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OBJECTIVES: The impact of skip N2 metastases (i.e. N2 lymph node metastases without N1) on survival in surgically resected non-small lung cancer remains an intriguing and rarely investigated topic. The goal of our study was to elucidate (i) skip N2 influence on overall survival (OS) and time to recurrence (TTR) in patients with resected lung adenocarcinoma and (ii) its link with epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. METHODS: A retrospective analysis of 279 consecutive patients with lung pN2 adenocarcinoma, operated in two institutions between 2003 and 2013, was conducted. OS and TTR were calculated using the Kaplan-Meier method. Crude and multivariable-adjusted comparisons by skip N2 for OS and TTR were performed using the Cox method with shared frailty (accounting for the within-centre correlation). Associations between skip N2 metastasis, clinicopathological characteristics and EGFR and KRAS mutations were investigated using the Fisher exact test and Cramé r's V-test. RESULTS: The mean age at the time of surgery was 63 years (±12), and the median follow-up time was 36 months (min 3; max 101). Skip N2 was observed in 54 patients (19%). EGFR mutations were observed in 38 patients (14%); KRAS mutations were seen in 86 patients (31%). Patients with skip N2 metastasis were predominantly non-smokers (P = 0.001), underwent segmentectomy or limited resections (P = 0.004) and were not submitted to adjuvant therapy (P = 0.022). Moreover, there was a correlation between EGFR mutations and skip N2 (Cramé r's V: 0.25, P < 0.001). Indeed, EGFR mutations were significantly more frequent in skip N2 tumours (33%) compared with non-skip tumours (10%), P < 0.001. No correlation between skip N2 and KRAS mutations was observed (Cramé r's V: 0.05, P = 0.46). The multivariable-adjusted model showed a significant skip N2 protective effect on OS (hazard ratio, HR 0.503; P = 0.014; 95% confidence interval, CI: 0.291-0.8704) but not on TTR (HR 0.788; P = 0.446; 95% CI: 0.427-1.454). CONCLUSIONS: In our series, lung adenocarcinoma skip N2 metastasis demonstrated a favourable prognosis. The presence of EGFR mutations could have significance in the better survival and in the specific anatomic pathway of lymphatic metastases exhibited by skip N2 tumours. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Early clinical stage (T1 and T2) non-small cell lung cancer (NSCLC) is commonly treated with anatomic lung resection and lymph node sampling or dissection. The aims of this study were to evaluate the incidence and the distribution of occult N2 disease according to tumour location and the short- and long-term outcomes. METHODS: We performed a retrospective review of patients with clinical stage I NSCLC who underwent anatomic lung resection and lymphadenectomy. Mediastinal lymphadenectomy (ML) was defined as resection of at least 2 mediastinal stations, always including station 7 lymph nodes. Patients who had a lobe-specific lymphadenectomy were excluded. RESULTS: One thousand six hundred and sixty-seven consecutive patients met inclusion criteria and were included. Overall, 9% (146/1667) of the patients had occult pN2 disease. At multivariable analysis, adenocarcinoma histology and vascular invasion were independently associated with greater risk of occult pN2 disease. In left and right upper lobe tumours, station 7 nodes were involved in 5 and 13% of pN2 positive cases, respectively. Station 5 and station 2/4 nodes were involved in 29 and 18% of left and right lower lobe pN2 tumours, respectively. There was no postoperative mortality, and postoperative morbidity was 28%. The median overall survival was 77.4 months. N0 patients had a median overall survival of 83.7 months vs 48.0 months and 37.9 months in N1 and N2 populations, respectively (P < 0.001). CONCLUSIONS: Sixteen percent of pN2 patients had mediastinal lymph node metastasis beyond the lobe-specific lymphatic drainage. We recommend a complete lymphadenectomy be performed, even in clinical stage I NSCLC. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer mortality in the USA. Within the past decade, two large trials (the National Lung Screening Trial Research and the International Early Lung Cancer Action Program) confirmed a significant role for low-dose CT (LDCT) screening in identifying early stages of cancer leading to reduced mortality in high-risk patients. Given the evidence, the US Preventive Services Task Force issued a recommendation in favour of LDCT screening for high-risk individuals. Despite the strong support for LDCT among physicians who treat lung cancer and cumulative data demonstrating a survival benefit for screening and early detection, it took more than a decade for lung cancer screening to be embraced at the policy level. With many lives lost in the interim, did we really need a randomized controlled trial to make this decision?. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Although video-assisted mediastinoscopic lymphadenectomy (VAMLA) has greatly increased the accuracy of mediastinal staging, its clinical value as a therapeutic tool for complete mediastinal lymph node dissection in the treatment of left-sided lung cancer is not well elucidated. METHODS: We identified the consecutive 649 patients with left-sided lung cancer undergoing minimally invasive pulmonary resection between July 2002 and June 2013. Among them, 225 patients underwent VAMLA combined with pulmonary resection (VAMLA + VATS group), while the remaining 424 patients underwent VATS procedure only (VATS group). Operative outcomes including procedural time, removed lymph nodes and node stations, complications and the final pathological mediastinal staging in the both groups were evaluated and compared. RESULTS: There was no significant difference in the baseline profiles between the two groups. The patients in the VATS + VAMLA group showed significantly shorter operative time (116.8 ± 39.8 vs 159.8 ± 44 .0 min; P < 0.001), more extensive lymph node dissection (total number of removed lymph nodes, 29.7 ± 10.8 vs 23.0 ± 8.6; P < 0.001) and the higher rates of patients with mediastinal lymph nodes removed: Station 2 on the right (12.4 vs 0.2%), Station 2 on the left (15.1 vs 0.2%), Station 4 on the right (42.7 vs 0.9%), Station 4 on the left (87.6 vs 57.3%) and Station 7 (100 vs 99.3%), while maintaining comparable surgical morbidities compared with the VATS group. Also, the patients in the VATS + VAMLA group tended to have higher rates of being upstaged with mediastinal involvement (8.0 vs 5.7%; P = 0.31). CONCLUSIONS: VAMLA is a clinically feasible procedure safely performed as a therapeutic tool for complete mediastinal lymph node dissection (MLND), and can be a good complement to minimally invasive pulmonary resection in left-sided lung cancer, where optimal MLND is not always feasible with VATS approach. Further studies are required to investigate the long-term clinical impacts of VAMLA with regard to survival and tumour recurrence. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Although the prognostic implications of visceral pleural invasion (VPI) are well established, it remains controversial whether the extent of VPI affects survival in patients with completely resected non-small-cell lung cancer (NSCLC). In addition, the impact of VPI according to nodal status is unclear. We evaluated the influence of the extent of pleural invasion on survival by analysing a multicentre retrospective database of patients who had undergone surgery for NSCLC. METHODS: We retrospectively reviewed the clinicopathological characteristics and outcomes of 639 patients with NSCLC who underwent anatomic complete resection from 2005 to 2007 at nine hospitals affiliated with the Yokohama Consortium of Thoracic Surgeons. RESULTS: The median follow-up was 65.0 months. The extent of pleural invasion was PL0 in 462 patients, PL1 in 135 and PL2 in 42. The 5-year overall survival rate was significantly higher in patients with PL0 tumours (75.9%) than in those with PL1 (63.6%) or PL2 tumours (54.1%). On subgroup analysis according to nodal status, PL0 was associated with a higher survival rate than that of PL1 or PL2 tumours in patients with N0 or N1 metastasis, but not in those with N2 metastasis. There was no difference between PL1 and PL2 in any subgroup. CONCLUSIONS: Our results suggest that the presence of VPI, rather than the extent, has an impact on postoperative survival in patients with NSCLC who have N0 or N1 metastasis. Because very few previous studies have addressed the effects of VPI in patients with N1 disease, further re-evaluation of the prognostic impact of VPI is necessary in this subgroup of patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We evaluated the clinical benefit of segmentectomy for patients with cT1bN0M0 lung cancer. METHODS: We retrospectively reviewed the medical records of 178 patients who underwent lobectomy or segmentectomy for cT1bN0M0 lung adenocarcinoma and squamous cell carcinoma from January 1995 to December 2005. We investigated the association of surgical outcomes with the presence of pathological invasion. RESULTS: The median follow-up period was 93.4 months. Of 178 patients, 37 were scheduled for segmentectomy, but 6 of these patients were switched to receive lobectomy due to surgical N1 or N2 in 3 patients and insufficient surgical margins in 3 patients. In total, 31 patients underwent segmentectomy, and 147 underwent lobectomy. The 5-year overall survival (OS) was similar between the patients who underwent lobectomy (5-year OS, 81.6%) and segmentectomy (5-year OS, 77.4%, P = 0.73). Among pN0 patients without pathological invasion, there was no difference in OS between patients who underwent lobectomy (5-year OS, 89.9%) and segmentectomy (5-year OS, 88.9%, P = 0.80). In contrast, among pN0 patients with pathological invasion, OS was greater in patients who underwent lobectomy (5-year OS, 80.9%) than in those who underwent segmentectomy (5-year OS, 54.6%; P = 0.19).Moreover, a significantly higher rate of local and local + distant recurrence was observed in patients who underwent segmentectomy (45%) than in those who underwent lobectomy (15%) in this group (P = 0.02). CONCLUSIONS: The results of our study suggest that segmentectomy may not be recommended for cT1b tumours if pathological invasion is suspected before surgery. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The number of elderly lung cancer patients requiring surgery has been increasing due to the ageing society and less invasive perioperative procedures. Elderly people usually have various comorbidities, but there are few simple and objective tools that can be used to determine prognostic factors for elderly patients with clinical stage I non-small-cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the prognostic factors of surgically treated, over 80-year old patients with clinical stage I NSCLC. METHODS: The preoperative data of 97 over 80-year old patients with clinical stage I NSCLC were collected at Nagasaki University Hospital from 1990 to 2012. As prognostic factors, inflammation-based scoring systems, including the Glasgow Prognostic Score (GPS) determined by serum levels of C-reactive protein and albumin, the neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) were evaluated, as well as other clinicopathological factors, including performance status, body mass index, carcinoembryonic antigen, Charlson comorbidity index and type of surgical procedure. RESULTS: The median age was 82 (range, 80-93) years. There were 62 (64.0%) clinical stage IA cases and 35 IB cases. Operations included 64 (66.0%) lobectomies, 15 segmentectomies and 18 wedge resections. The pathological stage was I in 76 (78.4%) patients, II in 12 (12.4%), III in 8 (8.2%) and IV in 1 (1.0%). Twelve (12.4%) patients underwent mediastinal lymph node dissection. Overall survival and disease-specific 5-year survival rates were 55.5 and 70.0%, respectively. The average GPS score was 0.4 (0-2). Diseasespecific 5-year survival was significantly longer with GPS 0 than with GPS 1-2. (74.2%, 53.7%, respectively, P = 0.03). Overall 5-year survival was significantly longer with GPS 0 than with GPS 1-2. (59.7%, 43.1%, respectively, P = 0.005). Both the NLR (median value = 1.9) and the PLR (median value = 117) were not correlated with disease-specific and overall 5-year survival. On multivariate analysis, pathological stage I (P = 0.01) and GPS 0 (P = 0.04, hazard ratio: 2.13, 95% confidence interval 1.036-4.393) were significant prognostic factors. CONCLUSIONS: The preoperative GPS appears to be a useful predictor of overall survival and could be a simple prognostic tool for elderly patients with clinical stage I NSCLC. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Treatment patterns and outcomes in a population-based database were examined to identify patients likely to benefit from surgical resection of locally advanced (T3N0-2) non-small-cell lung cancer (NSCLC). METHODS: Factors predicting the use of surgery for patients with T3N0-2M0 NSCLC in the Surveillance, Epidemiology and End Results (SEER) database from 1988 to 2010 were assessed using a multivariable logistic regression model. Survival was analysed using the Kaplan- Meier approach and Cox proportional hazard models. Propensity matching was used to compare outcomes after surgery and outcomes in patients who refused surgery and underwent radiation therapy (RT). RESULTS: Of 17 378 patients identified for study inclusion [8597 (50%) T3N0, 2304 (13%) T3N1 and 6477 (37%) T3N2], surgery was used in 7120 (41%). Only female sex and being married predicted the use of surgery, while older age, black race and N2 nodal disease predicted non-surgical management. Surgical patients overall had better long-term survival than non-surgical patients [odds ratio (OR) 0.42, 95% confidence interval (CI): 0.41-0.45, P < 0.001]. After propensity adjustment, patients who refused surgery and instead were treated with RT had significantly worse long-term survival than matched surgery patients (OR 0.65, 95% CI: 0.48-0.89, P = 0.0074). Sublobar resection and pneumonectomy predicted worse survival in patients who had surgery. Nodal disease also predicted worse survival after surgery, but surgery maintained an association with better overall survival compared with non-operative therapy among patients with both N1 (OR 0.53, P < 0.001) and N2 disease (OR 0.50, P < 0.001) in separate analyses stratified by nodal status. Older age also predicted worse survival after surgery, but patients older than 75 who were treated with surgery had significantly better long-term survival than non-operative patients (OR 0.49, 95% CI: 0.45-0.53, P < 0.001). CONCLUSIONS: Surgery is used in a minority of patients with locally advanced NSCLC, but is associated with better survival than non-surgical treatment, even for patients older than 75 and patients with nodal disease. Given the very poor outcomes observed with non-operative management, surgical resection should be carefully considered in all patients with locally advanced NSCLC and should not necessarily be denied because of patient age or nodal disease. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Understanding the clinicopathological features of patients with skip N2 metastases (SN2) in clinical early stage lung cancer is important for surgical planning and other treatment considerations; however, the factors associated with SN2 are unclear. This study aimed to investigate the clinicopathological features associated with SN2 in patients with clinical stage IA (cIA) non-small-cell lung cancer (NSCLC). METHODS: We retrospectively studied patients with cIA NSCLC who underwent pulmonary resection (at least lobectomy) and extensive lymphadenectomy (more than ND2a-1) at our institution between January 2004 and December 2010. We investigated the following factors for their association with SN2: age; sex; tumour marker (carcinoembryonic antigen); tumour size on computed tomography (CT), evaluated with a lung-window (LW) and a mediastinal-window (MW) setting; pathology, with or without adenocarcinoma; differentiation; visceral pleural invasion (VPI) and vascular/lymphatic invasion. RESULTS: In total, 422 patients were enrolled, with the following pathological node (pN) statuses: 331 pN0 (78.4%), 39 pN1 (9.3%) and 52 pN2 (12.3%). There were 21 (23.1%) SN2 cases among the patients with nodal metastases. When the cut-off level was defined as a receiver operating characteristic curve with MW (11.5 mm), the sensitivity and specificity of SN2 was 95.2% and 42.9%, respectively. VPI was a statistically independent relevant factor for SN2 in both the patients with cIA and in those with nodal involvement. The VPI classification comprised 59 PL-0 (64.8%), 12 PL-1 (13.2%) and 20 PL-2 (22.0%) with nodal metastases, and there was a significant difference between the three groups (P = 0.03) according to SN2 frequency. There was no difference between VPI 1 and 2 (P = 0.27). CONCLUSIONS: In conclusion, our study suggests that the incidence of SN2 is significantly associated with VPI in patients with cIA NSCLC. Although MW (>11.5 mm) had a low specificity in the assessment of SN2, it had a high sensitivity, suggesting the possibility of a superior benefit compared with LW. Standard hilar and mediastinal lymph node dissection should be required in patients with suspicious VPI and MW (>11.5 mm) on preoperative CT. [ABSTRACT FROM AUTHOR]

