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.     

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.     

Significant Prognostic Factors for Completely Resected pN2 Non-small Cell Lung Cancer without Neoadjuvant Therapy

Purpose: To identify prognostic factors for pathologic N2 (pN2) non-small cell lung cancer (NSCLC) treated by surgical resection.Methods: Between 1990 and 2009, 287 patients with pN2 NSCLC underwent curative resection at the Cancer Institute Hospital without preoperative treatment.Results: The 5-year overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) rates were 46%, 55% and 24%, respectively. The median follow-up time was 80 months. Multivariate analysis identified four independent predictors for poor OS: multiple-zone mediastinal lymph node metastasis (hazard ratio [HR], 1.616; p = 0.003); ipsilateral intrapulmonary metastasis (HR, 1.042; p = 0.002); tumor size >30 mm (HR, 1.013; p = 0.002); and clinical stage N1 or N2 (HR, 1.051; p = 0.030). Multivariate analysis identified three independent predictors for poor RFS: multiple-zone mediastinal lymph node metastasis (HR, 1.457; p = 0.011); ipsilateral intrapulmonary metastasis (HR, 1.040; p = 0.002); and tumor size >30 mm (HR, 1.008; p = 0.032).Conclusion: Multiple-zone mediastinal lymph node metastasis, ipsilateral intrapulmonary metastasis, and tumor size >30 mm were common independent prognostic factors of OS, CSS, and RFS in pN2 NSCLC.     

Pathologic N0 status in pulmonary adenocarcinoma is predictable by combining serum carcinoembryonic antigen level and computed tomographic findings

OBJECTIVES: It is not clear whether lymphadenectomy has therapeutic benefit in non-small cell lung cancer management. To avoid unnecessary lymphadenectomy, we attempted to identify clinical or radiologic predictors of pathologic N0 disease in patients with peripheral adenocarcinoma. METHODS: From August 1992 through April 1997, 269 consecutive patients with peripheral adenocarcinoma who underwent major lung resection and systematic lymph node dissection were enrolled in this study. We reviewed their contrast-enhancement computed tomographic scans and recorded the maximum dimension of tumors both on pulmonary (pDmax) and on mediastinal (mDmax) window setting images, the largest dimension perpendicular to the maximum axis on both pulmonary (pDperp) and mediastinal (mDperp) window setting images, and the size of all detectable hilar-mediastinal lymph nodes. We defined a new radiologic parameter, tumor shadow disappearance rate (TDR), which is calculated with the following formula: TDR = 1 - (mDmax x mDperp)/(pDmax x pDperp). RESULTS: In multivariable analysis a lower serum carcinoembryonic antigen level and a higher tumor shadow disappearance rate were significant predictors of pathologic N0 disease. Lymph node size on computed tomographic scanning was not a significant predictor. Among 59 patients with a normal preoperative carcinoembryonic antigen level and a tumor shadow disappearance rate of 0.8 or more, 58 (98%) patients had pathologic N0 disease, and the other patient had pathologic N1 disease. CONCLUSIONS: Mediastinal lymph node involvement was not found in patients with a normal preoperative serum carcinoembryonic antigen level and a tumor shadow disappearance rate 0.8 or more. The patients who meet these criteria may be successfully managed with major lung resection without systematic mediastinal lymphadenectomy.     

