-
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE:: This study investigated the prognostic value of the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification in resected stage I lung adenocarcinoma. METHODS:: Histological classification of 283 patients undergoing surgical resection for stage I lung adenocarcinoma was determined according to the IASLC/ATS/ERS classification after comprehensive histological subtyping with recording of the percentage of each histological component (lepidic, acinar, papillary, micropapillary, and solid) in 5% increments. Their impact on overall survival, recurrence, and postrecurrence survival was investigated. RESULTS:: The 5-year overall survival and recurrence-free rates were 81.6% and 76.9%, respectively. During follow-up, 57 (20.1%) patients developed recurrence. The 2-year postrecurrence survival rate was 72.3%. The solid predominant group is associated with significant more male sex, higher smoking exposure, larger tumor size, and more poorly differentiated histological grade. Lepidic predominant group had significantly better overall survival (P = 0.002). Micropapillary and solid predominant groups had significantly lower probability of freedom from recurrence (P = 0.004). Older age (P = 0.039), visceral pleural invasion to the surface (PL2) (P = 0.009), and high grade (micropapillary/solid predominant) of the new classification (P = 0.028) were predictors of recurrence in multivariate analysis. The solid predominant group tends to have significantly worse postrecurrence survival (P = 0.074). CONCLUSIONS:: The new adenocarcinoma classification has significant impact on death and recurrence in stage I lung adenocarcinoma. Patients with PL2 and micropapillary/solid predominant pattern have significant higher risk for recurrence. This information is important for patient stratification for aggressive adjuvant chemoradiation therapy.
Annals of surgery 03/2013; · 7.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Stage II non-small cell lung cancer (NSCLC) has been redefined in the 7th edn of Tumour-Node-Metastasis (TNM) classification for lung cancer. Stage IIa and Stage IIb both contain node-negative (N0) and node-positive (N1) subgroups. The aim of this study was to evaluate the prognostic factors for overall survival in patients with resected N1-stage II NSCLC.Between January 1992 and December 2010, we retrospectively reviewed the clinicopathological characteristics of 163 N1-stage II (T1a-T2bN1M0) NSCLC in patients undergoing curative resection as primary treatment.Median follow-up time was 37.2 months. The 1-, 3-, and 5-year overall survival rates were 85.3%, 62.1%, and 43.5%, respectively. Tumour involvement of hilar/interlobar nodal zone and poorly differentiated histological grade were significant predictors for worse overall survival using multivariate analysis (p=0.001 and p=0.015, respectively). There were trends toward worse overall survival in older patients and greater tumour size (p=0.063 and p=0.075, respectively).In resected N1-stage II NSCLC, hilar/interlobar nodal involvement and poorly-differentiated histologic grade were significant predictors of worse overall survival. The differences in survival between these subgroups of patients may lead to the use of different adjuvant therapies or postsurgical follow-up strategies.
European Respiratory Journal 07/2012; · 5.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study investigated the factors predicting recurrence and death in patients with resected stage-I non-small-cell lung cancers according to the 7th edition of tumor, node, metastasis (TNM) classification for lung cancer.
All patients undergoing surgical resection for pathological stage-I non-small-cell lung cancers at Taipei Veterans General Hospital between 1980 and 2000 were retrospectively reviewed. Those undergoing sublobar resection were excluded. The factors predicting overall survival (OS), overall recurrence, local recurrence, and distant metastasis were investigated.
A total of 756 patients were eligible. The 5-year OS rate and probability of freedom from recurrence were 57.3% and 70.2%, respectively. The 2-year local-recurrence-free and distant-metastasis-free rates were 90.7% and 82.1%, respectively. In multivariable analysis, the new T descriptor (T1a, T1b, and T2a) was the common factor that significantly affected OS (p = 0.003), overall recurrence (p = 0.004), and distant metastasis (p < 0.001). Smoking index more than 20, and number of mediastinal lymph nodes dissected/sampled of 15 or fewer were common factors that significantly predicted worse OS (p < 0.001, p < 0.001, respectively), lower probability of freedom from overall recurrence (p = 0.025, p = 0.009, respectively), and higher risk of local recurrence (p < 0.001, p = 0.030, respectively). Non-squamous-cell histology predicted higher risk of distant metastasis (p = 0.006).
