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.     

Evaluation of surgical indication for the small lesion of advanced lung cancer

This report analyzes the operative indication for the small lesion of advanced lung cancer. The subjects consisted of 25 patients with T1N2 lung cancer, one T1N3, four T1M1 and five small lung cancer lesion with dissemination, which was regarded as the small lesion of advanced lung cancer. The cumulative 5-year survival rate after operation for 25 patients with T1N2 lesion was 30.6%. Of 25 patients, 18 were selected patients who underwent a curative operation with a 5-year survival of 37.0%. In the remaining 7 patients, who underwent a non-curative operation, 5-year survival was 0%. As to mediastinal lymph node involvement, it is possible that metastasis to more than two levels of mediastinal lymph nodes or to the upper mediastinal lymph nodes (#1-3) are poor prognostic factors in T1N2 lesion. Another group except T1N2 could not be the comparative materials because they were much fewer in number. But T4 cases associated with small lung cancer lesion with dissemination and T1M1 cases associated with intrapulmonary metastasis encountered at thoracotomy could be expected to have a long-term survival. We conclude that T1N2 patients with metastasis to within one level of mediastinal lymph node, which will possibly have a curative operation, is a proper operative indication for the small lesion of advanced lung cancer.     

The Importance of Surgery to Non-Small Cell Carcinoma of Lung with Mediastinal Lymph Node Metastasis

In the past 25 years, 1,654 patients with non-small cell cancer underwent resection at National Cancer Center Hospital, Tokyo. A comparative study has been made of 5-year survival of patients who had pulmonary resection with and without mediastinal lymph node dissection.There were 426 patients (25.8% of the total) with N2 M0 disease. Of these, 345 underwent pulmonary resection with mediastinal lymph node dissection. The 5-year survival in this group was 15.9% (T1 N2 M0, 30.0%; T2 N2 M0, 14.5%; and T3 N2 M0, 12.9%). In the remaining 81 patients, who did not have mediastinal lymph node dissection, 5-year survival was 6.7%.Of the 426 patients with N2 M0 disease, 242 were select patients who underwent a curative operation with an overall 5-year survival of 19.2%. Sixty-six of them had squamous cell carcinoma and a 5-year survival of 30.8%; 153 had adenocarcinoma and a survival of 16.0%; 14 had large cell carcinoma and a survival of 12.8%; and 9 had adeno-squamous cell carcinoma, and none survived 5 years.To improve the end results, it is important to perform as many curative operations with mediastinal lymph node dissection as possible. Histological cell type and tumor status must be taken into consideration.     

Chest wall invasion in carcinoma of the lung. Therapeutic and prognostic implications

From 1974 through 1983, 125 patients underwent operation at Memorial Sloan-Kettering Cancer Center for non-small cell carcinoma of the lung invading the chest wall. (Excluded are those with superior sulcus tumors or distant metastases at presentation.) Eighty patients were male and 45 were female. Ages ranged from 33 to 88 years (median 60 years). Histologically, the tumors were epidermoid carcinoma in 46%, adenocarcinoma in 46%, and large cell carcinoma in 8%. All patients underwent thoracotomy (pneumonectomy 19, bilobectomy seven, lobectomy 75, wedge resection 10, and no pulmonary resection 14), with an operative mortality of 4%. At thoracotomy, mediastinal lymph node dissection was routinely performed, and the postsurgical stage was T3 N0 M0 in 53%, T3 N1 M0 in 13%, and T3 N2 M0 in 34%. Extrapleural resection was performed in 66 patients. En bloc resection of chest wall and lung was performed in 45 patients with an operative mortality of 2%. Complete resection of tumor was possible in 77 patients (62%). Extension of tumor beyond the parietal pleura significantly decreased resectability. The median survival of 48 patients having incomplete resection was 9 months, despite perioperative interstitial and external radiation. The actuarial 5 year survival rate (Kaplan-Meier) of 77 patients having complete resection was 40%. This percentage was not significantly influenced by the patient's age or sex or by tumor size or histologic type. Lymphatic metastases significantly reduced survival, with a 5 year actuarial survival rate of 56% for patients with T3 N0 M0 disease and 21% for those with T3 N1 M0 or T3 N2 M0 disease (p = 0.005). The extent of tumor invasion of the chest wall appeared to influence survival, but in the absence of lymphatic metastases the difference at 5 years was not significant. Complete resection offers a significant chance for long-term survival in lung cancer directly extending into parietal pleura and chest wall. Extrapleural resection or en bloc chest wall resection can be performed with a low operative mortality and an expected 5 year survival in excess of 50% in the absence of lymphatic metastases.     

