Border between N1 and N2 stations in lung carcinoma: lessons from lymph node metastatic patterns of lower lobe tumors

OBJECTIVE: Distinction of lymph node stations is one of the most crucial topics still not entirely resolved by many lung cancer surgeons. The nodes around the junction of the hilum and mediastinum are key points at issue. We examined the spread pattern of lymph node metastases, investigated the prognosis according to the level of the involved nodes, and conclusively analyzed the border between N1 and N2 stations. METHODS: We reviewed the records of 604 consecutive patients who underwent complete resection for non-small cell lung carcinoma of the lower lobe. RESULTS: There were 390 patients (64.6%) with N0 disease, 127 (21.0%) with N1, and 87 (14.4%) with N2. Whereas 11.3% of patients with right N2 disease had skip metastases limited to the subcarinal nodes, 32.6% of patients with left N2 disease had skip metastases, of which 64.2% had involvement of N2 station nodes, except the subcarinal ones. The overall 5-year survivals of patients with N0, N1, and N2 disease were 71.0%, 50.8%, and 16.7%, respectively (N0 vs N1 P = .0001, N1 vs N2, P < .0001). Although there were no significant differences in survival according to the side of the tumor among patients with N0 or N1 disease, patients with a left N2 tumor had a worse prognosis than those with a right N2 tumor (P = .0387). The overall 5-year survivals of patients with N0, intralobar N1, hilar N1, lower mediastinal N2, and upper mediastinal N2 disease were 71.0%, 60.1%, 38.8%, 24.8%, and 0%, respectively. Significant differences were observed between intralobar N1 and hilar N1 disease ( P = .0489), hilar N1 and lower mediastinal N2 disease (P = .0158), and lower and upper mediastinal N2 disease (P = .0446). Also, the 5-year survivals of patients with involvement up to station 11, up to station 10, and up to station 7 were 41.4%, 37.9% and 37.7%, respectively (difference not significant). CONCLUSIONS: N1 and N2 diseases appeared as a combination of subgroups: intralobar N1 disease, hilar N1 disease, lower mediastinal N2 disease, and upper mediastinal N2 disease. Interestingly, the survivals of patients with involvement up to interlobar nodes (station 11), main bronchus nodes (station 10), and subcarinal nodes (station 7) were identical. These data constitute the basis for a larger investigation to develop a lymph node map in lung cancer.     

Prolonged survival in patients with resected non-small cell lung cancer and single-level N2 disease

OBJECTIVES: To test the hypothesis that patients with non-small cell lung cancer and single-level N2 metastases constitute a favorable subgroup of patients with mediastinal metastases, we analyzed the results of the Eastern Cooperative Oncology Group 3590 (a randomized prospective trial of adjuvant therapy in patients with resected stages II and IIIa non-small cell lung cancer) by site of primary tumor and pattern of lymph node metastases. METHODS: Accurate staging was ensured by mandating either systematic sampling or complete dissection of the ipsilateral mediastinal lymph nodes. The overall survival of patients with left lung non-small cell lung cancer and metastases in only 1 of lymph node levels 5, 6, or 7 and right lung non-small cell lung cancer with metastases in only 1 of levels 4 or 7 was compared with that of patients with N1 disease originating in the same lobe. RESULTS: The median survival of the 172 patients with single-level N2 disease was 35 months (95% confidence interval: 27-40 months) versus 65 months (95% confidence interval: 45-84 months) for the 150 patients with N1 disease (median follow-up 84 months, P =.01). However, among patients with left upper lobe tumors, survival was not significantly different between patients with N1 disease and patients with single-level N2 disease (49 vs 51 months, P =.63). The median survival of the 71 patients with single-level N2 metastases without concomitant N1 disease (skip metastases) was 59 months (95% confidence interval: 36-107 months) versus 26 months (95% confidence interval: 16-36 months) for the 145 patients with both N1 and N2 metastases (P =.001). CONCLUSIONS: Survival of patients with left upper lobe non-small cell lung cancer and metastases to single-level N2 lymph nodes is not significantly different from that of patients with N1 disease. The presence of isolate N2 skip metastases is associated with improved survival when compared with patients with both N1 and N2 disease. Survival should be reported by the lobe of primary tumor and metastatic pattern to guide future clinical trial development, treatment strategies, and revisions of the TNM staging system.     

