周围型非小细胞肺癌CT影像学因素预后分析

目的探讨周围型非小细胞肺癌(NSCLCs)术前胸部CT影像学因素与预后的关系。方法回顾性收集周围型NSCLCs患者187例,对5例行平扫CT,182例行平扫+增强CT。由2名医师盲法独立阅片,记录肿瘤大小、肿瘤密度、空洞、毛刺、胸膜凹陷、与邻近结构接触面长度及临床N分期。采用Kaplan-Meier曲线及COX回归模型进行生存分析。结果 57例患者死亡,中位随访时间53个月(4~103个月)。Kaplan-Meier单因素分析结果显示:肿瘤大小(P0.001)、肿瘤密度(P=0.027)、空洞(P=0.013)、毛刺(P=0.004)、与邻近结构接触面长度(P=0.029)、临床N分期(P0.001)、血清CEA水平(P0.001)差异有统计学意义。COX多因素分析显示:临床N分期(P0.001,HR=3.617)、肿瘤大小(P=0.001,HR=2.885)、毛刺(P=0.003,HR=2.505)是周围型NSCLCs独立的预后因素。结论术前胸部CT显示临床N分期、肿瘤大小、毛刺是周围型NSCLCs的独立预后因素。     

Prognostic impact of thrombocytosis in resectable non-small cell lung cancer

Relationship between thrombocytosis and poor prognosis has been reported in lung cancer. However, the majority of previous studies included many advanced stage and small cell lung cancer patients. Few studies focused on resectable non-small cell lung cancer patients. In the present study, therefore, consecutive 240 non-small cell lung cancer patients who received surgical resection were reviewed retrospectively, and investigated the survival impact of preoperative platelet count. In our results, the frequency of preoperative thrombocytosis was only 5.83% (14/240). The 5-year survival of patients with and without thrombocytosis was 28.87% and 63.73%, respectively. Both univariate and multivariate analyses indicated the independent prognostic impact of thrombocytosis. The present study is the first evaluation of prognostic effect of thrombocytosis in patients with resectable non-small cell lung cancer. Preoperative platelet count was a prognostic factor for resectable non-small cell lung cancer patients.     

Analysis of mutant p53 and telomerase activity in non-small cell lung cancer.

The number of mutant p53 protein-positive tumor cells in primary non-small cell lung carcinoma (NSCLC) cases were quantitated by flow cytometry (FCM) and the relationships of these data to various factors were evaluated. Furthermore, the method of quantitating telomerase activity was investigated. Forty patients with primary lung carcinoma encountered between December 1995 and December 1997 were investigated. Among these cases, telomerase activity was measured. Using PAb421, cells were reacted with fluorescent antibody and fluorescence was quantitated by FCM. Fluorescence index (FI) was estimated in relation to the positivity rates of negative controls and were quantitatively evaluated. FI values of normal lung tissue were obtained from normal lung tissue excised from young patients with pulmonary bulla. Values that were 2SD or more above the mean value of normal lung tissue (> 2.19) were regarded as mutant p53-positive, and 14 (35.0%) of 40 lung carcinoma cases were positive by this criterion. Of 13 poorly differentiated carcinoma cases, seven cases (53.8%) were positive, which was significantly high. Furthermore, the telomerase activity was converted to numerical values in 40 cases using the telomelic repeat amplication protocol (TRAP) method as well as the total product generated (TPG) method. The mean TPG value of the 40 cases was 75.21 +/- 15.63. Among these cases, the mean value of fourteen p53-positive cases was 124.49 +/- 37.19, which was higher than that of 26 negative cases, 48.68 +/- 10.88, showing a significant difference. The method used in this study was considered a useful method that allows accurate and objective evaluation of mutant p53 expression. It was suggested that mutant p53 expression may affect the degree of tumor cell differentiation. Consequently, it was confirmed in this study that mutant p53 expression and telomerase activity were closely associated in lung cancer.     