Risks of death and recurrence increase as the T descriptor upgrades in the new TNM system. The combination of risk factors can be used to identify high-risk subgroups of local recurrence and distant metastasis.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2012; 7(7):1115-23. · 4.55 Impact Factor
-
02/2012; , ISBN: 978-953-51-0010-2
-
[show abstract]
[hide abstract]
ABSTRACT: Visceral pleural invasion (VPI) has been defined as invasion of the tumor beyond the elastic layer (PL1), including invasion to the visceral pleural surface (PL2). The aim of this study was to evaluate the prognostic factors and patterns of recurrence in resected node-negative non-small cell lung cancer (NSCLC) with VPI.
We retrospectively reviewed the clinicopathologic characteristics of 355 patients with resected node-negative NSCLC with VPI at Taipei Veterans General Hospital between 1990 and 2006. The prognostic value and patterns of recurrence were analyzed and compared between PL1 and PL2 groups.
The median follow-up time was 54.2 months. The 5-year overall survival rate and probability of freedom from recurrence were 61.9% and 66.2%, respectively. The extent of VPI was PL1 in 300 patients (84.5%) and PL2 in 55 (15.5%). During follow-up, 107 patients (30.1%) developed recurrence. The patterns of recurrence included local recurrence only in 20 patients (18.7%), distant metastasis only in 59 (55.1%), and both local recurrence and distant metastasis in 28 (26.2%). Thirteen of the 107 patients (12.1%) with recurrence developed malignant pleural effusion. The percentage of malignant pleural effusion in the PL2 group was significantly higher than that in the PL1 group (P = .006). Patients with PL2 had significantly worse overall survival (P = .046) and lower probability of freedom from recurrence (P = .028) in multivariate analysis.
PL2 was a significant prognostic factor for recurrence and worse overall survival in node-negative NSCLC with VPI. This information is important for further design of clinical trials for aggressive adjuvant therapy.
Chest 01/2012; 142(1):141-50. · 5.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The transcription factor E2F1 has been implicated in cell cycle control and DNA damage response. Paradoxically, E2F1 can promote apoptosis and function as tumor suppressor. In non-small cell lung cancer (NSCLC), there are conflicting data for clinical significance of E2F1 expression. In this study, we investigated the protein expression of E2F1 in patients with stage I-III NSCLC, and its correlation with clinical outcome.
56 paired adjacent non-tumor/tumor matched samples were prospectively obtained from patients undergoing surgery for stage I-III NSCLC at Taipei Veterans General Hospital. The protein expression of E2F1 was determined by Western blot analysis. The levels of E2F1 protein were significantly higher in tumor samples than in non-tumor lung specimens (P = 0.008). Overexpression of E2F1 was defined as a more than 2-fold expression in the tumorous sample compared with the corresponding nontumorous one, and was noted in 21 patients (37.5%). There was no significant difference in overall survival (P = 0.44) or probability of freedom from recurrence (P = 0.378) between patients with E2F1 overexpression vs. non-overexpressors. Additionally, there was no significant association between E2F1 overexpression and any clinicopathologic parameter such as histological type, stage, or angiolymphatic invasion of tumor.
E2F1 protein is frequently overexpressed in NSCLC. There is no correlation between E2F1 protein expression and clinical outcome such as survival and freedom from progression.
Experimental hematology & oncology. 01/2012; 1(1):18.