Patterns of allelic loss of synchronous adenocarcinomas of the lung

Distinction of multiple primary lung carcinomas from intrapulmonary metastases using empiric clinical and histopathologic criteria can be difficult. Recent advances have provided several molecular markers that can be used for clonal analysis of separate tumor nodules and enhance tumor staging and subsequent treatment and prognosis. To address this issue, we performed a microdissection-based allelotyping of 20 cases of histologically similar, pathologic stage T4 adenocarcinomas (ADCs). Loss of heterozygosity (LOH) analysis included a panel of 15 polymorphic microsatellite markers located on 1p, 3p, 5q, 9p, 9q, 10q, 17p, and 22q. The tumor size, visceral pleural and angiolymphatic invasion, lymph node status, outcome, and survival were assessed. Allelotypes of 60 cases of solitary primary non-small cell lung carcinomas (NSCLC) (stages I-II) were used to define the percentage of discordant LOH patterns within solitary primary lung carcinoma that would discriminate between survivors and nonsurvivors. These criteria were used in the analysis of pathologic stage T4 ADC. Two groups of stage T4 cases were created: molecularly homogenous (< or = 40% discordances) (14 cases, 70%), and molecularly heterogenous (>40% discordances) (6 cases, 30%). Molecularly homogenous tumors were more frequently associated with visceral pleural invasion (92% vs. 8%) (P = 0.018). Allelotype did not correlate with age, gender, tumor size, tumor differentiation, lymph node status, angiolymphatic invasion, survival, or outcome. Our study showed that discordant and concordant genotypic profiles exist in morphologically similar synchronous ADC of the lung.     

Molecular assessment of lymph nodes in patients with resected stage I non-small cell lung cancer: preliminary results of a prospective study

OBJECTIVES: Routine histologic examination of resected lymph nodes in patients with stage I non-small cell lung cancer may underestimate the incidence of advanced disease. The presence of occult lymph node metastases may predict a higher risk of recurrence after intended curative resection. The purpose of this study was to determine the prognostic significance of TP53 and K-ras mutations in histologically determined negative lymph nodes from patients with stage I non-small cell lung cancer who underwent intended curative surgical resection. METHODS: Between July 1995 and March 1998, clinical data and tissue samples of primary tumors and lymph nodes were collected in a prospective fashion from 102 patients undergoing resection for non-small cell lung cancer (stage I, n = 55; stage II, n = 32; stage IIIA, n = 15). TP53 and K-ras mutations were detected by direct sequencing. If molecular alterations were found in the primary tumor, the corresponding lymph nodes were examined for these same TP53 (by oligonucleotide hybridization) and K-ras (by allele-specific ligation) mutations. RESULTS: TP53 mutations were found in 47 of 94 primary tumors (50%), and K-ras mutations were present in 26 of 55 adenocarcinomas (47%). A total of 134 lymph nodes from 32 patients with stage I disease were analyzed. In 9 cases (28%) the same TP53 or K-ras mutations were found in tumor and lymph node specimens, suggesting occult metastasis. On the basis of nodal location, 7 patients had their disease upstaged by a single stage and 2 patients by two stages. All 28 patients with stage II or III disease had pathologically determined positive nodes that were confirmed as positive by molecular analysis. Standard histopathologic assessment of regional lymph nodes failed to detect metastases at levels below 0.9% tumor-specific mutant TP53 clones per node. No statistically significant difference in disease-specific or overall survival was observed between patients with stage I disease with and without molecular lymph node metastases. CONCLUSIONS: Occult lymph node metastases are present in a significant percentage of patients with stage I non-small cell lung cancer. These data suggest that molecular analysis allows a more accurate assessment of staging. However, larger studies are needed to determine the clinical role of molecular staging.     

Intentional limited resection for small peripheral lung cancer based on intraoperative pathologic exploration

OBJECTIVE: The aim of this study was to assess the adequacy of our intentional limited resection for small peripheral lung cancer based on intraoperative pathologic exploration. METHODS: Patients who had stage IA non-small cell lung cancer (NSCLC) with a maximum tumor diameter of 2 cm or less were candidates for limited resection. If bronchioloalveolar carcinoma (BAC) was suspected on computed tomography and intraoperative pathologic exploration revealed the lesion as BAC without foci of active fibroblastic proliferation (Noguchi type A and B), wedge resection was performed. If the tumor was not suspected of being Noguchi type A or B, extended segmentectomy with intraoperative lymph node exploration was performed. RESULTS: Limited resection was performed in 34 patients, wedge resection in 14, and extended segmentectomy in 20. The median follow-up period after wedge resection was 36 months, and all patients are alive with no signs of recurrence. The median follow-up period after extended segmentectomy was 54 months. No local recurrences were found, but distant metastasis was diagnosed in one patient. The 5-year survival rate after extended segmentectomy was 93%. In the same period, lobectomy was performed in 57 patients with stage IA NSCLC with a maximum tumor diameter of 2 cm or less, and the 5-year survival rate was 84%. There were no significant differences in 5-year survival between extended segmentectomy and lobectomy. CONCLUSIONS: Careful selection of patients based on high-resolution computed tomography findings and intraoperative pathologic exploration makes intentional limited resection an acceptable option for the treatment of small peripheral NSCLC.     

