Tumor size as a prognostic factor in limited-stage thymic epithelial tumors: A multicenter analysis.

OBJECTIVE: The prognostic significance of tumor size in thymic epithelial tumors (TETs) has not been fully evaluated. We aimed to clarify the prognostic value of tumor size in limited-stage and advanced-stage TETs. METHODS: Clinical records of patients with completely resected TETs were retrospectively collected from 4 tertiary centers between January 2000 and February 2013. Information on the Masaoka-Koga stage was available for 1215 patients (M-K group), and 433 patients were classified according to the eighth edition of the Tumor-Node-Metastasis staging system (TNM group). Limited-stage and advanced-stage TETs were defined according to whether they were confined within the surrounding fatty tissues without invasion. The optimal cutoff value was selected using a maximally selected log-rank statistic. RESULTS: The median tumor size was 6.0 ± 2.8 cm in the M-K group and 6.5 ± 3.0 cm in the TNM group. In the multivariable analysis, tumor size had a significant effect on both overall survival (P = .003) and recurrence-free survival (P < .001) for limited-stage tumors (M-K stage I or II or TNM stage I), but not for advanced-stage tumors (M-K stage III or IV or TNM stage II-IV; P = .349 for overall survival and P = .439 for recurrence-free survival). The optimal cutoff value for tumor size was >5.5 cm for both overall survival and recurrence-free survival in limited-stage TETs. CONCLUSIONS: Tumor size is an independent prognostic factor in patients with completely resected limited-stage TETs and a cutoff value >5.5 cm might help clinicians enact proper treatment strategies and surveillance.

The role of postoperative radiotherapy in stage II and III thymoma: a Korean multicenter database study.

BACKGROUND: Complete resection is a standard treatment for patients with Masaoka-Koga stages II and III thymoma, however the role of postoperative radiotherapy (PORT) is controversial. We analyzed data collected from 4 Korean hospitals to determine the effectiveness of PORT in stage II and III thymoma patients. METHODS: Between January 2000 and December 2013, 1,663 patients underwent surgery for thymic tumors at the 4 hospitals. Among them, 668 patients (527 with stage II and 141 with stage III) were investigated, among whom, 443 received PORT (335 with stage II and 108 with stage III). Propensity score matching (PSM) was performed, and 404 patients (346 with stage II and 58 with stage III) were selected. RESULTS: Perioperative characteristics were similar in the PORT and non-PORT groups after PSM. On survival analysis of stage II patients, the PORT and non-PORT groups showed no difference in either 5-year recurrence-free survival (RFS) (96.3% vs. 96.6%, P=0.622) or 5-year overall survival (OS) (94.6% vs. 93.8%, P=0.839). However, among stage III patients, the PORT group showed significantly better 5-year RFS (75.7% vs. 50.1%, P=0.040) and 5-year OS (86.5% vs. 54.7%, P=0.001). On multivariate Cox regression analysis, PORT was a significant positive prognostic factor in terms of both RFS (P=0.005) and OS (P=0.004) in patients with stage III thymomas, but not in those with stage II disease (P=0.987 and 0.968, respectively). CONCLUSIONS: PORT improved the RFS and OS in stage III thymoma patients, but showed no survival benefit in stage II patients.

Prediction of postoperative pulmonary complications using preoperative controlling nutritional status (CONUT) score in patients with resectable non-small cell lung cancer.