Neoadjuvant therapy in non-small cell lung cancer. Prognostic impact of "mediastinal downstaging"]

In the course of a prospective multicenter study, 40 (26 squamous cell and 14 adenocarcinomas) patients with stage IIIA and IIIB non-small cell lung cancer (NSCLC) were submitted to surgery after neoadjuvant radiochemotherapy. Pretherapeutic clinical lymph node status was compared to the lymph node involvement established in the resection specimens. Therapy-induced tumor regression was classified according to a three-step tumor regression grading system. In 29 patients (72.5%) a downward shift in lymph node involvement could be established,whereas in 27.5% ( n=11) pretherapeutic lymph node status was maintained. Of 26 patients with post-therapeutic N0 or N1 status, 21 revealed less than 10% vital tumor tissue in the resection specimens (regression grades IIb or III). Patients with post-therapeutic N0 or N1 lymph node status were found to have a survival benefit compared to patients with N2 lymph node involvement, though this difference was not statistically significant (p=0.27). On the other hand, tumor regression showed a significant correlation to the overall survival period (p=0.02). Thus, therapy-induced tumor regression grading seems to be a more precise method to predict the outcome of the disease.     

N2期非小细胞肺癌的预后因素分析

目的 探讨有纵隔淋巴结转移(N2期)的非小细胞肺癌(NSCLC)的外科治疗疗效及影响预后的因素.方法 回顾性分析1999年1月至2003年5月手术治疗的117例N2 NSCLC患者(男性88例,女性29例,年龄29～79岁)的生存率,分析手术方式(肺叶切除、全肺切除、姑息性切除),病理类型(腺癌、鳞状细胞癌、混合癌、大细胞癌和其他类型),T分期以及术后综合治疗对预后的影响.结果 中位生存期为22个月,3年和5年生存率分别为28.1%和19.0%.年龄、性别、病理类型、围手术期化疗、术后放疗均未见与5年生存率有相关性.肺叶切除者的5年生存率为22.2%,全肺切除者为25.0%,均高于姑息性切除者的9.1%(P=0.001).T4期患者5年生存率为11.1%,低于T1-2期患者的37.5%(P=0.01).COX多因素分析示,手术方式和T分期与5年生存率相关.结论 外科治疗对T1-2 N2期NSCLC是最佳选择.对于T4期患者,由于不完全切除比例大,术前新辅助治疗比率低,手术提高长期生存率的效果有限.     

Prognostic value of visceral pleura invasion in non-small cell lung cancer

Objectives: The purpose of this study was to clarify the prognostic significance of visceral pleura invasion in T2 non-small cell lung cancer (NSCLC). Materials and methods: Between 1990 and 2001, 439 consecutive patients with T2 NSCLC underwent curative surgical resection. The subjects included 234 patients with stage IB, 95 with stage IIB, and 110 with stage IIIA and B disease. The patients were divided into two groups according to the existence of visceral pleura invasion (group I without, group II with). Both groups were compared with regard to tumor size, histology, associated mediastinal lymph node involvement, and survival rates. Results: Visceral pleura invasion (group II) was identified in 114 patients (26%), and was present in 22% of patients with NSCLC with a tumor size of 3 cm or less and in 27% of those with a tumor larger than 3 cm (P=0.37). Visceral pleura invasion was associated with a higher frequency of mediastinal lymph node involvement (group I=22%, group II=34%, P=0.009). Five- and 10-year survival rates were 50 and 45% in group I, and 36 and 22% in group II (P=0.0006). In stage IB, visceral pleura invasion was identified in 53 patients (23%), and 5- and 10-year survival rates were 63 and 60% in the visceral pleura non-invasion group, and 44 and 28% in visceral pleura invasion group (P=0.0018). By multivariate Cox model analysis, age at intervention (relative RISK=1.03, P=0.0017), N status (relative RISK=1.53, P<0.0001), tumor size (relative RISK=1.83, P=0.0452) and visceral pleura invasion (relative RISK=1.42, P=0.0291) were independent predictors of poor prognosis. Conclusions: We were able to demonstrate that visceral pleura invasion was a factor of poor prognosis in T2 NSCLC. It was found to correlate with more extensive mediastinal lymph node involvement and a decreased survival rates. Therefore, the patients with visceral pleura invasion should be closely followed up especially.     

