Prognostic value of tumor-infiltrating lymphocytes differs depending on histological type and smoking habit in completely resected non-small-cell lung cancer.

BACKGROUND: T-cell infiltration in tumors has been used as a prognostic tool in non-small-cell lung cancer (NSCLC). However, the influence of smoking habit and histological type on tumor-infiltrating lymphocytes (TILs) in NSCLC remains unclear. PATIENTS AND METHODS: We evaluated the prognostic significance of TILs (CD4+, CD8+, CD20+, and FOXP3+) according to histological type and smoking habit using automatic immunohistochemical staining and cell counting in 218 patients with NSCLC. RESULTS: In multivariate survival analyses of clinical, pathological, and immunological factors, a high ratio of FOXP3+ to CD4+ T cells (FOXP3/CD4) [hazard ratio (HR): 4.46, P < 0.01 for overall survival (OS); HR: 1.96, P < 0.05 for recurrence-free survival (RFS)] and a low accumulation of CD20+ B cells (HR: 2.45, P = 0.09 for OS; HR: 2.86, P < 0.01 for RFS) were identified as worse prognostic factors in patients with adenocarcinoma (AD). In non-AD, a low number of CD8+ T cells were correlated with an unfavorable outcome (HR: 7.69, P < 0.01 for OS; HR: 3.57, P < 0.02 for RFS). Regarding smoking habit in AD, a high FOXP3/CD4 ratio was poorly prognostic with a smoking history (HR: 5.21, P < 0.01 for OS; HR: 2.38, P < 0.03 for RFS), whereas a low accumulation of CD20+ B cells (HR: 4.54, P = 0.03 for OS; HR: 2.94, P < 0.01 for RFS) was confirmed as an unfavorable factor in non-smokers with AD. CONCLUSIONS: A low number of CD8+ T cells in non-AD, a high FOXP3/CD4 ratio in smokers with AD, and a low number of CD20+ B cells in non-smokers with AD were identified as independent unfavorable prognostic factors in resected NSCLC. Evaluating the influence of histological type and smoking habit on the immunological environment may lead to the establishment of immunological diagnosis and appropriate individualized immunotherapy for NSCLC.

RET-rearranged non-small-cell lung carcinoma: a clinicopathological and molecular analysis.

BACKGROUND: To elucidate clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) cases carrying RET rearrangements causing oncogenic fusions to identify responders to therapy with RET tyrosine kinase inhibitors. METHODS: We investigated 1874 patients with carcinomas, including 1620 adenocarcinomas (ADCs), 203 squamous cell carcinomas (SCCs), 8 large cell carcinomas, and 43 sarcomatoid carcinomas (SACs). Fluorescence in situ hybridisation (FISH) and/or reverse transcription-PCR (RT-PCR) were performed to detect RET gene rearrangement. RESULTS: In all, 22 cases (1.2%) showed RET rearrangements; all cases were of ADC histology. Of the 22 patients, 19 possessed KIF5B-RET fusion genes, whereas 3 possessed CCDC6-RET fusion genes. The RET-rearranged tumours were significantly more common in younger patients (P=0.038) and tended to occur in patients with no history of smoking (P=0.051). In addition, RET rearrangements were not associated with gender, occupational history (particularly radioactive exposure), tumour size, lymph node status, tumour stage, or patient survival. The predominant growth pattern in RET-rearranged ADCs was lepidic in 6 cases, papillary in 9 cases, acinar in 2 cases, micropapillary in 1 case, and solid in 4 cases. Cells with cytoplasmic mucin production were at least focally present in 12 of the 22 (54.5%) RET-rearranged ADC cases. Among the 21 analysed RET-rearranged tumours, RET immunopositivity was observed in 15 cases (71.4%), and was significantly associated with RET rearrangement (P<0.001). CONCLUSIONS: The RET rearrangements were observed in 1.2% of NSCLCs. All cases of RET rearrangement were ADCs. The RET rearrangements were more likely to be observed in younger patients. Although cytoplasmic mucin production was at least focally present in 54.5% of RET-rearranged ADCs, specific histological features were not detected.

Clinicopathological features of nonsmall cell lung carcinomas with BRAF mutations.