Postoperative pulmonary complications (PPCs) significantly impact surgical outcome. We investigated the predictive ability of controlling nutritional status (CONUT) for PPC after lung resection in patients with non-small cell lung cancer (NSCLC). We retrospectively reviewed data of 922 patients with NSCLC who underwent complete resection from January 2016-December 2017. We analyzed the frequency and characteristics of PPCs and compared receiver operating characteristic (ROC) curves of various prognostic models to predict PPCs. A CONUT score higher than 1 was considered as a high CONUT score. Total incidence of PPCs was 8.6% (n = 79). The proportion of pneumonia was significantly larger in the high CONUT group (P < 0.05). The CONUT consistently had a higher area under curve (AUC) value (0.64) than other prognostic models (prognostic nutritional index (PNI): AUC = 0.61, Glasgow prognostic score (GPS): AUC = 0.57, and assessment of respiratory risk in surgical patients in Catalonia (ARISCAT): AUC = 0.54). Multivariate analysis identified underweight [Odds ratio (OR) = 4.57, P = 0.002] and high CONUT score (OR = 1.91, P = 0.009) as independent PPCs prognostic factors. One-year mortality rate for high CONUT score was significantly higher (hazard ratio = 7.97; 95% confidence interval, 1.78-35.59). Preoperative CONUT score is an independent predictor of PPCs and 1-year mortality in patients with resectable NSCLC.

Photoacoustic imaging to localize indeterminate pulmonary nodules: A preclinical study.

PURPOSE: Diagnosis and resection of indeterminate pulmonary nodules (IPNs) is a growing challenge with increased utilization of chest computed tomography. Photoacoustic (PA) -guided surgical resection with local injection of indocyanine green (ICG) may have utility for IPNs that are suspicious for lung cancer. This preclinical study explores the potential of PA imaging (PAI) to detect ICG-labeled tumors. MATERIALS AND METHODS: ICG uptake by H460 lung cancer cells was evaluated in vitro. A phantom study was performed to analyze PA signal intensity according to ICG concentration and tissue thickness/depth using chicken breast. PA signals were measured up to 48 hours after injection of ICG (mixed with 5% agar) into healthy subcutaneous tissue, subcutaneous H460 tumors and right healthy lung in nude mice. RESULTS: Intracellular ICG fluorescence was detected in H460 cells co-incubated with ICG in vitro. The concentration dependence of the PA signal was logarithmic, and PA signal decline was exponential with increasing tissue depth. The PA signal of 2 mg/mL ICG was still detectable at a depth of 22 mm in chicken breast. The PA signal from ICG mixed with agar was detectable 48 hours post injection into subcutaneous tissue and subcutaneous H460 tumors in nude mice. Similar features of PA signals from ICG-agar in mice lung were obtained. CONCLUSION: The results from this preclinical study suggests that PAI of injected ICG-agar may be beneficial for identifying deeply located tumors. These features may be valuable for IPNs.

Factors Affecting the Number of Stapler Cartridges in Complete Video-Assisted Thoracoscopic Surgery Lobectomy for Non-small Cell Lung Cancer.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) lobectomy has become the major surgical option for the treatment of non-small cell lung cancer (NSCLC). Endoscopic instruments such as stapler cartridges are essential for VATS procedures. In this study, we investigated the factors that affect the number of stapler cartridges used in VATS lobectomy. METHODS: A retrospective analysis was conducted of patients who underwent complete VATS lobectomy for NSCLC from January 2013 to December 2015. RESULTS: In total, 596 patients underwent complete VATS lobectomy. The average number of stapler cartridges used for VATS lobectomy was 5.3±1.9. The number of stapler cartridges used for VATS lobectomy was higher in men (5.5±1.9 vs. 5.0±18, p=0.006), those aged older than 70 years (5.5±2.1 vs. 5.1±1.7, p=0.038), those who underwent upper or middle lobectomy procedures (5.7±1.9 vs. 4.1±1.2, p<0.001), those with a higher fissure sum average (p<0.001), and those in whom surgery was performed by a surgeon with a preference for staplers (5.6±2.0 vs. 4.9±1.6, p<0.001). CONCLUSION: The number of stapler cartridges required to perform VATS lobectomy in NSCLC patients appears to be influenced by sex, age, the location of the tumor, the degree of fissure development, and the surgeon's preference.

Predictors of post-thymectomy long-term neurological remission in thymomatous myasthenia gravis: an analysis from a multi-institutional database.

