Prognostic significance of cyclin D1 expression in resected stage I, II non-small cell lung cancer in Arabs

The aim of this study was to evaluate the prognostic significance of cyclin D1 expression in primary, resected stage I and II non-small cell lung cancer (NSCLC) in Arabs. A longitudinal cohort study of 98 consecutive patients with resected stage I and II NSCLC were evaluated immunohistochemically for the expression of cyclin D1 and determined its prognostic significance by comparison with follow-up data from January 1994 to December 1999. This study included 76 male and 22 female patients. They represented 31 stage I NSCLC and 67 stage II tumors. Expression of cyclin D1 was detected immunohistochemically in 48 (49%) of the 98 NSCLC. Cyclin D1 expression had significantly higher positive results in patients with chronic obstructive pulmonary disease (P=0.001), poorly differentiated carcinoma (P=0.001), presence of vascular invasion (P=0.003), and visceral pleural invasion (P=0.005). Patients with cyclin D1-positive tumors had shorter survival than those with cyclin D1-negative tumors (5-year survival rates, 48% and 74%, respectively; P=0.006 by the log-rank test). In conclusion, a higher percentage of NSCLC with visceral pleural invasion, vascular invasion, poor differentiation of the tumor, patients with chronic obstructive pulmonary disease have positive cyclin D1 expression than other lung tumors.     

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.     

Risk factors of recurrence in resected stage I non-small cell lung cancer

We reviewed risk factors of recurrence in resected pathological stage I non-small cell lung cancer (I NSCLC). Objective is 229 complete resected I NSCLC in our department. Risk factors of recurrence were carcinoembryonic antigen (CEA), histology, differentiation, lymphatic invasion, blood vessel invasion, pleural invasion and tumor size. By univariate analysis, lymphatic invasion (p=0.009), blood vessel invasion (p=0.008), pleural invasion, p1 (p=0.013), p2 (p=0.001), and tumor size (value of cut off was 2 cm) were significant risk factors of recurrence. By multivariate analysis, blood vessel invasion (p=0.004), pleural invasion (p1 or p2) [p=0.001], were significantly risk factors of recurrence. It was suggested that I NSCLC presenting pathological blood vessel invasion and/or pleural invasion should be recognized as cases with a high risk of recurrence, and a strict follow-up and adjuvant therapy should be in consideration.     

Cytologically malignant margins of wedge resected stage I non-small cell lung cancer

BACKGROUND: We have developed a novel test for the surgical margin of pulmonary malignant tumor using a cytologic technique (the run-across method in which a glass slide is run across the staple site), and we have assessed whether this method is useful in predicting margin relapse and prognosis. METHODS: From April 1996 to March 1999, 15 lesions of stage I non-small cell lung cancer (NSCLC) (maximum diameter ranged from 10 to 35 mm with a median of 20 mm) from 15 patients with cardiopulmonary impairment were excised without additional proximal resections. The surgical margin was examined using the run-across method. There were 8 male 7 female patients whose ages ranged from 51 to 80 years. One patient underwent video-assisted thoracic surgery and 14 underwent thoracotomy. The preoperative diagnoses of the patients were 13 adenocarcinomas, 2 squamous cell carcinomas, and 1 undiagnosed lesion (1 adenocarcinoma). The follow-up period ranged from 37 to 63 months. RESULTS: The rate of positive cytology was 47% in comparison with the rate of positive histology of 20%. There were 4 patients with margin relapse (3 of them contained negative histology margins) at a rate of 57% among the positive cytology patients in comparison with 0% among the negative cytology patients (p = 0.03). In a comparison of survival between the negative cytology group and the positive cytology group, there were no statistically significant differences. CONCLUSIONS: The run-across method is also useful in confirming complete resection. A positive cytology margin could lead to margin relapse even if a non-small cell lung cancer is resected with a negative histology margin.     

