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Ann Thorac Surg 2004;77:1781-1785
© 2004 The Society of Thoracic Surgeons
a Thoracic Surgery Unit, Carlo Forlanini Hospital, Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy
c Pathology Unit, Carlo Forlanini Hospital, Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy
b Clinical Epidemiology Unit, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Rome, Italy
Accepted for publication October 24, 2003.
* Address reprint requests to Dr Cardillo, Thoracic Surgery Unit, Carlo Forlanini Hospital, Via Portuense 332-00149, Rome, Italy
e-mail: gcardillo{at}scamilloforlanini.rm.it
Presented at the Poster Session of the Thirty-ninth Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 31Feb 2, 2003.
| Abstract |
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METHODS: We conducted a retrospective single institutional review of 163 patients surgically treated from January 1990 to April 2002. According to 1999 World Health Organization criteria, cases were segregated into typical (<2 mitoses per 2 mm, no necrosis) and atypical carcinoids (2 to 10 mitoses per 2 mm or necrosis).
RESULTS: There were 86 men and 77 women with a mean age of 49.5 ± 11 years. Symptoms were present in 89 patients (54.6%). Operations included 145 formal lung resections (89%), 9 wedge resections (5.52%), 8 sleeve lobectomies (4.9%), and 1 segmental resection (0.61%) plus radical mediastinal lymphadenectomy in all cases. No operative mortality was reported. Histologic examination showed 121 (74.2%) typical carcinoids (107 N0 and 14 N1), and 42 (25.8%) atypical carcinoids (15 N0, 18 N1, 9 N2). All patients were included in a follow-up (median, 54 months; mean, 58 months; range, 4 to 150 months), which included total body computed tomographic scan and bronchoscopy every year. Overall 5-year survival was 90.3% with a mean survival time of 139 months (95% confidence interval, 133 to 145). In N0 patients with either typical or atypical carcinoid tumors, no disease-related mortality was reported (100% 5-year survival). In N1 patients, 5-year survival was 90.0% for those with typical carcinoids, and 78.8% for those with atypical carcinoids (p = 0.394). In atypical carcinoids with N2 disease, 5-year survival was 22.2%.
CONCLUSIONS: Prognosis in bronchial carcinoid tumors is more related to nodal status than to histologic subtype. In N0 and N1 patients no statistical significant difference has been found between typical and atypical subtype. However, N2 bronchial carcinoid tumors show a dismal prognosis.
| Introduction |
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| Material and methods |
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The histologic diagnosis of pulmonary carcinoid tumor was confirmed by review of all histologic sections by a single pathologist (P.G.) with special expertise in neuroendocrine tumors, who ignored the initial diagnosis (ie, TC or AC tumor). All tumors were classified according to the 1999 newly proposed World Health Organization/International Association for the Study of Lung Cancer classification scheme [8]. Tumors were staged according to the 2002 TNM classification for nonsmall-cell lung carcinoma [14].
Operative complications were classified as pulmonary (air leak > 6 days, pneumonia, pulmonary infiltrate, loculated pleural effusions requiring thoracentesis), cardiovascular (myocardial infarction, arrhythmia, pulmonary embolism), other (bleeding, wound infection, recurrent nerve injury, bronchopleural fistula, empyema, and other miscellaneous conditions), and mixed. Operative mortality included those patients who died within the first 30 days after the operation and those who died later but during the same hospitalization.
All patients were included in a follow-up program, which included physical examination and chest roentgenogram every 6 months, bronchoscopy, and total body computed tomography scan every year. Since January 2000, in patients with suspicious signs of metastases, scintigraphy with indium 111labeled octreotide was also performed. Survival and tumor recurrence were measured from the date of operation.
Cumulative survival probabilities were estimated by the method of Kaplan and Meier. Differences in survival distributions by age, sex, smoking status, histologic type, dimension of the tumors, lymph node involvement, and surgical procedures were tested with the log-rank test.
| Results |
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According to the histologic findings, 121 patients had a TC and 42 had an AC. Mean age was 54 ± 15.5 years for TC, and 54 ± 12.6 years for AC (Table 2).