Fluorine 18-tagged fluorodeoxyglucose positron emission tomographic scanning to predict lymph node metastasis, invasiveness, or both, in clinical T1 N0 M0 lung adenocarcinoma

OBJECTIVE: We sought to predict lymph node metastasis and tumor invasiveness in clinical T1 N0 M0 lung adenocarcinomas, and we measured fluorodeoxyglucose uptake on positron emission tomography. METHODS: Fluorodeoxyglucose positron emission tomography was performed on 44 patients with adenocarcinomas of 1 to 3 cm in size clinically staged as T1 N0 M0 before major lung resection with lymph node dissection. Fluorodeoxyglucose uptake was evaluated by using the contrast ratio between the tumor and contralateral healthy lung tissue. Lymphatic and vascular invasion within tumors, pleural involvement, and grade of histologic differentiation were examined. RESULTS: The pathologic tumor stage was T1 N0 M0 in 36 patients, and a more advanced stage was found in 8 patients. Although all 22 adenocarcinomas with a contrast ratio of less than 0.5 in fluorodeoxyglucose uptake were pathologic T1 N0 M0 tumors, 8 (36%) of 22 with a contrast ratio of 0.5 or greater were of a more advanced stage than T1 N0 M0, with the difference being significant (P =.002). Adenocarcinomas with a contrast ratio of less than 0.5 showed less lymphatic and vascular invasion and less pleural involvement than those with a contrast ratio of 0.5 or greater (P =.006, P =.004, and P =.02, respectively). The grade of histologic differentiation was well differentiated in 19 of 22 adenocarcinomas with a contrast ratio of less than 0.5 (86%), which was a greater frequency than the 4 (18%) of 22 adenocarcinomas with a contrast ratio of 0.5 or greater (P <.001). CONCLUSION: Clinical T1 N0 M0 lung adenocarcinomas with a contrast ratio of less than 0.5 usually did not have lymph node metastasis, had less tumor involvement of vessels or pleura, and were more frequently well differentiated than those with a contrast ratio of 0.5 or greater. Limited lung resection could be indicated, lymph node dissection or mediastinoscopy could be reduced, or both in this type of adenocarcinoma.     

Strategy for surgical treatment for small peripheral carcinoma of the lung especially on systemic nodal dissection

The diagnosis of small-sized (< or = 2 cm) non-small cell lung cancer (NSCLC) has increased with the development of computed tomography (CT), whereas unexpected extensive mediastinal involvement has been occasionally detected in such a small-sized lung cancer. We retrospectively analyzed the clinicopathological features to determinate the predictors for lymph node involvement in patients with a small-sized adenocarcinoma. One hundred and eighty one patients who underwent pulmonary resection and systematic nodal dissection for a peripheral small-sized adeno-carcinoma were reviewed. Of these, 24 patients (13.3%) had lymph node involvement. These patients were divided into 2 groups according to the existence of lymph node involvement, and the predictors for lymph node involvement were determined using univariate analysis and multivariate regression analysis. Univariate analysis revealed GGOR (ground glass opacity area/tumor area at the level of the greatest dimension of the lesion on chest computer tomography) > or = 25% (p = 0.0137) and pleural lavage fluid involvement (p = 0.0467) as predictors for lymph node involvement. No patients had lymph node involvement if their GGOR was higher than 50%. Multivariate regression analysis revealed GGOR > or = 25% (p = 0.0274), pleural tags on the lesion on chest CT (p = 0.0138) and pleural lavage fluid involvement (p = 0.0415) as predictors. We recommend performing systemic nodal dissection even if small peripheral adeno-carcinoma's maximal diameter is 20 mm or less. Systemic nodal dissection is unnecessary if the patients' GGOR > or = 50% or they do not have pleural tags or pleural lavage fluid involvement.     