Prognosis of completely resected pN2 non-small cell lung carcinomas: What is the significant node that affects survival?

OBJECTIVE: We analyzed the effect of the station of mediastinal metastasis with regard to the location of the primary tumor on the prognosis in patients with non-small cell lung cancer. METHODS: Of 956 consecutive patients who underwent operation for primary lung carcinoma between 1986 and 1996, 760 patients (79.5%) were diagnosed as having non- small cell carcinoma and were subjected to complete removal of hilar and mediastinal lymph nodes together with the primary tumor. RESULTS: The status of lymph node involvement was N0 in 480 patients (63.2%), N1 in 139 patients (18.3%), and N2 in 141 patients (18.6%). The 5- and 10-year survival of patients with N2 disease were 26% and 17%, respectively. Neither cell type nor the extent of procedure was a significant survival determinant. Patients having involvement of subcarinal nodes from upper-lobe tumors had a significantly worse prognosis than those patients with metastases only to the upper mediastinal or aortic nodes (P =.003). Patients with nodal involvement of the upper mediastinum from lower-lobe tumors had a significantly worse survival than those patients with metastases limited to the lower mediastinum (P =.039). Furthermore, patients with involvement of the aortic nodes alone from left upper-lobe tumors had a significantly better survival than those patients with metastasis to the upper or lower mediastinum beyond the aortic region (P =.044). CONCLUSIONS: When mediastinal metastasis is limited to upper nodes from upper-lobe tumor, to lower nodes from lower-lobe tumor, or to aortic nodes from left upper-lobe tumor, acceptable survival could be expected after radical resection.     

Type of lymph node involvement and survival in pathologic N1 stage III non-small cell lung carcinoma.

BACKGROUND: Survival of patients with stage II non-small lung cancer by the 1986 classification depends on the type of lymph node involvement (by direct extension or by metastases in lobar or hilar lymph nodes). The influence of these types of lymph node involvement on survival was investigated in pathologic N1 stage III patients. METHODS: Of 2,009 patients having operation from 1977 through 1993, the cases of 123 patients with pathologic N1 stage III disease (80 T3 N1 and 43 T4 N1) were reviewed. The N1 status was refined by the specific type of lymph node involvement. RESULTS: The cumulative 5-year survival rate of all hospital survivors (n = 111) was 27.2%. A significant difference in mean 5-year survival rate was observed between patients who underwent complete resection and those with incomplete resection (34.4% versus 11.4%; p = 0.0001). Further analysis was performed with hospital survivors having complete resection only (n = 76). The cumulative 5-year survival rate was 34.4%. Type of lymph node involvement did not relate to survival for the group as a whole or for the T3 and T4 subsets. Survival was not related to age, histology, type of resection, or tumor size. CONCLUSIONS: Moderately good results can be obtained with surgical resection for stage III patients with pathologic N1 disease. In contrast with stage II, complete resection of pathologic N1 higher-stage non-small cell lung carcinoma is not influenced by type of lymph node involvement.     

Bronchogenic carcinoma: incidence of metastases to normal sized lymph nodes.

BACKGROUND--The incidence of metastases to mediastinal lymph nodes was evaluated in patients with normal sized mediastinal nodes on the computed tomographic (CT) scan who underwent thoracotomy. The use of hilar lymph nodes in predicting mediastinal lymph node metastases was also assessed. METHODS--Ninety patients with non-small cell lung cancer who later underwent thoracotomy wer prospectively examined by CT scanning. Lymph nodes with a short axis diameter of 10 mm or more were considered abnormal. RESULTS--Mediastinal lymph node metastases were present at thoracotomy in 19 patients (21%). In 14 these lymph node metastases were misdiagnosed because the nodes were normal in size on the CT scan. In only one of the 19 patients with N2 nodes was an N1 lymph node enlarged, and four of the 19 patients with N2 nodes had metastases to these mediastinal nodes without N1 disease ("skipping metastases"). CONCLUSIONS--Metastases in normal sized nodes seen on the CT scan are a major problem in staging. Hilar lymph nodes did not help to predict reliably the presence or absence of metastases to the mediastinal lymph nodes.     