-
Di-Cing Wei,
Yi-Chen Yeh, Jung-Jyh Hung,
Teh-Ying Chou,
Yu-Chung Wu,
Pei-Jung Lu,
Hui-Chuan Cheng,
Yu-Lin Hsu,
Yu-Lun Kuo,
Kuan-Yu Chen,
Jin-Mei Lai
[show abstract]
[hide abstract]
ABSTRACT: Tumor recurrence is the most common cause of disease failure after surgical resection in early-stage lung adenocarcinoma. Identification of clinically relevant prognostic markers could help to predict patients with high risk of disease recurrence. A meta-analysis of available lung adenocarcinoma microarray datasets revealed that T-LAK cell-originated protein kinase (TOPK), a serine/threonine protein kinase, is overexpressed in lung cancer. Using stable cell lines with overexpression or knockdown of TOPK, we have shown that TOPK can promote cell migration, invasion, and clonogenic activity in lung cancer cells, suggesting its crucial role in lung tumorigenesis. To evaluate the prognostic value of TOPK expression in resected stage I lung adenocarcinoma, a retrospective analysis of 203 patients diagnosed with pathological stage I lung adenocarcinoma was carried out to examine the expression of TOPK by immunohistochemistry (IHC). The prognostic significance of TOPK overexpression was examined. Overexpression of TOPK (IHC score >3) was detected in 67.0% of patients, and these patients were more frequently characterized with disease recurrence and angiolymphatic invasion. Using multivariate analysis, patient age (>65 years old; P = 0.002) and TOPK overexpression (IHC score >3; P < 0.001) significantly predicted a shortened overall survival. Moreover, TOPK overexpression (IHC score >3; P = 0.005) also significantly predicted a reduced time to recurrence in the patients. Our results indicate that overexpression of TOPK could predetermine the metastatic capability of tumors and could serve as a significant prognostic predictor of shortened overall survival and time to recurrence.
Cancer Science 12/2011; 103(4):731-8. · 3.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The seventh edition of the tumor, node, metastasis classification for lung cancer has been published in 2009. The aim of this study is to evaluate time trends of surgical outcomes and clinicopathologic factors in patients with pathological stage I non-small cell lung cancer according to the seventh edition of the tumor, node, metastasis classification.
We retrospectively reviewed the clinicopathologic characteristics of 1249 patients with pathological stage I non-small cell lung cancer from Taipei Veterans General Hospital between January 1980 and December 2006, during the three periods of 1980-1990, 1991-2000, and 2001-2006. The overall survival, disease-specific survival, and postrecurrence survival were analyzed.
The 5-year overall survival rates during the three periods improved significantly: 53.7, 59.9, and 69.3%, respectively (p < 0.001). The 2-year postrecurrence survival rates during the three periods improved significantly: 10.6, 25.4, and 43.2%, respectively (p < 0.001). The percentage of female patients increased during each period: 15.4, 24.9, and 32.0%, respectively (p < 0.001). The percentage of adenocarcinoma also increased during each period: 51.2, 62.2, and 74.9%, respectively (p < 0.001). Tumor size during each period was 3.2, 3.2, and 2.8 cm, tending to be smaller when diagnosed in the last period (p < 0.001). The overall survival in patients with squamous cell carcinoma and those undergoing pneumonectomy or bilobectomy did not improve over time.
Stage migration, improved postrecurrence survival, increased frequencies of female gender and adenocarcinoma, and decreased tumor size lead to improved overall survival over the past three decades.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2011; 7(2):397-405. · 4.55 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cancer metastasis is the major cause of cancer-related death despite significant improvements in multimodal cancer therapy. Epithelial-mesenchymal transition (EMT), a major mechanism of cancer metastasis, is a process that generates cells with stem cell-like properties (cancer stemness). Cancer stemness is a concept that describes a minor population of cells (cancer stem cells) residing within a tumour that are able to self-renew and are resistant to conventional therapy. The mechanisms delineating the generation of cancer stemness and its connection to cancer metastasis remain largely unknown. Twist1 is an EMT regulator and increased Twist1 expression, which has prognostic significance in various human cancers, has been widely reported. Bmi1 is a critical component of polycomb repressive complex (PRC) 1, which maintains self-renewal and stemness. Bmi1 is frequently overexpressed in different types of human cancers and can induce drug resistance (Table 2). Recent studies have shown that Twist1 directly activates Bmi1 expression and that these two molecules function together to mediate cancer stemness and EMT. These results present a unique mechanism of EMT-induced cancer metastasis and stemness. Further investigation of the mechanisms of EMT-mediated cancer metastasis and stemness will contribute to the management and treatment of metastatic cancers.
