

Iterative surgical resections for local recurrent and second primary bronchogenic carcinoma Abstract Objective: To report our experience with repeated pulmonary resection in patients with local recurrent and second primary bronchogenic carcinoma, to assess operative mortality and late outcome. Methods: The medical records of all patients who underwent a second lung resection for local recurrent and second primary bronchogenic carcinoma from 1978 through 1998 were reviewed. Results: There were 27 patients. They constituted 2.5% of 1059 patients who had undergone lung resection for bronchogenic carcinoma in the same period. Twelve patients (1.1%) (group 1) had a local recurrence that developed at a median interval of 24 months (range 4–83).The first pulmonary resection was lobectomy in ten patients and segmentectomy in two. The second operation consisted of completion pneumonectomy in ten cases, completion lobectomy in one and wedge resection of the right lower lobe after a right upper lobectomy in one. The other 15 patients (1.4%) (group 2) had a new primary lung cancer that developed at a median interval of 45 months (range 21–188).The first pulmonary resection was lobectomy in 12 patients, bilobectomy in one and pneumonectomy in two. The second pulmonary resection was controlateral lobectomy in seven patients, controlateral sleeve lobectomy in two, controlateral pneumonectomy in 1, controlateral wedge resection in four and completion pneumonectomy in one. Overall hospital mortality was 7.4%, including one intraoperative and one postoperative death in group 1 and 2, respectively. Five-year survival after the second operation was 15.5 and 43% with a median survival of 26 and 49 months in groups 1 and 2, respectively (P=ns). Conclusions: Long-term results justify complete work-up of patients with local recurrent and second primary bronchogenic carcinoma. Treatment should be surgical, if there is no evidence of distant metastasis and the patients are in good health. Early detection of second lesions is possible with an aggressive follow-up conducted maximally at 4 months intervals for the first 2 years and 6 months intervals thereafter throughout life. Bronchogenic carcinoma, Local recurrence, Second primary lung cancer, Completion pneumonectomy 1 Introduction Pulmonary resection remains the treatment of choice for patients with non-small cell lung cancer (NSCLC). When recurrence or second primary lung cancer (SPLC) is detected during follow-up, the decision on which is the best therapy is more difficult. The extent of surgery is a well-recognized risk factor and a mortality rate ranging 3–17% following pneumonectomy has been reported [1]. Pulmonary resection is still considered the most effective treatment for patients with SPLC, whenever possible, as the survival rate after this aggressive approach is quite good [2–5]. On the other hand, many doubts have been expressed in literature concerning the warranty of repeated surgery for recurrent bronchogenic carcinoma, that is associated with a poor overall survival [6–8]. Consequently, it is very important, although sometimes very difficult in clinical practice, to distinguish between a new lung cancer and a recurrence of the first tumour. However, we believe that with an aggressive follow-up, early detection of recurrence is possible and some selected patients can benefit from surgical therapy. The extent of resection is also an area of concern in treating a SPLC or a recurrence. Recommended treatments have ranged from lesser resection or non-operative treatment for what was considered recurrent disease, to standard lobectomy or completion pneumonectomy, when possible. The aim of this study is to report our experience with the iterative surgical resections for local recurrent and SPLC focusing on morbidity, mortality and survival characteristics of these two groups of patients. 2 Materials and methods Patients who underwent lung resection for NSCLC in our Institute between January 1, 1978, and December, 31, 1998, were reviewed. All hospital charts and outpatient data of patients who had undergone a second lung resection for local recurrent (group 1) or second primary bronchogenic carcinoma (group 2) were selected for analysis. Variables analyzed included type of operation, histology, time between the two surgical interventions, operative finding, operative and post-operative complications and hospital mortality, as well as late death. Tumour histology was classified according to the World Health Organization Classification [9]. All cases of bronchio–alveolar carcinoma were excluded only because of the question of multicentricity of those primary cancers. Staging was done according to the International TNM Classification for Lung Cancer [10] and was based on data obtained from imaging, bronchoscopy, invasive diagnostic techniques, operative findings, and pathologic findings. Mediastinoscopy was selectively performed in suspected N2 disease on high resolution CT scan, to exclude patients with N2 disease from operation. Careful intra-operative staging was done by dissecting intrapulmonary, hilar and ipsilateral mediastinal nodes. A set of criteria modified from Martini and Melamed [11] were applied to differentiate between recurrent and SPLC. A neoplasm was defined as a local recurrence if it was histologically similar to the original tumour and occurred in an area anatomically contiguous to the resected area, in the bronchial stump, in hilar or mediastinal lymph-nodes (despite a careful mediastinal lymph-nodes dissection at the first operation), or in the mediastinal fat. All other sites of recurrence were referred to a distant recurrence. A neoplasm was considered a SPLC when a neoplasm of different cell type developed in lung parenchima. For tumour with a cell type similar to that of the original lesion, a new cancer was considered a second primary when it occurred outside the area defined as a local recurrence with no carcinoma in lymphatics common to both, no extrapulmonary metastases at the time of diagnosis, and when the new lesion was a solitary one in lung parenchima. Follow-up was complete and closed on February 28, 1999. The Kaplan–Meier method was used for calculation of survival rates, and differences in survival were determined by log-rank analysis. Hospital mortality (all intra-operative and post-operative deaths during hospitalization or within 30 days after operation) was included in calculation of survival rate. 3 Results In 1978–1998, 1059 patients underwent radical pulmonary resection for NSCLC. Twenty-seven patients (2.5%) were found to have undergone a second operation for local recurrence (12 patients: 1.1%) (group 1) or second primary bronchogenic carcinoma (15 patients: 1.4%) (group 2). Three other patients were found to have undergone two staged lung resections for synchronous bilateral lung tumours. Since the tumours had similar cell types at the final histological examination, we excluded these patients from the analysis. 