Prognostic significance of surgical-pathologic N1 disease in non-small cell carcinoma of the lung

Background. N1 disease represents a heterogeneous group of non-small cell lung carcinoma with varying 5-year survival rates. Specific types of N1 lymph node involvement need to be further investigated and their prognostic significance clarified.

Methods. From 1984 to 1993, 1,174 patients with non-small cell lung cancer had complete mediastinal lymph node dissection: N0, 50.25% (n = 590); N1, 21.8% (n = 256); and N2, 27.95% (n = 328). The N1 subgroup cases were reviewed. Four levels of N1 nodes were identified using the New Regional Lymph Node Classification for Lung Cancer Staging. Their prognostic significances were tested and 5-year survival rates were compared with those of N0 and N2 patients of the whole group.

Results. The overall 5-year survival rate of N1 patients was 47.5%. Survival was not related to site of the primary lung cancer, pathologic T factor, histologic type, type of resection, number of N1 station involved, nor type of N1 involvement (direct extension or metastases). Five-year survival was significantly better when N1 involvement was intralobar (levels 12 and 13, n = 102), as compared with extralobar (hilar) involvement (levels 10 and 11, n = 154): 53.6% versus 38.5% (p = 0.02). Intralobar N1 5-year survival was similar to that of N0 (53.6% vs 56.5%, p = 0.01), and extralobar 5-year survival with that of N2 (38.5 vs 28.3%, p = 0.01) when N2 was present in only one station in the ipsilateral mediastinum.

Conclusions. N1 disease is a compound of two subgroups: one located inside the lobes is related to N0, and the other (extralobar or hilar) behaves like an early stage of N2 disease. This offers further information for clinical, therapeutic, and research purposes.     

Lymph node staging in non-small cell lung cancer: evaluation by [18F]FDG positron emission tomography (PET)

BACKGROUND: A study was undertaken to investigate the accuracy of positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D- glucose (FDG) in the thoracic lymph node staging of non-small cell lung cancer (NSCLC). METHODS: Forty six patients with focal pulmonary tumours who underwent preoperative computed tomographic (CT) and FDG- PET scanning were evaluated retrospectively. Thirty two patients had NSCLC and 14 patients had a benign process. The final diagnosis was established by means of histopathological examination at thoracotomy, and the nodal classification in patients with lung cancer was performed by thorough dissection of the mediastinal nodes at surgery. RESULTS: FDG-PET was 80% sensitive, 100% specific, and 87.5% accurate in staging thoracic lymph nodes in patients with NSCLC, whereas CT scanning was 50% sensitive, 75% specific, and 59.4% accurate. The absence of lymph node tumour involvement was identified by FDG-PET in all 12 patients with NO disease compared with nine by CT scanning. Lymph node metastases were correctly detected by FDG-PET in three of five patients with N1 disease compared with two by CT scanning, in nine of 11 with N2 disease compared with six by CT scanning, an in all four with N3 nodes compared with two by CT scanning. CONCLUSIONS: FDG-PET provides a new and effective method for staging thoracic lymph nodes in patients with lung cancer and is superior to CT scanning in the assessment of hilar and mediastinal nodal metastases. With regard to resectability, FDG-PET could differentiate reliably between patients with N1/N2 disease and those with unresectable N3 disease.     

Sentinel node sampling limits lymphadenectomy in stage I non-small cell lung cancer.

