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.     

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.     

Resection of multifocal non-small cell lung cancer when the bronchioloalveolar subtype is involved

OBJECTIVE: Bronchioloalveolar lung cancer is commonly multifocal and can also present with other non-small cell types. The staging and treatment of multifocal non-small cell cancer are controversial. We evaluated the current staging of multifocal bronchioloalveolar carcinoma and the therapeutic effectiveness of resection when this tumor type is involved. METHODS: We reviewed our experience between 1992 and 2000 with complete pulmonary resections for bronchioloalveolar carcinoma. Kaplan-Meier survival curves were calculated from the dates of pulmonary resection. RESULTS: Among 73 patients with bronchioloalveolar carcinoma, 14 patients, 7 male and 7 female with a mean age of 65 years (51-87 years), had multifocal lesions without lymph node metastases. Follow-up was 100% for a median of 5 years (range 2.6-8.5 years). Tumor distribution was unilateral in 9 patients and bilateral in 5 patients. The multifocal nature of the disease was discovered intraoperatively in 4 patients. Nine patients had 2 lesions, 4 patients had 3 lesions, and 1 patient had innumerable discrete foci in a single lobe. Operative mortality was 0. Postoperatively, 10 patients were staged pIIIB or pIV on the basis of multiple foci of similar morphology; 4 patients had some differences in histology (implying multiple stage 1 primaries). The median survival time to death from cancer was 14 months (141 days-5.6 years). The overall 5-year survival after resection of multifocal bronchioloalveolar carcinoma was 64%. Unilateral or bilateral distribution had no impact on survival. CONCLUSIONS: The current staging system is not prognostic for multifocal bronchioloalveolar carcinoma without lymph node metastases. Complete resection of multifocal non-small cell lung cancer when bronchioloalveolar carcinoma is a component may achieve survivals similar to that of stage I and II unifocal non-small cell lung cancer. When bronchioloalveolar carcinoma is believed to be one of the cell types in multifocal disease without lymph node metastases, consideration should be given to surgical resection.     

Genetic detection of lymph node micrometastases: a selection criterion for liver transplantation in patients with liver metastases after colorectal cancer

BACKGROUND: Liver transplantation for nonresectable liver metastases from colorectal cancer was abandoned in 1994 on account of high recurrence rates. The aim of this study was to investigate whether the genetic detection of micrometastases in histologically negative lymph nodes of the primary colon cancer could be applied to select patients for liver transplantation. METHODS: We analyzed 21 patients with colorectal cancer who had undergone liver transplantation between 1983 and 1994 for liver metastases. Eleven patients were histologically lymph node negative at the time of surgery; ten patients with lymph node metastases served as control group. DNA sequencing was used to screen tumor material for p53 and K-ras mutations. Mutant allele-specific amplification (MASA) was then used to search for micrometastases in DNA from regional lymph nodes of the primary colorectal cancer. RESULTS: p53 and K-ras mutations were detected in 12 (57%) and 3 (14%) of 21 patients in the colorectal cancer, respectively. The mutations were confirmed in the corresponding liver metastases. Of 11 patients with histologically negative lymph nodes, nine were eligible for MASA due to presence of p53 or K-ras mutation. MASA revealed six of nine patients to be genetically positive for micrometastases. Three patients were both genetically and histologically negative. These three patients showed a significantly longer overall survival (P = 0.011) of 4, 5, and 20 years, respectively. CONCLUSIONS: We conclude that the genetic detection of micrometastases by MASA could be a powerful prognostic indicator for selecting patients with colorectal liver metastases who could benefit from liver transplantation.     

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.     

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.     