Prognostic factors in patients with surgically resected stages I and II non-small cell lung cancer

BACKGROUND: About one-third to one-half of patients with early stages of non-small cell lung cancer (NSCLC) succumb to their disease. In this study, we attempted to identify prognostic factors that predict outcome in patients with stages I and II NSCLC. METHODS: A retrospective evaluation of 454 patients with surgically resected stages I and II NSCLC was performed to determine the impact of various clinical, laboratory, and pathological factors on patient outcome such as overall survival (OS) and event-free survival (EFS). RESULTS: Patients older than 65 years had shorter EFS and OS than younger patients (p = 0.002). Patients with preoperative hemoglobin less than or equal to 10 g% had shorter EFS and OS compared to patients with a hemoglobin greater than 10 g% (p = 0.001). Expectedly, OS and EFS were shorter in patients with stage II as compared to stage I patients (p < 0.001). In a multivariate analysis, age, hemoglobin level, and stage remain significant predictors for EFS and OS. CONCLUSIONS: Older age, anemia, and higher stage are important prognostic factors in patients with surgically resected stage I and II NSCLC.     

Prognostic significance of preoperative plasma D-dimer level in patients with surgically resected clinical stage I non-small cell lung cancer: a retrospective cohort study

Flowable haemostatic agents have been shown to be superior to non-flowable agents in terms of haemostatic control and need for transfusion products in patients undergoing cardiac surgery. We investigated the economic impact of the use of a flowable haemostatic agent (Floseal) compared with non-flowable oxidised regenerated cellulose (ORC) agent in primary elective cardiac surgery from the perspective of the UK National Health Service (NHS). A cost-consequence framework based upon clinical data from a prospective trial and an observational trial and NHS-specific actual reference costs (2016) was developed to compare the economic impact of Floseal with that of ORC. The individual domains of care investigated comprised complications (major and minor) avoided, operating room time savings, surgical revisions for bleeding avoided and transfusions avoided. The cost impact of Floseal versus ORC on ICU days and extended bed days avoided was modelled separately. Compared with ORC, the use of Floseal would be associated with overall net savings to the NHS of £178,283 per 100 cardiac surgery patients who experience intraoperative bleeding requiring haemostatic therapy. Cost savings were apparent in all individual domains of care (complications avoided: £83,536; operating room time saved: £63,969; surgical revisions avoided: £34,038; and blood transfusions avoided: £22,317). Cost savings per 100 patients with Floseal over ORC in terms of ICU days avoided (n = 30) and extended bed days avoided (n = 51.7) were £57,960 and £21,965, respectively. A sensitivity analysis indicated that these findings remained robust when the model parameters representing the clinical benefit of Floseal over ORC were reduced by up to 20%. Despite higher initial acquisition costs, the use of flowable haemostatic agents achieves substantial cost savings over non-flowable agents in cardiac surgery. These cost savings commence during the operating theatre and appear to continue to be realised throughout the postoperative period.     

Ki-67 expression and prognosis for smokers with resected stage I non-small cell lung cancer

BACKGROUND: The cigarette smoking status of patients before surgery is an important prognostic factor in evaluation of stage I non-small cell lung cancer, and the proliferative activity of lung tumors is also related to the patient's prognosis. This study evaluates relationships between various clinicopathologic factors, including tumor proliferative activity and smoking status, and the patient's prognosis in stage I non-small cell lung cancer. METHODS: One hundred eighty-seven stage I adenocarcinoma and squamous cell carcinoma cases were evaluated. The patients underwent complete resection between 1988 and 1993 at Chiba University Hospital. Expression levels of Ki-67 nuclear antigen, p53 protein, and retinoblastoma protein were determined immunohistochemically, and postoperative survival rates for patients in the categories of clinicopathologic factors were estimated. RESULTS: The mean Ki-67 labeling index (LI) for all cases was 19.3%. Labeling index values were significantly higher in squamous cell carcinoma than in adenocarcinoma (p < 0.0001). Postoperative survival of adenocarcinoma patients was significantly related to the LI values and to the patient's smoking status (p = 0.0164 and 0.0268, respectively). The LI values were also related to smoking status and the extent of histologic differentiation (p = 0.0112 and p < 0.0001, respectively). For non-smoking adenocarcinoma patients, higher LI values were associated with abnormalities in p53 expression (p = 0.0048). Retinoblastoma protein abnormalities were not related to LI values. CONCLUSIONS: In smokers with stage I pulmonary adenocarcinoma, tumor proliferative activity and smoking status before surgery were important prognostic determinants. The LI values were related to several clinicopathologic factors.     