Clinical and Experimental Pharmacology and Physiology 08/2011; 39(8):668-73. · 1.85 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of the study is to investigate the prognosis of non-small-cell lung cancer (NSCLC) with unexpected pleural spread at thoracotomy.
We conducted a retrospective review of the clinicopathologic characteristics of NSCLC patients with unexpected pleural spread at thoracotomy in Taipei Veterans General Hospital between January 1990 and December 2008. Inclusion criteria were patients with frozen section of pleural nodules identified as metastatic carcinoma during operation. A survival analysis was done.
There were 138 patients included in this study. The median follow-up time was 19.9 mo. The overall 1, 3, and 5-year survival rates were 72.9%, 26.8%, and 16.6%, respectively. Multivariate analysis showed that main tumor resection and mediastinal lymph nodal involvement (P < 0.001 and 0.002, respectively) were significant predictors for overall survival rate. Patients who underwent main tumor resection and those without mediastinal lymph node metastasis had better outcomes.
Among the unexpected pleural spread detected at thoracotomy, limited pulmonary resection was an alternative surgical procedure for these patients without mediastinal nodal metastasis.
Journal of Surgical Research 07/2011; 169(1):e1-5. · 2.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The goal of this study was to investigate the prognostic factors and patterns of recurrence in patients with resected non-small cell lung cancer (NSCLC) < or = 1 cm in diameter.
We conducted a retrospective review of the clinicopathological characteristics of 71 patients with NSCLC < or = 1 cm in diameter in Taipei Veterans General Hospital between 1982 and 2007. Overall survival and its predictors were analyzed.
Median follow-up time of the 71 patients was 33.3 months. Complete resection was performed in 68 patients (95.8%) with stage I disease. The 5- and 10-year overall survival rates of patients who underwent complete resections were 81.7% and 44.9%, respectively. There was tumor recurrence in 6 (8.8%) of these 68 patients. Five (9.3%) of 54 patients who underwent standard resection experienced tumor recurrence, but only 1 (7.1%) of 14 patients who received sublobar resection had recurrent disease. The difference was not statistically significant (p = 0.569). Multivariate analysis revealed that sublobar resection (hazard ratio, 5.00; 95% confidence interval, 1.28-20.00; p = 0.020) was a significant predictor for worse overall survival.
Survival in patients with NSCLC pound 1 cm in diameter is satisfactory. Sublobar resection, performed in patients unfit for standard resection, is a poor prognostic factor for overall survival.
Journal of the Chinese Medical Association 06/2010; 73(6):308-13. · 0.79 Impact Factor
-
The lancet oncology 05/2010; 11(5):412-3; author reply 413. · 14.47 Impact Factor
-
Annals of surgery 05/2010; 251(5):990; author reply 990-1. · 7.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Distant metastasis after surgical resection is the most frequent cause of death in patients with non-small cell lung cancer (NSCLC). This study aimed to investigate the patterns of distant metastasis and the prognostic factors of postrecurrence survival in patients with resected stage I NSCLC with distant metastases.
The clinicopathological characteristics of 166 patients with distant metastases after complete resection of stage I NSCLC at Taipei Veterans General Hospital between 1980 and 2000 were retrospectively reviewed. The patients were divided into two groups according to patterns of distant metastasis (single or multiple organ metastases). Predictors of postrecurrence survival were analysed.