3.1 Group 1: recurrences Four hundred and eighteen patients (3.9%) had tumour recurrence, of whom 49 (12%) with local tumour recurrence only. Of these 49 recurrent lesions, 21 were judged to be resectable, but surgery was denied to nine patients because of poor cardiopulmonary reserve or concomitant illness. Thus, 12 patients underwent a second pulmonary resection. There were ten men and two women. Mean age at the time of the first operation was 61 years (range, 41–78 years). Recurrent lung cancer was initially suggested by chest radiography alone in nine cases, by sputum cytological findings alone in one, by bronchoscopy in one, and by a combination of these methods in one. Only two patients were symptomatic at the time of detection. In the other ten patients the recurrence of cancer was detected at the scheduled 4–6-months examination. The local recurrences developed at a mean interval of 24 months (range 4–83). Sites of recurrence, interval between the 1st operation and tumour recurrence and survival after the 2nd operation are described in Table 1 . Table 2 shows operative procedures, histology and postoperative staging. Table 1 Open in new tabDownload slide Group 1: sites of recurrence, interval between the 1st operation and tumor recurrence and survival after the 2nd operation Table 1 Open in new tabDownload slide Group 1: sites of recurrence, interval between the 1st operation and tumor recurrence and survival after the 2nd operation Table 2 Open in new tabDownload slide Group 1: histology, operative procedures and postoperative staginga Table 2 Open in new tabDownload slide Group 1: histology, operative procedures and postoperative staginga The first resection was always considered radical; postoperative adjuvant therapy was given to four patients: two received chemotherapy and two radiotherapy. The second resection was considered radical in all but one patient; adjuvant therapy was administered to three patients: two of which received chemotherapy and the other chemo- and radio-therapy. Complications occurred in four out of 12 patients, and included cardiac arrhythmias in two patients, recurrent nerve paralysis in one and empyema in another patient. One patient died intraoperatively of fatal bleeding, because of laceration of the pulmonary artery. The mean follow-up for the 11 patients who survived the second operation was 21 months (range, 2–60 months). Currently, four out of 12 patients are alive and free of any known recurrent cancer after 27, 2, 6 and 60 months from the second operation, respectively. Of the eight patients who have died, recurrent lung cancer was known to be present and to be the cause of death in six. One patient died intraoperatively and another patient died of unrelated cause. Five-year survival after the second operation was 15.5% with a median survival of 26 months (Fig. 1) . Fig. 1 Open in new tabDownload slide Survival (death from any cause) after the second operation for the 15 patients of group 2 compared with the 12 patients of group 1. Fig. 1 Open in new tabDownload slide Survival (death from any cause) after the second operation for the 15 patients of group 2 compared with the 12 patients of group 1. 3.2 Group 2: second primary lung carcinomas Twenty other patients were found during follow-up to have a SPLC. This represents 2% of all resected lung carcinoma. Of these, five patients were excluded from surgery: two because of poor cardio–respiratory reserve and three because judged inoperable. Among 15 patients who were operated on also for the second lung tumour, two were women and 13 men. Average age at presentation of the first primary cancer was 65.5 years (range 43–78). The criteria used to define that the second lung tumour was a new primary cancer consisted of different cell type in seven patients, controlateral pulmonary location in seven, and location in a different ipsilateral lobe in one. Type of resections, histology, postoperative staging and interval between the first and the second operations are shown in Table 3 . Table 3 Open in new tabDownload slide Group 2: type of resections, histology, pathological staging and time between 1st and 2nd operationa Table 3 Open in new tabDownload slide Group 2: type of resections, histology, pathological staging and time between 1st and 2nd operationa The SPLC was detected by chest roentgenogramm alone in 11 patients, and by sputum cytologic examination alone in one, at the scheduled time. The second cancer was symptomatic in only three patients. The mean interval time between the initial and second treatment was 45 months (range 21–188). More than 90% of SPLC was detected after 1991. The only case, whose interval was less than 2 years had a histologically different tumour. The first and the second tumour shared the same histology in eight patients (53%). Resection of the tumour was complete in all cases. All stage III A patients received postoperative irradiation. Complications occurred in five patients (33.3%) after the second pulmonary resection and included cardiac arrhythmia in one, prolonged air leak in three, and bronchial stenosis resolved after the placement of a bronchial silicone stent in one. One patient of the three who presented prolonged air leak died in the postoperative period because of respiratory failure, for a mortality rate of 6.6%. The mean follow-up for the 14 patients who survived the second operation was 24 months (range 2–60 months). Currently eight out of 15 patients are alive, without evidence of recurrent cancer. Among the seven patients who have died, recurrent lung cancer was the cause of death in six. Five-year survival of group 2, from the time of the second resection, was longer than that of group 1, without statistical significance (Fig. 1). Overall hospital mortality of patients of both groups (27 patients) was 7.4%. The overall 5-year survival rates following the second operation was 30% (Fig. 2) . Fig. 2 Open in new tabDownload slide Overall survival from the time of the second operation for patients with local recurrent and second primary lung tumour (27 cases). Fig. 2 Open in new tabDownload slide Overall survival from the time of the second operation for patients with local recurrent and second primary lung tumour (27 cases). 4 Discussion At present, results after re-operation for a recurrent lung cancer are discouraging. Pairolero et al. [8] reported a 23% 2-year survival, and Green and Kern [12] a 5% 4-year survival in patients with locally recurrent disease. Our results after re-operation for locally recurrent bronchogenic carcinoma are a little more promising: the 5-year survival after the second operation was 15.5%. This can be explained by the fact that in previously published series the authors have included apart from local recurrences even the intrathoracic metastasis that represent a different situation. Another explanation might be that we re-operated on only 12 patients out of 49 (24%) who developed local recurrence. In fact, the incidence of operable recurrent bronchial carcinoma was only 1.1% (12/1059 cases), that is lower than earlier published articles, against 1.7% [13], 1.5% [6], 1% [14] of, respectively, 906, 1153, 3083 patients. All these results indicate that surgery for local recurrent bronchogenic carcinoma is more the exception than the rule, because the vast majority of patients will present contraindication to surgery. In evaluating a re-operation it is mandatory to follow some general rules: (1) the first resection must be complete; (2) there must be no evidence of