Clinical significance of nm23 expression in resected pathologic-stage I, non-small cell lung cancer

BACKGROUND: Clinical significance of the status of nm23 gene, originally identified as an antimetastatic gene, in non-small cell lung cancer remains unestablished, whereas many clinical studies have demonstrated that reduced nm23 expression is correlated with tumor progression and poor prognosis in a variety of malignant tumors such as breast carcinoma. METHODS: nm23 expression was examined immunohistochemically in a total of 117 patients with completely resected pathologic stage I non-small cell lung cancer. RESULTS: nm23 expression was positive in 73 (62.4%) patients, and there was no correlation between nm23 expression and age, sex, performance status, pathologic T factor, histologic type, or degree of cancer cell differentiation. The 5-year survival rates of nm23-positive and nm23-negative patients were 79.7% and 57.8%, respectively, demonstrating a significantly poorer prognosis in nm23-negative patients (p = 0.013), which was confirmed by a multivariate analysis. nm23 was not correlated with the incidence of apoptosis, proliferative activity, or p53 status. CONCLUSIONS: nm23 expression was a significant factor for predicting a favorable prognosis, suggesting antimetastatic potential of the nm23 gene in non-small cell lung cancer.     

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.     

Serum carcinoembryonic antigen level in surgically resected clinical stage I patients with non-small cell lung cancer

BACKGROUND: There is little general agreement concerning the effectiveness of serum carcinoembryonic antigen (CEA) as a prognostic indicator for non-small cell lung cancer (NSCLC) in clinical stage I patients. We conducted a retrospective study to investigate the relationship between serum CEA level and survival. METHODS: We assessed 297 consecutive patients with clinical stage I NSCLC who underwent surgical resection at Toneyama National Hospital from 1985 to 1998. Serum CEA levels were measured with an enzyme-linked immunosorbent assay kit with the upper limit of normal defined as 7.0 ng/mL based on the 95% specificity level for benign lung disease, in our hospital. RESULTS: There were 56 (19%) patients with serum CEA greater than 7.0 ng/mL. The high CEA group had a median survival time of 50 months and a 5-year survival rate of 49% compared with a 5-year survival rate of 72% (p < 0.0001) for the normal CEA group (n = 241). Patients with postoperatively high CEA levels (n = 15) had the worse prognosis (median survival time 35 months, and 5-year survival 18%) compared with patients whose levels returned to normal (n = 41, median survival time 8.8 months, and 5-year survival 68%; p = 0.01). These differences were also observed in patients with pathologic stage I or II tumors but not in those with pathologic stage III or IV tumors. CONCLUSIONS: Serum CEA level is a useful predictor of survival for patients with clinical stage I NSCLC, and a persistently high CEA level after surgery is an especially strong indicator of a very poor prognosis.     

Tumor angiogenesis and recurrence in stage I non-small cell lung cancer.

BACKGROUND: Tumor angiogenesis appears to relate to recurrence after an operation as a route for distant metastasis. We assessed the association of vascular endothelial growth factor (VEGF) expression and intratumoral microvessel density (MD) with recurrence in primary lung cancer. METHODS: Samples were randomly obtained from 104 stage I lung cancer patients who underwent curative operations (43 recurrent, 61 nonrecurrent patients). Microvessels were highlighted by staining endothelial cells for factor VIII and VEGF antigen was detected using a polyclonal antibody. RESULTS: VEGF antigen was detected in large amounts in both recurrent (100%) and nonrecurrent tumors (73.8%). The percentages of patients with the strongest VEGF stain (more than 50% of staining area in tumor cells) were 46.5% in tumors with recurrence and 11.5% in tumors without recurrence. The mean MD in recurrent and nonrecurrent tumors were 18.2+/-10.5 and 8.5+/-5.0, respectively, resulting in a significantly greater value in tumors with recurrence (p<0.0001). Although there were no significant differences in mean MD according to pathological types, in adenocarcinoma and adenosquamous carcinoma, the mean value in the recurrent group was significantly greater than that in the nonrecurrent one. CONCLUSIONS: An evaluation of VEGF expression and MD in tumors may contribute to the estimation of the risk of recurrence of non-small cell lung cancer in early stages.     