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Most of the tumors (n = 98; 60.1%) could be visualized during bronchoscopy and were classified as central tumors: 89 tumors (54.6%) were biopsied, and in 78 cases (47.9%) a diagnosis of a carcinoid tumor was achieved. The remaining 65 cases (39.9%) were classified as peripheral tumors: of these, 41 patients (25.2%) underwent fine-needle aspiration biopsy, achieving a diagnosis of carcinoid tumor in 13 cases (8%). By means of bronchoscopy and fine-needle aspiration biopsy a preoperative diagnosis of carcinoid tumor was achieved in 91 cases (55.8%) in our series.
Operations included 145 (89%) formal lung resections (59 inferior lobectomies, 35 upper lobectomies, 18 middle lobectomies, 21 bilobectomies, 12 pneumonectomies), 8 (4.9%) sleeve lobectomies (4 right upper, 2 left upper, 2 left inferior), 9 (5.52%) wedge resections, and 1 segmental resection.
Radical mediastinal lymphadenectomy was added in all cases with a mean of 12 ± 7 nodes per patient.
The median length of hospital stay was 7.2 days (range,5 to 18 days). No operative mortality was reported. Operative complications included seven pulmonary complications, five cardiovascular complications, eight other complications, and four mixed complications (morbidity rate, 14.7%)
In the TC group (n = 121 patients), involvement of the ipsilateral hilar lymph nodes (N1 disease) was found in 14 patients (11.57%); no patient showed N2 or N3 disease; 107 patients were N0 (88.43%).
In the AC group (n = 42), 18 patients showed N1 disease (42.86%), 9 patients were N2 (21.43%), and 15 were N0 (35.71%); no patient was N3.
All patients (n = 163) were followed for a total of 9,524 months with a median time of observation of 54 months (mean, 58 months; range, 6 to 150 months). Follow-up ended August 1, 2002. Sixteen patients died, 11 with evidence of disease and 5 of unrelated causes (2 myocardial infarction, 2 traffic accident, 1 cerebral stroke). Among patients who died with disease, 10 were AC (7 N2 and 3 N1) and 1 was N1 TC; 8 of these had been treated with lobectomies (4 upper and 4 lower), and 3 with bilobectomies.
Among survivors (n = 147), 2 were alive with disease: 1 TC with bone and liver metastases (previously treated with bilobectomies) and 1 AC with liver metastases (previously treated with upper lobectomy).
The overall 5-year survival was 90.3% (mean, 139 months). The mean survival time was 139 months (95% confidence interval, 133 to 145). According to the sex of the patients, 5year survival was 88.9% in male patients (n = 86) and 91.6% in female patients (n = 77; p = 0.716). According to the age of the patients, 5-year survival was 94.6%, 81.3%, 95.7%, respectively in the age range 18 to 45 years, 46 to 60 years, and 60 to 80 years (p = 0.118). According to the smoking history, overall 5-year survival was 92.4% in smokers and 89.1% in nonsmokers (p = 0.560)
Overall 5-year survival was 98.6% in TC tumors (n = 121), and 70.1% in AC tumors (n = 42; p = 0.000). According to N0 status (n = 122), 5-year survival was 100% either in TC tumors (n = 107) or in AC tumors (n = 15). According to N1 status (n = 32), overall 5-year survival was 84.2%: 5-year survival was 90.0% and 78.8%, respectively, in N1 TC tumors (n = 14) and in N1 AC tumors (n = 18; p = 0.394). In N2 patients (n = 9), all of them having AC tumors, 5-year survival was 22.2% (p = 0.000).
Among patients who died of disease (n = 11), 7 were N2 (63.64%) and 4 N1 (36.36%).
| Comment |
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Bronchial carcinoids occur in patients who are on average a decade younger than patients with nonsmall-cell lung cancer, and the male-to-female ratio is almost 1 [4]. The mean age was 54 ± 14.8 years in our experience, 56.4 years in the multicenter study by Ferguson and coworkers [10], 52 years in the paper by Fink and associates [1], and 47 years in the paper by Filosso and colleagues [13]. In our experience no differences were found between the mean age at diagnosis in patients with TC and AC, whereas El Jamal and coworkers [16] and Filosso and associates [13] found patients with AC to be older than patients with TC. The male-to-female ratio was 1.11 in our experience, and 1.33, 0.65, 0.57, and 0.56, respectively, in the papers by Filosso and colleagues [13], Fink and associates [1], El Jamal and coworkers [16], and Ferguson and associates [10]. Bronchial carcinoids do not show a strict correlation with tobacco use in our experience, and the survival rate does not show any difference between smokers and nonsmokers. This finding is in line with most reports [10] although some authors indicate a possible association between AC and smoking [13, 16]. Most of the patients with bronchial carcinoids were symptomatic at presentation: 54.6% in our experience, 52% in the paper by Filosso and colleagues [13], and 65.3% in the paper by El Jamal and coworkers [16].