BACKGROUND: Recently, driver tyrosine kinase gene mutations have been detected in malignant tumors, including lung tumors. Notwithstanding their attractiveness as targets for molecular therapy, limited information is available regarding BRAF-mutated lung carcinomas. MATERIALS AND METHODS: BRAF mutation status was determined in 2001 surgically resected nonsmall-cell lung cancer (NSCLC) cases using high-resolution melting analysis (HRMA) followed by Sanger sequencing and/or deep sequencing using next generation sequencer. RESULTS: BRAF mutations were detected in 26 (1.3%) of 2001 NSCLC cases (25 adenocarcinomas and 1 squamous cell carcinoma). In the 26 cases, 13 mutation genotypes were identified, including V600E (8 of 26; 30.8%), G469A (6 of 26; 23.1%), K601E (4 of 26; 15.4%), and other residual mutations (1 of 26; 0.04%). Of the 13 genotypes, 4 genotypes (G464E, G596R, A598T, and G606R) had not been previously reported in lung cancer. The overall survival rate was not significantly different between patients with wild-type BRAF and those with V600E or non-V600E BRAF mutations (P = 0.49 and P = 0.15, respectively). Histomorphological analysis revealed that focal clear cell changes were present in 75% of V600E-mutated tumors. All V600E BRAF-mutated tumors were negative for other driver gene alterations including epidermal growth factor receptor (EGFR) and KRAS mutations and the anaplastic lymphoma kinase gene translocation, whereas five tumors with non-V600E BRAF mutations (four G469A and one G464E/G466R) showed concomitant EGFR mutations. CONCLUSION: The frequency of BRAF mutations in lung cancer was low in an Asian cohort. Furthermore, BRAF mutation status lacked prognostic significance in this patient population.

Diagnostic and prognostic significance of the alternatively spliced ACTN4 variant in high-grade neuroendocrine pulmonary tumours.

BACKGROUND: High-grade neuroendocrine tumours (HGNTs) of the lung manifest a wide spectrum of clinical behaviour, but no method for predicting their outcome has been established. MATERIALS AND METHODS: We newly established a monoclonal antibody specifically recognizing the product of the alternatively spliced ACTN4 transcript (namely, variant actinin-4), and used it to examine the expression of variant actinin-4 immunohistochemically in a total of 609 surgical specimens of various histological subtypes of lung cancer. RESULTS: Variant actinin-4 was expressed in 55% (96/176) of HGNTs, but in only 0.8% (3/378) of non-neuroendocrine (NE) lung cancers. The expression of variant actinin-4 was significantly associated with poorer overall survival in HGNT patients (P=0.00021, log-rank test). Multivariate analysis using the Cox proportional hazards model showed that the expression of variant actinin-4 was the most significant independent negative predictor of survival in HGNT patients (hazard ratio (HR), 2.15; P=0.00113) after the presence of lymph node metastasis (HR, 2.25; P=0.00023). CONCLUSIONS: The expression of variant actinin-4 is an independent prognostic factor for patients with HGNTs. This protein has a high affinity for filamentous actin polymers and likely promotes aggressive behaviour of cancer cells. The present clinical findings clearly support this notion.

Distinct outcome of stage I lung adenocarcinoma with ACTN4 cell motility gene amplification.

BACKGROUND: Even if detected at an early stage, a substantial number of lung cancers relapse after curative surgery. However, no method for distinguishing such tumors has yet been established. PATIENTS AND METHODS: The copy number of the actinin-4 (ACTN4) gene was determined by fluorescence in situ hybridization on tissue microarrays comprising 543 surgically resected adenocarcinomas of the lung. RESULTS: Amplification (an increase in the copy number by ≥ 2.0 fold) of the ACTN4 gene was detected in two of seven lung adenocarcinoma cell lines and 79 (15%) of 543 cases of pathological stage I-IV lung adenocarcinoma. Multivariate analysis revealed that ACTN4 gene amplification was the most significant independent factor associated with an extremely high risk of death (hazard ratio, 6.78; P = 9.48 × 10(-5), Cox regression analysis) among 290 patients with stage I lung adenocarcinoma. The prognostic significance of ACTN gene amplification was further validated in three independent cohorts totaling 1033 patients. CONCLUSIONS: Amplification of the ACTN4 gene defines a small but substantial subset of patients with stage I lung adenocarcinoma showing a distinct outcome. Such patients require intensive medical attention and might benefit from postoperative adjuvant chemotherapy.

Protein expression and gene copy number changes of receptor tyrosine kinase in thymomas and thymic carcinomas.