OBJECTIVES Solid lung cancers, even subcentimetre lesions, are considered to be invasive pathologically. However, the clinicopathological features and appropriate operative strategies in patients with these small lesions are still controversial, especially for those with a radiologically solid appearance. METHODS Between 2004 and 2011, 135 patients underwent pulmonary resection for subcentimetre lung cancer with clinical-N0 (c-N0) status. The findings of preoperative thin-section computed tomography (CT) were reviewed, and subcentimetre lung cancer was divided into three groups: pure ground-glass nodule, part-solid and pure-solid lesions. RESULTS Among the 135 subcentimetre lung cancer patients with c-N0 status, 71 showed a solid appearance on thin-section CT scan. Furthermore, pathological nodal examinations were performed in 49 patients, and nodal involvement was found pathologically in 6 (12.2%) patients. All of them had pure-solid tumours (P = 0.0010). Among the patients with solid subcentimetre lung cancers, the maximum standardized uptake value (SUVmax) was the only significant predictor of nodal involvement by a multivariate analysis (P = 0.0205). With regard to the surgical outcomes, the overall 5-year survival and disease-free survival rates were 100 and 97.8% for part-solid lesions, and 87.3 and 74.8% for pure-solid lesions, respectively. Moreover, there was a significant difference in disease-free survival between a high SUVmax group (60.0%) and a low SUVmax group (94.9%) (P = 0.0013). CONCLUSIONS There might be a possibility of lymph node metastasis despite subcentimetre lung cancer, especially for radiological pure-solid nodules that show a high SUVmax. If limited surgery is indicated for solid subcentimetre lung cancer, a thorough intraoperative evaluation of lymph nodes is needed to prevent loco-regional failure. [ABSTRACT FROM AUTHOR]

