Search

Introduction: The appropriate therapeutic strategy and postoperative management for patients with stage IA non-small-cell lung cancer (NSCLC) still remain a matter of debate because of the prognostic heterogeneity of this population, including the risk of cancer recurrence. The objective of the current study was to identify the clinicopathological factors that affect overall prognosis and cancer recurrence of stage IA NSCLC., Methods: We reviewed the data of 532 patients in whom complete resection of stage IA NSCLC had been performed. Overall survival and recurrence-free proportion (RFP) were estimated using the Kaplan-Meier method. RFP was estimated from the date of the primary tumor resection to the date of the first recurrence or last follow-up. We performed univariate and multivariate analyses to determine the independent prognostic factors., Results: On multivariate analyses, three variables were shown to be independently significant recurrence risk factors: histological differentiation (hazard ratio [HR] = 1.925), blood-vessel invasion (HR = 1.712), and lymph-vessel invasion (HR = 1.751). On subgroup analyses combining these risk factors, the 5-year RFP was 91.3% for patients with no risk factors, 79.5% for those with either poorly differentiated carcinoma or vascular invasion, (p < 0.001 for both), and 62.9% for those with both poorly differentiated carcinoma and vascular invasion (p = 0.068)., Conclusion: These results indicated that vascular invasion and tumor differentiation have a significant impact on the prediction of cancer recurrence in patients with stage IA NSCLC. Patients with these predictive factors of recurrence may be good candidates for adjuvant chemotherapy.

Background: Lymph node (LN) status is a major determinant of stage and survival in patients with lung cancer. In the 7th edition of the TNM Classification of Malignant Tumors, the number of involved LNs is included in the definition of pN factors in breast, stomach, esophageal, and colorectal cancer, and the pN status significantly correlates with prognosis., Methods: We retrospectively investigated the prognostic impact of the number of resected LNs (RLNs) and involved LNs in the context of other established clinical prognostic factors, in a series of 928 consecutive patients with non-small cell lung cancer (NSCLC) who underwent complete resection at our institution between 2000 and 2007., Results: The mean number of RLNs was 15. There was a significant difference in the total number of RLNs categorized between less than 10 and ≥10 (p = 0.0129). Although the incidence of LN involvement was statistically associated with poor prognosis, the largest statistically significant increase in overall survival was observed between 0 to 3 and ≥4 involved LNs (hazard ratio = 7.680; 95% confidence interval = 5.051-11.655, p < 0.0001). On multivariate analysis, we used the ratio between the number of involved LNs and RLNs. The number of RLNs was found to be a strong independent prognostic factor for NSCLC (hazard ratio = 6.803; 95% confidence interval = 4.137-11.186, p < 0.0001)., Conclusion: Complete resection including 10 or more LNs influenced survival at complete NSCLC resection. Four involved LNs seemed to be a benchmark for NSCLC prognosis. The number of involved LNs is a strong independent prognostic factor in NSCLC, and the results of this study may provide new information for determining the N category in the next tumor, node, metastasis classification.

Background: The therapeutic strategies for non-small cell lung carcinoma (NSCLC) with N1 and N2 disease differ remarkably. Debate exists about the definition of the borderline between N1 and N2 stations. This study evaluated the prognostic effect of N1 disease, especially focused on the significance of the main bronchial node (No. 10) vs N2 disease., Methods: The records of 1601 patients who underwent complete pulmonary resection for NSCLC were reviewed to examine the clinical features of lymph nodal involvement., Results: There were 1086 patients (67.8%) with pN0 disease, 202 (12.6%) with pN1, and 274 (17.1%) with pN2 disease; overall 5-year survival rates were 74.7%, 56.1% and 28.9%, respectively (p < 0.001). Overall 5-year survival rates were 60.2% in hilar N1 and 49.6% in intralobar N1. Overall 5-year survival rates were 58.6% in N1 without node 10 and 35.1% in N1 with node 10. A significant difference was observed between N0 and N1 without node 10 (p < 0.001), and N1 without node 10 and N1 with node 10 (p = 0.033); however, the difference between N1 with node 10 and N2 was not significant. The status of node 10 involvement was an independent prognostic factor of pN1 patients, as well as age and gender., Conclusions: Patients with node 10-positive N1 disease have an unfavorable prognosis, and the disease behaves like N2 disease. The definition of clear borderline between N1 and N2 is mandatory to achieve a uniform classification map. This study offers further information for clinical and therapeutic purposes.

Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancers, with patients having a poor prognosis. Approximately one third of NSCLC patients present with early-stage disease in which potentially curative resection and multi-modality therapy. Although adjuvant chemotherapy is the standard practice for patients with stages I-III breast and colorectal cancer, the therapeutic efficacy of adjuvant chemotherapy, following complete surgical resection of early stage NSCLC, has not been fully established. Several prospective randomized trials for patients with early stage NSCLC (stages I-IIIA) have confirmed a survival benefit with cisplatin-based adjuvant chemotherapy, as demonstrated in the 1995 meta-analysis performed by the NSCLC Collaborative Group. Studies from Japan have reported that adjuvant therapy with uracil-tegaful (UFT) afforded an improvement of 4% in the 5-year survival rate and a relative risk reduction of 26% in mortality at 5 years among patients with T1-2N0 (stage I) disease. In particular, the Japan Lung Cancer Research Group has demonstrated an improvement in the 5-year survival rate of 11%, favoring chemotherapy with UFT in the subset of patients with T2N0 (stage IB) disease. Two published meta-analyses based on abstracts have estimated a relative risk reduction in mortality of 11-13% at 5 years. The Lung Adjuvant Cisplatin Evaluation (LACE), which was based on a pooled analysis of five randomized trials, has demonstrated that cisplatin-based adjuvant chemotherapy improved survival in patients with completely resected NSCLC. This benefit depended on stage, being greatest in patients with stage II or IIIA disease. This analysis has suggested that platinum-based adjuvant chemotherapy may have no benefit for patients with stage IA and only a marginal benefit for patients with stage IB. Thus, the information available at the current time supports the administration of adjuvant chemotherapy for patients who have undergone complete resection of stages IB-IIIA NSCLC. Further research is needed to define the role of adjuvant platinum-based chemotherapy and its use, in conjunction with chest radiotherapy as the treatment for patients with resected stages IB and IIIA NSCLC.

Recently we reported the systemic antitumor efficacy of intratumoral naive dendritic cell injection (IT-DC) in combination with local photodynamic therapy in Clinical Cancer Research 2006. In general, tumor cells secrete several immune suppression cytokines which could induce immune tolerance in a tumor microenvironment. The rationale and advantages of IT DC in combination with conventional antitumor therapy are as follows: (1) dying tumor cells release some tumor antigens, (2) sufficient number of DC recruiting occurs at tumor site, (3) there is naive DC capturing some tumor antigens in vivo, (4) DC activation by inflammatory cytokines are released from dying tumor cells, and (5) DC migration happens in regional lymph nodes and induces adoptive tumor immunity. Conventional antitumor therapy before IT DC could destroy the immune tolerance at a tumor site and induce durable DC vaccination. In this report, we demonstrated the mechanism of (4) and (5) by radiofrequency ablation plus IT DC using mouse tumor model.

Recent studies have evaluated the cytokine network involved in the local immune response to tumors. In addition to infiltrating inflammatory cells, tumors also produce cytokines and growth factors that may alter tumor growth and tumor immunogenicity. Ninety-one samples of NSCLC were used in this study. We measured the expression of VEGF, TNF-alpha, TGF-beta, IL-6, IL-8, IL-12, INF-gamma, and MCP-1 in NSCLC tissues, by ELISA. The expression of IL-6 and IL-8 were significantly higher in squamous cell carcinoma than in adenocarcinoma (p=0.016 and p<0.001, respectively). The expression of TGF-beta, MCP-1 and IL-8 were significantly higher in pulmonary metastasis positive than negative cases (p=0.002, p=0.001, and p=0.008, respectively). In multivariate logistic regression analysis, the expression of TGF-beta was an independent risk factor for the occurrence of pulmonary metastasis (p=0.008, 95% CI=1.002-1.011). We confirmed that tumor infiltrating stromal cells were major sources of TGF-beta by immunohistochemical analysis. The expression of VEGF and IL-8 were significantly higher in cases with central necrosis (p=0.006 and p=0.011, respectively). We speculated that TGF-beta expression in tumor infiltrating stromal cells may regulate the occurrence of spontaneous pulmonary metastasis in NSCLC. (Ann Thorac Cardiovasc Surg 2003; 9: 295-300)