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.     

Immunohistochemically detected micrometastases in peribronchial and mediastinal lymph nodes from patients with T1, N0, M0 pulmonary adenocarcinomas

The T1, N0, M0 subset of stage I lung adenocarcinoma is a tumor that has a 5-year disease-free survival rate of 66% to 85%. To date, there has not been a rigorous immunohistochemically detected lymph node micrometastasis study composed of patients with identical stage and type of tumors, and in which standard histologic features were incorporated into multivariate analyses. We immunohistochemically examined the peribronchial and mediastinal lymph nodes from 80 consecutively accrued patients with T1, N0, M0 adenocarcinomas and bronchioloalveolar carcinomas unselected for distant metastasis, and an additional 39 patients with similar stage and type neoplasms who were selected for their development of metastases to evaluate the prevalence of micrometastases, their association with distant metastases, and their relationship with other pathologic prognostic features. All slides were stained with keratin AE1/3. Micrometastases were confirmed with Ber-Ep4. Three immunohistochemically detected lymph node micrometastases were identified in three of 80 consecutively accrued patients (4%). These three positive stains constituted 0.5% of the 573 stains required to immunohistochemically screen all of the lymph node blocks from these patients. Among the 39 patients who were selected because they developed distant metastases, three immunohistochemically detected lymph node micrometastases from three patients were identified, which constituted 8% of patients in this group and 1% of the 280 stains required to screen all of these patients' lymph nodes. Small vessel invasion, maximum tumor dimension, and immunohistochemically detected lymph node micrometastases were independently associated with metastases on multivariate analysis. Among patients who developed metastases, there was no significant difference in the disease-free survival rate between those with and those without immunohistochemically detected lymph node micrometastases. Given the low sensitivity in terms of the number of immunohistochemical stains performed, and the prognostic significance of standard histologic features, the use of immunohistochemical screening lymph nodes from all patients with T1, N0, M0 adenocarcinomas is questionable.     

Multimodal treatment of non small cell lung cancer

The primary treatment of lung cancer depends on tumor stage. Chest CT scan and bronchoscopy are used to define the TNM stage and resectability. In case of lung cancer without mediastinal lymph node enlargement or direct mediastinal involvement (clinical stage I-IIb + T3N1) surgical treatment is recommended. The use of adjuvant chemotherapy has to be defined, but will be indicated in stage II and IIIa. Expected 5-year survival achieves 40 to 80 % depending on tumor stage. Exceeds the shorter diameter of mediastinal lymph nodes in chest CT scan more than 1 cm (or in case of positive PET scan) mediastinoscopy is indicated. In case of N2-disease and after tumor response to preoperative chemotherapy (about 60 %) secondary resection of the tumor leads to higher 5-year survival rates (20-40 %) compared to patients without induction therapy (5-20 %). In these patients and after unexpected detection of solitary lymph node metastasis by primary resection adjuvant mediastinal radiotherapy should be added. If the tumor has infiltrated the mediastinum or the upper sulcus (T3/4) and/or mediastinal lymph nodes are obviously tumor burden (e. g. > 3 cm, N2 bulky, N3) radical primary resection may not be possible. In these patients combined radio- and chemotherapy induces a high percentage of tumor regression and can be used before secondary resection (5-year survival 5-20 %). Locally advanced tumors infiltrating the main bronchus close to the carina or the carina itself and tumors with metastases in the same lobe, both without mediastinal lymph node metastases (T3/4N0-1), can be resected by sleeve pneumonectomy and lobectomy with satisfactory results respectively. In patients with resectable lung cancer and no clinical sign of tumor disease (f. e. anemia, weight loss, pain) limited staging procedure with chest CT scan including upper abdomen and bronchoscopy is reasonable. In the remaining patients complete staging is necessary. We recommend an interdisciplinary approach to patients with lung cancer.     