OBJECTIVES Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has a high diagnostic value for preoperative mediastinal staging in patients with lung cancer. In this study, the utility of EBUS-TBNA for the pathological diagnosis of postoperative lymph node recurrence was investigated and compared with that of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS Patients who received both EBUS-TBNA and FDG-PET for the diagnosis of postoperative lymph node recurrence were retrospectively investigated. They underwent routine chest computed tomography (CT) follow-up after thoracotomy, and when hilar or mediastinal lymph nodes showed enlargement on CT compared with the previous chest CT, they were referred for FDG-PET and EBUS-TBNA. We compared the diagnostic performance of these two modalities. In addition, pathological findings of the biopsied sample were evaluated precisely and compared with the results of FDG-PET. Positivity for hypermetabolism on FDG-PET was defined as a standardized uptake value (SUV) greater than 2.5. RESULTS A total of 40 patients were retrospectively reviewed. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of EBUS-TBNA were 100% for each parameter, whereas those of FDG-PET were 95.8, 12.5, 62.2, 66.7 and 62.5%, respectively. The SUV of true-positive nodes was significantly higher than that of false-positive nodes (P = 0.001). Twenty-two of 24 patients who were confirmed for recurrence by EBUS-TBNA underwent anticancer treatment. The pathological diagnoses of 14 false-positive cases by FDG-PET were chronic inflammation in 12 and non-specific granuloma in 2. CONCLUSIONS The diagnostic yield of EBUS-TBNA is higher than that of FDG-PET when postoperative lymph node recurrence is suspected. [ABSTRACT FROM AUTHOR]