Pathologic N1 non-small cell lung cancer: correlation between pattern of lymphatic spread and prognosis

OBJECTIVES: Patients with N1 non-small cell lung cancer represent a heterogeneous population with varying long-term survivals. Prognosis and pattern of recurrence seem to be particularly affected by the level of lymph node involvement. METHODS: From 1990 to 1995, a total of 1954 consecutive patients underwent surgical resection for non-small cell lung cancer: 549 (28%) had ipsilateral pulmonary lymph node metastases (N1). The hospital survivors (n = 535) were reviewed. Three levels of lymph node metastases (hilar, interlobar, and lobar) were identified according to the new Regional Lymph Node Classification for Lung Cancer Staging and differentiated from lymph node involvement on the basis of direct invasion. RESULTS: 1 The overall 5-year survival of patients with N1 disease was 40%. Survival was related in the univariate analysis to T classification, level-type of N1 involvement, number of involved nodes, multilevel involvement, Karnofsky Index, R status, and adjuvant therapy. In the multivariate analysis, only T classification and level-type of N1 involvement clearly showed statistical power (P =.000 and P =.001, respectively). The pattern of cancer relapse according to level-type of N1 involvement differed significantly: hilar N1 disease recurred at distant sites in 41% of patients and locoregionally in 12% of patients, whereas N1 disease by direct invasion occurred in 24% and 17% of patients, respectively (P =.030). CONCLUSIONS: Metastases to ipsilateral hilar, interlobar, or both, lymph nodes are associated with a poorer prognosis compared with metastases in intralobar lymph nodes or with lymph node involvement by means of direct invasion. Although surgical resection remains the mainstay of treatment, the high rate of tumor recurrence in both groups mandates further randomized studies with multimodality therapy approaches.     

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.     

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.     

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.     

A clinical study for improving the survival rate of pN2 lung cancer through our case of 53 patients]

BACKGROUND: In management of non-small cell lung cancer, the evaluation and treatment of N2 disease has a lot of controversy. MATERIALS AND METHODS: Between 1983 and 1998, 53 patients of pN2 non-small cell lung cancer were operated by standard lymph node dissection method (R2) using CUSA system. We studied the sensitivity of the diagnosis of preoperative N factor, survival rate, and analysed the relationship between the postoperative mediastinal lymph node metastasis and the site of recurrence. RESULTS: Three-year and five-year survival rates for 53 cases were 46.8% and 33.4% respectivery. Preoperative sensitivity of CT scan for N factors were only 45% in squamous cell carcinoma and 24.2% in adenocarcinoma. Even with intraoperative findings, the sensitivity was not better. In a follow up survey, ipsilateral mediastinal lymph node recurrence was not detected, contralateral mediastinal lymph node recurrences were rare and the distant metastases were common cause of death. CONCLUSION: It is more important to accomplish the standard lymph node dissection completely in all cN cases than to evaluate the preoperative node stage aggressively using invasive methods.     

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.     

Thoracoscopic mediastinal lymph node dissection for lung cancer

Mediastinal lymph node staging is an important component of the assessment and management of patients with operable non-small cell lung cancer and is necessary to achieve complete resection. During minimally invasive surgery, performance of an equivalent oncologic resection, including adequate lymph node dissection similar in extent to open thoracotomy, is absolutely necessary. We describe our techniques for video-assisted thoracic surgery (VATS) and Robot-assisted VATS (R-VATS) mediastinal lymph node dissection when performing thoracoscopic lobectomy for lung cancer. Between 2008 and 2011, 200 consecutive patients who underwent VATS or R-VATS lobectomies for early stage lung cancer were analyzed. In our series, we removed about 25 lymph nodes per case in both complete VATS and R-VATS. A thorough lymph node dissection in lung cancer is possible with either VATS or R-VATS technique without oncological compromise.     

In patients undergoing lung resection for non-small cell lung cancer, is lymph node dissection or sampling superior?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'In patients undergoing lung resection for non-small cell lung cancer, is lymph node dissection or sampling superior?' Altogether 845 papers were found using the reported search, of which 14 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that in stage I tumours there is little difference in survival when performing either mediastinal lymph node dissection (MLND) or lymph node sampling. However, survival is increased when performing MLND in stage II to IIIa tumours. Increased accuracy in staging is not observed with MLND. However, MLND reliably identifies more positive N2 nodes which may offer advantages in postoperative adjuvant treatment in more advanced disease.     