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.     

临床ⅠA期周围型非小细胞肺癌纵隔淋巴结转移危险因素

目的 探讨临床Ⅰ A期周围型非小细胞肺癌(NSCLC)纵隔淋巴结转移情况,分析早期周围型NSCLC纵隔淋巴结转移的影响因素.方法 2000年1月至2010年12月治疗临床Ⅰ A期的周围型NSCLC 281例,男152例,女129例;年龄19～86岁,平均(60.31±12.13)岁.行肺叶切除或肺局限性切除加系统性纵隔...     

Analyses of segmental lymph node metastases and intrapulmonary metastases of small lung cancer

BACKGROUND: Curativity and indications for limited resection of small peripheral lung cancer remain controversial. METHODS: Pathologic investigations of segmental lymph node metastases and intrapulmonary metastases in the resected lobe were performed for 94 small peripheral lung cancers (3.0 cm or less in diameter). RESULTS: Nine patients had segmental lymph node metastases, 1 had intrapulmonary metastases, and 1 had both. Of these 11 patients, 5 had metastases limited to the primary tumor-bearing segments, 2 had metastases in nonprimary tumor-bearing segments, and 4 had metastases in both. Of the 10 patients with segmental lymph node metastases, 7 had metastases in both lobar-hilar and mediastinal lymph nodes, and 3 of 8 with adenocarcinoma had a tumor 2.0 cm or less. CONCLUSIONS: Segmentectomy seems more favorable than wedge resection, but the risk of remnant tumor remains as compared with lobectomy. Evaluation of lobar-hilar or mediastinal lymph nodes is helpful to determine the presence or absence of segmental lymph node metastases. Limited resection can be undertaken with smaller tumors to allow preservation of more lung function while accepting a somewhat enhanced risk of recurrence.     

Intentional limited resection for small peripheral lung cancer based on intraoperative pathologic exploration

Objective: The aim of this study was to assess the adequacy of our intentional limited resection for small peripheral lung cancer based on intraoperative pathologic exploration. Methods: Patients who had stage IA non-small cell lung cancer (NSCLC) with a maximum tumor diameter of 2 cm or less were candidates for limited resection. If bronchioloalveolar carcinoma (BAC) was suspected on computed tomography and intraoperative pathologic exploration revealed the lesion as BAC without foci of active fibroblastic proliferation (Noguchi type A and B), wedge resection was performed. If the tumor was not suspected of being Noguchi type A or B, extended segmentectomy with intraoperative lymph node exploration was performed. Results: Limited resection was performed in 34 patients, wedge resection in 14, and extended segmentectomy in 20. The median follow-up period after wedge resection was 36 months, and all patients are alive with no signs of recurrence. The median follow-up period after extended segmentectomy was 54 months. No local recurrences were found, but distant metastasis was diagnosed in one patient. The 5-year survival rate after extended segmentectomy was 93%. In the same period, lobectomy was performed in 57 patients with stage IA NSCLC with a maximum tumor diameter of 2 cm or less, and the 5-year survival rate was 84%. There were no significant differences in 5-year survival between extended segmentectomy and lobectomy. Conclusions: Careful selection of patients based on high-resolution computed tomography findings and intraoperative pathologic exploration makes intentional limited resection an acceptable option for the treatment of small peripheral NSCLC. Read at the Fifty-sixth Annual Meeting of the Japanese Association for Thoracic Surgery, Panel Discussion, Tokyo, November 19–21, 2003.     