OBJECTIVES This study reviews survival outcomes and cost of lung cancer care over multiple decades at a single high-volume institution. METHODS All patients with a diagnosis of lung cancer were analysed at a single institution from 1959 to 2010. Data were extracted from a tumour registry, which was linked to a longitudinal medical record, clinical data repository and social security master death index. In-depth survival analyses by stage were performed using Kaplan–Meier methods from 1981 to 2010. The analysis contains hospital billing data on 1025 lung cancer patients from 2004 to 2010. RESULTS A total of 17 025 patients with lung cancer were identified over the study period. The 1-year, 5-year and 10-year all-cause mortality rates were 41, 78 and 87%, respectively. Non-small-cell lung cancer comprised 73% (n = 12 361) of cases where the median survival = 2.5 years and the population was 94% Caucasian. Lung cancer was most prevalent between ages 60–79 years of life. Female gender and adenocarcinoma were increasingly more prevalent over the decades. The 5-, 10- and 15-year survival for non-small-cell lung cancer (NSCLC) patients were 27, 15 and 5%, respectively. Death rates measured at 1 year after diagnosis were reduced; however, 5-year survival over each subsequent decade did not significantly change. In patients where the full scope of cost data were available, the median cost/patient with any stage NSCLC = $40 500, where 63% of the cost is expended in the first year after diagnosis. The average length of treatment for NSCLC was 20.2 months. The greatest single category of expense was chemotherapy (31%), followed by surgery (24%), inpatient medical (17%), radiation therapy (12%) and diagnostics (5%). For surgically treated patients, Stage II–IV costs were roughly twice those of Stage I. CONCLUSIONS There has been no evident improvement over the past 3 decades in 5-year survival (∼27%) in patients diagnosed with NSCLC at a single high-volume institution. Improvement in 1-year survival is thought to be attributed to improvements in diagnosing lung cancer earlier. Most of the healthcare expenditure for lung cancer is incurred during the first year after diagnosis despite stage. [ABSTRACT FROM AUTHOR]