BACKGROUND: Insulin-like growth factor-1 receptor (IGF-1R), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-type 2 (HER2), and c-Met are members of the receptor tyrosine kinases (RTKs). The associations between the RTK status [protein expression and gene copy number (GCN)] and patient characteristics and between the RTK status and prognosis remain undetermined. MATERIALS AND METHODS: The study included 140 patients who underwent surgery for thymic tumors. Protein expression was evaluated by immunohistochemistry (IHC) and GCN was evaluated by bright-field in situ hybridization (BISH). The correlations between the RTK status and clinicopathological findings were examined. RESULTS: IGF-1R protein was frequently detected in thymic carcinoma (83.8%) and EGFR in thymic tumors (91.4%). Thirty-six and 39 tumors were BISH high for IGF-1R and EGFR, respectively: 28 and 25 exhibited high polysomy; 8 and 14 exhibited gene amplification. No tumor was positive for HER2 or c-Met by IHC and BISH. Multivariate analysis revealed that IGF-1R gene amplification (P = 0.027), thymic carcinoma histology, and higher tumor stage were significantly correlated with an adverse prognosis. CONCLUSIONS: Thymic epithelial tumors frequently express IGF-1R and/or EGFR proteins. IGF-1R gene amplification is suggested to define an unfavorable subset for thymic epithelial tumors.

Surgical implications of the new IASLC/ATS/ERS adenocarcinoma classification.

A new adenocarcinoma classification was recently introduced by a joint working group of the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS) and European Respiratory Society (ERS). A distinction is made between pre-invasive lesions, and minimally invasive and invasive adenocarcinoma. The confusing term "bronchioloalveolar carcinoma" is not used any more and new subcategories include adenocarcinoma in situ and minimally invasive adenocarcinoma. Due to a renewed interest in screen-detected nodules and early-stage lung cancers of <2 cm, this classification also has profound implications for thoracic surgeons. In this article, surgical topics are discussed: the role of a minimally invasive approach, especially video-assisted thoracic surgery, limited resection for early-stage lung cancer, the extent of lymph node dissection, the accuracy of intraoperative frozen section analysis, management of multiple lung nodules and prognostic factors in operated patients. Specific key issues are presented based on the current evidence and areas of surgical uncertainty are defined providing a basis for further studies. Thoracic surgeons will play a major role in the application and global introduction of this new adenocarcinoma classification. The remaining controversies regarding the precise diagnosis and management of early-stage lesions will have to be resolved by multidisciplinary and international collaboration.

Solitary pulmonary granuloma caused by Mycobacterium avium-intracellulare complex.

OBJECTIVES: To analyse the clinical features and high resolution computed tomography (HRCT) findings of solitary pulmonary granulomas caused by the Mycobacterium avium-intracellulare (MAI) complex. METHODS: We retrospectively analysed a series of 73 consecutive patients with solitary pulmonary granuloma and negative sputum smear and culture results, in whom the diagnosis was established by histological examination of specimens obtained by partial pulmonary resection or lobectomy. We compared the clinical features and HRCT findings of the solitary pulmonary granulomas definitively diagnosed to be caused by the MAI complex with those of granulomas of other causes by univariate and multivariate analyses. RESULTS: In this study series of 24 patients with solitary pulmonary granuloma, the aetiological agent was established as being the MAI complex. According to the results of the multivariate analysis, 'female sex', 'pleural indentation' and 'lobulation' on the HRCT images were significantly associated with solitary pulmonary granuloma caused by the MAI complex. CONCLUSION: This study demonstrated several characteristics of solitary pulmonary granulomas caused by the MAI complex, and suggested that it might be a subtype of pulmonary MAI complex infection without the typical radiographic features of the infection.

Histopathologic prognostic factors in resected adenocarcinomas: is nuclear DNA content prognostic?