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.     

Chest wall invasion in lung cancer patients

This study was performed to assess the prognosis in patients with non-small cell lung cancer invading the chest wall. In this study, the data from 43 patients who were operated on between January 1990-January 1998, for non-small cell lung cancer with pathologically verified parietal pleural and chest wall invasion were retrospectively reviewed. The median and 3-year survival of the population was calculated to be 16.8 months and 34%. The pathologic stages were T3N0 in 31 (72.09%) patients, T3N1 in 5 (11.62%) and T3N2 in 7 (16.27%). The median survival of the T3N0M0 patients was 24 months but in the same T3 population with pathologically verified N1 and N2, the median survival was 7.4 months (p < 0.01). A complete resection was achieved in 37 (86.84%) patients. The median and 3-year survival of the patients with complete resection were 20.60 months and 41% respectively. In six patients, who had incomplete resection, median survival was noted to be 7.4 months. Patients who received adjuvant radiotherapy in the N2 positive group and the incomplete resection group, did not benefit (p > 0.05). The results of this study confirmed that the lung cancer patients with chest wall invasion had different survival curves. The survival of patients changed according to the completeness of the resection and lymphatic metastases of either N1 or N2.     

Lymphatic mapping and sentinel lymphadenectomy for primary and metastatic pulmonary malignant neoplasms

BACKGROUND: Mediastinal lymph node sampling understages a significant number of lung cancers, even when nodes are evaluated by immunohistochemical techniques. Intraoperative lymphatic mapping and sentinel lymphadenectomy allows focused pathologic evaluation of a few lymph nodes that accurately stage the entire basin. HYPOTHESIS: Lymphatic mapping and sentinel lymphadenectomy is a practical and accurate method of staging lymph nodes that drain primary and metastatic neoplasms of the lung. DESIGN AND SETTING: Retrospective review at a tertiary referral center. PATIENTS: Sixty-seven patients undergoing resection of lung tumors. MAIN OUTCOME MEASURES: Sentinel lymph node (SN) identification rate, number of SNs, nodal pathologic features, and survival. RESULTS: Twenty-eight patients had primary lung cancer and 39 had pulmonary metastases from melanoma (33 cases), squamous cell carcinoma (2 cases), colon cancer (2 cases), or other cancers (2 cases). Lymphatic mapping and sentinel lymphadenectomy was successful in all patients. The median number of lymph nodes identified by dye alone was 2 (range, 1-7); the median number identified by dye plus radiocolloid was 4 (range, 1-9). Most SNs (69%) were N1; 31% were N2. Lower lobe lesions drained to upper mediastinal nodes in 3 (13%) of 24 cases. Lymph node metastases were found in 11 patients with lung cancer (39%) and 8 patients with pulmonary metastases (21%). Ten (91%) of the 11 patients with lung cancer had SN involvement. In the 33 patients with metastatic melanoma, SN involvement significantly reduced the rate of 2-year survival (0% vs 48%). CONCLUSIONS: Lymphatic mapping and sentinel lymphadenectomy of intrapulmonary malignancies is technically challenging but feasible. Blue dye is most useful for in vivo identification of SNs; ex vivo radioactivity can confirm that excised nodes are SNs. Lymphatic mapping and sentinel lymphadenectomy can provide important prognostic information for patients with melanoma and lung metastases, and it may improve the staging of primary lung cancer.     

Risk analysis and long-term survival in patients undergoing resection of T4 lung cancer.