other site of recurrence after the patient is scanned very carefully for metastasis; (3) the patient must not suffer of other disease that would be life-shortening more than the tumour itself. The indication in re-operations depends also on the site and stage of recurrent tumour and the time between first resection and tumour recurrence. A radical resection of recurrent lung cancer can be attempted in a considerable percentage of peripheral recurrent tumour, but very rarely, if ever, in hilar recurrent cancer. Patients with hilar recurrent neoplasm often present a widespread mediastinal involvement, precluding any possibility of curative resection. We attempted re-thoracotomy in only one patient with a mediastinal recurrence, whereas the major part of our patients (67%) presented intrapulmonary recurrence. Before proceeding to re-operation for local recurrence, the clinical staging must be as accurate as possible. Patients are completely scanned for distant metastases even in the absence of symptoms or abnormal liver function. Moreover, it is our practice to perform mediastinoscopy because the presence of mediastinal lymphnodes involvement is considered a contraindication to re-operation. Although we tried to be very accurate in re-staging, three patients presented an advanced stage (two T3N2M0, one T4N2M0) at the pathological examination. Finally, the time between first resection and tumour recurrence must be taken into consideration. Our results of re-operation for a recurrence performed after a short interval (less than 14 months) are discouraging: no patient survived more than 2 years after the second operation. On the other hand, the other treatment modalities are of little if any benefit for these patients. In a study of 49 patients treated by radiotherapy for post-resection locally recurrent lung cancer [15] the 3- and 5-year survival rate was both 5%, and the median survival was 11 months. A study on the spread of lung cancer assessed by autopsy in patients who had undergone a pulmonary resection showed that the metastasis are often, and for quite long time, limited to the chest. This means that with a close follow-up we could detect some recurrences at an early stage, making possible a re-operation. We believe that these patients should be seen maximally at 4-months intervals for the first 2 years and 6 months interval thereafter throughout life. At every visit physical examination and chest radiographs should be performed. It is very useful that the last chest radiogram be compared with the oldest one, because only in this way early subtle changes can be detected. We use CT scan to solve question posed by the X-rays. An increasing number of patients with SPLC are reported in literature. It may be related to the increased incidence of the bronchogenic carcinoma, the increased rate of patients who survive a first pulmonary resection, and the use of developed radiographic techniques, such as computed tomography. The reported incidence is 1–5% in clinical observation [16], but it can be as high as 10–25% in patients who survive more than 3 years after curative resection for lung cancer, emphasizing the fact that most patients will not survive long enough to develop a second primary lung tumour [17]. A study from the Mayo Clinic in 1990 showed an incidence of 1.2% including patients who did not undergo resection and patients in which the SPLC was diagnosed at necropsy [3], while Shields [18] reported an incidence of 1.7% out of 2836. A more recent experience [5] showed an higher incidence (6.3%), probably related to the systematic use of CT scan. Our personal experience includes 20 patients found to have a SPLC during follow-up; these constitute 2% of all patients with resected lung cancer during the last 20 years. The criteria set by Martini et al. [11] in 1975 for defining the methacronous second primary lung cancers have been used by many in the field, even if there is still some controversy regarding the disease-free interval to be used. However, when a methacronous pulmonary lesion is detected, whether with the same cell type (more likely a recurrence) or with different cell type (more likely a SPLC) from the first primary tumour, if it is the only one present in the lung and there is no evidence of extrapulmonary metastasis, it should be always removed. In doing so, a prolonged survival rate can be expected. The reported 5-year survival rate [2–5,13], including our experience ranged from 25 to 52.5% after the second resection for methacronous second cancer, proves the effectiveness of this principle. Whether the new lesion is a primary lung tumour, or a metastasis of the first tumour is only a question of prognosis. We know that prognosis after a second primary lung tumour is better than that after recurrence [3,5], but the treatment plan is basically the same. We only observed a trend toward improved survival in group 2 compared with group 1 without statistical significance. This is probably related to the small number of patients. Much more debated is the surgical indication for synchronous multiple primary lung tumour, that is related to the difficulty in their diagnostic definition. In these cases the results of surgical therapy are very poor and the patients often die of disseminate disease, indicating that most of these tumour are indeed pulmonary metastasis. Pairolero [19] has proposed to classify these patients in stage IV and has led us to consider for them a conservative treatment or very selective indications to surgery. In our retrospective study we found too few synchronous lung tumours to reach any conclusions. Regarding the type of surgical treatment, in case of metachronous second primary lung tumour, the wedge resection is a reasonable and safe alternative to the standard resections in the elderly, in patients with poor respiratory reserve and after a pneumonectomy (two cases in our experience). However, the Lung Cancer Study Group [20] showed that resection less extensive than lobectomy places the patient at an increased risk of local recurrence and decreases the chances of long-term survival. Moreover, in almost all articles [2–5] an inferior survival of metachronous second lesions compared with first lesion is reported. This could be related to underestimating of stage because of technical difficulties during the second procedure, but it might be related to employing of more lesser resections. Thus, if the tumour is not peripheral and less than 2 cm in diameter, we consider lobectomy the treatment of choice even for the second resection. In one case we performed a left pneumonectomy after a right upper lobectomy without any postoperative complications; the patient is alive and doing well after 36 months from the second operation. The bronchoplastic procedures are particularly helpful in these type of patients. On the first resection they allow the pulmonary function to be preserved sufficiently for a second lung resection. Moreover, they make possible the resection of a centrally located second primary tumour (two cases in our experience). The second resection can be almost uniformly performed safely, as indicated by our and other morbidity and mortality data [3–5]. Complications occurred in 33% of our patients after the second