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Abstract Purpose This study investigated whether the number of involved lymph nodes is associated with the prognosis in patients that underwent surgery for pathological stage (p-stage) III/N2 NSCLC. Subjects This study evaluated 121 patients with p-stage III/N2 NSCLC. Results The histological types included 65 adenocarcinomas, 39 squamous cell carcinomas and 17 others. The average number of dissected lymph nodes was 23.8 (range: 6-55). The average number of involved lymph nodes was 5.9 (range: 1-23). The 5-year survival rate of the patients was 51.0% for single lymph node positive, 58.9% for 2 lymph nodes positive, 34.2% for 3 lymph nodes positive, and 30.0% for 4 lymph nodes positive, and 20.4% for more than 5 lymph nodes positive. The patients with either single or 2 lymph nodes positive had a significantly more favorable prognosis than the patients with more than 5 lymph nodes positive. A multivariate analysis revealed that the number of involved lymph nodes was a significant independent prognostic factor. Conclusion Surgery appears to be preferable as a one arm of multimodality therapy in p-stage III/N2 patients with single or 2 involved lymph nodes. The optimal incorporation of surgery into the multimodality approach therefore requires further clinical investigation.

Background. This study retrospectively investigated the clinical significance of undiagnosed solitary lung nodules removed by surgical resection. Patients and methods. We retrospectively collected data on the age, smoking, cancer history, nodule size, location and spiculation of 241 patients who had nodules measuring 7 mm to 30 mm and a final diagnosis established by histopathology. We compared the final diagnosis of each patient with the probability of malignancy (POM) which was proposed by the American College of Chest Physicians (ACCP) guidelines. Results. Of the 241 patients, 203 patients were diagnosed to have a malignant lung tumor, while 38 patients were diagnosed with benign disease. There were significant differences in the patients with malignant and benign disease in terms of their age, smoking history, nodule size and spiculation. The mean value and the standard deviation of the POM in patients with malignant tumors were 51.7 + 26.1%, and that of patients with benign lesions was 34.6 + 26.7%. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.67. The best cut-off value provided from the ROC curve was 22.6. When the cut-off value was set at 22.6, the sensitivity was 83%, specificity 52%, positive predictive value 90%, negative predictive value 36% and accuracy 77%, respectively. Conclusions. The clinical prediction model proposed in the ACCP guidelines showed unsatisfactory results in terms of the differential diagnosis between malignant disease and benign disease of solitary lung nodules in our study, because the specificity, negative predictive value and AUC were relatively low. [ABSTRACT FROM AUTHOR]

OBJECTIVES Immune therapy targeting cancer/testis (CT) antigens improve the survival in several types of solid tumours. The expression of CT antigens is related to poor survival in non-small-cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) mutation is the best predictive factor for the sensitivity to tyrosine kinase inhibitors in lung adenocarcinoma. The aim of this study was to elucidate the correlation between the expression of CT antigens and clinicopathological factors, including the EGFR mutation, and to analyse the prognosis in lung adenocarcinoma. METHODS Data were collected from a total of 281 lung adenocarcinoma patients who underwent surgery. Among them, 125 cases, whose specimens were too small to extract sufficient DNA and/or RNA, and 2 cases with the coexistence of another histological lung cancer were excluded. A total of 154 patients were reviewed. The expression of CT antigens (melanoma-associated antigen gene [MAGE]-A4 and KK-LC-1) and the EGFR-activating mutation (L858R point mutation in exon 21 and inframe deletion in exon 19) was evaluated by using polymerase chain reaction amplification. RESULTS The expression of MAGE-A4 and KK-LC-1 was detected in 14 (9%) and 54 patients (35%) with adenocarcinoma. The EGFR-activating mutation was found in 64 patients (42%). Univariate and multivariate analyses demonstrated that tumours expressing at least one CT antigen were associated with no EGFR mutation (odds ratio = 0.3; 95% confidence interval, 0.14–0.71; P < 0.01). A survival analysis was performed in 135 patients who underwent complete resection and the 5-year overall survival rate was 71.1% in those with any expression of CT antigens and 83.2% in those without expression of the genes (P < 0.04). CONCLUSION Two different therapeutic targets, EGFR-activating mutation and CT antigen, have a negative relationship with each other. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: This study investigated the preoperative serum levels of CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer. Subjects: This study evaluated 341 patients who had undergone a complete resection for stage I NSCLC between 2002 and 2008. Results: The patients included 193 males and 148 females. The mean age of the patients was 69.2 years (range: 19–88). The histological types included 264 adenocarcinomas, 56 squamous cell carcinomas, 11 large cell carcinomas, and 10 other types of carcinoma. A pneumonectomy was performed in 2 patients, a bilobectomy in 7, a lobectomy in 255, a segmentectomy in 46, and partial resection of the lung in 31 patients. The positive rates for CYFRA 21-1 in the adenocarcinoma and squamous cell carcinoma patients were 33.3% and 76.8%, respectively. The positive rates for CEA in adenocarcinoma and squamous cell carcinoma patients were 23.8% and 26.8%, respectively. The 5-year survival rate after surgery in the normal CYFRA 21-1 group and the high CYFRA 21-1 groups were 92.8% and 75.4%, respectively, in the patients with stage I NSCLC. There was a significant difference between the 2 groups (p <0.0001). The 5-year survival rate according to the serum level of CEA in the patients with stage I NSCLC were 88.3% for the normal group and 76.3% for the high group. In a multivariate analysis using the variables found to be significant prognostic factors in univariate analysis, a high CYFRA 21-1 level was found to be a significant independent prognostic factor (95% confidence interval 1.213–5.442, p =0.014). Conclusion: A high preoperative CYFRA 21-1 level was a significant independent prognostic factor in patients with stage I NSCLC. The patients with a high CYFRA 21-1 level should carefully followed-up to rule out occult metastasis. Further clinical studies will be necessary to evaluate the efficacy of adjuvant therapy for the patients selected according to this criterion. [Copyright &y& Elsevier]