OBJECTIVES: Thymectomy is the treatment of choice for thymomatous myasthenia gravis (MG) for both oncological and neurological aspects. However, only a few studies comprising small numbers of patients have investigated post-thymectomy neurological outcomes. We examined post-thymectomy long-term neurological outcomes and predictors of thymomatous MG using a multi-institutional database. METHODS: In total, 193 patients (47.3 ± 12.0 years; male:female = 90:103) with surgically resected thymomatous MG between 2000 and 2013 were included. Complete stable remission (CSR) and composite neurological remission (CNR), defined as the achievement of CSR and pharmacological remission after thymectomy, were evaluated. Predictors for CSR and CNR were examined by Cox regression analysis. RESULTS: The median duration between MG and thymectomy was 3.1 months. In addition, 161 patients (83.4%) had symptoms less than Myasthenia Gravis Foundation of America clinical classification III. All patients underwent an extended thymectomy; there were no perioperative deaths. The 10-year cumulative probability of CSR and CNR was 36.9% and 69.1%, respectively. Mild preoperative symptoms were a significant predictor for CSR (P = 0.040), and a large tumour was a predictor for CNR (P < 0.001). Patients with a large tumour were associated with early MG onset and no steroid treatment. Surgical methods, thymoma stage and histological subtypes were not associated with long-term neurological remission. CONCLUSIONS: Large tumour size and preoperative mild symptoms were predictors for long-term neurological outcome in thymomatous MG. Considering that patients with early onset of MG and no immunosuppressive treatment tend to have large tumours, early surgical intervention for patients with thymomatous MG having mild symptoms might be beneficial for controlling neurological outcomes.

Tumor microenvironment dictates regulatory T cell phenotype: Upregulated immune checkpoints reinforce suppressive function.

BACKGROUND: Regulatory T (Treg) cells have an immunosuppressive function in cancer, but the underlying mechanism of immunosuppression in the tumor microenvironment (TME) is unclear. METHODS: We compared the phenotypes of T cell subsets, including Treg cells, obtained from peripheral blood, malignant effusion, and tumors of 103 cancer patients. Our primary focus was on the expression of immune checkpoint (IC)-molecules, such as programmed death (PD)-1, T-cell immunoglobulin and mucin-domain containing (TIM)-3, T cell Ig and ITIM domain (TIGIT), and cytotoxic T lymphocyte antigen (CTLA)-4, on Treg cells in paired lymphocytes from blood, peritumoral tissue, and tumors of 12 patients with lung cancer. To identify the immunosuppressive mechanisms acting on tumor-infiltrating Treg cells, we conducted immunosuppressive functional assays in a mouse model. RESULTS: CD8+, CD4+ T cells, and Treg cells exhibited a gradual upregulation of IC-molecules the closer they were to the tumor. Interestingly, PD-1 expression was more prominent in Treg cells than in conventional T (Tconv) cells. In lung cancer patients, higher levels of IC-molecules were expressed on Treg cells than on Tconv cells, and Treg cells were also more enriched in the tumor than in the peri-tumor and blood. In a mouse lung cancer model, IC-molecules were also preferentially upregulated on Treg cells, compared to Tconv cells. PD-1 showed the greatest increase on most cell types, especially Treg cells, and this increase occurred gradually over time after the cells entered the TME. PD-1 high-expressing tumor-infiltrating Treg cells displayed potent suppressive activity, which could be partially inhibited with a blocking anti-PD-1 antibody. CONCLUSIONS: We demonstrate that the TME confers a suppressive function on Treg cells by upregulating IC-molecule expression. Targeting IC-molecules, including PD-1, on Treg cells may be effective for cancer treatment.

Impact of Lymph Node Dissection on Thymic Malignancies: Multi-Institutional Propensity Score Matched Analysis.