The patterns of distant metastasis included single organ metastasis in 106 (63.9%) and multiple organ metastases in 60 (36.1%) patients. The 1- and 2-year postrecurrence survival rates for those with single organ metastasis were 30.2% and 15.1%, respectively. The most common site of single organ metastasis was bone (32.1%), followed by the brain (29.2%). Multivariate analysis revealed that disease-free interval >16 months (HR 0.534; 95% CI 0.288 to 0.990; p=0.046) and treatment for distant metastasis (including re-operation, chemotherapy and/or radiotherapy) (HR 0.245; 95% CI 0.089 to 0.673; p=0.006) were significant predictors of better postrecurrence survival in resected stage I NSCLC with single organ metastasis.
A longer disease-free interval is a favourable prognostic predictor for postrecurrence survival in resected stage I NSCLC with single organ metastasis. Treatment for distant metastasis significantly prolongs postrecurrence survival.
Thorax 03/2010; 65(3):241-5. · 6.84 Impact Factor
-
New England Journal of Medicine 10/2009; 361(16):1606-7; author reply 1608. · 53.30 Impact Factor
-
American Journal of Respiratory and Critical Care Medicine 10/2009; 180(8):794; author reply 794-5. · 11.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Metastasis is the most common cause of disease failure and mortality for non-small cell lung cancer (NSCLC) after surgical resection. Snail and TWIST1 are epithelial-mesenchymal transition (EMT) regulators which induce metastasis. Intratumoral hypoxia followed by stabilisation of hypoxia-inducible factor 1alpha (HIF-1alpha) promotes metastasis through regulation of certain EMT regulators. The aim of this study was to evaluate the prognostic value of HIF-1alpha, TWIST1 and Snail expression in patients with resectable NSCLC.
A retrospective analysis of 87 patients with resectable NSCLC from Taipei Veterans General Hospital between 2003 and 2004 was performed using immunohistochemistry to analyse HIF-1alpha, TWIST1 and Snail expression. The association between HIF-1alpha, TWIST1 and Snail expression and patients' overall and recurrence-free survivals was investigated.
Overexpression of HIF-1alpha, TWIST1 or Snail was shown in 32.2%, 36.8% and 55.2% of primary tumours, respectively. Overexpression of HIF-1alpha, TWIST1 or Snail in primary NSCLCs was associated with a shorter overall survival (p = 0.005, p = 0.026, p = 0.009, respectively), and overexpression of HIF-1alpha was associated with a shorter recurrence-free survival (p = 0.016). We categorised the patients into four groups according to the positivity of HIF-1alpha/TWIST1/Snail to investigate the accumulated effects of these markers on survival. Co-expression of more than two markers was an independent prognostic indicator for both recurrence-free survival and overall survival (p = 0.004 and p<0.001, respectively, by multivariate Cox proportional hazards model).
Co-expression of more than two markers from HIF-1alpha, TWIST1 and Snail is a significant prognostic predictor in patients with NSCLC.
Thorax 09/2009; 64(12):1082-9. · 6.84 Impact Factor
-
The Journal of thoracic and cardiovascular surgery 08/2009; 138(1):260-1. · 3.41 Impact Factor
-
Chest 07/2009; 135(6):1695; author reply 1695-6. · 5.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Carcinoma is rare in an esophageal diverticulum. The case of a 53-year-old man with a large mass in a long-standing symptomatic epiphrenic esophageal diverticulum is presented in this study. Squamous cell carcinoma in the diverticulum with pleural invasion was diagnosed after surgical diverticulectomy. The patient underwent subtotal esophagectomy with locoregional lymph node dissection and reconstruction with gastric tube because of micro-invasion at the surgical margin. The patient developed malignant pleural effusion at 6 months after surgery, and he eventually expired 3 months later. Carcinoma can develop in esophageal diverticula and is usually diagnosed at an advanced stage with poor prognosis.
Digestive Diseases and Sciences 02/2009; 54(6):1365-8. · 2.12 Impact Factor