OBJECTIVE: The aim of this study is to identify the risk group of patients with T4 lung cancer who could more likely benefit from surgical resection. METHODS: Between January 1, 1990, and December 31, 1998, 77 patients underwent pulmonary resection for T4 lung cancer: lobectomy (n = 20), bilobectomy (n = 4) and pneumonectomy (n = 53). The T4 sites of mediastinal involvement were: Intrapericardiac portions of the pulmonary artery (n = 30), left atrium (n = 19), aorta (n = 8), superior vena cava (n = 8), carina (n = 7), the esophagus (n = 8) and the vertebral body (n = 6). Ten patients had multiple neoplastic nodules in the same lobe of the lung. RESULTS: Overall survival rates at 1, 2 and 3 years were 46, 31 and 21%, respectively. Factors adversely affecting survival with univariate analysis included the localization of tumours in the lower lobe (P = 0.04) and both the involvement of superior and inferior mediastinal lymph nodes (P = 0.03). Multivariate analysis included two factors adversely affecting survival: the location of the primary tumour and the nodal stations involved. Regression tree analysis classified the patients into low-risk group (primary tumour in upper lobe or in main stem bronchus and pN0 or pN1 or superior or inferior mediastinal nodes involved), intermediate-risk group (primary tumour in upper lobe or in main stem bronchus and both superior and inferior mediastinal nodes involved, primary tumour in inferior lobe and pN0 or pN1 or inferior mediastinal nodes involved) and high-risk group (primary tumour in inferior lobe and both superior and inferior nodes involved). The 3-year survival rates were 36% for the low-risk group, 4% for the intermediate-risk group and 0% for the high-risk group (P = 0.006). CONCLUSIONS: In patients with T4 lung cancer, the surgery can justify itself for tumours in the upper lobe or in the main stem bronchus and with pN0 or pN1.     

Chest Wall Invasion In Lung Cancer Patients

This study was performed to assess the prognosis in patients with non-small cell lung cancer invading the chest wall.

In this study, the data from 43 patients who were operated on between January 1990-January 1998, for non-small cell lung cancer with pathologically verified parietal pleural and chest wall invasion were retrospectively reviewed. The median and 3-year survival of the population was calculated to be 16.8 months and 34%. The pathologic stages were T3N0 in 31 (72.09%) patients, T3N1 in 5 (11.62%) and T3N2 in 7 (16.27%). The median survival of the T3N0M0 patients was 24 months but in the same T3 population with pathologically verified N1 and N2, the median survival was 7.4 months (p < 0.01). A complete resection was achieved in 37 (86.84%) patients. The median and 3-year survival of the patients with complete resection were 20.60 months and 41% respectively. In six patients, who had incomplete resection, median survival was noted to be 7.4 months. Patients who received adjuvant radiotherapy in the N2 positive group and the incomplete resection group, did not benefit (p > 0.05).

The results of this study confirmed that the lung cancer patients with chest wall invasion had different survival curves. The survival of patients changed according to the completeness of the resection and lymphatic metastases of either N1 or N2.     

Immunostaining for Detecting Lymph Node Metastases in Non-small Cell Lung Cancer

Objective- To detect lymph node metastases by immunohistochemistry, where previously undetected by routine histopathology. Design- Immunostaining was carried out for high- and low molecular weight cytokeratins, and Ber-EP4 in 19 consecutive lung cancer patients who had undergone systematic mediastinal lymph node dissection. Results- Eleven (58%) epidermoid carcinomas, 6 (32%) adenocarcinomas, and 2 (10%) bronchiolo-alveolar carcinomas were detected. These included 4 (21%) stage IA carcinomas, 6 (32%) stage IB, 6 (32%) stage IIB, 1 (5%) stage IIIB and 2 (10%) stage IV. Immunostaining did not reveal any undetected metastases. Two patients (squamous cell carcinoma T1N0; adenocarcinoma T1N0) had metastases (skeletal; ipsilateral lung) at time of surgery, and one patient (squamous cell carcinoma T₂N0) had a regional and systemic relapse 10 months later. Serial sectioning with immunostaining of the lymph nodes from these three patients was also negative. Conclusion- We conclude that, even with the use of immunostaining, negative lymph nodes will not assure a good prognosis, and different determinants probably exist for lymphatic and hematogenic metastases in non-small cell lung cancer.     