OBJECTIVES Bilobectomy is considered to be a risky procedure due to space mismatch between the pleural space and the remnant lung. The objective of this study was to evaluate if postoperative complications related or not to size mismatch are more frequent after bilobectomy compared with right lobectomy cases. METHODS Retrospective case-control study on a series of matched non-small-cell lung cancer patients. Cases were patients who underwent right bilobectomy (upper and middle or lower and middle) and controls, patients who underwent right upper or lower lobectomy. Cases and controls were matched by propensity scoring according to site, age, ppoFEV1, type of postoperative management (intensive physiotherapy or not), cardiac comorbidity and pT status. We selected two primary outcomes for comparison: occurrence of any cardiorespiratory complication and occurrence of any complication related to space discrepancies. For the latter, all complicated case records were reviewed and two blinded observers agreed on the probability of each complication to be related to space discrepancies. Agreement was measured by the κ statistic. The overall odds ratio (OR) and 95% confidence interval (CI) for each outcome were calculated on 2 × 2 tables for the whole population and for cases with upper or lower resections. RESULTS The study included 689 patients: 572 right lobectomy (419 upper and 153 lower) and 117 bilobectomy cases (30 upper and middle and 87 lower and middle). The overall mortality rate of the series was 2.03% (14/689), and cardiorespiratory complications were recorded in 14.4% (99/689) and space-related complications in 19.59% (135/689) cases. Both observers agreed on space-related complications in 86% of the 135 cases (κ: 0.72). After matching, 234 cases entered the study (117 with right lobectomy, including 83 lower and 34 upper, and 117 with bilobectomy, including 87 lower and 30 upper). The prevalence of cardiorespiratory complications was higher after lower and middle lobectomy compared with lower lobectomy (P = 0.0002; OR: 7.96, 95% CI: 2.19–43.16). No differences were found in death rates or in space-related complications between groups of lobectomy and bilobectomy cases. CONCLUSIONS This study failed to demonstrate a higher space-related complication rate in bilobectomy cases but cardiorespiratory complications were statistically higher after lower and middle lobectomy compared with lower lobectomy in matched cases. [ABSTRACT FROM PUBLISHER]

OBJECTIVES Preoperative evaluation of patients with suspected or confirmed lung cancer consists of clinical and radiological staging. Malignant pleural effusion is a poor prognosticator in non-small-cell lung cancer. Pleural ultrasound (PU) allows for the assessment of pleural effusion, providing real-time guidance for its aspiration and cytological analysis. Pleural Ultrasonography in Lung Cancer (PULC) as an adjunct to physical examination has the potential to improve preoperative staging of non-small-cell lung cancer during first surgical encounter by allowing the evaluation of previously unassessed pleural effusion. METHODS This study consisted of a prospective trial of surgeon-performed PU in the preoperative evaluation of lung cancer patients. All patients evaluated in the thoracic surgery clinic with the new or presumed diagnosis of lung cancer were eligible. A portable ultrasound machine was used to evaluate pleural fluid in the bilateral costophrenic sulci with pleural fluid aspiration for cytological analysis. RESULTS Forty-five patients were prospectively enrolled over a 3-month period. Thirteen patients had ultrasound evidence of a pleural effusion, of which 3 were significant enough for aspiration. Cytological analysis of these effusions yielded malignant cells in 1 patient. Positive PULC evaluation led to a change in clinical staging (M0 to M1a) in 10 patients and a change in pathological staging (pleural fluid cytology positive) in 1 patient. The time required for PULC examination was 15 ± 7 min. There were no complications related to the procedures. CONCLUSIONS Preoperative pleural ultrasonography is a rapid and effective way to improve precision of staging in patients with lung cancer. More precise staging may allow for more appropriate testing, patient prognostication and operative planning. [ABSTRACT FROM AUTHOR]

OBJECTIVE Video-assisted thoracoscopic surgery (VATS) lobectomy has been gradually accepted as an alternative surgical approach to open thoracotomy for selected patients with non-small-cell lung cancer (NSCLC) over the past 20 years. The aim of this project was to standardize the perioperative management of VATS lobectomy patients through expert consensus and to provide insightful guidance to clinical practice. METHODS A panel of 55 experts on VATS lobectomy was identified by the Scientific Secretariat and the International Scientific Committee of the ‘20th Anniversary of VATS Lobectomy Conference—The Consensus Meeting’. The Delphi methodology consisting of two rounds of voting was implemented to facilitate the development of consensus. Results from the second-round voting formed the basis of the current Consensus Statement. Consensus was defined a priori as more than 50% agreement among the panel of experts. Clinical practice was deemed ‘recommended’ if 50–74% of the experts reached agreement and ‘highly recommended’ if 75% or more of the experts reached agreement. RESULTS Fifty VATS lobectomy experts (91%) from 16 countries completed both rounds of standardized questionnaires. No statistically significant differences in the responses between the two rounds of questioning were identified. Consensus was reached on 21 controversial points, outlining the current accepted definition of VATS lobectomy, its indications and contraindications, perioperative clinical management and recommendations for training and future research directions. CONCLUSION The present Consensus Statement represents a collective agreement among 50 international experts to establish a standardized practice of VATS lobectomy for the thoracic surgical community after 20 years of clinical experience. [ABSTRACT FROM AUTHOR]

OBJECTIVES Phase III trials regarding the feasibility of segmentectomy for lung cancer ≤2 cm in size are now underway in Japan and the USA. However, despite their small size, lung cancers that show a pure-solid appearance on thin-section computed tomograpy (CT) are considered to be invasive with a high frequency of nodal involvement. METHODS Between 2008 and 2011, 556 clinical Stage IA lung cancer patients underwent pulmonary resection. For all patients, the findings obtained by preoperative thin-section CT were reviewed and the maximum standardized uptake value (SUVmax) on positron emission tomography was recorded. Several clinicopathological features were investigated to identify predictors of nodal metastasis using multivariate analyses. RESULTS One hundred and eighty-four clinical Stage IA lung cancer patients showed a pure-solid appearance on thin-section CT. Among them, air bronchogram was found radiologically in 58 (32%) patients. Nodal involvement was observed in 10 (17%) patients with air bronchogram, compared with 43 (34%) without air bronchogram, in clinical Stage IA pure-solid lung cancer. A multivariate analysis revealed that air bronchogram, clinical T1a and SUVmax were significant predictors of postoperative nodal involvement (P < 0.01, <0.01, and 0.03, respectively). Furthermore, nodal metastasis was never seen in patients with clinical T1a pure-solid lung cancers who had both air bronchogram and low SUVmax. CONCLUSIONS The presence of air bronchogram was a novel predictor of negative nodal involvement in clinical Stage IA pure-solid lung cancer. Segmentectomy with thorough lymph node dissection is a feasible option for these patients despite a pure-solid appearance. [ABSTRACT FROM AUTHOR]