OBJECTIVE: It is controversial whether a systematic mediastinal lymph node dissection (MLND) needs to be performed in all patients with stage I lung cancer. The present study was done to examine the new sentinel lymph nodes hypothesis based on the lobe of the primary tumor. METHODS: In our first study, the lymph node (LN) metastases were assessed in 291 stage I non-small cell lung cancer (NSCLC) patients who had a major lung resection with a systematic mediastinal lymph node dissection. We evaluated the validity of using our new sentinel lymph nodes method based on the lobe of the primary tumor as follows: the pretracheal (#3), tracheobronchial (#4), and hilar nodes (#10) for right upper lobe tumors; #4, subcarinal (#7), and #10 for middle lobe tumors; the subaortic (#5), paraaortic (#6), and #10 for left upper lobe tumors; and the #7, #10, and interlobar nodes (#11) for tumors in either lower lobes. In the second study, we performed a lobectomy with new sentinel node sampling in 64 patients with preoperative complications. If all of the sampling nodes showed no metastases on frozen section diagnosis, systematic node dissections were not performed. RESULTS: Six of 291 patients in the first study had skip metastases that did not involve the new sentinel nodes; 5 of the 6 patients had macroscopic pleural invasion. Thus, we defined pleural invasion as an exclusion criterion for the second study. In the second study, the median follow-up time was 39 months. Metastatic lymph nodes were detected in 11 of 64 patients. Fifty-three patients (83%) had no metastasis in the sampled nodes, and, therefore, a mediastinal lymph node dissection was not done. The morbidity rate in the sampling group was 36%, and there was no mortality. In the sampling group, local recurrences were observed in two patients, distant metastases in eight, and carcinomatous pleuritis in one; the overall 5-year survival rate was 82%. CONCLUSIONS: We found that it is possible to perform a less invasive lymphadenectomy for patients with stage I lung cancer using intra-operative sampling of new sentinel lymph nodes.     

Analysis of lobectomy for small peripheral lung cancer supports extended segmentectomy

We reviewed the records of 53 patients who underwent lobectomy for peripheral non-small cell lung cancer under 2 cm in diameter and established a rationale for segmentectomy with intraoperative lymph nodes dissection (extended segmentectomy). Five patients (9.4%) had intrapulmonary metastases. Nodal status was NO in 34 patients (64.2%), N1 in 7 (13.2%), and N2 in 12 (22.6%). Based on examination of intraoperative frozen sections, 31 patients lacking lymph node metastases and visceral pleural involvement could have been candidates for extended segmentectomy. Twenty-seven had stage I disease on postoperative examination of paraffin-embedded sections. Of the remaining 4 patients, 1 had involvement of intrapulmonary lymph nodes in the segment where the primary lesion originated. Another patient had involvement only at the first mediastinal lymph node level, representing a “skipping metastasis”. The remaining 2 patients had no lymph node involvement, but had intrapulmonary metastases in the same segments as the primary lesion. We conclude that an extended segmentectomy may be as effective as lobectomy for treatment of peripheral non-small cell lung cancer under 2 cm in diameter without evident lymph node involvement.     

ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer.

The European Society of Thoracic Surgeons (ESTS) organized a workshop dealing with lymph node staging in non-small cell lung cancer. The objective of this workshop was to develop guidelines for definitions and the surgical procedures of intraoperative lymph node staging, and the pathologic evaluation of resected lymph nodes in patients with non-small cell lung cancer (NSCLC). Relevant peer-reviewed publications on the subjects, the experience of the participants, and the opinion of the ESTS members contributing on line, were used to reach a consensus. Systematic nodal dissection is recommended in all cases to ensure complete resection. Lobe-specific systematic nodal dissection is acceptable for peripheral squamous T1 tumors, if hilar and interlobar nodes are negative on frozen section studies; it implies removal of, at least, three hilar and interlobar nodes and three mediastinal nodes from three stations in which the subcarinal is always included. Selected lymph node biopsies and sampling are justified to prove nodal involvement when resection is not possible. Pathologic evaluation includes all lymph nodes resected separately and those remaining in the lung specimen. Sections are done at the site of gross abnormalities. If macroscopic inspection does not detect any abnormal site, 2-mm slices of the nodes in the longitudinal plane are recommended. Routine search for micrometastases or isolated tumor cells in hematoxylin-eosin negative nodes would be desirable. Randomized controlled trials to evaluate adjuvant therapies for patients with these conditions are recommended. The adherence to these guidelines will standardize the intraoperative lymph node staging and pathologic evaluation, and improve pathologic staging, which will help decide on the best adjuvant therapy.     