INTRODUCTION: Surgical resection is a standard treatment for thymic malignancies. However, prognostic significance of nodal metastases and lymph node dissection remains unclear. The aim of this study is to determine prognostic significance of nodal metastases and the role of lymph node dissection (LND) in thymic malignancies. METHODS: Between 2000 and 2013, 1597 patients who underwent thymectomy due to thymic malignancy were included. Predictive factors for nodal metastasis and prognostic significance of LND were evaluated. Patients were divided into two groups: (1) LND+ group, with intentional LND (446 patients, 27.9%); and (2) LND- group, without intentional LND (1151 patients, 72.1%). Propensity score matching was performed between the two groups. RESULTS: Lymph node metastasis was identified in 20 (6.7%) of 298 patients with thymoma and 47 (31.7%) of 148 patients with thymic carcinoma. In multivariable analysis, thymic carcinoma (hazard ratio: 19.2, p < 0.001) and tumor size (hazard ratio: 1.09, p = 0.02) were significant predictive factors for lymph node metastasis. The 10-year freedom from recurrence rate of pN1 and pN2 was significantly worse than that of pN0 (p < 0.001). LND did not increase operative mortality or complication. There was no significant difference in 10-year freedom from recurrence rate between LND+ and LND- groups (82.4% versus 80.9%, p = 0.46 in thymoma; 45.7% versus 44.0%, p = 0.42 in thymic carcinoma). CONCLUSIONS: Lymph node metastasis was a significant prognostic factor in thymic malignancies. Although LND did not improve long-term outcomes in thymic malignancies, LND played a role in accurate staging, and improved prediction of prognosis.

Validation of the T descriptor in the new 8th TNM classification for non-small cell lung cancer.

BACKGROUND: To validate new proposals for the revision of T descriptors and to compare the prognostic value of the seventh and forthcoming eighth edition of the tumor, node and metastasis (TNM) classification for lung cancer. METHODS: A retrospective analysis was conducted of 1,316 patients with non-small lung cancer who underwent pulmonary resection between 1999 and 2012. Patients who had a positive nodal status or distant metastasis were excluded. We classified these patients according to the seventh and eighth edition of the TNM system, and analyzed differences in stage specific survival. Harrell's concordance (C)-index and Heagerty's integrated area under the curve (iAUC) were used to assess the overall predictive ability of the different TNM versions. RESULTS: There were no significant survival differences between each stage based on the T stage criteria of the eighth edition, most notably between T1a and T1b (P=0.752), and T1c, T2a, and T2b (P=0.832). The C-indices of the classification based on the seventh and eighth edition were 0.681 and 0.675, respectively. There was no significant difference in the C-indices between the seventh and eighth edition. The iAUC value for overall survival of the seventh and eighth staging editions was 0.637 and 0.631, respectively. The differences in iAUC between the seventh and eighth editions were also not statistically significant. CONCLUSIONS: The newly proposed T descriptors in the eighth TNM classification system did not allow a more accurate prediction of prognosis compared with the current seventh edition in our population.

Prognostic factors for resected non-small cell lung cancer in patients with type 2 diabetes mellitus.

BACKGROUND: For diabetic patients with lung cancer, blood glucose levels and medications such as metformin and statins may influence survival. OBJECTIVES: This study aimed to determine prognostic survival factors for diabetic patients with resected non-small cell lung cancer. PATIENTS AND METHODS: Between January 2005 and December 2013, 301 patients with type 2 diabetes mellitus who underwent curative resection for non-small cell lung cancer were identified and reviewed retrospectively. RESULTS: The median follow-up period was 48 months. In multivariate analysis for lung cancer-specific survival, older age, forced expiratory volume in 1 s (FEV1) <80% predicted, and advanced pathologic stage were significant negative prognostic factors; statin use was a positive prognostic factor (hazard ratio (HR), 0.468). In multivariate analysis for overall survival, male sex, older age, comorbidity index, and advanced pathologic stage were significant negative prognostic factors and proper glycemic control (HR, 0.621) and statin use (HR, 0.585) were positive prognostic factors. CONCLUSIONS: Proper glycemic control (glycated hemoglobin A1c <7%) is recommended for diabetic patients undergoing lung cancer operations. Further studies are required to elucidate associations between type 2 diabetes mellitus and antineoplastic effects of statins and to evaluate statins as a novel adjuvant treatment for lung cancer.