OBJECTIVES The purpose of this study was to elucidate the detectability of recurrence and the prognostic significance of the serum carcinoembryonic antigen (CEA) levels in patients with completely resected non-small-cell lung cancer (NSCLC). METHODS Five hundred and eighteen NSCLC patients who underwent complete resection at Aichi Cancer Center between April 2001 and March 2006 were enrolled in this study. The patient characteristics were as follows: the median age was 63 years; 331 tumours were classified as pathological stage I, 88 tumours were pathological stage II and 99 tumours were pathological stage III; 140 tumours were adenocarcinomas with epidermal growth factor receptor (EGFR) mutations, 268 tumours were adenocarcinomas with EGFR wild-type mutations and 110 tumours were other NSCLCs. The patients were divided into three groups: those with a normal CEA level before and 1–3 months after surgery (N group, n = 380), those with an elevated CEA level before surgery and a normal CEA level 1–3 months after surgery (HN group, n = 105) and those with an elevated CEA level 1–3 months after surgery regardless of the preoperative CEA level (H group, n = 33). The correlations between the changes in the serum CEA levels and the clinical outcomes were analysed. RESULTS Recurrence developed in 122 patients (32%) in the N group, 49 patients (47%) in the HN group and 19 patients (58%) in the H group (P = 0.001). The sensitivity and specificity of an elevated serum CEA level during the follow-up period for detecting recurrence were 30 and 98% in the N group and 82 and 73% in the HN group, respectively. Twenty-seven asymptomatic recurrent tumours combined with an elevated serum CEA level were detected in the HN group. In the multivariate Cox regression analysis, the serum CEA level 1–3 months after surgery had prognostic value for overall survival. CONCLUSIONS In completely resected NSCLC patients, measuring the serum CEA level during the follow-up period is useful in patients in whom an elevated level normalizes after surgery, and the serum CEA level 1–3 months after surgery is considered to have prognostic significance regarding survival. [ABSTRACT FROM AUTHOR]

OBJECTIVES To determine whether patient sex has a significant effect on long-term outcomes post curative resection of non-small-cell lung cancer. METHODS We retrospectively analysed a prospectively validated thoracic surgery database (n = 4212), from a single institution, from September 2001 to October 2012. Univariate, Cox multivariate and propensity analysis was performed. Long-term follow-up was carried out via the National Strategic Tracing Service that operates in the United Kingdom. RESULTS One hundred per cent follow-up was achieved. Overall institutional in-hospital mortality was 2.0% for all thoracic resections. Median survival was 2.78 years (range 0–13 years). Two thousand two hundred and thirty-three males and 1979 females were included. Kaplan–Meier survival of all the patients demonstrated superior survival of females for all stages, P = 0.0003, and stage I, P = 0.0006. Female sex conferred no survival advantage in stage II, P = 0.7, and IIIa, P = 0.1. Sub-analysis by histological type demonstrated that females had superior survival with adenocarcinoma compared with males, P < 0.001, but no sex difference existed with squamous carcinomas, P = 0.2. Cox analyses demonstrated that female sex was an advantageous prognostic factor for the entire study group [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.69–0.96] and Stage I only (HR 0.70, 95% CI 0.57–0.63). Sex was of no significance in Stage II and IIIa disease with regard to survival. Sub-analysis demonstrated that female sex was not a significant factor determining survival in patients with squamous carcinoma; however, it was significantly associated with increased survival in patients with adenocarcinoma (HR 0.63, 95% CI 0.51–0.78). A 1:1 propensity analysis confirmed the above findings. CONCLUSION Propensity matching and Cox multivariate regression analysis confirmed the univariate finding that female sex is only associated with improved survival in patients with Stage I adenocarcinoma. Patient sex does not affect survival of patients with squamous carcinoma. [ABSTRACT FROM AUTHOR]

Video-assisted thoracic surgery (VATS) lobectomy is an appealing alternative to open lobectomy via thoracotomy for non-small-cell lung cancer. However, there is no clear consensus in regard to the superior approach for long-term outcomes. The data are limited to small series, which precludes further clarification. Meta-analysis of these studies was performed in order to obtain a more objective determination of the oncological feasibility of VATS lobectomy. A systematic review of the PubMed and Embase databases was performed. Twenty observational studies reporting long-term outcomes were included, involving 2106 VATS and 2661 thoracotomy patients. There was an advantage in long-term mortality for patients who underwent VATS vs patients who underwent thoracotomy (meta difference in survival: 5%; 95% CI: 3–6%) with large heterogeneity among studies (Q = 42.6; P-value: 0.001; I2 = 55.7%). There was no evidence of publication bias. Compared with open lobectomy, VATS lobectomy appears to have improved long-term outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVES Non-small-cell lung cancer (NSCLC) following pulmonary or pharyngolaryngeal malignancies has been widely studied, but only a few articles have focussed on lung cancers following other solid malignancies. Our purpose was to compare the characteristics and prognosis of patients with NSCLC according to the medical history of the extra-pulmonary and extra-pharyngolaryngeal solid malignancy. METHODS Patients who underwent surgery for NSCLC from January 1980 to December 2009 in two French thoracic centres were reviewed. We compared patients with no history of cancer (Group 1) and patients with a history of extra-pulmonary and extra-pharyngolaryngeal solid malignancy (Group 2). RESULTS There were 4992 patients: 4603 (92%) in Group 1 and 389 (8%) in Group 2. In comparison with Group 1, Group 2 showed an increasing incidence over the last 3 decades (2–8%), an older population (65.9 vs 61 years, P < 0.001), a higher proportion of women (34 vs 18%, P < 0.001), non-smokers (20 vs 10%, P < 0.001), adenocarcinomas (53 vs 40%, P < 0.001), T1 (16 vs 14%, P = 0.047) and second nodule in the same lobe (4 vs 2%, P < 0.001). The overall survival was not significantly different between the two groups (P = 0.09). In multivariate analysis, older age, male gender, pneumonectomy, higher T, higher N, incomplete resection and history of extra pulmonary—extra pharyngolaryngeal solid malignancy were significantly associated with a worse prognosis. CONCLUSIONS Despite an earlier diagnosis, a history of extra-pulmonary and extra-pharyngolaryngeal solid malignancy is associated with a worse prognosis in patients with NSCLC undergoing surgical resection. Overall survival is particularly low after a history of bladder and upper gastrointestinal malignancies. [ABSTRACT FROM AUTHOR]