Abstract: Purpose: The clinical features of large cell carcinoma (LCC) of the lung have remained unclear due to the low incidence of the disease. This study investigated the clinicopathological features and the surgical outcome in patients with LCC. Subjects: This study clinicopathologically evaluated 975 patients who had undergone a resection for non-small cell carcinoma between 1994 and 2007. There were 57 (5.8%) patients with LCC among them. Results: The LCC patients included 49 males and 8 females and included 9 patients with large cell neuroendocrine carcinoma. All patients excluding 1 had a smoking habit. The mean smoking pack-year index was 49.9 in the patients with LCC, 27.1 in 625 patients with adenocarcinoma, and 52.5 in 266 patients with squamous cell carcinoma, and this was significantly higher in the patients with LCC than in those with adenocarcinoma. The mean tumor diameter was 38 mm for LCC, 28 mm for adenocarcinoma, and 39 mm for squamous cell carcinoma. The pathological stage was IA in 11 patients, IB in 11, II in 12, IIIA in 16, IIIB in 5, and IV in 2. The post-operative 5-year survival rate was 60.5% for LCC, 64.3% for large cell neuroendocrine carcinoma, 67.0% for adenocarcinoma, and 50.1% for squamous cell carcinoma. Conclusion: The tumor diameter was significantly larger for LCC than for adenocarcinoma at the time of diagnosis. The proportion of smokers and the smoking pack-year index in patients with LCC were significantly higher than those of adenocarcinoma. The surgical results were similar between LCC and other non-small cell lung carcinomas. [Copyright &y& Elsevier]

Abstract: Purpose: A sleeve lobectomy for lung cancer is a procedure intended both for the maintenance of lung function and for radical treatment. We investigated the clinico-pathological features and treatment responses of lung cancer patients who underwent sleeve lobectomy in our department. Subjects: Among the 984 patients with non-small cell lung cancer who underwent resection in our department between 1994 and 2007, the subjects were 24 patients in whom a sleeve lobectomy was performed. Results: There were 18 male and 6 female patients, with a mean age of 65 years. The histological type was diagnosed as squamous cell carcinoma in 14 patients, and adenocarcinoma in 10. Patients with either mucoepidermoid carcinoma (n =1) or carcinoid tumor (n =1) were excluded. The pathological stage was evaluated as IA, IB, II, IIIA, IIIB, and IV in 4, 1, 8, 8, 2, and 1 patient, respectively. Regarding post-operative complications, 4 patients required sputum aspiration with a bronchoscope from the 2nd to 7th post-operative day due to sputum retention. The 5-year survival rate in patients who underwent sleeve lobectomy was 70.0%. According to the pathological nodal status, the 5-year survival rates of N0, N1, and N2 were 100.0%, 87.5%, and 41.7%, respectively. The 5-year survival rates in squamous cell carcinoma and adenocarcinoma were 83.0% and 45.7%, respectively. Conclusion: Sleeve lobectomy facilitated the maintenance of residual lung function without serious perioperative complications. This finding suggests that patients with direct tumor invasion to the bronchus might be good candidates for a sleeve lobectomy, but not those with extra-nodal invasion. [Copyright &y& Elsevier]