Mediastinoscopy in patients with clinical stage I non-small cell lung cancer

BACKGROUND: The aim of this study was to investigate the significance of mediastinoscopy for clinical stage I non-small cell lung cancer. METHODS: We reviewed 291 patients who underwent mediastinoscopy from January 1995 to December 2001 for clinical stage I non-small cell lung cancer. The patients who presented tumor-negative lymph nodes on mediastinoscopy underwent thoracotomy for pulmonary resection and mediastinal lymph node dissection in the same operative session. Mediastinoscopy-positive patients were referred for neoadjuvant therapy. RESULTS: Of the 291 patients, 20 patients (6.9%) were found with N2 or N3 disease on mediastinoscopy. Among 271 mediastinoscopy-negative patients, thoracotomy-proven N0 was found in 201 patients (74.2%), N1 in 44 patients (16.2%), and N2 in 25 patients (9.2%). Seventeen of 25 patients with unforeseen N2 disease had positive lymph nodes in the station that could be approached by mediastinoscopy only. The positive rate of mediastinoscopy was significantly higher in the patients with nonbronchioloalveolar-type adenocarcinoma than in squamous cell carcinoma (11.5% vs 3.3%, p = 0.013). However, there was no difference in the mediastinoscopy-positive rate between clinical T1 and T2 status. CONCLUSIONS: Though there are still controversies about routine mediastinoscopy in patients without mediastinal nodal enlargement on chest computed tomography scan, this study demonstrates that routine mediastinoscopy is necessary, especially for nonbronchioloalveolar-type adenocarcinoma patients.     

Limited mediastinal lymph node dissection for non-small cell lung cancer according to intraoperative histologic examinations

BACKGROUND: Although radioisotopic procedures are commonly used to detect sentinel lymph nodes in breast cancer surgery, these procedures are often problematic and not necessarily suitable for lung cancer surgery. METHODS: Our previous study revealed that the mediastinal sentinel lymph node, defined as the regional mediastinal lymph node, consisted of nodes 2, 3, or 4 in right upper lobe cancers; 3, 7, or 8 in right lower lobe cancers; 4, 5, or 7 in left upper lobe cancers; and 4, 7, or 8 in left lower lobe cancers. On the basis of these findings, we pathologically investigated one representative lymph node at each of the 3 levels dissected during surgical intervention in 69 patients with non-small cell lung cancer from September 1993 through December 2002. Fifty-eight patients with lung cancer underwent lobectomies with limited mediastinal lymph node dissection according to this strategy. RESULTS: Mediastinal lymph node recurrence was observed in only one patient during 41 +/- 25 months (maximum, 98 months) of follow-up. The cancer-specific 5-year survivals were 96.6% in patients with pathologic stage IA disease (n = 31) and 67.4% in patients with stage IB disease (n = 16). CONCLUSION: These results suggested that limited mediastinal lymph node dissection is applicable to patients with non-small cell lung cancer whose regional mediastinal lymph nodes are not metastatic.     

Pattern and predictors of occult mediastinal lymph node involvement in non-small cell lung cancer patients with negative mediastinal uptake on positron emission tomography.