Extent of Mediastinal Lymphadenectomy and Survival in Superficial Esophageal Squamous Cell Carcinoma.

BACKGROUND: The aim of this study is to investigate the utility of total mediastinal lymphadenectomy (ML) in superficial esophageal squamous cell carcinoma (ESCC). METHODS: The medical records of 129 patients who underwent esophagectomy and lymph node dissection for pathologically confirmed pT1 ESCC between July 2006 and December 2014 were retrospectively reviewed. Limited ML, such as traditional 2-field or transhiatal esophagectomy, was performed in 42 patients (group 1), and total ML, including the bilateral recurrent laryngeal nerve nodes, was performed in 87 patients (group 2). RESULTS: R0 resection was achieved in all patients, and the number of dissected nodes was 28.0 ± 11.4 and 44.8 ± 16.1 in groups 1 and 2 (p < 0.001), respectively. The complication profile was similar in the two groups, but there were two operative mortalities in group 2. During a median follow-up of 32.4 months, loco-regional failure was found in 14.3% of group 1 and 3.5% of group 2 (p = 0.001). There was a significant difference in the 3-year overall survival (95.1% in group 2 vs. 83.3% in group 1, p = 0.043), and the 3-year disease-free survival rates (92.3% in group 2 vs. 73.7% in group 1, p = 0.001). On multivariate analysis, the extent of ML (HR, 5.200; 95% CI, 1.532 ~ 17.645; p = 0.008) and pT1b lesion classification (HR, 4.747; 95% CI, 1.024 ~ 21.997; p = 0.047) was a factor predictive of disease-free survival. CONCLUSIONS: Total ML might be beneficial, especially in cases of pT1b ESCC, because it could lead to a lower incidence of recurrence and longer survival times.

Limited thymectomy as a potential alternative treatment option for early-stage thymoma: A multi-institutional propensity-matched study.

OBJECTIVES: For early-stage thymoma, complete thymectomy has classically been regarded as the standard treatment protocol. However, several studies have shown that limited thymectomy may be an alternative treatment option for thymoma. This study compared perioperative outcomes, survival, and recurrence rates between patients undergoing limited thymectomy and complete thymectomy. MATERIALS AND METHODS: Between January 2000 and December 2013, a total of 762 patients underwent thymectomy for stage I or II thymomas at four institutions participating in the Korean Association for Research on the Thymus. Patients were divided into two groups: limited thymectomy group (n=295) and complete thymectomy group (n=467). Comparative clinicopathological, surgical, and oncological features were reviewed retrospectively. RESULTS: The median follow-up time was 49 months (range: 0.2-189 months). A propensity score-matching analysis, based on seven variables (age, sex, surgical approach, tumor size, WHO histological type, Masaoka-Koga stage, and adjuvant radiotherapy), was performed using 141 patients selected from each group. The 5- and 10-year freedom-from-recurrence rates in the limited thymectomy group were 96.3% and 89.7%, respectively, and those in the complete thymectomy group were 97.0% and 85.0%, respectively. No significant differences in these rates were observed between groups (p=0.86). A multivariate Cox regression analysis showed that overall survival and freedom-from-recurrence rates did not significantly differ by surgery extent (p=0.27, 0.66, respectively). Perioperative outcomes were better in the limited thymectomy group. CONCLUSION: Limited thymectomy was not inferior to complete thymectomy with respect to recurrence, and had better perioperative outcomes. Limited thymectomy may be a viable treatment option for early-stage thymoma.

Pulmonary fissure development is a prognostic factor for patients with resected stage I lung adenocarcinoma.