Rational lymph node dissection for lung cancer according to the occurrence lobe and histological type]

Between January 1989 and December 1998, 134 cases of squamous cell carcinoma and 244 cases of adenocarcinoma underwent surgical resection of the lung with systematic lymph node dissection in our hospital. The cN diagnosis by CT scan and pN diagnosis were compared. In squamous cell carcinoma pN 2-3 cases were only one patient (2%) out of 60 patients with cN 0, 5 patients (18%) out of 28 patients with cN 1, and 21 patients (46%) out of 46 patients with cN 2-3. On the other hand in adenocarcinoma pN 2-3 cases were 27 patients (14%) out of 193 patients with cN 0, 3 patients (25%) out of 12 patients with cN 1, and 24 patients (62%) out of 39 patients with cN 2-3. The pathways of the lymphatic metastases to the mediastinal nodes were analized in 27 patients with squamous cell carcinoma and 54 patients with adenocarcinoma undergoing systematic lymph node dissection. All patients had histologically proven mediastinal metastasis. Histologically there was no difference in pathways of the lymphatic metastases to the mediastinal nodes. 1. The dominant lymphatic drainage from the right upper lobe flowed into the superior mediastinal nodes. The direct metastatic passages to the superior mediastinal nodes were observed (47%). Subcarinal and inferior mediastinal node involvement was rare (3%). 2. The dominant lymphatic drainage from the middle and the lower lobe flowed into the subcarinal nodes (85%). The involvement of the superior mediastinal nodes occurred in 53% of subcarinal node positive patients on the right side. 3. The dominant lymphatic drainage from the left upper lobe flowed into the subaortic or paraaortic nodes (69%). Subcarinal and inferior mediastinal node involvement was rare (6%). We conclude that subcarinal and inferior mediastinal lymph node dissection is not necessary for upper lobe lung cancers, and that superior mediastinal lymph node dissection can be omitted in middle and lower lobe lung cancers without hilar and subcarinal lymph node involvement, especially in the cases of cN 0.     

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.     

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.     

Lymphogenous and hematogenous metastasis of thymic epithelial tumors

BACKGROUND: A TNM classification has been established for various tumors. However, the TNM classification of thymic epithelial tumor has not been established yet. METHODS: We received replies to a questionnaire on thymic epithelial tumors from 115 institutes. We compiled a database of 1,320 patients with thymic epithelial tumor (1,093 thymomas, 186 thymic carcinomas, and 41 thymic carcinoids) who were treated between 1990 and 1994. We used a tentative TNM classification of thymoma presented by Yamakawa and associates in 1991. The regional lymph nodes of the thymus were classified into three groups: anterior mediastinal lymph nodes (N1), intrathoracic lymph nodes (N2), and extrathoracic lymph nodes (N3). RESULTS: The rate of lymphogenous metastasis in thymoma, thymic carcinoma, and thymic carcinoid was 1.8%, 27%, and 28%, respectively. Most tumors with lymph node metastasis metastasized to N1 (thymoma, 90%; thymic carcinoma, 69%; thymic carcinoid, 91%). The 5-year survival rates of N0, N1, and N2 thymoma were 96%, 62%, and 20%, respectively. The 5-year survival rates of N0, N1(,) N2, and N3 thymic carcinoma were 56%, 42%, 29%, and 19%, respectively. The 5-year survival rates of M0 and M1 thymoma were 95% and 57%. The 5-year survival rates of M0 and M1 thymic carcinoma were 51% and 35%. Multivariate analysis demonstrated that survival of patients with thymoma was dependent on the clinical stage of Masaoka and complete resection. In thymic carcinoma, survival was dependent on lymph node metastasis and complete resection. CONCLUSIONS: The N factor was one of the predictors of survival in thymoma and thymic carcinoma. However, M factor showed less influence on survival than T or N factors.     

Extent of chest wall invasion and survival in patients with lung cancer.