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.     

纵隔淋巴结清扫对Ⅰ期非小细胞肺癌预后的影响

目的探讨纵隔淋巴结清扫范围对I期非小细胞肺癌预后的影响。方法回顾性分析从1994年1月至2003年12月在我院接受手术切除的330例I期非小细胞肺癌患者的临床、病理和随访资料。根据纵隔淋巴结清扫范围将全组患者分为纵隔淋巴结清扫组（LND）和淋巴结取样组（LNS）。运用Kaplan—Meier生存分析和COX比例风险模型,对影响预后的因素进行单因素和多因素分析。结果本组患者男性233例,女性97例;中位年龄60岁。IA期98例,IB期232例。LND组140例,LNS组190例;平均每例患者淋巴结清扫个数两组分别为（13,3±4,7）个和（5,2±3,0）个（P〈0,01）;平均每例患者纵隔淋巴结清扫组数两组分别为（3．7±0,9）组和（1．3±1．1）组（P〈0．01）。LND组5年和10年生存率分别为72,0％和66,1％,LNS组为65,9％和43．0％（P〈0,05）。其他影响预后的因素包括诊断时是否出现症状、肿瘤分期、是否侵犯脏层胸膜和肿瘤大小。COX比例风险模型分析结果显示,淋巴结清扫范围和术前有无症状是影响预后的因素。结论纵隔淋巴结清扫可以提高I期非小细胞肺癌术后的生存率。     

Completely resected stage IIIA non-small cell lung cancer: the significance of primary tumor location and N2 station

BACKGROUND: The number of N2 stations (single vs multiple N2 stations) is an important prognostic factor in patients with completely resected stage IIIA-N2 non-small cell lung cancer. However, the significance of both the N2 station(s) actually involved and the primary tumor location remains unclear. METHODS: The database was built with the use of a questionnaire survey on the survival of patients with pathologic stage IIIA-N2 non-small cell lung cancer completely resected between January 1992 and December 1993. The survey was performed by the Japan Clinical Oncology Group as of July 1999. The data include information on the survival and N2 stations of 402 patients. RESULTS: A frequently metastasized single N2 station was the lower pretracheal station in primary tumors in the right upper lobe, the subaortic station in the left upper lobe, and the subcarinal station in the right middle or lower lobe and the left lower lobe. In multiple N2 stations, the frequency of metastasis of the N2 station observed in a single N2 station was as high as 72% to 89%, and one or two other frequently metastasized stations were added to each group. Regarding the survival of patients with a primary tumor in each lobe except for the left lower lobe, a single N2 station resulted in a significantly better survival than did multiple N2 stations. Furthermore, the overall survivals classified according to each primary site showed a significant difference among the four primary sites (P =.04). CONCLUSIONS: The primary tumors in each lobe showed a prevalence of N2 station(s). The number of N2 stations is a good prognosticator except in patients with a primary tumor in the left lower lobe. In addition, the site of a primary tumor itself is also considered to influence the survival of the patients.     

Prognostic significance of computed tomography in resected N2 lung cancer.

We reviewed 124 patients from 1982 to 1988 who had a resected primary non-small cell lung cancer metastatic to mediastinal (N2) lymph nodes and a preoperative assessment of the mediastinum with computed tomography of the chest. Sixty-three patients studied had computed tomographic evidence of mediastinal lymph node enlargement. In these patients the survival at 5 years was only 6.6%, compared with the 5-year survival of 13.5% in 61 patients in whom the mediastinum was normal. Plain chest roentgenography with evidence of mediastinal adenopathy did not predict a poorer outcome. In addition, patients with tumors located in the left upper lobe were found to have an improved survival. These patients had a 5-year survival of 20.8%. Tumor histology, central location of the tumor, extranodal extension, and type of resection did not result in a significant survival difference.     

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.