resection, which is not very different from that previously reported for undergoing pulmonary resection for first lung cancer [21].The overall mortality rate after the second operation for recurrence and SPLC in our study was 7%. Although higher than the overall 3.7% mortality rate reported by the Lung Cancer Study Group [22] for patients undergoing all types of pulmonary resection for the first lung cancer, it was acceptable. At present, we agree with the consideration that cancer recurrence means an insufficient clearing of the tumour, whereas second primary lung tumour suggests a continuous exposure to etiologic risk factor. It is noteworthy that in many reports [2–5] the stage of second new tumour was more advanced than that of the first tumour with a survival rate obviously better for the early stages. Consequently it is imperative to continue surveillance beyond 5 years, and the follow-up intervals are particularly important for detecting a recurrence or a new primary tumour in early stage. In conclusion, long-term results justify complete work-up of patients with local recurrent and second primary bronchogenic carcinoma. Treatment should be surgical if there is no evidence of distant metastasis and the patient presents an adequate cardio–respiratory reserve. Early detection of second lesion is possible with an aggressive follow-up with resultant prolonged survival. ✩ Presented at the 13th Annual Meeting of the European Association for Cardio-thoracic Surgery, Glasgow, Scotland, UK, September 5–8, 1999. References [1] Licker M. , de Perrot M. , Hohn L. , Tschopp J.-G. , Robert J. , Frey J.-G. , Schweizer A. , Spiliopoulos A. . Perioperative mortality and major cardio-pulmonary complications after lung surgery for non-small cell carcinoma , Eur J Cardio-thorac Surg , 1999 , vol. 15 (pg. 314 - 319 ) Google Scholar Crossref Search ADS WorldCat [2] Rosengart T.D. , Martini N. , Ghosn P. , Burt M. . Multiple primary lung carcinomas: prognosis and treatment , Ann Thorac Surg , 1991 , vol. 52 (pg. 773 - 779 ) Google Scholar Crossref Search ADS PubMed WorldCat [3] Deschamps C. , Pairolero P.C. , Trastek V.F. , Payne W.S. . Multiple primary lung cancers: results of surgical treatment , J Thorac Cardiovasc Surg , 1990 , vol. 99 (pg. 769 - 778 ) Google Scholar PubMed OpenURL Placeholder Text WorldCat [4] Antakli T. , Schaefer R.F. , Rutherford J.E. , Read R.C. . Second primary lung cancer , Ann Thorac Surg , 1995 , vol. 59 (pg. 863 - 867 ) Google Scholar Crossref Search ADS PubMed WorldCat [5] Okada M. , Tsubota N. , Yoshimura M. , Miyamoto Y. . Operative approach for multiple primary lung carcinomas , J Thorac Cardiovasc Surg , 1998 , vol. 115 (pg. 836 - 840 ) Google Scholar Crossref Search ADS PubMed WorldCat [6] Gabler A. , Liebig S. . Reoperation for bronchial carcinoma , Thorax , 1980 , vol. 35 (pg. 668 - 680 ) Google Scholar Crossref Search ADS PubMed WorldCat [7] Nielsen O.S. , Boas J. , Bertelsen S. . Reoperation for recurrent bronchogenic carcinoma , Scand J Thorac Cardiovasc Surg , 1984 , vol. 18 (pg. 249 - 250 ) Google Scholar Crossref Search ADS PubMed WorldCat [8] Pairolero P.C. , Williams D.E. , Bergstalh E.J. , Piehler J.M. , Bernatz P.E. . Postsurgical stage I bronchogenic carcinoma: morbid implications of recurrent disease , Ann Thorac Surg , 1984 , vol. 38 (pg. 331 - 336 ) Google Scholar Crossref Search ADS PubMed WorldCat [9] World Health Organization . The WHO histological typing of lung tumours , Am J Clin Pathol , 1982 , vol. 77 (pg. 123 - 136 ) Crossref Search ADS PubMed WorldCat [10] Mountain C.F. . A new international staging system for lung cancer , Chest , 1986 , vol. 89 (pg. 2255 - 2335 ) Google Scholar Crossref Search ADS WorldCat [11] Martini N. , Bains M.S. , Burt M.E. , Zakowski M.F. , McCormack P. , Rusch V.W. , Ginsberg R.J. . Incidence of local recurrence and second primary tumors in resected stage 1 lung cancer , J Thorac Cardiovasc Surg , 1995 , vol. 109 (pg. 120 - 129 ) Google Scholar Crossref Search ADS PubMed WorldCat [12] Green N. , Kern W. . The clinical course and treatment results of patients with postresection locally recurrent lung cancer , Cancer , 1978 , vol. 42 (pg. 2478 - 2485 ) Google Scholar Crossref Search ADS PubMed WorldCat [13] Watanabe Y. , Shimizu J. , Oda M. , Tatsuzawa Y. , Hayashi Y. , Iwa T. . Second surgical intervention for recurrent and second primary bronchogenic carcinoma , Scand J Thorac Cardiovasc Surg , 1992 , vol. 26 (pg. 73 - 78 ) Google Scholar Crossref Search ADS PubMed WorldCat [14] Dartevelle P. , Khalif J. . Delarue N.C. , Eschapasse H. . Surgical approach to local recurrence and the second primary lesion , International trend in general thoracic surgery , 1985 Philadelphia, PA W.B. Saunders (pg. 156 - 163 ) Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC [15] Salerno T.A. , Munro D.D. , Blundell P.E. , Chiu R.C.J. . Second primary bronchogenic carcinoma: life-table analysis of surgical treatment , Ann Thorac Surg , 1979 , vol. 27 (pg. 3 - 6 ) Google Scholar Crossref Search ADS PubMed WorldCat [16] Reynolds R. , Pajak J. , Greenberg B. . Lung cancer as a second primary , Cancer , 1978 , vol. 42 (pg. 2887 - 2893 ) Google Scholar Crossref Search ADS PubMed WorldCat [17] Martini N. , Ghosn P. , Melamed M.R. . Delarue N.C. , Eschapasse H. . Local recurrence and new primary carcinoma after resection , International trends in general thoracic surgery , 1985 Philadelphia, PA W.B. Saunders (pg. 164 - 169 ) Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC [18] Shields T.W. . Discussion of Deshamps C, Pairolero PC, Trastek VF, Payne WS. Multiple primary lung cancers , J Thorac Cardiovasc Surg , 1990 , vol. 99 (pg. 769 - 778 ) Google Scholar PubMed OpenURL Placeholder Text WorldCat [19] Pairolero P.C. . Discussion of Rosengart TK, Martini N, Ghosn P, Burt M. Multiple primary lung carcinomas: prognosis and treatment , Ann Thorac Surg , 1991 , vol. 52 (pg. 773 - 779 ) Google Scholar Crossref Search ADS PubMed WorldCat [20] Ginsberg R.J. , Rubinstein L.V. . (for the LCSG) Randomized Trial of lobectomy versus limited resection for T1N0M0 non-small cell lung cancer , Ann Thorac Surg , 1995 , vol. 60 (pg. 615 - 623 ) Google Scholar Crossref Search ADS PubMed WorldCat [21] Nagasaki F. , Flehinger B.J. , Martini N. . Complications of surgery in the treatment of carcinoma of the lung , Chest , 1982 , vol. 82 (pg. 25 - 29 ) Google Scholar Crossref Search ADS PubMed WorldCat [22] Ginsberg R.J. , Hill L.D. , Eagen R.T. , Thomas P. , Mountain C.F. , Deslauries J. , Fry W.A. , Butz R.O. , Goldberg M. , Waters P.F. . Modern thirty-day operative mortality for surgical resections in lung cancer , J Thorac Cardiovasc Surg , 1983 , vol. 86 (pg. 654 - 658 ) Google Scholar PubMed OpenURL Placeholder Text WorldCat © 2000 Elsevier Science B.V. All rights reserved. Elsevier Science B.V. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Cardio-Thoracic Surgery Oxford University Press

Iterative surgical resections for local recurrent and second primary bronchogenic carcinoma

Loading next page...
 
/lp/oxford-university-press/iterative-surgical-resections-for-local-recurrent-and-second-primary-KLBNq1CFqM

References (23)

Publisher
Oxford University Press
Copyright
© 2000 Elsevier Science B.V. All rights reserved.