BACKGROUND: The long-term survival after operation of patients with lung cancer involving the chest wall is known to be related to regional nodal involvement and completeness of resection, but it is not known whether the depth of chest wall involvement or the type of resection (extrapleural or en bloc) affects either the rate of local recurrence or survival. METHODS: We retrospectively reviewed the Memorial Sloan-Kettering Cancer Center experience between 1974 and 1993 of 334 patients undergoing surgical exploration for lung cancer involving the chest wall or parietal pleura. RESULTS: Of 334 patients who underwent exploration, 175 had apparently complete (R0) resections, 94 had incomplete (R1 or R2) resections, and 65 underwent exploration without resection. The overall 5-year survival of R0 patients was 32%, of R1 or R2 patients 4%, and of patients undergoing exploration without resection 0%. In the patients undergoing R0 resections, the extent of chest wall involvement was limited to the parietal pleura in 80 patients, and extended into the ribs or soft tissues in 95. The 5-year survival of R0 patients with T3 N0 M0 disease was 49%, T3 N1 M0 disease 27%, and T3 N2 M0 disease 15% (p < 0.0003). Independent of lymph node involvement, a survival advantage was observed in R0 patients if the chest wall involvement was limited to parietal pleura only, rather than invading into the chest wall musculature or ribs. CONCLUSIONS: Survival of patients with lung cancer invading the chest wall after resection with curative intent is highly dependent on the extent of nodal involvement and the completeness of resection, and much less so on the depth of chest wall invasion.     

Radical extensive surgery for renal cell carcinoma: long-term results and prognostic factors

We studied 200 consecutive patients with renal cell carcinoma who underwent radical nephrectomy and extensive lymphadenectomy. Of the patients 25% already had distant metastasis at operation. Higher T stages tended to be associated with positive nodes (p less than 0.01) and distant metastasis (p less than 0.001). However, in patients with stage N0M0V0 tumors we found no statistically significant difference in survival in relationship to the T stage of the disease (5-year survival: stage T1 80%, stage T2 68% and stage T3 70%). Of all patients 10% had positive nodes without distant metastases and no venous spread of the tumor, and the 5-year survival rate was 52%. The 5-year survival rate of patients with distant metastases was 7%. Patient survival in the presence of a vena caval tumor thrombus is similar to that of patients with distant metastases. Based on our results the different stages in disease progression may be classified as having a good prognosis--intracapsular tumors (stages T1 to T2, N0M0V0) and tumors with involvement of perirenal fat (stage T3N0M0V0), an intermediate prognosis--tumors with nodal metastases alone (stages T1 to T3, N1 to 2, M0V0) and a poor prognosis--tumors with venous invasion and/or distant metastases. Histological grading and size of tumor can be used to assess prognosis but are not more accurate than pathological staging.     

Resection and radical lymphadenectomy for lung cancer: prognostic significance of lymphatic metastases

From 1979 to 1987, 1103 thoracotomies were performed in patients with lung cancer: 824 (74.7%) radical resections, 141 (12.7%) palliative resections and 138 (12.5%) exploratory thoracotomies. Among the 965 patients who underwent resection, 539 patients were N0, 190 patients N1 and 236 patients N2. Among patients with N1 disease we observed more frequent hilar metastases in the more advanced tumors (p less than 0.05). In 84 out of the 232 N2 patients (36.2%; 13.4% of all patients) a skipping of all pulmonary sites was observed. The most commonly invaded mediastinal levels were the paratracheal nodes on the right and the aortic nodes on the left, followed by the subcarinal nodes. The greater the neoplastic involvement of pulmonary nodal sites, the higher the percentage of patients with N2 disease and the number of mediastinal levels with tumor cells (p less than 0.05). The 5-year survival rate is 60% for N0, 46% for N1 and 23% for N2 disease. There is no significant difference in survival between N2 and N1 + N2 patients. Metastatic involvement of both upper and lower mediastinal levels carries a poorer prognosis compared to involvement of one compartment only (p less than 0.02). Patients with findings of mediastinal metastatic involvement should be selected: studies on lymphatic metastases are useful to better establish surgical indications for N2 patients.