Surgical treatment of primary lung cancer with synchronous brain metastases

OBJECTIVES: The role of surgical resection for brain metastases from non-small cell lung cancer is evolving. Although resection of primary lung cancer and metachronous brain metastases is superior to other treatment modalities in prolonging survival and disease-free interval, resection of the primary non-small cell lung cancer and synchronous brain metastases is controversial. METHODS: From January 1975 to December 1997, 220 patients underwent surgical treatment for brain metastases from non-small cell lung cancer at our institution. Twenty-eight (12.7%) of these patients underwent surgical resection of synchronous brain metastases and the primary non-small cell lung cancer. RESULTS: The group comprised 18 men and 10 women. Median age was 57 years (range 35-71 years). Twenty-two (78.6%) patients had neurologic symptoms. Craniotomy was performed first in all 28 patients. Median time between craniotomy and thoracotomy was 14 days (range 4-840 days). Pneumonectomy was performed in 4 patients, bilobectomy in 4, lobectomy in 18, and wedge excision in 2. Postoperative complications developed in 6 (21.4%) patients. Cell type was adenocarcinoma in 11 patients, squamous cell carcinoma in 9, and large cell carcinoma in 8. After pulmonary resection, 17 patients had no evidence of lymph node metastases (N0), 5 had hilar metastases (N1), and 6 had mediastinal metastases (N2). Twenty-four (85.7%) patients received postoperative adjuvant therapy. Follow-up was complete in all patients for a median of 24 months (range 2-104 months). Median survival was 24 months (range 2-104). Survival at 1, 2, and 5 years was 64.3%, 54.0%, and 21.4%, respectively. The presence of thoracic lymph node metastases (N1 or N2) significantly affected 5-year survival (P =.001). CONCLUSION: Although the overall survival for patients who have brain metastases from non-small cell lung cancer is poor, surgical resection may prove beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.     

How should interlobar pleural invasion be classified? Prognosis of resected T3 non-small cell lung cancer

Background. The results of surgical treatment for non-small cell lung cancer with interlobar pleural involvement and direct invasion of the other lobe have seldom been documented.

Methods. Of 1,130 consecutive patients who were operated on for primary bronchogenic carcinoma between 1984 and 1997, we studied 132 patients who had complete resection of T3 non-small cell carcinoma.

Results. The structures involved were as follows: parietal pleura, 49 patients; chest wall, 45; interlobar pleura, 19; main bronchus within 2 cm of the carina, 11; mediastinal pleura, 6; and diaphragm, 1. Patients with N2 disease had a significantly worse survival than those with N0 (p = 0.0054) and N1 disease (p = 0.0165). The survival of patients with involvement of the interlobar pleura was significantly worse than that of patients with T1 (p = 0.0001) or T2 disease (p = 0.0484), and was similar to that of patients with T3 disease (p = 0.9821).

Conclusions. In patients with T3 disease, mediastinal lymph node involvement influenced survival significantly. Patients with involvement of the interlobar pleura should be regarded as having T3 lesions.     

Abnormal carcinoembryonic antigen levels and medullary thyroid cancer progression: a multivariate analysis

HYPOTHESIS: Medullary thyroid cancer cells are capable of secreting carcinoembyronic antigen (CEA). An abnormal preoperative CEA level may have important implications for the management of this condition. DESIGN: Retrospective analysis. SETTING: Tertiary referral center at a university hospital. PATIENTS: One hundred fifty patients with a histopathologic diagnosis of medullary thyroid cancer and preoperative CEA measurements using the same assay. Main Outcome Measure We used univariate and multivariate analyses to quantify the relationship between preoperative CEA level and tumor progression. RESULTS: On multivariate analysis, abnormal preoperative CEA levels were significantly associated with the initial operation rather than reoperation, larger primary tumors, positive lymph nodes, and distant metastasis. When analyses were limited to the 54 patients with increased CEA levels before the initial operation, there was a respective significant association between successive CEA levels (4.7-10.0, 10.1-30.0, 30.1-100.0, and >100.0 ng/mL) and lymph node metastases (>10 positive nodes: 0%, 9%, 53%, and 69% [P<.001]), involvement of cervical lymph node compartments (central: 33%, 36%, 73%, and 93% [P=.002]; lateral [ipsilateral]: 20%, 27%, 67%, and 88% [P=.001]; and lateral [contralateral]: 22%, 10%, 36%, and 73% [P=.008]), and distant metastasis (0%, 27%, 13%, and 75% [P<.001]). When CEA levels exceeded 30.0 ng/mL, surgical cure was exceptional. CONCLUSIONS: In medullary thyroid cancer, an abnormal CEA level heralds advanced disease. Carcinoembryonic antigen levels greater than 30.0 ng/mL indicate central and lateral (ipsilateral) lymph node metastases, whereas CEA levels greater than 100.0 ng/mL signify lateral (contralateral) lymph node metastases and distant metastasis.     