BACKGROUND: The pathobiological characteristics of lung adenocarcinoma are still unclear. To identify the factors that may affect the survival of patients undergoing pulmonary resections for adenocarcinoma of the lung, univariate and multivariate analyses were performed for 17 variables of the host, histopathology, nuclear DNA content (NDC), and morphometry of nucleus (nuclear area [NA]) of tumor cells. METHODS: Seventy-two consecutive patients who underwent resection at the National Cancer Center in Tokyo were studied. They consisted of 45 men and 27 women with an average age of 61.7 years (range, 27 to 83 years). For these patients, NDC and NA were prospectively measured by cytofluorometry and morphometry, respectively. For univariate analysis, 17 factors were studied, including age, sex, TNM stage, diameter of the tumor, pleural involvement, degree of differentiation, scar grade, nuclear atypia, mitotic index, histogram pattern of NDC, mean NDC, number of aneuploid stem cell lines, and mean and SD of NA. A multivariate analysis was performed with Cox's regression model for 16 variables. RESULTS: In the univariate analysis, 12 factors were significantly related to postoperative survival, including TNM stage, diameter, pleural involvement, nuclear atypia, mitotic index, mean NA, mean NDC, number of aneuploid stem cell lines, and the DNA histogram pattern. In the multivariate analysis, M, T, and the histogram pattern of NDC were significantly associated with survival while N showed a strong, but not significant, association. CONCLUSIONS: Multivariate analysis of histopathologic prognostic factors indicated that the TNM stage, as well as each component independently, still provided the greatest prognostic value in resected adenocarcinomas of the lung. Among other factors, only NDC significantly affected survival. The importance of NDC measurement should be stressed for predicting the survival after surgical resection more accurately and for selecting patients with a higher risk of recurrence.

Nuclear DNA content by cytofluorometry of stage I adenocarcinoma of the lung in relation to postoperative recurrence.

Forty-six cases of adenocarcinoma of the lung, categorized as stage I (T1N0M0, T2N0M0) pathologically, were studied in terms of nuclear DNA content (NDC) determined by cytofluorometry. They comprised 23 cases each with and without tumor recurrence within five years postoperatively, and the NDC was compared in 23 pairs in which the tumor size and the degree of histologic differentiation were completely matched. The NDC was larger in the recurrent group than in the nonrecurrent group in terms of mean nuclear DNA content (MNDC), DNA histogram pattern, and occurrence of the aneuploid stem cell line, of which the difference in MNDC was statistically significant (p less than 0.05). When the comparison of NDC was made between the nonrecurrent and recurrent groups in the well differentiated (W/D), moderately to poorly differentiated (M.P/D), T1, and T2 subgroups, the NDC of the recurrent group was significantly larger than that of the nonrecurrent group in the W/D (MNDC, p less than 0.01 and DNA histogram pattern, p less than 0.005) and T1 subgroups (MNDC, p less than 0.05), but not in the M.P/D and T2 subgroups. The results indicate that the NDC is a good predictor of prognosis in stage I adenocarcinoma of the lung and its prognostic importance increases in more differentiated and smaller tumors, compared to less differentiated and larger tumors.

Video-assisted lobectomy in the elderly.

STUDY OBJECTIVES: Video-assisted lobectomy for pulmonary malignancy seems to have potential merits, especially in compromised patients such as the elderly. This study was undertaken to assess the feasibility of this new approach in this special age group. PATIENTS: Video-assisted lobectomy was attempted in eight patients older than 78 years of age with preoperatively diagnosed T1N0 or T2N0 lung carcinomas of peripheral origin. In one patient with squamous cell carcinoma, the tumor was diagnosed after surgery as metastasis from tongue carcinoma. The patients ranged in age from 78 to 85 years (average, 81.3 years). RESULTS: The procedure was completed successfully in six patients (75%), while the other two patients underwent lobectomy after conversion to open thoracotomy because of bleeding from the pulmonary artery at the hilum in one and extensive pleural adhesions in another. Among the six patients who underwent video-assisted lobectomy, there were no operative deaths or serious complications attributable to this technique, although two patients had prolonged air leakage for 7 and 11 days, respectively. CONCLUSIONS: This approach, which is feasible even in patients older than 80 years, is likely to offer a benefit to such patients if they are selected properly. During this procedure, the possibility of wound extension in case of an intraoperative accident must always be borne in mind, especially in elderly patients. The advantage of this approach remains undetermined in this special age group.

Implications of staging in lung cancer.