OBJECTIVES To examine the relationship between preoperative serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (I-CTP) levels and postoperative distant metastasis in patients with non-small-cell lung cancer (NSCLC). METHODS We retrospectively reviewed 143 patients in whom preoperative serum I-CTP level was measured from January 2006 to March 2011, including 91 males and 52 females with an average age of 70.1 ± 8.2 years. Histological subtypes included adenocarcinoma (n = 95), squamous cell carcinoma (n = 34) and other (n = 14). Preoperative serum carcinoembryonic antigen (CEA) and cytokeratin-19 fragment (CYFRA) levels were also measured. Patients with abnormal renal function or preoperative bone fractures were excluded. RESULTS The mean preoperative serum I-CTP level was 4.1 ± 1.6 ng/ml, and the preoperative serum I-CTP level was elevated (>4.5 ng/ml) in 29 patients. Distant metastasis was detected in 21 patients during the 39 ± 18 (range 1–79) months of follow-up. The rate of distant metastasis was significantly higher in patients with elevated preoperative serum I-CTP levels than those with normal preoperative I-CTP levels (≤4.5 ng/ml) (P < 0.0001). The 5-year recurrence-free survival rate was lower in patients with elevated preoperative serum I-CTP levels than those with normal preoperative I-CTP levels (41.8 vs 92.9%; P < 0.0001). CONCLUSIONS An elevated preoperative serum I-CTP level predicts postoperative distant metastasis in patients with NSCLC. [ABSTRACT FROM AUTHOR]

The study aimed to compare the reported oncological outcomes based on satisfactory lymph node dissection (LND) or lymph node sampling (LNS), systemic and loco-regional recurrence rate and long-term survival rate of patients with early-stage non-small-cell lung cancer (NSCLC) who underwent video-assisted thoracic surgery (VATS) lobectomy or thoracotomy lobectomy. A systematic review was conducted using PubMed, EMBASE and OVID-EBMR databases ranging from 1990 to 2011. The studies compared VATS and thoracotomy for patients with NSCLC, with results including LND or LNS where recurrence as well as survival rates were identified. Data were abstracted by two reviewers independently. Mean difference or risk ratio (RR) were pooled using RevMan 5.0 statistical software. 5389 cases were included, of which 2380 underwent VATS and 3009 underwent thoracotomy. There was no significant difference in the number of total LND or LNS procedures (MD: −0.63; 95% confidence intervals (95% CI): −1.47 to 0.21; P = 0.14) or mediastinal LND or LNS (MD: −0.51; 95% CI: −1.58 to 0.56; P = 0.35) between the two groups. Systemic (RR: 0.61; 95% CI: 0.48 to 0.78; P < 0.01) and loco-regional (RR: 0.66; 95% CI: 0.46 to 0.95; P = 0.03) recurrence rates were significantly lower in the VATS group. Moreover, a significantly higher survival rate (RR: 1.09; 95% CI: 1.03 to 1.15; P < 0.01) was also demonstrated by a Forest plot in the VATS group. These results suggest that VATS lobectomy might be an eligible alternative in place of thoracotomy in patients with early-stage NSCLC by reducing recurrence and improving survival rates. [ABSTRACT FROM AUTHOR]

OBJECTIVES The objective of this study was to assess the prognostic role of preoperative quality of life (QoL) in patients operated on for early-stage non-small-cell lung cancer (NSCLC). METHODS This is an observational analysis of 131 consecutive patients (2003–08) submitted to pulmonary lobectomy and systematic nodal dissection for pathological pT1N0 or pT2N0 stages NSCLC with a complete follow-up (median 40 months). QoL was measured by the Short Form 36v2, a multidimensional survey assessing eight domains and two composite scales (physical component score [PCS] and mental component score [MCS]). Survival was calculated by the Kaplan–Meier method. The log-rank test was used to assess differences between groups. The relationships between survival and QoL composite scales were determined by Cox proportional hazards regression analysis adjusting for the effect of several baseline and clinical variables. PCS and MCS were categorized according to their values greater or lower than 50 percentiles (general population norms). RESULTS Fifty-three (40%) patients had PCS <50 and 71 (54%) had MCS <50. Results from physical functioning (P = 0.03) and general health (P = 0.03) scales were directly associated with survival. Multivariable regression showed that significant factors associated with overall survival were age >70 (hazard ratio [HR] 2.4, 95% confidence interval [95% CI] 1.2–4.8, P = 0.01) and PCS <50 (HR 2.3, 95% CI 1.4–4.4, P = 0.01). MCS, pT stage, histology, forced expiratory volume in 1 s, DLCO were not associated with prognosis. Patients with PCS >50 lived longer than those with PCS <50 (5-year overall survival 79 vs 49%, P = 0.01), in both pT1 (5-year overall survival 80 vs 49%) and pT2 stages (5-year overall survival 78 vs 48%). Cancer-specific 5-year survival was better in patients with a preoperative PCS >50 compared with those with PCS <50 (89 vs 73%, P = 0.05). Deaths due to cancer recurrence were similar in patients with PCS <50 and >50 (55 vs 53%, P = 0.9). CONCLUSIONS The physical component of QoL was associated with overall and cancer-specific survivals in patients operated on for early-stage NSCLC. Supportive interventions aimed at improving the perception of physical well-being should be tested to verify whether they can improve long-term prognosis after lung cancer surgery. [ABSTRACT FROM AUTHOR]