Pattern of lymph node involvement and prognosis in pancreatic adenocarcinoma: direct lymph node invasion has similar survival to node-negative disease

Lymph node status is one of the most important predictors of survival in pancreatic ductal adenocarcinoma. Surgically resected pancreatic adenocarcinoma is often locally invasive and may invade directly into peripancreatic lymph nodes. The significance of direct invasion into lymph nodes in the absence of true lymphatic metastases is unclear. The purpose of this study was to retrospectively compare clinical outcome in patients with pancreatic ductal adenocarcinoma with direct invasion into peripancreatic lymph nodes with patients with node-negative adenocarcinomas and patients with true lymphatic lymph node metastasis. A total of 380 patients with invasive pancreatic ductal adenocarcinoma classified as pT3, were evaluated: ductal adenocarcinoma with true lymphatic metastasis to regional lymph nodes (248 cases), ductal adenocarcinoma without lymph node involvement (97 cases), and ductal adenocarcinoma with regional lymph nodes involved only by direct invasion from the main tumor mass (35 cases). Isolated lymph node involvement by direct invasion occurred in 35 of 380 (9%) patients. Overall survival for patients with direct invasion of lymph nodes (median survival, 21 mo; 5-year overall survival, 36%) was not statistically different from patients with node-negative adenocarcinomas (median survival, 30 mo; 5-year overall survival, 31%) (P=0.609). Patients with node-negative adenocarcinomas had an improved survival compared with patients with lymph node involvement by true lymphatic metastasis (median survival, 15 mo; 5-year overall survival, 8%) (P<0.001) regardless of the number of lymph nodes involved by adenocarcinoma. There was a trend toward decreased overall survival for patients with 1 or 2 lymph nodes involved by true lymphatic metastasis compared with patients with direct invasion of tumor into lymph nodes (P=0.056). However, this did not reach statistical significance. Our results indicate that patients with isolated direct lymph node invasion have a comparable overall survival with patients with node-negative adenocarcinomas as opposed to true lymphatic lymph node metastasis.     

Verteilungsmuster und Befall regionärer Lymphknoten bei nicht-kleinzelligem Bronchialcarcinom

Despite the important role of lymph node infiltration for the classification and prognosis of non-small-cell lung cancer (NSCLC), no standards exist to evaluate the quality of mediastinal lymphadenectomy. Researches at several centers are not convinced that complete ipsilateral lymphadenectomy is necessary. We investigated 270 consecutive patients undergoing a potential curative operation for NSCLC including complete ipsilateral lymph node dissection in order to ascertain whether or not there is a correlation between tumor localization and lymph node infiltration. Patients were classified into the UICC (1987) stages I (n = 115), II (n = 42), and IIIa (n = 113). In patients with N1-positive lymph nodes (n = 61) we found higher 5-year survival for patients with only intrapulmonary lymph node infiltration (39%) than for patients with hilar infiltration (21%). Patients with N2 disease showed skip metastases in up to 81% of cases. We found that no tumor location predicted the lymph node infiltration. Due to the variability of lymph node infiltration and the frequently occurring skip metastases, complete ipsilateral lymphadenectomy should be the standard for curative operations for NSCLC.     