Lung cancer staging, based on anatomic extent of disease and described by the TNM staging system (T, primary tumor; N, regional lymph nodes; M, distant metastasis), is an important parameter for determining the clinical course of this disease. To evaluate the prognostic importance of TNM staging for lung cancer, we conducted a retrospective study analyzing survival rates according to TNM staging in 2,382 patients who had pulmonary resection for non-small cell lung cancer. Postoperatively, 3 patients were classified in stage 0, 796 in stage I, 304 in stage II, 719 in stage IIIA, 233 in stage IIIB, and 327 in stage IV. The 5-year survival rates for these patients were as follows: stage I, 68.5%; stage II, 46.9%; stage IIIA, 26.1%; stage IIIB, 9.0%; and stage IV, 11.2% (including ipsilateral, intrapulmonary metastases); 5-year survival rates for 140 patients with stage IV disease with intrapulmonary metastases in either the same lobe or another ipsilateral lobe were 17.8% and 8.3%, respectively. There was prognostic significance between stage I and stage II disease, stage II and stage IIIA disease, and stage IIIA and stage IIIB disease, but not between stage IIIB and stage IV disease. Only a few modifications will be required for the TNM staging system, which at present accurately reflects the prognosis of patients with lung cancer and is helpful in determining treatment.

Lobe-specific extent of systematic lymph node dissection for non-small cell lung carcinomas according to a retrospective study of metastasis and prognosis.

BACKGROUND: Complete lymphadenectomy of the mediastinum is advised for patients with lung cancer to provide prognostic information and possible survival benefit. The proper extent of dissection should be further defined. METHOD: The lymphatic metastatic patterns according to the primary site and prognoses were retrospectively analyzed in 166 patients with non-small cell carcinoma who underwent at least lobectomy with hilar and mediastinal lymphadenectomy. All patients had histologically proven mediastinal metastasis (pN2). RESULTS: Among 54 right upper lobe tumors the most common site of metastasis was the lower pretracheal station (74%), whereas metastases to the subcarinal station were seen only in 13%. Among 8 patients with right middle lobe tumors and 41 patients with right lower lobe tumors, both superior mediastinal and subcarinal stations were involved. The 34 left upper segment tumors metastasized to the aorticopulmonary window most commonly (71%) and to the subcarina only in 12% of cases. Inversely, the 10 left lingular tumors metastasized to the subcarina most commonly (50%) and to the aorticopulmonary window only in 20% of cases. Among 44 left lower lobe tumors the subcarinal station was most common for metastasis (58%), with infrequent metastases to the aorticopulmonary window. The 5-year survival for all 166 patients was 35%. Patients with single-station and single-node metastases had a significantly better prognosis than those with more extensive metastases. Right lower lobe tumors with superior mediastinal metastasis carried a particularly poor 5-year survival of only 4.1%. COMMENT: Subcarinal lymphadenectomy is not always necessary for tumors of the right upper lobe and left upper segment. For tumors of other lobes both superior mediastinal dissection and subcarinal dissection are advised. However, superior mediastinal metastasis should be recognized as an indicator of poor prognosis in tumors of both lower lobes.

Intrapulmonary metastasis of non-small cell lung cancer: a prognostic assessment.

OBJECTIVE: According to the revised TNM classification in 1997, intrapulmonary metastasis within the same lobe of the primary tumor is designated as T4 and intrapulmonary metastasis in a different lobe is M1. However, their prognostic implications remain unclear. To assess their prognoses, we retrospectively analyzed the postoperative survival of patients with and without intrapulmonary metastasis. METHODS: From January 1982 to December 1996, 2340 patients with non-small cell lung cancer underwent surgical resection. The survival of patients having complete resection (n = 1534) was analyzed according to their intrapulmonary metastasis status: patients without intrapulmonary metastasis (n = 1393), those with metastasis in the same lobe (n = 105), and those with metastasis in a different lobe (n = 18). For comparison, patients with T4 disease without intrapulmonary metastasis in the same lobe (n = 54) and those with M1 disease without metastasis in a different lobe (distant M1, n = 18) were also analyzed. RESULTS: The overall 5-year survivals were as follows: no intrapulmonary metastasis, 60%; stage T4 disease with no intrapulmonary metastasis, 34%; pulmonary metastasis in the same lobe, 34%; pulmonary metastasis in a different lobe, 11%; and distant M1, 6%. The differences in survival between patients with no pulmonary metastasis and those with metastasis in the same lobe (P <.001, log-rank test) and between patients with metastasis in the same lobe and those with distant M1 (P <.001) were significant. In contrast, there was no significant difference between patients with metastasis in the same lobe and those with T4 disease and no intrapulmonary metastasis or between patients with metastasis to a different lobe and those with distant M1. CONCLUSIONS: Prognostically, intrapulmonary metastasis within the same lobe of the primary tumor was comparable with T4 and that in a different lobe was comparable with M1. In terms of postoperative prognosis, the revised TNM classification for intrapulmonary metastasis seems to be appropriate.

