N2 Disease in T1 NonSmall Cell Lung Cancer文档格式.docx

1、 Email: wigle.dennismayo.edu The publishers final edited version of this article is available at Ann Thorac SurgSee commentary Sonic Hedgehog （SHH） Promotes the Differentiation of Mouse Cochlear Neural Progenitors via the Math1Brn3.1 Signaling pathway in vitro in J Neurosci Res, volume 88 onpage928.

2、 Other Sections o Abstracto Material and Methodso Resultso Commento ReferencesAbstractBackgroundThe optimal management strategy for mediastinal staging in early-stage non-small cell lung cancer （NSCLC） is not clearly defined. The true prevalence of mediastinal lymph node metastases （N2 disease） in r

3、esected pathologic T1 （pT1） NSCLC must be known to define the role of invasive mediastinal staging in these patients.MethodsData of patients with pT1 lesions resected at Mayo Clinic between 1998 and 2006 were retrospectively reviewed. Patients with N2 disease were identified from pathology and opera

4、tive reports. We reviewed demographics, radiologic data, and surgical procedures for those with pathologic T1 N2 NSCLC.ResultsWe identified 968 cases of pT1 lesions, 59 with pN2 disease （6.1%）. For those with T1 N2 disease, the primary lung lesion was peripheral in 18 （31%） and central in 41 （69%）.

5、Of these, 36 had negative non-invasive mediastinal staging （3.7%） and were incidentally discovered. The most frequently affected lymph node station was 7 in 22 patients （37%）, followed by 5,6 in 18 （31%）. Mediastinoscopy found positive lymph nodes in 3 of 16 patients （19%） in which it was performed.

6、 Overall 5-year survival for pT1 N2 incidentally discovered during mediastinal lymph node dissection at the time of lung resection was 46% （95% confidence interval, 31% to 68%）.ConclusionsTrue pT1 NSCLC harbors a relatively low rate of N2 disease. The rate of occult N2 disease not observed on noninv

7、asive preoperative mediastinal staging is even lower. For patients with T1 NSCLC and negative mediastinal imaging, routine mediastinoscopy results in a low yield of occult N2 disease discovery.Current treatment algorithms for locally advanced stage III non-small cell lung cancer （NSCLC） typically in

8、volve neoadjuvant or definitive chemoradiation therapy. Surgical resection is not normally used as initial treatment in most North American centers. As a consequence, much effort is directed toward the assessment of mediastinal lymph nodes for metastatic disease before any planned surgical resection

9、.Computed tomography （CT） has a sensitivity of 50% to 76% and specificity of 55% to 86% for predicting meta-static involvement of mediastinal lymph nodes when they exceed 1 cm in the short axis 13. Positron emission tomography （PET） has emerged as a useful tool to evaluate the mediastinum, with a se

10、nsitivity of 83% to 91% and specificity of 70% to 91% for lymph node metastases 3, 4. Despite these numbers, pathologic tissue confirmation is desirable to prove that a lesion is indeed malignant and not exclude potentially resectable tumors from surgical treatment and potential cure.Some have sugge

11、sted that the incidence of lymph node metastases in patients with clinical T1 NSCLC and negative noninvasive mediastinal staging might be low enough to preclude routine invasive staging by mediastinoscopy 5, 6. Reports vary about the true rate of occult N2 disease in NSCLC patients with negative non

12、invasive staging, particularly for patients with T1 lesions. The objective of this study was to describe the incidence of N2 disease in 968 consecutive cases of resected pathologic T1 （pT1） NSCLC and make inferences about the utility of invasive mediastinal staging in this subgroup of patients.Mater

13、ial and MethodsThis study was approved by the Mayo Clinic College of Medicines Institutional Review Board.PatientsWe reviewed our prospective database for all patients that underwent resection for pT1 NSCLC between 1998 and 2006 at Mayo Clinic, Rochester, Minnesota. All pathology reports for these p

14、atients were reviewed. We identified 968 cases involving surgical procedures in patients with pT1 NSCLC. Of these, 59 （6.1%） were found to have pathologic N2 （pN2） disease. Preoperative data were reviewed for this group, including age, gender, pulmonary function tests, localization of the primary tu

15、mor, presence of adenopathy on CT scan, and size and metabolic activity on PET scan in those patients for which it was performed. The surgical and pathology reports were reviewed for the mediastinal lymph nodes stations that were sampled and which of them contained metastases.Lesions were staged acc