影响非小细胞肺癌全肺切除术预后的因素

目的　探讨影响非小细胞肺癌患者全肺切除术预后的因素 ,为手术适应证的修正提供依据。　方法　回顾性分析行全肺切除术的 81例非小细胞肺癌患者的临床及随访资料。随访时间 5年以上。运用 χ2 检验、Kaplan Meier生存分析和COX模型多因素分析 ,对影响预后的因素进行单因素和多因素分析。　结果　本组患者肿瘤的组织学类型主要为鳞癌 (5 4 3% )、腺癌 (2 4 7% )和腺鳞癌(17 3% )。非小细胞肺癌全肺切除术后N0 、N1和N2 期患者的 5年生存率分别为 (2 0 8± 9 9) %、(15 4± 10 0 ) %和 (4 0± 2 8) % ,无围手术期死亡病例。术后合并症发生率为 2 2 2 %。单因素分析结果显示 :影响非小细胞肺癌患者全肺切除术预后的因素为年龄 ,术后合并症 ,肿瘤的组织学类型、部位和大小 ,胸壁侵犯和纵隔淋巴结转移。COX模型多因素分析结果显示 :影响患者预后的因素为术后合并症、肿瘤大小、胸壁侵犯和淋巴结转移状况。　结论　全肺切除术具有较高的术后合并症发生率。高龄、腺癌、心肺合并症和N2 期淋巴结转移是影响预后的不利因素。术前准确的肿瘤分期和心肺功能评估是病例选择的重要依据     

Prognostic factors in clinical stage I non-small cell lung cancer.

BACKGROUND: Management of patients with early-stage lung cancer but a poor prognosis is controversial. METHODS: Between January 1987 and December 1994, 365 patients with clinical stage I disease underwent surgical resection at our hospital. Eight preoperative clinical variables were entered into univariate and multivariate analyses to determine their impacts on 5-year survival. RESULTS: The 3-year and 5-year survival rates were 78.1% and 66.5%, respectively. In the multivariate analysis, clinical T2 status and preoperative high serum carcinoembryonic antigen levels were independent significant factors indicative of a poor prognosis (hazard ratio, 2.20 and 1.88, respectively). Patients with both of these factors had 3-year and 5-year survival rates of 65% and 38% (p<0.001), and the risk of death for this subgroup was 4.14 times greater than that of the overall clinical stage I population. CONCLUSIONS: A subgroup with clinical T2 disease and preoperative high serum carcinoembryonic antigen levels had a significantly poorer prognosis among patients with clinical stage I lung cancer. For this subgroup, a complete preoperative staging workup and multimodal therapy, especially induction chemotherapy, instead of surgical intervention alone could be beneficial.     

Prognostic significance of dysadherin expression in patients with non-small cell lung cancer

OBJECTIVE: The aim of this study was to evaluate the expression of dysadherin and E-cadherin and to investigate their clinical significance as prognostic factors in non-small cell lung cancer. METHODS: Non-small cell lung cancer specimens were obtained from 131 patients undergoing clinically indicated operations at the Department of General and Cardiothoracic Surgery, Kanazawa University Hospital, between 1995 and 1997. All patients had undergone curative resection of the primary tumor, including systematic lymph node dissection. The avidin-biotin-peroxidase complex method was used for immunostaining of dysadherin and E-cadherin. RESULTS: Among the 131 lung cancer specimens, 46 (35.1%) tumors were positively stained with dysadherin. Preserved membranous E-cadherin staining was present in 45.8% (60/131) of cases. In this analysis dysadherin expression was not correlated with E-cadherin expression (P = .1333), but a significant association was observed between dysadherin expression and survival time. The overall survival of patients with dysadherin-positive tumors was significantly worse than that of those with dysadherin-negative tumors (P = .0059). Patients with reduced E-cadherin immunopositivity survived significantly shorter than those with preserved E-cadherin immunopositivity (P = .0406). The overall survival of patients with positive dysadherin and reduced E-cadherin expression was significantly worse than that of patients with negative dysadherin and preserved E-cadherin expression (P = .0002). Multivariate analysis revealed the independent prognostic value of dysadherin positivity, reduced E-cadherin expression, and lymph node metastasis on overall survival. CONCLUSIONS: Dysadherin expression is an independent prognostic factor of survival in patients with non-small cell lung cancer, and combined immunohistochemical analysis of dysadherin and E-cadherin expression might provide further prognostic information.     