OBJECTIVE: We sought to assess the incidence, pattern and predictors of occult mediastinal lymph node involvement (N2) in non-small cell lung cancer patients with negative mediastinal uptake of 2-deoxy-2-[(18)F]-fluoro-d-glucose ((18)FDG) on integrated positron emission tomography-computerised tomography (PET-CT). METHODS: All patients who underwent surgical resection in our unit over a 30-month period were reviewed (n=215). All patients had preoperative PET-CT prior to lung resection as an adjunct to a dedicated chest CT. Diabetic patients, patients who received neoadjuvant chemotherapy and those with positive mediastinal nodes on PET-CT (N2/N3) were excluded from this study. The population of interest was 153 non-small cell cancer patients (NSCLC), all of which had no FDG uptake in the mediastinum. No preoperative mediastinoscopy was carried out in this group and all underwent curative intent surgical resection. The pathological results were retrospectively reviewed and correlated with CT and integrated PET-CT findings. RESULTS: The incidence of occult N2 disease in NSCLC patients with negative mediastinal uptake of (18)FDG on PET-CT was 16% (25 of 153). The highest incidence of occult N2 involvement was in American thoracic society (ATS) 7 (16 of 25 patients, 64%) followed by ATS 4 (seven patients of 25, 28%). In univariate analysis, the following were significant predictors of occult N2 disease: centrally located tumours (P=0.049), right upper lobe tumours (P=0.04), enlarged lymph nodes (>1cm) on CT (P=0.048) and PET positive uptake in N1 nodes (P=0.006). In multivariate analysis, the following were independent predictors of occult N2 disease: centrally located tumours, right upper lobe tumours and PET positive uptake in N1 nodes (P<0.05). CONCLUSIONS: In NSCLC patients who are clinically staged as N2/N3 negative in the mediastinum by integrated PET-CT, 16% will have occult N2 disease following resection. Patients with the following: centrally located tumours, right upper lobe tumours and positive N1 nodes on PET should have preoperative cervical mediastinoscopy to rule out N2 nodal involvement, especially in ATS stations 7 and 4 as the incidence of occult nodal metastasis in these nodes is high. This study has potential implications in decision-making and planning best treatment approach.     

A biologic risk model for stage I lung cancer: immunohistochemical analysis of 408 patients with the use of ten molecular markers

OBJECTIVE: The standard treatment of patients with stage I non-small cell lung cancer is resection of the primary tumor; however, the recurrence rate is 28% to 45%. This study evaluates a panel of molecular markers in a large population of patients with stage I non-small cell lung cancer to determine the prognostic value of each marker and to create a biologic risk model. METHODS: Pathologic specimens were collected from 408 consecutive patients after complete resection for stage I non-small cell lung cancer at a single institution, with follow-up of at least 5 years. A panel of 10 molecular markers was chosen for immunohistochemical analysis of the primary tumor on the basis of differing oncogenic mechanisms. Local tumor expansion requires growth regulating proteins (epidermal growth factor receptor, the protooncogene erb-b2); apoptosis proteins (p53, bcl-2); and cell cycle regulating proteins (retinoblastoma recessive oncogene, KI-67). Local tumor invasion requires angiogenesis (factor viii). The development of distant metastases involves the expression of adhesion proteins (CD-44, sialyl-Tn, blood group A). Cox proportional hazards regression analysis was used to construct an independent risk model for cancer recurrence and death. RESULTS: Multivariable analysis demonstrated significantly elevated risk for the following molecular markers: p53 (hazard ratio, 1.68; P =.004); factor viii (hazard ratio, 1.47 P =. 033); erb-b2 (hazard ratio, 1.43; P =.044); CD-44 (hazard ratio, 1. 40; P =.050); and retinoblastoma recessive oncogene (hazard ratio, 0. 747; P =.084). CONCLUSIONS: Five molecular markers were associated with the risk of recurrence and death, representing independent metastatic pathways: apoptosis (p53), angiogenesis (factor viii), growth regulation (erb-b2), adhesion (CD-44), and cell cycle regulation (retinoblastoma recessive oncogene). This study demonstrates the validity of this molecular biologic risk model in patients with stage I non- small cell lung cancer.     

Recurrence in regional pulmonary lymph nodes after surgery for isolated pulmonary metastasis from hepatocellular carcinoma

Hepatocellular carcinoma occasionally metastasizes to extrahepatic organs, rarely to the mediastinal lymph nodes. We present the case of a 64-year-old man who presented with nodules in the upper and right lower lobes of the lung 4 years after undergoing resection of a hepatocellular carcinoma. We performed wedge resection of both lesions. Pathological examination showed that the lesion in the right upper lobe was non-small cell lung cancer and that in the right lower lobe hepatocellular carcinoma. We accordingly performed right upper lobectomy with lymph node dissection. Nine months later, enlarged subcarinal and segmental lymph nodes were detected and mediastinal lymph node metastases from the hepatocellular carcinoma diagnosed by transbronchial needle aspiration.