Prognostic significance of pleural lavage cytology immediately after thoracotomy in patients with lung cancer.

Pleural lavage cytology immediately after thoracotomy was performed in 467 patients with lung cancer who had little or no pleural effusion. Forty-two patients (9.0%) had positive results. The positivity of pleural lavage cytology was significantly related to the degree of pleural extension of the tumor, microscopic pleural dissemination, cytologic results of minimal pleural effusion, pathologic stage, presence of lymphatic permeation or vascular invasion, and cell type (adenocarcinoma was predominant). The 3-year survival of the patients having negative and positive results of cytology were 68.7% and 22.9%, respectively. The prognosis of the group with positive results was as poor as that of patients with stage IIIB or IV disease. Pleural lavage cytology is an important prognostic factor that indicates microscopic exfoliation of cancer cells into the pleural cavity, that is, subclinical malignant pleural effusion.

What are the risk factors for arrhythmias after thoracic operations? A retrospective multivariate analysis of 267 consecutive thoracic operations.

Two hundred sixty-seven operations performed consecutively at the National Cancer Center Hospital, Tokyo, in 1990 were reviewed to define the prevalence, type, clinical course, and, especially, risk factors for arrhythmias after thoracic operations. Arrhythmias were identified in 63 operations (23.6%) and were more prevalent in several subgroups of patients than in others--those with lung cancer, pneumonectomy, mediastinal lymph node dissection, and those older than 70 years of age. Supraventricular tachycardias, of which atrial fibrillation was the most common, comprised 95.3% of the cases; bradyarrhythmia and ventricular ectopic beats were seen in only three and four cases, respectively. Arrhythmias were most likely to develop on the second day after the operation. Eighty percent of the arrhythmias disappeared within 3 days after onset, and sinus rhythm was finally restored with digitalis or other antiarrhythmic drugs in all patients except one, who had a myocardial infarction. Arrhythmias were not the direct cause of any of the seven in-hospital deaths. A multivariate analysis of 16 variables revealed that age and extent of pulmonary resection were significant risk factors. Despite these significant risk factors, arrhythmias after thoracic operations could be managed without special prophylaxis and were not closely related to higher mortality.

Bronchopleural fistulas associated with lung cancer operations. Univariate and multivariate analysis of risk factors, management, and outcome.

During a 28-year period, 52 bronchopleural fistulas developed after pulmonary resection of 49 primary and three recurrent lung cancers at the National Cancer Center Hospital, Tokyo. During the same period there were 2359 pulmonary resections for primary lung cancer; the prevalence of bronchopleural fistula was 2.1%. Multivariate analysis on 15 variables in the most recent 1360 resections revealed significant risk factors for bronchopleural fistula: wider resection such as pneumonectomy, residual carcinomatous tissue at the bronchial stump, preoperative irradiation, and diabetes. Univariate analysis further recognized a risk in preoperative bronchial arterial infusion and the postsurgical stage of lung cancer. Six patients were not treated. Apart from chest tube drainage in seven patients, surgical repair was attempted in 39, direct resuture of the stump in 16, wrapping in 25, thoracoplasty in 31, completion pneumonectomy in 6, and other treatments. Despite various treatments, 37 patients (71.2% mortality) died from fistula-related complications (such as regurgitation of infected pleural fluid through the fistula and airway/intrathoracic bleeding). Even for patients whose fistulas were cured and who were discharged, the average hospital stay was 189 days. Further investigation is necessary to answer whether prevention by flap coverage is of any benefit.

Pulmonary resection for metastatic colorectal cancer: experiences with 159 patients.