Prognostic significance of cyclooxygenase 2 mRNA expression in non-small cell lung cancer

OBJECTIVE: To investigate cyclooxygenase-2 (COX-2) mRNA expression in curatively resected non-small cell lung cancer (NSCLC) and to determine its association with prognosis. SUMMARY BACKGROUND DATA: Lung cancer is one of the most common malignancies in the world. Despite improvements in the diagnosis and treatment of NSCLC, the 5-year survival rate remains less than 15%. Identification of prognostic predictors based on molecular alterations could lead to additional diagnostic tools and eventually to more effective therapeutic options. Overexpression of COX-2 has been reported in several human malignancies, including lung cancer, but the prognostic importance of this overexpression has not been elucidated. METHODS: COX-2 mRNA expression was analyzed using a quantitative real-time polymerase chain reaction (Taqman) method in surgically resected tumor specimens from 89 patients with curatively resected NSCLC. RESULTS: COX-2 mRNA was detectable in all 89 (100%) tumor tissues. High COX-2 expression in tumors was significantly associated with inferior survival. Multivariate analysis showed that high COX-2 expression is an independent predictor of worse survival in patients with NSCLC. CONCLUSIONS: High COX-2 mRNA expression is an important biomarker for biologically aggressive disease in NSCLC and might be helpful in identifying patients who would benefit from additional therapies for controlling their disease.     

Prognostic implications of microscopic proximal bronchial extension in non-small cell lung cancer

BACKGROUND: The loss of approximately one third of early stage lung cancer patients undergoing complete resection by the end of 5 years implies the existence of unknown or undetected factors at the time of operation. We investigated the possible correlation between microscopic proximal bronchial extension (MPBE) and survival with clinicopathologic features in patients with non-small cell lung cancer. METHODS: The bronchial tree with the tumor was dissected and extracted from the lung parenchyma in a total of 62 surgical specimens with non-small cell lung cancer. The tumor-related bronchus was sectioned into serial blocks at a thickness of 5 mm in the transverse plane. Histologically, cut serial sections were examined for MPBE. RESULTS: A total of 15 (24.2%) specimens showed MPBE, whereas 47 (75.8%) specimens showed no evidence of MPBE. The median survival time of MPBE-positive patients was 10.0 months, whereas that of MPBE-negative patients was 42.0 months. The 5-year survival rates of MPBE-positive and MPBE-negative groups were 13.3% and 35.8%, respectively, which was a significant difference (p = 0.0203). Multivariate analysis revealed lymph node status (p = 0.0161), histology (p = 0.0268), and MPBE-positivity (p = 0.0447) as independent prognostic factors. CONCLUSIONS: Microscopic proximal bronchial extension has an adverse effect on survival in non-small cell lung cancer.     

Prognostic value of FDG uptake in early stage non-small cell lung cancer

Background: Non-small cell lung cancer (NSCLC) has a poor prognosis even for early stages of the disease (stage I and II). We studied the prognostic value of PET FDG in patients with completely resected stage I and II NSCLC. Methods: Retrospective study of 96 patients with NSCLC whose staging included ¹⁸F-FDG PET (fluoro deoxy glucose positron emission tomography). Histopathological stage was either stage I (75) or stage II (n = 21). FDG uptake was measured as maximal standardized uptake value for body weight (SUVmax). Mean follow-up was 45 ± 30 months (1–142 months). Overall and cancer-free survival rates were recorded. Results: SUVmax were higher for stage II than for stage I (10.5 ± 4.5 vs 8.5 ± 5, p = 0.04). Mean tumor volumes were equivalent for both stages (33 cm³, p = 0.18), excluding a partial volume effect. The median SUVmax in the whole study population was 7.8. The median survival was significantly longer in patients with a lower (SUVmax ≤ 7.8) FDG uptake (127 months vs 69 months, p = 0.001). For stage I tumors (n = 75), high FDG uptake was significantly associated with reduced median survival: 127 months if SUVmax ≤ 7.8 and 69 months if SUVmax > 7.8 (p = 0.001). For stage II tumors (n = 21), no statistical difference was observed: 72 months vs 40 months for SUVmax ≤ 7.8 and for SUVmax > 7.8, respectively (p = 0.11), although there was a clear trend towards reduced survival for highly metabolic tumors. Disease-free survival was also significantly better for lower metabolic tumors: 96.1 months vs 87.7 months (p = 0.01). Conclusion: High FDG uptake is associated with reduced overall survival and disease-free survival of patients with completely resected stage I–II NSCLC. Whether patients with highly metabolic tumors should undergo a closer postoperative surveillance or adjuvant chemotherapy has to be addressed in a properly designed prospective trial.     