Highlights • The 6MWD was associated with the 5-year survival rates in patients with NSCLC. • After adjustment for confounding factors, this relationship remained significant. • The 6MWT provides additional prognostic information for surgical patients with NSCLC. Abstract Objectives Whether or not the preoperative exercise capacity, as assessed by 6-min walk test, influences the survival of patients undergoing thoracoscopic lobectomy for lung cancer is unclear. We therefore investigated the prognostic value of the 6-min walk distance in this population. Materials and methods This prospective cohort study was conducted between 2005 and 2013. We studied 224 consecutive subjects with stage I-II non-small cell lung cancer who underwent thoracoscopic lobectomy. Survival was calculated by the Kaplan-Meier method. The log-rank test was used to assess the survival rate. Cox proportional hazards models were used to estimate the risk of 5-year all-cause mortality based on the preoperative 6-min walk distance with adjustment for other prognostic factors, including the age, performance status, postoperative cardiopulmonary complication, and pathological stage. Results The median follow-up period was 60.8 months. During this period, 38 deaths were recorded. The 5-year overall survival rate of the subjects with a preoperative 6-min walk distance of <400 m were significantly lower than those with a 6-min walk distance of ≥400 m (65.3% vs. 88.0%; p < 0.001). A multivariate analysis showed that the 6-min walk distance was significantly associated with the overall survival after adjusting for the age and pathologic stage (hazard ratio, 2.40; 95% confidence interval, 1.20–4.79), but it did not provide additional prognostic value beyond the performance status. Conclusion The preoperative 6-min walk distance may be useful as an additional prognostic factor for patients at an increased risk of mortality after thoracoscopic lobectomy for stage I-II non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The purpose of this study was to assess the toxicity and efficacy of re-irradiation plus regional hyperthermia for recurrent NSCLC and to identify the predictors of long-term survival. Methods and materials: A total of 33 patients with recurrent NSCLC treated with re-irradiation plus regional hyperthermia were retrospectively analyzed. The median total dose of initial radiotherapy and re-irradiation were 70Gy and 50Gy, respectively. A median of 5 hyperthermia treatments using an 8-MHz radiofrequency-capacitive device were applied during re-irradiation in all patients. Results: Toxicity of Grade 3 was seen in 3 (9%) patients, and no Grade 4 or 5 toxicity was observed. The median overall survival, local control, and disease progression-free survival times after re-irradiation were 18.1, 12.1, and 6.7months, respectively. Eight patients achieved a long-term survival (more than 3years after re-irradiation), and 4 of them underwent a third round of irradiation for re-recurrent tumors. Univariate analyses showed that a smaller tumor size (<4cm) and the absence of distant metastases were significant predictors for a better overall survival. The absence of distant metastases was also found to be a significant predictor for better disease progression-free survival in the univariate analyses. In the subset analyses of 23 patients treated with hyperthermia using electrodes of 30cm in diameter, the use of a higher radiofrequency-output power tended to be associated with a better prognosis in terms of the local control rate. Conclusions: Re-irradiation plus regional hyperthermia for recurrent NSCLC appears feasible, with acceptable toxicity, and may be a promising treatment that can result in the long-term survival of patients without distant metastasis and larger recurrent tumors. [Copyright &y& Elsevier]

Abstract: Purpose: To assess the efficacy and toxicity of definitive radiotherapy (RT) plus regional hyperthermia (HT) in treating superior sulcus tumors (SSTs), and to identify predictors of positive outcomes. Methods and materials: Twenty-four patients with SSTs treated with definitive RT plus regional HT were retrospectively analyzed. The median total dose of RT was 70Gy. All patients were treated with an 8-MHz RF-capacitive heating device. Twelve of 24 (50%) patients also underwent chemotherapy. Those with either subcutaneous fat measuring 2.5cm or greater, or any other serious complications did not undergo this therapy. Results: Overall survival, local control, and distant metastasis-free survival rates at 3 years were 47%, 55%, and 71%, respectively. Chemotherapy and younger age (<65 years) were significant predictors of the overall survival rate. Clinical stage (IIB) was a statistically significant prognostic indicator for local control survival rate. Toxicities were mild, with Grade 3 dermatitis seen in one patient. Conclusions: Definitive RT plus regional HT with chemotherapy may be a promising treatment for SSTs. The results justify further evaluation with detailed treatment protocols in a large number of patients. [Copyright &y& Elsevier]