Positron emission tomography has been recently added in the workup of patients with nonsmall-cell lung cancer. Positron emission tomography imaging of bronchial carcinoid tumors demonstrates lower uptake than nonsmall-cell lung cancer, and it appears to be unreliable in the differentiation of benign processes from nonbenign ones[17]. Scintigraphy with 111In-labeled octreotide has demonstrated reliable uptake in primary carcinoids and the ability to detect early recurrences and metastases even in asymptomatic patients, suggesting that it might be a useful tool for routine staging in the future [18].
The most important tool for the evaluation of centrally located carcinoids, which represent 60.1% of the cases reported in our series, is bronchoscopy: it should be done early in the workup of such patients to achieve a histologic diagnosis, and it often should be redone intraoperatively to better define the precise extent of bronchial resection in cases of central tumors. Among 89 patients who underwent endobronchial biopsies in our series, we did not report any significant bleeding.
As regards the surgical treatment, we believe that either typical or atypical bronchial carcinoids should be managed by an anatomic resection (lobectomy if pulmonary tests are adequate, or segmentectomy) [10, 16], even if the surgical procedure itself did not affect survival in our series. In centrally located tumors sleeve resection is a good option. Some authors believe a wedge resection to be safe for small peripheral TC [10]. A radical mediastinal lymphadenectomy should always be associated even if there are very little data on this issue [19, 20]: some authors [13, 16] prefer sampling, whereas Ferguson and colleagues [10] believe lymph node dissection to be important only in patients with AC. It is often difficult to ascertain during surgery the typical or atypical feature of a bronchial carcinoid: much has been written about the difficulty in counting mitotic figures, and there are equally difficult problems in identifying such things as "cellularity and atypia" [20].
In general the prognosis of bronchial carcinoids looks to be good: apart from the study of Todd and colleagues [6], who reported in 1980 a 5-year survival rate of only 65% in a study conducted on 65 patients, the overall 5-year survival currently reported in the literature was as high as 78%, 86%, 87%, 88%, 92%, and 96%, respectively, by Harpole and colleagues [12], Ferguson and associates [10], Fink and coworkers [1], Bertelsen and colleagues [21], McCaughon and associates [11], and by Hurt and Bates [22]. The 5-year survival rate in TC is 97.5% in the experience of Stamatis and coworkers [23], 90% in the experience of Ferguson and colleagues [10], 89% in the study of Fink and associates [1], and 77% in the study of Filosso and colleagues [13]. In AC the 5-year survival rate was 70% in the paper of Ferguson and coworkers [10], and 75% in the paper of Fink and associates [1] (Table 3).
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In our study, of 163 patients surgically treated for bronchial carcinoids in a 12-year period, with formal lung resection plus radical mediastinal lymphadenectomy, we found lymph node metastases in 41 patients (25.15%). In the TC group (n = 121), the percentage of lymph node metastases (N1) was 11.57% (14 of 121). In the AC group (n = 42), the percentage of lymph node metastases reached a remarkable 64.28% (27 of 42: 18 N1 and 9 N2 patients). The difference in nodal involvement between TC and AC (11.57% versus 64.28%) is statistically significant (p < 0.0001).
The overall 5-year survival between TC and AC (98.6% versus 70.1%) is also statistically significant (p = 0.000). The stratified analysis (Table 4) shows the difference to be related to the N status. In N0 patients the 5-year survival is 100% either in TC or AC. In N1 patients the 5-year survival between TC and AC shows a nonsignificant difference (90.0% versus 78.8%; p = 0.394). Nine patients with N2 status (all of them belonging to the AC subtype) with a 22.2% 5-year survival explain the difference between typical and atypical bronchial carcinoids.
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| Acknowledgments |
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| References |
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