Use of technetium-99m tin colloid for sentinel lymph node identification in non-small cell lung cancer

BACKGROUND: To test the reliability of sentinel lymph node identification in non-small cell lung cancer, sentinel nodes were localized with a radioactive colloid in patients undergoing surgery. METHODS: Forty-six patients with non-small cell lung cancer undergoing curative resection with mediastinal lymph node dissection were examined. The day before surgery, technetium-99m ((99m)Tc) tin colloid was injected into the peritumoral region. At operation, the radioactivity of the lymph nodes was counted with a handheld gamma counter before (in vivo) and after (ex vivo) dissection. Lymph nodes with an ex vivo radioactive count more than 10 times the background value were identified as sentinel nodes. The correlation between the in vivo and ex vivo results was examined. RESULTS: Lymphoscintigraphy revealed that it took longer than 6 hours for sufficient (99m)Tc tin colloid to reach the sentinel nodes. Sentinel nodes could be identified in 40 patients (87%). Patients whose sentinel nodes could not be identified had a significantly lower ratio of forced expiratory volume in 1 second to forced vital capacity than did those with identifiable sentinel nodes (P =.03). No false-negative sentinel nodes were detected in 14 patients with N1 or N2 disease (0%). In the hilar lymph node stations, the lobar lymph nodes were most frequently identified as sentinel nodes (as often as 85% of the time). Fourteen patients (35%) had sentinel nodes in the mediastinum, the distribution of which depended on the lobe. In vivo and ex vivo counting showed 88% concurrence for the identification of sentinel nodes in mediastinal lymph node stations. CONCLUSION: The identification of sentinel nodes with (99m)Tc tin colloid is a reliable method of establishing the first site of nodal metastasis in non- small cell lung cancer. Sentinel nodes could be hardly identified in patients with a low ratio of forced expiratory volume in 1 second to forced vital capacity because of such conditions as chronic obstructive pulmonary disease. In vivo identification of sentinel nodes in the mediastinum could be useful approach to guide mediastinal lymph node sampling or dissection.     

Predictors of lymph node and intrapulmonary metastasis in clinical stage IA non-small cell lung carcinoma

BACKGROUND: The feasibility of limited surgical resection for clinical stage IA non-small cell lung cancer still remains controversial. METHODS: From July 1987 through April 1998, 389 patients with clinical stage IA disease underwent major lung resection and complete mediastinal lymph node dissection. Univariate and multivariable analyses were performed to determine predictors of local or regional tumor spread: pathologic lymph node involvement, intrapulmonary metastases, and lymphatic invasion. RESULTS: Of the 389 patients, 88 (23%) had lymph node involvement or intrapulmonary metastases pathologically. According to multivariable analyses, grade of differentiation and pleural involvement were significant predictors of local or regional tumor spread (p < 0.01). Based on these results, more than 40% of clinical stage IA non-small cell lung cancer patients showed pathologic lymph node involvement or intrapulmonary metastases, or both, if the patients had both of the predictors of pathologic local or regional involvement: moderate or poor differentiation of the primary tumor and pleural involvement by tumor cells. CONCLUSIONS: Limited surgical resection is not feasible for clinical stage IA non-small cell lung cancer, especially when the tumor shows moderate or poor differentiation, or pleural involvement.     

Prognostic impact of lymph node involvement in pulmonary metastases from colorectal cancer.

OBJECTIVE: The purpose of this study was to identify the prognostic impact of unexpected lymph node metastases in patients undergoing resection of pulmonary metastases from colorectal cancer and specify the influence of pulmonary and mediastinal nodal involvement according to the modified Narukes lymph node mapping [Mountain CF, Dresler CM. Regional lymph node classification for lung cancer. Chest 1997;111(6):1718-23.]. METHODS: From January 1993 to December 2003, 175 patients were diagnosed and resected for pulmonary metastases of colorectal cancer. Follow up informations were collected for 169 patients and an analysis of prognostic factors was performed. Ninety-six men (56.8%) and 73 women (43.2%) with a median age of 62 (range 34-81) were identified, 28 (16.7%) patients were found to have lymph node metastases, five of them were identified during a recurrent procedure. Probability of survival was calculated according to the method of Kaplan-Meier. The prognostic influence of lymph node metastases on survival was analyzed with the log-rank test. RESULTS: Median survival was 47.2 months after first metastasectomy. Ten patients with intrapulmonary nodal involvement had a median survival of 86 months whereas 12 patients with hilar and six patients with mediastinal lymph node metastases had a median survival of 24.5 and 34.7 months. The survival difference between pulmonary and hilar/mediastinal metastases was statistically significant (p=0.008/p=0.07). Five year survival with pulmonary, hilar, and mediastinal metastases was 78.5, 0, and 0%, respectively. Perioperative mortality was 0%. CONCLUSIONS: Resection of pulmonary metastases secondary to colorectal cancer is safe and indicated in highly selected patients. Because tumor involvement of lymph nodes has a strong impact on survival; depending on their location, at least a lymph node sampling should always be performed. Adjuvant chemotherapy in case of proven lymph node metastases might be a good option to improve prognosis.     