We reviewed the clinical courses of 159 patients between February 1967 and May 1995 for the purpose of examining the survival of patients who had pulmonary resection for metastatic colorectal cancer. The cumulative survivals at 5 years and 10 years were 40.5% and 27.7%, respectively. Fifteen patients (10%) were alive more than 10 years after the thoracotomy without any evidence of recurrence. The cumulative survival at 5 years for 39 patients who had hepatic metastases before thoracotomy was 33%. There was a statistically significant difference in survival between patients with extrapulmonary metastases and those with only intrapulmonary metastases before thoracotomy. The number of pulmonary metastases and the presence of hilar or mediastinal lymph node metastases affected postthoracotomy survival. There was no significant difference in survival on the basis of sex, age, location of the primary cancer, size of the pulmonary tumors, mode of operation, or disease-free interval. Surgical treatment for pulmonary metastases from colorectal cancer in selected patients, even those who had hepatic metastases before thoracotomy, might improve prognosis.

Lymph node involvement, recurrence, and prognosis in resected small, peripheral, non-small-cell lung carcinomas: are these carcinomas candidates for video-assisted lobectomy?

To determine the clinicopathologic characteristics of peripheral non-small-cell carcinomas, the cases of 337 patients undergoing major pulmonary resection with complete lymphadenectomy were retrospectively reviewed with regard to lymph node involvement, recurrence, and prognosis. All of the tumors were 3.0 cm or less in diameter and were categorized as T1 (318 patients) or T2 (19). Eighty-eight patients (26.1%) had lymph node involvement: 32 (9.5%) at N1 nodes, 55 (16.3%) at N2 nodes, and 1 (0.3%) at N3 nodes. Although the prevalence of lymph node involvement did not differ significantly with tumor histologic type, it was quite low in squamous cell carcinomas 2.0 cm or less in diameter. Of the 56 N2/3 metastases, 14 (25%) occurred in a "skipping" manner, and all but one had a nonsquamous histologic makeup. Of the 213 patients with a follow-up period of 5 years or more, 59 patients (27.7%) showed cancer recurrence. This occurred at a distant site in 67.8% of the cases. Five-year survival rates based on nodal status were 91.9% (NO), 61.8% (N1), 44.5% (N2), and 0% (N3). Because of the relatively high prevalence of lymph node involvement, complete hilar/mediastinal lymphadenectomy should be routinely done regardless of tumor histologic type and size, as long as patients are at good risk. However, in squamous cell histologic types, mediastinal lymphadenectomy might be dispensable if the tumor is less than 2.0 cm in diameter, or if the hilar node is proved to be tumor-free on pathologic examination of the frozen section during operation. Although video-assisted major pulmonary resection currently has limited application, this new technique may represent a surgical option in resection without complete lymphadenectomy.

T2 tumors larger than five centimeters in diameter can be upgraded to T3 in non-small cell lung cancer.

OBJECTIVE: Among the TNM criteria, tumor size is a well-assessed factor in the prognosis of small tumors. A 3-cm cutoff point separates T1 from T2 tumors, whereas a size larger than 3 cm is not ascribed any prognostic value. Instead, N2 is considered to be the worst prognostic factor for intrathoracic extended disease. METHOD: The prognosis of 545 patients with non-small cell lung cancer larger than 3 cm in diameter (T2, T3, and T4) was studied. These tumors were completely resected by pneumonectomy (n = 126) or lobectomy (n = 411) or were partially resected (n = 8). Survivals were compared according to the following factors: tumor size (3.1-5 cm, 5.1-7 cm, >7 cm), nodal status, age, sex, histologic type, degree of pleural involvement, operative procedure, stage, and T factor. For the multivariate analysis, the Cox proportional hazard model was used with the same variables. RESULTS: The univariate analysis showed that age, sex, degree of pleural involvement, operative procedure, tumor size, nodal status, and stage were all significant prognostic factors. Further comparison of survival between different tumor sizes (< or =5 cm vs >5 cm) in the same nodal category demonstrated a significantly poor prognosis for larger tumors in N0 (P =.00374) and N2+N3 (P =.0157), but not in N1 (P =.3452). T2 tumors (n = 349) were divided, according to size, into T2a (n = 238) and T2b (n = 111), and survival was compared with those in T3 and T4. The 5-year survivals were 51.3%, 35.1%, 47.8%, and 25.3%, respectively. The difference between T2a and T2b was statistically significant (log-rank P =.0170, Breslow P =.0055). CONCLUSIONS: A tumor size of more than 5 cm in diameter was indicative of a poor prognosis in non-small cell lung cancer, because patients with T2b tumors had a significantly different survival from that of patients with T2a tumors, and the survival curve was located between those for patients with T3 and T4 tumors. Consequently, T2b might be upgraded to at least T3.