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.     

Visceral pleural invasion is an invasive and aggressive indicator of non-small cell lung cancer

OBJECTIVE: Although visceral pleural invasion by non-small cell lung cancer is considered a poor-prognostic factor, further information is lacking, especially in relation to other clinicopathologic prognostic factors. We assessed the relationship between visceral pleural invasion and other clinicopathologic characteristics and evaluated its significance as a prognostic factor. METHODS: We reviewed 1074 patients with surgically resected T1/2 non-small cell lung cancer for their clinicopathologic characteristics and prognoses. The patients were divided into 2 groups according to visceral pleural invasion status (visceral pleural invasion group and non-visceral pleural invasion group). Both groups were compared with regard to age, sex, histology, tumor size, tumor differentiation, lymph node involvement, lymphatic invasion, vascular invasion, scar grade, nuclear atypia, mitotic index, serum carcinoembryonic antigen level, and survival. Univariate and multivariate analyses were conducted. RESULTS: Visceral pleural invasion was identified in 288 (26.8%) of the resected specimens. Survival was 76.0% at 5 years and 53.2% at 10 years in the non-visceral pleural invasion group and was 49.8% at 5 years and 37.0% at 10 years in the visceral pleural invasion group. The difference between groups was highly significant ( P < .0001). Visceral pleural invasion was also significantly associated with a higher frequency of lymph node involvement. However, regardless of N status (N0 or N1/2), there was a significant difference in survival when the visceral pleura was invaded. Visceral pleural invasion was observed significantly more frequently in tumors with factors indicative of tumor aggressiveness/invasiveness: moderate/poor differentiation, lymphatic invasion, vascular invasion, high scar grade, high nuclear atypia grade, high mitotic index, and high serum carcinoembryonic antigen level. By multivariate analysis, visceral pleural invasion proved to be a significant independent predictor of poor prognosis in non-small-cell lung cancer patients with or without lymph node involvement. CONCLUSIONS: Visceral pleural invasion is a significant poor-prognostic factor, regardless of N status. Our analyses indicated that visceral pleural invasion is an independent indicator of non-small cell lung cancer invasiveness and aggressiveness.     

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.     

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.     

Diagnosis and treatment of lung cancer – Non-small cell lung cancer, small cell lung cancer and carcinoids

Summary BACKGROUND: The prognosis of lung tumors is determined by histology and staging (nodal status). The most common tumor is non-small cell lung carcinoma (NSCLC) with a 5-year survival rate of 67 % (stage IA) to <5 % (stage IV). METHODS: By reviewing the literature guidelines for diagnosis and treatment of non-small cell lung cancer and neurendocrine tumors are presented. RESULTS: Functional operability provided, (bi)lobectomy or pneumonectomy with mediastinal lymph node dissection are the standard procedures. In case of positive mediastinal lymph nodes (stage IIIA/IIIB) induction chemo(radio)therapy is indicated. Cervical mediastinoscopy is performed in patients with enlarged mediastinal nodes (CT >1 cm), especially in PET-positive cases. Adjuvant chemotherapy is used in clinical trials. Small-cell lung cancer (SCLC, neuroendocrine tumor grade III) has a poor prognosis, and is treated with chemotherapy; resection may be performed in early stages. Neuroendocrine tumors grade I (typical carcinoid) are resected by segmentectomy, lobectomy, or bronchoplastic resection. Neuroendocrine tumors grade II (atypical carcinoids) are treated like NSCLC. CONCLUSIONS: The incidence of lung cancer is decreased by tobacco control, and the chances of survival are improved by early detection and multimodality regimens.      