BACKGROUND: Pulmonary fissure differs among patients, but the relationship between pulmonary fissure development and survival in patients with resected lung adenocarcinoma has not been evaluated. In this study, we analyzed the effect of fissure development on prognosis in patients with stage I lung adenocarcinoma. METHODS: From January 2009 to December 2012, data, including pulmonary fissure development, were collected prospectively for all lung cancer, and this was a retrospective study of prospectively collected data. In total, 297 patients who had undergone a lobectomy and had pathologic stage I adenocarcinoma were analyzed. Patients were categorized into two groups based on fissure sum average (FSA) fissure development scores. Group A patients ranged from complete to 30% incomplete (0 ≤ FSA ≤ 1) while in Group B patients development was more than 30% incomplete (1 < FSA ≤ 3). RESULTS: In univariate analysis, Group B had poorer overall 5 year survival than did Group A (83.1% vs. 96.5%, P = 0.015). Multivariate analysis revealed that the level of fissure development was a significant prognostic factor for overall survival (HR = 3.905, CI = 1.168-13.057, P = 0.027). CONCLUSIONS: The overall survival of patients with resected stage I adenocarcinoma was adversely affected by incomplete fissure development. J. Surg. Oncol. 2016;114:848-852. © 2016 2016 Wiley Periodicals, Inc.

Three-Dimensional Ground Glass Opacity Ratio in CT Images Can Predict Tumor Invasiveness of Stage IA Lung Cancer.

PURPOSE: We investigated the relationship between various parameters, including volumetric parameters, and tumor invasiveness according to the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification. MATERIALS AND METHODS: We retrospectively reviewed 99 patients with completely resected stage IA lung adenocarcinoma. The correlation between several parameters [one-dimensional ground glass opacity (1D GGO) ratio, two-dimensional (2D) GGO ratio, three-dimensional (3D) GGO ratio, 1D solid size, 2D solid size, and 3D solid size] and tumor invasiveness according to IASLC/ATS/ERS classification was investigated using receiver operating characteristic (ROC) analysis. Adenocarcinoma in situ and minimally invasive adenocarcinoma were referred to as noninvasive adenocarcinoma. RESULTS: The areas under the curve (AUC) to predict invasive adenocarcinoma for the 1D, 2D, and 3D GGO ratios were 0.962, 0.967, and 0.971, respectively. The optimal cut-off values for the 1D, 2D, and 3D GGO ratios were 38%, 62%, and 74%, respectively. The AUC values for 1D, 2D, and 3D solid sizes to predict invasive adenocarcinoma were 0.933, 0.944, and 0.903, respectively. The optimal cut-off values for 1D, 2D, and 3D solid sizes were 1.2 cm, 1.5 cm², and 0.7 cm³, respectively. The difference in the ROC curves for 3D GGO ratio and 3D solid size was significant (p=0.01). CONCLUSION: Computed tomography image-related parameters based on GGO were well correlated with and predictive of invasiveness according to IASLC/ATS/ERS classification. 3D GGO ratio was more strongly correlated with pathologic invasiveness than 3D solid size.

Tumor perimeter and lobulation as predictors of pleural recurrence in patients with resected thymoma.