Prognostic value of the histological subtype in completely resected non-small cell lung cancer

Non-small cell lung cancer (NSCLC), which includes several different histological subtypes, is usually treated by the same strategy. However, the biological behavior of each cell type appears to be different. We retrospectively reviewed the clinical records of 1119 consecutive NSCLC patients who underwent a complete resection, in order to investigate whether a histological cell type is a powerful prognostic factor. The overall 5- and 10-year survivals of the patients with adenocarcinoma (AD), squamous cell carcinoma (SQ), large cell carcinoma (LA), and adenosquamous cell carcinoma (AS) were 54.2 and 40.2%, 51.6 and 30.3%, 40.9 and 18.7%, and 35.1 and 30.1%, respectively. The AD patients had a significantly better survival than the non-AD patients in Stage I (P=0.0004), whereas the SQ patients had a better survival than the non-SQ patients in Stage II (P=0.018). A multivariate survival analysis indicated the AD patients to have a significantly better survival than the SQ patients in Stage IA (P=0.04), while the SQ patients had a better survival than the AD patients in Stage II (P=0.03). These above observations suggest that the prognosis after complete resection is different between adenocarcinoma and squamous cell carcinoma in Stage IA and II.     

Prognostic markers in resectable non-small cell lung cancer: a multivariate analysis.

OBJECTIVE: To identify the prognostic significance of certain clinical, cellular and immunologic markers in resectable non-small cell lung cancer (NSCLC). DESIGN: A cohort of patients with resectable NSCLC was prospectively followed up for 8 years (100% follow-up). SETTING: A university hospital in a large Canadian city. PATIENTS: One hundred and thirteen consecutive patients who underwent surgical resection of primary NSCLC. MAIN OUTCOME MEASURES: Presence of peritumoral B lymphocytes (identified with antibody to CD20) and T lymphocytes (antibody to CD43), along with tumour markers (carcinoembryonic antigen [CEA], keratin, cytokeratin, S-100 protein, vimentin, chromogranin) and other factors such as age, sex, cell type, American Joint Committee on Cancer (AJCC) stage, histologic grade, DNA ploidy and S-phase fraction were correlated with survival. RESULTS: The mean age of patients in the study was 66.0 years; 60% were male. Histologic types of the tumours were: adenocarcinoma 57 (50.4%), squamous cell 47 (41.6%), adenosquamous 6 (5.3%) and large cell 3 (2.6%). AJCC stages were: I 66 (58.4%), II 20 (17.7%) and III 27 (23.9%). Histologic grades were: I (well differentiated) 31 (27.4%), II 50 (44.2%), III 29 (25.7%) and IV 3 (2.6%). Survival was 85% at 1 year (95% confidence interval [CI] 76%-90%), 44% at 5 years (95% CI 34%-53%) and 34% at 10 years (95% CI 22%-46%). Multivariate analyses using the Cox proportional hazards model for survival confirmed AJCC stage (p < 0.001) in all histologic subtypes to be the strongest factor of independent prognostic significance. It also revealed the presence of CD20-stained B lymphocytes (p = 0.04) in the peritumoral region of all tumours to be a positive prognostic factor. This relation was especially strong for nonsquamous cell carcinomas (p < 0.001). For squamous cell carcinomas, the immunohistochemical presence of CEA was of marginally negative prognostic value (p = 0.04). DNA ploidy and a high S-phase fraction showed no evidence of prognostic value for stage I tumours, but for stages II and III tumours there was strong evidence of prognostic value (p < 0.001 jointly). The evidence for DNA ploidy was especially strong in stages II and III squamous cell tumours (p = 0.008), and for a high S-phase fraction was strongest in stages II and III nonsquamous cell tumours (p = 0.002). CONCLUSIONS: AJCC stage remains the most important prognostic indicator from a variety of clinical variables and tumour markers in postoperative patients with resectable NSCLC. For nonsquamous cell lung carcinomas, the presence of peritumoral B lymphocytes was strongly associated with improved survival, suggesting an important role for humoral mediated immunity.