Subject
Articles
ISSN
1010-7940
eISSN
1873-734X
DOI
10.1016/S1010-7940(00)00572-8
Publisher site
See Article on Publisher Site

Abstract

Abstract Objective: To report our experience with repeated pulmonary resection in patients with local recurrent and second primary bronchogenic carcinoma, to assess operative mortality and late outcome. Methods: The medical records of all patients who underwent a second lung resection for local recurrent and second primary bronchogenic carcinoma from 1978 through 1998 were reviewed. Results: There were 27 patients. They constituted 2.5% of 1059 patients who had undergone lung resection for bronchogenic carcinoma in the same period. Twelve patients (1.1%) (group 1) had a local recurrence that developed at a median interval of 24 months (range 4–83).The first pulmonary resection was lobectomy in ten patients and segmentectomy in two. The second operation consisted of completion pneumonectomy in ten cases, completion lobectomy in one and wedge resection of the right lower lobe after a right upper lobectomy in one. The other 15 patients (1.4%) (group 2) had a new primary lung cancer that developed at a median interval of 45 months (range 21–188).The first pulmonary resection was lobectomy in 12 patients, bilobectomy in one and pneumonectomy in two. The second pulmonary resection was controlateral lobectomy in seven patients, controlateral sleeve lobectomy in two, controlateral pneumonectomy in 1, controlateral wedge resection in four and completion pneumonectomy in one. Overall hospital mortality was 7.4%, including one intraoperative and one postoperative death in group 1 and 2, respectively. Five-year survival after the second operation was 15.5 and 43% with a median survival of 26 and 49 months in groups 1 and 2, respectively (P=ns). Conclusions: Long-term results justify complete work-up of patients with local recurrent and second primary bronchogenic carcinoma. Treatment should be surgical, if there is no evidence of distant metastasis and the patients are in good health. Early detection of second lesions is possible with an aggressive follow-up conducted maximally at 4 months intervals for the first 2 years and 6 months intervals thereafter throughout life. Bronchogenic carcinoma, Local recurrence, Second primary lung cancer, Completion pneumonectomy 1 Introduction Pulmonary resection remains the treatment of choice for patients with non-small cell lung cancer (NSCLC). When recurrence or second primary lung cancer (SPLC) is detected during follow-up, the decision on which is the best therapy is more difficult. The extent of surgery is a well-recognized risk factor and a mortality rate ranging 3–17% following pneumonectomy has been reported [1]. Pulmonary resection is still considered the most effective treatment for patients with SPLC, whenever possible, as the survival rate after this aggressive approach is quite good [2–5]. On the other hand, many doubts have been expressed in literature concerning the warranty of repeated surgery for recurrent bronchogenic carcinoma, that is associated with a poor overall survival [6–8]. Consequently, it is very important, although sometimes very difficult in clinical practice, to distinguish between a new lung cancer and a recurrence of the first tumour. However, we believe that with an aggressive follow-up, early detection of recurrence is possible and some selected patients can benefit from surgical therapy. The extent of resection is also an area of concern in treating a SPLC or a recurrence. Recommended treatments have ranged from lesser resection or non-operative treatment for what was considered recurrent disease, to standard lobectomy or completion pneumonectomy, when possible. The aim of this study is to report our experience with the iterative surgical resections for local recurrent and SPLC focusing on morbidity, mortality and survival characteristics of these two groups of patients. 2 Materials and methods Patients who underwent lung resection for NSCLC in our Institute between January 1, 1978, and December, 31, 1998, were reviewed. All hospital charts and outpatient data of patients who had undergone a second lung resection for local recurrent (group 1) or second primary bronchogenic carcinoma (group 2) were selected for analysis. Variables analyzed included type of operation, histology, time between the two surgical interventions, operative finding, operative and post-operative complications and hospital mortality, as well as late death. Tumour histology was classified according to the World Health Organization Classification [9]. All cases of bronchio–alveolar carcinoma were excluded only because of the question of multicentricity of those primary cancers. Staging was done according to the International TNM Classification for Lung Cancer [10] and was based on data obtained from imaging, bronchoscopy, invasive diagnostic techniques, operative findings, and pathologic findings. Mediastinoscopy was selectively performed in suspected N2 disease on high resolution CT scan, to exclude patients with N2 disease from operation. Careful intra-operative staging was done by dissecting intrapulmonary, hilar and ipsilateral mediastinal nodes. A set of criteria modified from Martini and Melamed [11] were applied to differentiate between recurrent and SPLC. A neoplasm was defined as a local recurrence if it was histologically similar to the original tumour and occurred in an area anatomically contiguous to the resected area, in the bronchial stump, in hilar or mediastinal lymph-nodes (despite a careful mediastinal lymph-nodes dissection at the first operation), or in the mediastinal fat. All other sites of recurrence were referred to a distant recurrence. A neoplasm was considered a SPLC when a neoplasm of different cell type developed in lung parenchima. For tumour with a cell type similar to that of the original lesion, a new cancer was considered a second primary when it occurred outside the area defined as a local recurrence with no carcinoma in lymphatics common to both, no extrapulmonary metastases at the time of diagnosis, and when the new lesion was a solitary one in lung parenchima. Follow-up was complete and closed on February 28, 1999. The Kaplan–Meier method was used for calculation of survival rates, and differences in survival were determined by log-rank analysis. Hospital mortality (all intra-operative and post-operative deaths during hospitalization or within 30 days after operation) was included in calculation of survival rate. 3 Results In 1978–1998, 1059 patients underwent radical pulmonary resection for NSCLC. Twenty-seven patients (2.5%) were found to have undergone a second operation for local recurrence (12 patients: 1.1%) (group 1) or second primary bronchogenic carcinoma (15 patients: 1.4%) (group 2). Three other patients were found to have undergone two staged lung resections for synchronous bilateral lung tumours. Since the tumours had similar cell types at the final histological examination, we excluded these patients from the analysis. 