Prognostic factors in surgically resected N2 non-small cell lung cancer: the importance of patterns of mediastinal lymph nodes metastases.

OBJECTIVE: Patients with non-small cell lung cancer (NSCLC) with metastases to ipsilateral mediastinal lymph nodes (N2) are an heterogeneous group of patients as regard to prognosis and treatment. Indication and timing of surgery remain controversial. The present study investigates the prognostic factors, in order to identify homogenous subgroups of patients. METHODS: Histologically proven N2-NSCLC patients, who underwent a complete surgical resection were retrospectively reviewed. Clinical and pathological features were reported and analyzed, and survival study was performed. RESULTS: One hundred eighty-three patients were analyzed. Overall 1.3 and 5 years survival rates were, respectively, 70, 35 and 20%, with a median survival time of 24 months. Univariate analysis showed a significant better prognosis for: incidental N2 respect to clinical N2 (5-years 35.4 vs 17.4%); single level lymph node involvement respect to multiple levels (5-years 23.8 vs 14.7%); metastases to superior mediastinal or aortic nodes respect to lower mediastinal nodes (5-years 32 and 24.3 vs 16.3%); right upper lobe tumors with superior mediastinal nodes and left upper lobe tumors with aortic nodes respect to lower lobes tumors with lower mediastinal nodes (5-years 31.8 and 26.9 vs 15.7%). Skip metastases had not a significant survival advantage respect to continuous lymphatic spread. N2 clinical status, the number of levels involved and the two specific patterns of lymphatic spread resulted significant prognostic factors at multivariate analysis. CONCLUSIONS: Clinical N2 status, number of lymph nodes levels involved and specific patterns of lymphatic spread identify homogenous subgroups of patients that can be proposed for different therapeutic strategies.     

Re-evaluation of non-palpable scalene lymph node biopsy for the staging of non-small cell lung cancer.

OBJECTIVES: The purpose of this study was to determine the most suitable candidates for scalene lymph node biopsy to detect non-palpable scalene lymph node metastasis (N(3)-scalene) in non-small cell lung cancer patients. METHODS: Standard cervical mediastioscopies and ipsilateral scalene lymph node biopsies were performed preoperatively by a single surgeon on 121 consecutive patients with non-small cell lung cancer scheduled to have surgical resection between January 1997 and August 2002, who had neither evidence of distant metastasis on imaging diagnosis nor palpable supraclavicular lymph nodes. RESULTS: N(3)-scalene was detected in six patients (5.0%), who all had non-squamous cell carcinoma, including one (1.0%) out of 98 patients with negative standard cervical mediastinoscopy and five (21.7%) out of the remaining 23 patients with positive mediastinal lymph node involvement. There was a significant difference in the incidence of the N(3)-scalene between the two groups (P<0.01). Five patients with N(3)-scalene had metastatic lesions in the multilevel mediastinal lymph node station on the same side as the cancer (multilevel N(2)), and accounted for 31.3% of 16 patients with multilevel N(2) disease. The N(3)-scalene was detected in 5 (45.5%) of 11 patients with lung cancer classified as non-squamous cell carcinoma with multilevel N(2) disease. CONCLUSIONS: The results of the present study suggest that non-palpable scalene lymph node biopsy is indicated for lung cancer patients diagnosed as having non-squamous cell carcinoma with mediastinoscopic multilevel N(2) disease.