Background: We have previously reported that the most significant immunological prognostic factors in patients with lung cancer are the percentages of peripheral HLA-DR+ lymphocytes., Patients and Methods: We performed two-color flow cytometric analyses using two combinations of double-staining to identify lymphocyte phenotypes HLA-DR/CD4 and HLA-DR/CD8, and examined the correlation between the expression of these subsets and survival in 51 patients with non-small cell lung cancer., Results: The percentages of HLA-DR+, HLA-DR+/CD4+ (activated helper/inducer T cells) and HLA-DR+/CD8+ (activated cytotoxic/suppressor T cells) did not correlate with survival. However, survival was better when the percentage of HLA-DR+/CD8- was below normal (p = 0.0267). The 4-year survival rate in patients with high and low percentages of peripheral HLA-DR+/CD8- lymphocytes was 26.0% and 53.2%, respectively., Conclusion: The subset of HLA-DR+/CD8- lymphocytes powerfully predicts the survival of patients with non-small cell lung cancer.

Purpose: Chromosomal instability (CIN) in non-small cell lung cancer (NSCLC) has yet to be well studied. We examined the relationship between CIN detected by fluorescence in situ hybridization and survival in patients with NSCLC., Experimental Design: Touch preparations from 50 surgical specimens of NSCLC were studied. Tumors included 34 adenocarcinomas, 15 squamous cell carcinomas, and 1 large cell carcinoma. The pathologic stage was IA in 14, IB in 17, IIB in 8, IIIA in 9, and IIIB in 2 cases. Enumeration of chromosomes 3, 10, 11, and 17 was used to determine which tumors carried CIN. The association between CIN and survival was also analyzed., Results: Disomy was most common, but tetrasomy and trisomy of the examined chromosomes were seen frequently. Fourteen tumors (28%) showed heterogeneity of all four chromosomes examined and were judged to be carrying CIN. Both univariate and multivariate analyses revealed that two factors, lymph node metastasis and CIN, were significant poor prognostic factors., Conclusions: CIN in NSCLC detected by fluorescence in situ hybridization is an independent factor predicting a poor prognosis.

Background/aims: The aim of this study is to assess whether selective transection of tumor-bearing portal pedicle before dissection of the liver parenchyma in hepatectomy for hepatocellular carcinoma can prevent intraoperative spread of the tumor and can lead to the prolongation of postoperative survival., Methodology: Survival for 159 patients who underwent hepatectomies with selective portal transection by Glissonean pedicle transection method was retrospectively compared with that of 100 patients who underwent hepatectomies with Pringle maneuver. According to the number of recurrent tumors, intrahepatic recurrence was divided into two types: nodular type of 3 or less, diffuse type of 4 or more., Results: The 5-year survival for the patients who underwent hepatectomies with Glissonean pedicle transection method was significantly higher than that with Pringle maneuver (64.7% vs. 36.4%, p < 0.0001, log-rank test). The diffuse type recurrence, which occurred early and resulted in the unfavorable prognosis compared with the nodular type, was significantly reduced in patients treated with Glissonean pedicle transection method compared with those with Pringle maneuver (p = 0.0013). Multivariate analyses demonstrated that Glissonean pedicle transection method was a potent independent prognostic indicator for survival., Conclusions: Glissonean pedicle transection method prevented intraoperative metastasis and significantly improved the postoperative survival in patients with hepatocellular carcinoma.