3.1 Group 1: recurrences Four hundred and eighteen patients (3.9%) had tumour recurrence, of whom 49 (12%) with local tumour recurrence only. Of these 49 recurrent lesions, 21 were judged to be resectable, but surgery was denied to nine patients because of poor cardiopulmonary reserve or concomitant illness. Thus, 12 patients underwent a second pulmonary resection. There were ten men and two women. Mean age at the time of the first operation was 61 years (range, 41–78 years). Recurrent lung cancer was initially suggested by chest radiography alone in nine cases, by sputum cytological findings alone in one, by bronchoscopy in one, and by a combination of these methods in one. Only two patients were symptomatic at the time of detection. In the other ten patients the recurrence of cancer was detected at the scheduled 4–6-months examination. The local recurrences developed at a mean interval of 24 months (range 4–83). Sites of recurrence, interval between the 1st operation and tumour recurrence and survival after the 2nd operation are described in Table 1 . Table 2 shows operative procedures, histology and postoperative staging. Table 1 Open in new tabDownload slide Group 1: sites of recurrence, interval between the 1st operation and tumor recurrence and survival after the 2nd operation Table 1 Open in new tabDownload slide Group 1: sites of recurrence, interval between the 1st operation and tumor recurrence and survival after the 2nd operation Table 2 Open in new tabDownload slide Group 1: histology, operative procedures and postoperative staginga Table 2 Open in new tabDownload slide Group 1: histology, operative procedures and postoperative staginga The first resection was always considered radical; postoperative adjuvant therapy was given to four patients: two received chemotherapy and two radiotherapy. The second resection was considered radical in all but one patient; adjuvant therapy was administered to three patients: two of which received chemotherapy and the other chemo- and radio-therapy. Complications occurred in four out of 12 patients, and included cardiac arrhythmias in two patients, recurrent nerve paralysis in one and empyema in another patient. One patient died intraoperatively of fatal bleeding, because of laceration of the pulmonary artery. The mean follow-up for the 11 patients who survived the second operation was 21 months (range, 2–60 months). Currently, four out of 12 patients are alive and free of any known recurrent cancer after 27, 2, 6 and 60 months from the second operation, respectively. Of the eight patients who have died, recurrent lung cancer was known to be present and to be the cause of death in six. One patient died intraoperatively and another patient died of unrelated cause. Five-year survival after the second operation was 15.5% with a median survival of 26 months (Fig. 1) . Fig. 1 Open in new tabDownload slide Survival (death from any cause) after the second operation for the 15 patients of group 2 compared with the 12 patients of group 1. Fig. 1 Open in new tabDownload slide Survival (death from any cause) after the second operation for the 15 patients of group 2 compared with the 12 patients of group 1. 3.2 Group 2: second primary lung carcinomas Twenty other patients were found during follow-up to have a SPLC. This represents 2% of all resected lung carcinoma. Of these, five patients were excluded from surgery: two because of poor cardio–respiratory reserve and three because judged inoperable. Among 15 patients who were operated on also for the second lung tumour, two were women and 13 men. Average age at presentation of the first primary cancer was 65.5 years (range 43–78). The criteria used to define that the second lung tumour was a new primary cancer consisted of different cell type in seven patients, controlateral pulmonary location in seven, and location in a different ipsilateral lobe in one. Type of resections, histology, postoperative staging and interval between the first and the second operations are shown in Table 3 . Table 3 Open in new tabDownload slide Group 2: type of resections, histology, pathological staging and time between 1st and 2nd operationa Table 3 Open in new tabDownload slide Group 2: type of resections, histology, pathological staging and time between 1st and 2nd operationa The SPLC was detected by chest roentgenogramm alone in 11 patients, and by sputum cytologic examination alone in one, at the scheduled time. The second cancer was symptomatic in only three patients. The mean interval time between the initial and second treatment was 45 months (range 21–188). More than 90% of SPLC was detected after 1991. The only case, whose interval was less than 2 years had a histologically different tumour. The first and the second tumour shared the same histology in eight patients (53%). Resection of the tumour was complete in all cases. All stage III A patients received postoperative irradiation. Complications occurred in five patients (33.3%) after the second pulmonary resection and included cardiac arrhythmia in one, prolonged air leak in three, and bronchial stenosis resolved after the placement of a bronchial silicone stent in one. One patient of the three who presented prolonged air leak died in the postoperative period because of respiratory failure, for a mortality rate of 6.6%. The mean follow-up for the 14 patients who survived the second operation was 24 months (range 2–60 months). Currently eight out of 15 patients are alive, without evidence of recurrent cancer. Among the seven patients who have died, recurrent lung cancer was the cause of death in six. Five-year survival of group 2, from the time of the second resection, was longer than that of group 1, without statistical significance (Fig. 1). Overall hospital mortality of patients of both groups (27 patients) was 7.4%. The overall 5-year survival rates following the second operation was 30% (Fig. 2) . Fig. 2 Open in new tabDownload slide Overall survival from the time of the second operation for patients with local recurrent and second primary lung tumour (27 cases). Fig. 2 Open in new tabDownload slide Overall survival from the time of the second operation for patients with local recurrent and second primary lung tumour (27 cases). 4 Discussion At present, results after re-operation for a recurrent lung cancer are discouraging. Pairolero et al. [8] reported a 23% 2-year survival, and Green and Kern [12] a 5% 4-year survival in patients with locally recurrent disease. Our results after re-operation for locally recurrent bronchogenic carcinoma are a little more promising: the 5-year survival after the second operation was 15.5%. This can be explained by the fact that in previously published series the authors have included apart from local recurrences even the intrathoracic metastasis that represent a different situation. Another explanation might be that we re-operated on only 12 patients out of 49 (24%) who developed local recurrence. In fact, the incidence of operable recurrent bronchial carcinoma was only 1.1% (12/1059 cases), that is lower than earlier published articles, against 1.7% [13], 1.5% [6], 1% [14] of, respectively, 906, 1153, 3083 patients. All these results indicate that surgery for local recurrent bronchogenic carcinoma is more the exception than the rule, because the vast majority of patients will present contraindication to surgery. In evaluating a re-operation it is