16、ording to the staging system and mediastinal lymph node map described by Mountain 7, 8. The size of the lesion was determined from the greatest dimension measured in the pathology laboratory.Imaging DataAll the available CT scans were reviewed. Peripheral lung nodules were defined on CT scan as tumo

17、rs with the center located in the outer third of the lung in either the sagittal or coronal plane. If CT images were not available, a peripheral lesion was defined according to its relation to the pleural surface as described in the pathology report. Mediastinal lymph nodes were considered to be pos

18、itive by CT scan criteria when their short axis was 10 mm or more in size. In patients in whom PET scans were performed, reports were reviewed and considered positive if the described metabolic activity in the mediastinum exceeded 1.5-fold over background levels.MediastinoscopyCervical mediastinosco

19、py was performed in the standard fashion and selectively, determined by the presence of significant lymph nodes in the mediastinum observed on CT scan, by increased metabolic activity on PET, or by surgeon preference. After introduction of the mediastinoscope, biopsy specimens from station 4R, 7, an

20、d 4L were typically obtained. Biopsy specimens were also obtained from other stations when lymph nodes were encountered or specifically sought out.Mediastinal Lymph Node DissectionMediastinal lymph node dissection （MLND） was performed as part of lung resections. For right-sided procedures, the lymph

21、 node stations 2R, 4R, 7, and 9 were routinely dissected; for left-sided procedures, the nodes from stations 5, 6, 7, and 9 were included. On both sides, other lymph node stations encountered or specifically sought out at the time of the lung resection were also removed.StatisticsDescriptive statist

22、ics are reported as median and range for continuous variables and as frequency and percentage for discrete variables, based on tumor status （N2 vs N0/N1）. Associations with tumor status were made using the Wilcoxon rank sum test for continuous variables and 2 test or Fisher exact test as appropriate

23、 for discrete variables. The -level was set at 0.05 for statistical significance.Between 1998 and 2006, 968 patients underwent lung resection for pT1 NSCLC. Of these, 59 （6.1%） were found to have N2 disease （32 men, 27 women）. Peripheral lesions were found in 18 patients and central lesions in 41 （6

24、9%）. Lung tumors were on the right side in 25 （43%） and on the left side in 34 （57%）. Lobectomy by open thoracotomy was performed in 54 （92%）, and wedge resection in 5 （8%）. Patient characteristics are listed in Table 1.Table 1 Characteristics for pT1 N2 PatientsCT criteria were used to establish me

25、diastinal adenopathy in 17 of 59 patients （29%）. The most frequent lymph node station found to be positive by CT scan criteria was station 4R in 10 patients （17%）, followed by station 7 in 6 （10%）. In 8 patients （14%）, CT showed adenopathy in N1-level lymph nodes.PET scan was done in 27 patients （46

26、%）, resulting in 18 （31%） with negative mediastinal lymph nodes and 9 （15%） with positive nodes. In 3 patients the CT and PET scans were both positive for the same lymph node stations. In 2 patients this involved station 4R with metastases found at time of operation after a negative mediastinoscopy.

27、 The remaining case involved a 5,6 lymph node station, with metastasis confirmed during left-sided lung resection.Surgical DataMediastinoscopy was performed in 16 of 59 T1 N2 patients （27%）, and in 11 of 23 with preoperative features of N2 disease. In 3 of 16 patients （19%）, mediastinoscopy found ly

28、mph node metastases in the mediastinum, and 2 subsequently received neoadjuvant chemoradiation therapy, followed by pulmonary resection. The third patient had complications with bleeding during the mediastinoscopy procedure, for which a thoracotomy was performed along with the lung resection. In the

29、 remaining 13 patients （81%）, mediastinoscopy did not reveal the presence of lymph node metastases, despite the discovery of N2 disease during MLND at the time of lung resection. Overall, mediastinoscopy was able to identify mediastinal lymph node involvement in only 3 of 9 patients （33%） where the

30、positive lymph nodes were within the field accessible by cervical mediastinoscopy.In N2-positive cases, the median size of the T1 pulmonary lesions was 2 cm （range, 0.9 to 3 cm）. Only 1 lesion was less than 1 cm, 37 lesions measured between 1 and 2 cm, and 21 lesions were more than 2 cm in the greatest dimension. The location of the primary lesion for specific N2-positive stations is described in Table 2.Table 2 Fr