Survival, disease-free interval, and associated tumor features in patients with colon/rectal carcinomas and their resected intra-pulmonary metastases

Objective: Colon/rectum cancer often presents with intrapulmonary metastases. Surgical resection can be performed in a selected group of patients. In this study, the search for possible prognostic factors of patients with primary colon/rectum cancer and lung metastases was performed. Methods: Medical records of 110 patients operated on pulmonary metastases of primary colon/rectum cancer were reviewed. The clinical parameters include age, sex, pTNM/UICC stage, grading, localization, surgical and adjuvant therapy of the primary cancer. The number, maximum diameter and total intra-thoracic resected tumor-mass (‘load’), the pre-thoracotomy serum carcinoembryonic antigen (CEA) levels, localization of the metastases (uni- vs. bilateral), the presence of hilar/mediastinal tumor-infiltrated lymph nodes, the surgical procedure and performed therapy schemes of lung metastases were recorded. Results: The cumulated 5- and 10-year total survival after diagnosis of the primary carcinomas was estimated to 71 and 33.7%, respectively. After resection of the pulmonary metastases, the 3- and 5-year post-thoracotomy survival measured 57 and 32.6%, respectively. The median time interval between diagnosis of the primary cancer and thoracotomy (disease free interval (DFI)) was found to be 35 months. A non-negligible percentage of patients (15.4%) displayed limited tumor stages of the primary cancer (pT1/2, pN0). The median diameter of the largest metastasis measured 28 mm, and the median resected intrathoracic tumor-load was calculated to 11.4 cm³. In only 8 patients hilar or mediastinal tumor-involved lymph nodes were found. A potentially curative resection of lung metastases was recorded in 96 patients. The overall survival was significantly correlated with the DFI and the number of intrapulmonary metastases. The DFI correlated significantly with the tumor load and the number of metastases; the post-thoracotomy survival with the number of metastases, tumor-load and pre-thoracotomy serum CEA level. Treatment, stage and grade of the primary cancer, occurrence of liver metastases and local recurrences, mode of treatment of metastases and postoperative residual stage had no significant correlation with either total nor post-thoracotomy survival. Conclusions: Pulmonary metastases occur even in patients with limited tumor-stages of primary colon/rectum cancer. DFI is the major parameter to estimate the total survival of patients with lung metastases. The survival after thoracotomy depends on the number of metastases, the intrapulmonary tumor load and the presence of elevated serum CEA level prior to thoracotomy.     

Pleural lavage cytology in non-small cell lung cancer: lessons from 1000 consecutive resections

OBJECTIVE: Intraoperative pleural lavage cytology for lung cancer has not been widely accepted. The prognostic significance of this procedure has yet to be intensively analyzed because the reports published thus far have involved small patient populations. We therefore performed a large prospective trial of pleural lavage cytology to elucidate its importance. METHODS: Cytologic status of pleural lavage fluid before any manipulation of the lung was examined in 1000 consecutive patients with non-small cell lung cancer but no pleural effusion who underwent tumor resection. RESULTS: Forty-five (4.5%) of 1000 patients had positive cytologic findings. Positive cytologic findings were observed more frequently in patients with adenocarcinoma, advanced stage, higher involvement of lymph nodes, pleural involvement of the tumor, lymphatic permeation, vascular invasion, high level of serum carcinoembryonic antigen, and male sex. The survival rate for 5 years was 28% in patients with positive findings and 67% in patients with negative findings (P <.0001). Among 587 patients with stage I disease, 13 (2.2%) had positive findings, and their 5-year survival was 43%, which was significantly poor compared with that of patients with negative findings (81%, P =.0009). Multivariable analysis demonstrated that pleural lavage cytology was an independent prognostic determinant (P =.0290). Regarding the recurrence pattern in patients with positive findings, distant metastases (19/45 [42.2%]) were observed more frequently rather than local recurrences (19/45 [22.2%]). CONCLUSIONS: Cytologic status of pleural lavage fluid immediately after thoracotomy, an independent significant prognostic factor, constitutes valuable information to detect patients at a high risk of recurrence. Therefore cytology should be performed at the time of curative resection for non-small cell lung cancer.