mandatory to follow some general rules: (1) the first resection must be complete; (2) there must be no evidence of other site of recurrence after the patient is scanned very carefully for metastasis; (3) the patient must not suffer of other disease that would be life-shortening more than the tumour itself. The indication in re-operations depends also on the site and stage of recurrent tumour and the time between first resection and tumour recurrence. A radical resection of recurrent lung cancer can be attempted in a considerable percentage of peripheral recurrent tumour, but very rarely, if ever, in hilar recurrent cancer. Patients with hilar recurrent neoplasm often present a widespread mediastinal involvement, precluding any possibility of curative resection. We attempted re-thoracotomy in only one patient with a mediastinal recurrence, whereas the major part of our patients (67%) presented intrapulmonary recurrence. Before proceeding to re-operation for local recurrence, the clinical staging must be as accurate as possible. Patients are completely scanned for distant metastases even in the absence of symptoms or abnormal liver function. Moreover, it is our practice to perform mediastinoscopy because the presence of mediastinal lymphnodes involvement is considered a contraindication to re-operation. Although we tried to be very accurate in re-staging, three patients presented an advanced stage (two T3N2M0, one T4N2M0) at the pathological examination. Finally, the time between first resection and tumour recurrence must be taken into consideration. Our results of re-operation for a recurrence performed after a short interval (less than 14 months) are discouraging: no patient survived more than 2 years after the second operation. On the other hand, the other treatment modalities are of little if any benefit for these patients. In a study of 49 patients treated by radiotherapy for post-resection locally recurrent lung cancer [15] the 3- and 5-year survival rate was both 5%, and the median survival was 11 months. A study on the spread of lung cancer assessed by autopsy in patients who had undergone a pulmonary resection showed that the metastasis are often, and for quite long time, limited to the chest. This means that with a close follow-up we could detect some recurrences at an early stage, making possible a re-operation. We believe that these patients should be seen maximally at 4-months intervals for the first 2 years and 6 months interval thereafter throughout life. At every visit physical examination and chest radiographs should be performed. It is very useful that the last chest radiogram be compared with the oldest one, because only in this way early subtle changes can be detected. We use CT scan to solve question posed by the X-rays. An increasing number of patients with SPLC are reported in literature. It may be related to the increased incidence of the bronchogenic carcinoma, the increased rate of patients who survive a first pulmonary resection, and the use of developed radiographic techniques, such as computed tomography. The reported incidence is 1–5% in clinical observation [16], but it can be as high as 10–25% in patients who survive more than 3 years after curative resection for lung cancer, emphasizing the fact that most patients will not survive long enough to develop a second primary lung tumour [17]. A study from the Mayo Clinic in 1990 showed an incidence of 1.2% including patients who did not undergo resection and patients in which the SPLC was diagnosed at necropsy [3], while Shields [18] reported an incidence of 1.7% out of 2836. A more recent experience [5] showed an higher incidence (6.3%), probably related to the systematic use of CT scan. Our personal experience includes 20 patients found to have a SPLC during follow-up; these constitute 2% of all patients with resected lung cancer during the last 20 years. The criteria set by Martini et al. [11] in 1975 for defining the methacronous second primary lung cancers have been used by many in the field, even if there is still some controversy regarding the disease-free interval to be used. However, when a methacronous pulmonary lesion is detected, whether with the same cell type (more likely a recurrence) or with different cell type (more likely a SPLC) from the first primary tumour, if it is the only one present in the lung and there is no evidence of extrapulmonary metastasis, it should be always removed. In doing so, a prolonged survival rate can be expected. The reported 5-year survival rate [2–5,13], including our experience ranged from 25 to 52.5% after the second resection for methacronous second cancer, proves the effectiveness of this principle. Whether the new lesion is a primary lung tumour, or a metastasis of the first tumour is only a question of prognosis. We know that prognosis after a second primary lung tumour is better than that after recurrence [3,5], but the treatment plan is basically the same. We only observed a trend toward improved survival in group 2 compared with group 1 without statistical significance. This is probably related to the small number of patients. Much more debated is the surgical indication for synchronous multiple primary lung tumour, that is related to the difficulty in their diagnostic definition. In these cases the results of surgical therapy are very poor and the patients often die of disseminate disease, indicating that most of these tumour are indeed pulmonary metastasis. Pairolero [19] has proposed to classify these patients in stage IV and has led us to consider for them a conservative treatment or very selective indications to surgery. In our retrospective study we found too few synchronous lung tumours to reach any conclusions. Regarding the type of surgical treatment, in case of metachronous second primary lung tumour, the wedge resection is a reasonable and safe alternative to the standard resections in the elderly, in patients with poor respiratory reserve and after a pneumonectomy (two cases in our experience). However, the Lung Cancer Study Group [20] showed that resection less extensive than lobectomy places the patient at an increased risk of local recurrence and decreases the chances of long-term survival. Moreover, in almost all articles [2–5] an inferior survival of metachronous second lesions compared with first lesion is reported. This could be related to underestimating of stage because of technical difficulties during the second procedure, but it might be related to employing of more lesser resections. Thus, if the tumour is not peripheral and less than 2 cm in diameter, we consider lobectomy the treatment of choice even for the second resection. In one case we performed a left pneumonectomy after a right upper lobectomy without any postoperative complications; the patient is alive and doing well after 36 months from the second operation. The bronchoplastic procedures are particularly helpful in these type of patients. On the first resection they allow the pulmonary function to be preserved sufficiently for a second lung resection. Moreover, they make possible the resection of a centrally located second primary tumour (two cases in our experience). The second resection can be almost uniformly