OBJECTIVES: Recurrence of resected thymoma frequently occurs during follow-up, with pleural recurrence as the most common type. The aim of our study was to identify risk factors for pleural recurrence after complete resection of thymoma by investigating clinical, radiological, surgical, and pathological findings. MATERIALS AND METHODS: Retrospective study was performed with 309 patients who had undergone complete resection of thymoma between January 2000 and December 2013. Among these cases, the patients were divided into the no pleural recurrence group (n=285) and the pleural recurrence group (n=24). Radiologic parameters such as maximum tumor diameter, tumor perimeter that contacted the lung (TPCL) and lobulated tumor contour were measured based on computed tomography. A multivariate analysis was performed to estimate risk factors for pleural recurrence including maximum tumor diameter, TPCL, lobulated tumor contour, World Health Organization (WHO) histologic classification, and Masaoka-Koga (M-K) stage. RESULTS: The median follow-up period was 62 months. The pleural recurrence rate was 7.8% (24/309). After univariate analysis, longer maximum tumor diameter (p<0.001), longer TPCL (p<0.001), lobulated tumor contour (p=0.001), WHO histologic type B2, B3 (p=0.002), and M-K stage III/IV (p<0.001) demonstrated significant differences with risk factors of pleural recurrence. Multivariate analysis revealed that TPCL (per 1cm increase: hazard ratio [HR]: 1.040, 95% confidence interval [CI]: 1.019-1.061, p<0.001), lobulated tumor contour (HR: 5.883, CI: 1.201-28.824, p=0.029), WHO histologic classification B2/B3 (HR: 5.331, CI: 1.453-19.558, p=0.012) and advanced M-K stage (HR: 3.900, CI: 1.579-9.632, p=0.003) were significantly associated with pleural recurrence. CONCLUSION: TPCL and lobulated tumor contour as well as WHO histologic classification and M-K stage were independent predictors of pleural recurrence after thymoma resection. Our study demonstrated that radiologic parameters could be useful predictor of pleural recurrence in patients with resected thymoma.

Value of 18F-FDG PET/CT for Predicting the World Health Organization Malignant Grade of Thymic Epithelial Tumors: Focused in Volume-Dependent Parameters.

PURPOSE: We investigated whether preoperative parameters of 18F-FDG PET/CT were correlated with the World Health Organization (WHO) classification and/or Masaoka staging of thymic epithelial tumors. PATIENTS AND METHODS: We reviewed 61 patients retrospectively who were diagnosed with thymic epithelial tumors after surgical resection and PET/CT. A volume of interest was drawn on the primary lesion, using an SUV cutoff of 2.5, and metabolic indices such as SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. RESULTS: There were 24 male patients (38.7%), and the mean (SD) age was 50.23 (12.54) years. The mean (SD) tumor size was 6.11 (3.41) cm. There were 22 low-risk thymomas (36.9%) (A, AB, B1), 32 high-risk thymomas (51.6%), and 7 thymic carcinomas (11.5%). The Masaoka stage was I in 15 (24.6%), II in 30 (49.2%), III in 11 (18.0%), and IV in 5 patients (8.2%). Mean (SD) SUVmax was 3.43 (1.01) in low-risk thymomas, 4.42 (1.70) in high-risk thymomas, and 8.23 (2.61) in thymic carcinoma; the differences were significant (P < 0.001). Mean (SD) MTV and TLG were 90.74 (114.56) and 229.36 (300.56) in low-risk thymomas, 80.82 (112.49) and 233.93 (340.91) in high-risk thymomas, and 90.63 (90.74) and 390.94 (437.62), respectively, in thymic carcinomas. MTV and TLG showed no correlation with the WHO classification. On receiver operating characteristic curve analysis, the cutoff value for discriminating thymomas and thymic carcinomas was 5.05. SUVmax and TLG were correlated with Masaoka stage. CONCLUSIONS: Although volume-dependent parameters were not correlated with the WHO classification, a significant relationship was observed between SUVmax and WHO classification and Masaoka stage.

Safety of thoracoscopic surgery for lung cancer without interruption of anti-platelet agents.