performed safely, as indicated by our and other morbidity and mortality data [3–5]. Complications occurred in 33% of our patients after the second resection, which is not very different from that previously reported for undergoing pulmonary resection for first lung cancer [21].The overall mortality rate after the second operation for recurrence and SPLC in our study was 7%. Although higher than the overall 3.7% mortality rate reported by the Lung Cancer Study Group [22] for patients undergoing all types of pulmonary resection for the first lung cancer, it was acceptable. At present, we agree with the consideration that cancer recurrence means an insufficient clearing of the tumour, whereas second primary lung tumour suggests a continuous exposure to etiologic risk factor. It is noteworthy that in many reports [2–5] the stage of second new tumour was more advanced than that of the first tumour with a survival rate obviously better for the early stages. Consequently it is imperative to continue surveillance beyond 5 years, and the follow-up intervals are particularly important for detecting a recurrence or a new primary tumour in early stage. In conclusion, long-term results justify complete work-up of patients with local recurrent and second primary bronchogenic carcinoma. Treatment should be surgical if there is no evidence of distant metastasis and the patient presents an adequate cardio–respiratory reserve. Early detection of second lesion is possible with an aggressive follow-up with resultant prolonged survival. ✩ Presented at the 13th Annual Meeting of the European Association for Cardio-thoracic Surgery, Glasgow, Scotland, UK, September 5–8, 1999. References [1] Licker M. , de Perrot M. , Hohn L. , Tschopp J.-G. , Robert J. , Frey J.-G. , Schweizer A. , Spiliopoulos A. . Perioperative mortality and major cardio-pulmonary complications after lung surgery for non-small cell carcinoma , Eur J Cardio-thorac Surg , 1999 , vol. 15 (pg. 314 - 319 ) Google Scholar Crossref Search ADS WorldCat [2] Rosengart T.D. , Martini N. , Ghosn P. , Burt M. . Multiple primary lung carcinomas: prognosis and treatment , Ann Thorac Surg , 1991 , vol. 52 (pg. 773 - 779 ) Google Scholar Crossref Search ADS PubMed WorldCat [3] Deschamps C. , Pairolero P.C. , Trastek V.F. , Payne W.S. . Multiple primary lung cancers: results of surgical treatment , J Thorac Cardiovasc Surg , 1990 , vol. 99 (pg. 769 - 778 ) Google Scholar PubMed OpenURL Placeholder Text WorldCat [4] Antakli T. , Schaefer R.F. , Rutherford J.E. , Read R.C. . Second primary lung cancer , Ann Thorac Surg , 1995 , vol. 59 (pg. 863 - 867 ) Google Scholar Crossref Search ADS PubMed WorldCat [5] Okada M. , Tsubota N. , Yoshimura M. , Miyamoto Y. . Operative approach for multiple primary lung carcinomas , J Thorac Cardiovasc Surg , 1998 , vol. 115 (pg. 836 - 840 ) Google Scholar Crossref Search ADS PubMed WorldCat [6] Gabler A. , Liebig S. . Reoperation for bronchial carcinoma , Thorax , 1980 , vol. 35 (pg. 668 - 680 ) Google Scholar Crossref Search ADS PubMed WorldCat [7] Nielsen O.S. , Boas J. , Bertelsen S. . Reoperation for recurrent bronchogenic carcinoma , Scand J Thorac Cardiovasc Surg , 1984 , vol. 18 (pg. 249 - 250 ) Google Scholar Crossref Search ADS PubMed WorldCat [8] Pairolero P.C. , Williams D.E. , Bergstalh E.J. , Piehler J.M. , Bernatz P.E. . Postsurgical stage I bronchogenic carcinoma: morbid implications of recurrent disease , Ann Thorac Surg , 1984 , vol. 38 (pg. 331 - 336 ) Google Scholar Crossref Search ADS PubMed WorldCat [9] World Health Organization . The WHO histological typing of lung tumours , Am J Clin Pathol , 1982 , vol. 77 (pg. 123 - 136 ) Crossref Search ADS PubMed WorldCat [10] Mountain C.F. . A new international staging system for lung cancer , Chest , 1986 , vol. 89 (pg. 2255 - 2335 ) Google Scholar Crossref Search ADS WorldCat [11] Martini N. , Bains M.S. , Burt M.E. , Zakowski M.F. , McCormack P. , Rusch V.W. , Ginsberg R.J. . Incidence of local recurrence and second primary tumors in resected stage 1 lung cancer , J Thorac Cardiovasc Surg , 1995 , vol. 109 (pg. 120 - 129 ) Google Scholar Crossref Search ADS PubMed WorldCat [12] Green N. , Kern W. . The clinical course and treatment results of patients with postresection locally recurrent lung cancer , Cancer , 1978 , vol. 42 (pg. 2478 - 2485 ) Google Scholar Crossref Search ADS PubMed WorldCat [13] Watanabe Y. , Shimizu J. , Oda M. , Tatsuzawa Y. , Hayashi Y. , Iwa T. . Second surgical intervention for recurrent and second primary bronchogenic carcinoma , Scand J Thorac Cardiovasc Surg , 1992 , vol. 26 (pg. 73 - 78 ) Google Scholar Crossref Search ADS PubMed WorldCat [14] Dartevelle P. , Khalif J. . Delarue N.C. , Eschapasse H. . Surgical approach to local recurrence and the second primary lesion , International trend in general thoracic surgery , 1985 Philadelphia, PA W.B. Saunders (pg. 156 - 163 ) Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC [15] Salerno T.A. , Munro D.D. , Blundell P.E. , Chiu R.C.J. . Second primary bronchogenic carcinoma: life-table analysis of surgical treatment , Ann Thorac Surg , 1979 , vol. 27 (pg. 3 - 6 ) Google Scholar Crossref Search ADS PubMed WorldCat [16] Reynolds R. , Pajak J. , Greenberg B. . Lung cancer as a second primary , Cancer , 1978 , vol. 42 (pg. 2887 - 2893 ) Google Scholar Crossref Search ADS PubMed WorldCat [17] Martini N. , Ghosn P. , Melamed M.R. . Delarue N.C. , Eschapasse H. . Local recurrence and new primary carcinoma after resection , International trends in general thoracic surgery , 1985 Philadelphia, PA W.B. Saunders (pg. 164 - 169 ) Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC [18] Shields T.W. . Discussion of Deshamps C, Pairolero PC, Trastek VF, Payne WS. Multiple primary lung cancers , J Thorac Cardiovasc Surg , 1990 , vol. 99 (pg. 769 - 778 ) Google Scholar PubMed OpenURL Placeholder Text WorldCat [19] Pairolero P.C. . Discussion of Rosengart TK, Martini N, Ghosn P, Burt M. Multiple primary lung carcinomas: prognosis and treatment , Ann Thorac Surg , 1991 , vol. 52 (pg. 773 - 779 ) Google Scholar Crossref Search ADS PubMed WorldCat [20] Ginsberg R.J. , Rubinstein L.V. . (for the LCSG) Randomized Trial of lobectomy versus limited resection for T1N0M0 non-small cell lung cancer , Ann Thorac Surg , 1995 , vol. 60 (pg. 615 - 623 ) Google Scholar Crossref Search ADS PubMed WorldCat [21] Nagasaki F. , Flehinger B.J. , Martini N. . Complications of surgery in the treatment of carcinoma of the lung , Chest , 1982 , vol. 82 (pg. 25 - 29 ) Google Scholar Crossref Search ADS PubMed WorldCat [22] Ginsberg R.J. , Hill L.D. , Eagen R.T. , Thomas P. , Mountain C.F. , Deslauries J. , Fry W.A. , Butz R.O. , Goldberg M. , Waters P.F. . Modern thirty-day operative mortality for surgical resections in lung cancer , J Thorac Cardiovasc Surg , 1983 , vol. 86 (pg. 654 - 658 ) Google Scholar PubMed OpenURL Placeholder Text WorldCat © 2000 Elsevier Science B.V. All rights reserved. Elsevier Science B.V.

Journal

European Journal of Cardio-Thoracic SurgeryOxford University Press

Published: Nov 1, 2000

Keywords: Bronchogenic carcinoma Local recurrence Second primary lung cancer Completion pneumonectomy

There are no references for this article.