BACKGROUND: Perioperative bleeding concerns have led to the general recommendation that antiplatelet agents (APAs) be discontinued 7-10 days preoperatively, but this could increase the risk of perioperative cardiovascular events. This retrospective study aimed to evaluate the safety of APA continuation during thoracoscopic surgery for lung cancer. METHODS: Between January 2009 and February 2015, 164 patients taking APAs underwent curative resection. Comparisons were conducted between two groups: preoperatively interrupted APA administration (group I, n=106) and continued APA administration (group N, n=58). RESULTS: Group N had a significantly higher revised cardiac risk index (rCRI) (P=0.001). Lobectomy was performed in the majority of patients [95 (89.6%) in group I; 52 (89.7%) in group N]. There were no significant differences in intraoperative outcomes, such as the thoracotomy conversion rate, operating time, intraoperative transfusion, and amount of blood loss during the operation, or postoperative outcomes, such as postoperative bleeding and thrombotic complications, postoperative transfusions, and operative mortality. Within group N, the patients taking aspirin + clopidogrel (n=11) had significantly greater postoperative bleeding (P=0.005), and more postoperative transfusions (P=0.003) and chest tube drainage over a 3-day period (P=0.049) compared with other antiplatelet regimens. CONCLUSIONS: Continued use of APAs during thoracoscopic surgery for lung cancer could be safely done in patients at high risk of cardiac or thrombotic events. However, in patients administered aspirin + clopidogrel, it may be the best to continue aspirin only because of an increased risk of postoperative bleeding and transfusion requirements.

Autophagy contributes to the chemo-resistance of non-small cell lung cancer in hypoxic conditions.

BACKGROUND: The development of chemo-resistance in non-small lung cancer is a major obstacle in treating patients. Hypoxia is a commonly faced microenvironment in solid tumor and suggested to be related to both autophagy and chemo-resistance. METHODS: In this study, we investigated the role of hypoxia-induced autophagy in acquiring chemo-resistance in both cancer cell (A549) and human cancer tissue RESULTS: Hypoxic exposure (1 % O2) of A549 cell stimulated autophagic induction in cancer cells, shown by increase of LC3BI to LC3BII conversion and decrease of p62/sequestosome1 in Western blot, increased GFP-LC puncta in confocal microscopy, and increased number of double-membrane autophagic vacuoles in electron micrographs. Hypoxic exposure also induced resistance of cancer cells to cisplatin, and LC3B siRNA restored the sensitivity of cancer cells to chemotherapy. Furthermore, Human lung cancer tissues that experienced chemotherapy showed increase of LC3BI to LC3BII conversion and decrease of p62/sequestosome1 compared with chemo-naïve cancer tissue in Western blot. CONCLUSION: Autophagy may play an important role in acquiring resistance to chemotherapy in lung cancer and hypoxia related pathway seems to be involved in autophagy induction.

Analysis of Unexpected Conversion to Thoracotomy During Thoracoscopic Lobectomy in Lung Cancer.

BACKGROUND: Since anatomical lung resection by video-assisted thoracoscopic surgery (VATS) was first introduced, VATS has played a major role in lung cancer. However, conversion to thoracotomy is a major concern because an unexpected thoracotomy increases the risk of potentially adverse outcomes. Therefore, we compared patients who were and were not converted to thoracotomy and identified the risk factors for thoracotomy conversion. METHODS: Between January 2005 and December 2013, 69 of 1,110 VATS lobectomies for lung cancer required an unexpected conversion to thoracotomy. Each converted patient was individually matched to 3 randomly selected nonconverted patients based on date of operation, type of operation, and pathologic stage. RESULTS: The most common cause of conversion was fibrocalcified lymph nodes, found in 28 patients (40.6%), followed by vascular injury in 20, tumor invasion or extension in 11, pleural adhesion in 5, incomplete interlobar fissure in 3, and failure of single-lung ventilation in 2. The differences in overall postoperative complications and in-hospital deaths were not significant; however, respiratory complications were significantly more common in the conversion group (p = 0.012). The independent risk factors for conversion were age 65 years and older, forced expiratory volume in 1 second of less than 1.8 L, and the presence of fibrocalcified lymph nodes on preoperative chest computed tomography. CONCLUSIONS: Unexpected conversion to thoracotomy during VATS lobectomy in lung cancer does not appear to increase overall surgical morbidity and mortality. However, with high-risk patients, the surgeon requires careful selection for VATS candidate. Also, if necessary, the decision to convert must be made promptly to reduce possible critical respiratory complications.