OBJECTIVES Survival of patients with left-sided stage I non-small cell lung cancer (NSCLC) is unsatisfactory, probably because of the high incidence of contralateral mediastinal node involvement. In this study, occult micrometastases to the right upper mediastinal nodes were retrospectively investigated in patients with left-sided stage I NSCLC. METHODS Nineteen patients with clinical stage I NSCLC underwent video-assisted thoracoscopic lobectomy and bilateral mediastinal node dissection (BMD). Clinical data and survival of patients with BMD were compared with those of 25 left-unilateral mediastinal node dissection (UMD) patients. Occult micrometastases were detected using the cytokeratin 19 mRNA reverse transcription–polymerase chain reaction method. RESULTS Pathological N2 disease was found in 1 patient, and 18 had pN0 disease. The operative time, blood loss, duration of chest tube drainage and duration of postoperative hospital stay were not different between BMD and UMD patients. Nodal micrometastases were detected in 11/19 (57.8%) patients. Skip micrometastases to the level N3 nodes without N1 and N2 node involvement were observed in 8/11 (72.7%) patients. Patients with BMD are all alive and have had no recurrence during the median follow-up period of 21.4 months. Overall 3-year survival and disease-free 3-year survival were not significantly different between the two groups. CONCLUSION In this preliminary study, occult micrometastases to the level N3 nodes occurred frequently in patients with left-sided clinical N0 stage I NSCLC. Postoperative survival of patients with occult micrometastases to the level N3 node does not appear to be poor. Further follow-up and work are needed. [ABSTRACT FROM AUTHOR]

OBJECTIVES Since few large-scale studies of patients with pleomorphic carcinoma have been documented, factors affecting survival after pulmonary resection for pleomorphic carcinoma, as well as its clinicopathological characteristics, are still unknown. For a better understanding of the patients undergoing resection of pulmonary pleomorphic carcinoma, we reviewed our experience with these patients. METHODS Between 2002 and 2010, 26 patients with pulmonary pleomorphic carcinoma underwent macroscopically complete pulmonary resections. Various perioperative variables were investigated retrospectively to confirm a role for pulmonary resection and to analyse prognostic factors for overall survival and disease-free survival after lung resection. RESULTS Twenty-four patients (92%) were male. Twenty-one patients (81%) were smokers and all of them smoked more than 30 pack-years. In 25 patients (96%), the tumour was located peripherally. Twenty-three of these 25 patients revealed the tumour touching the visceral pleura widely in the preoperative chest computed tomography. In all 26 patients, the tumour was completely resected macroscopically; however, three patients (12%) had microscopically positive surgical margins. Among them, additional irradiation was conducted in two patients and additional surgical resection was performed in one patient. Combined resections were performed in 11 patients (42%), including chest wall resections in 7 patients. Overall survival rate after pulmonary resection was 48% at 5 years. Disease-free survival rate after pulmonary resection was 33% at 5 years. Patients with tumours invading the visceral pleural surface and microscopically positive surgical margin had significantly worse overall survivals (P = 0.048 and 0.037, respectively). However, there were no significant prognostic factors for disease-free survival. CONCLUSIONS Despite small number of cases, we found that pleural invasion suggested a worse prognosis for resection of pulmonary pleomorphic carcinoma. Surgical strategy might be constructed to achieve not only macroscopically, but also microscopically complete resection for such large tumours with aggressive nature and peripheral preference. [ABSTRACT FROM AUTHOR]

OBJECTIVES The prognosis of non-small-cell lung cancer (NSCLC) patients with malignant pleural disease (MPD), characterized by malignant pleural effusion and/or malignant pleural nodules, is reported to be poor, and patients with MPD are generally not subjected to surgery. However, whether or not the primary tumor should be resected, when MPD is first detected at thoracotomy, is controversial. METHODS The clinical records of 1623 consecutive NSCLC patients, who underwent surgery between 1990 and 2007, were retrospectively reviewed. A hundred patients (6.2%) were classified with pathological stage IV disease according to the seventh edition of the Union for International Cancer Control (UICC) staging system. There were 73 patients with MPD, which included 32 with effusion without nodules (MPE) and 41 with nodules with or without effusion (MPN). Intra- or postoperative pleural chemotherapy was administered to 37 MPD patients. RESULTS The median survival time, the 3-year survival rate and the 5-year survival rate for MPD patients were 25.9 months, 41.4%, and 23.7%, respectively, which are better outcomes than those for M1b patients (8.7 months, 18% and 18%, respectively) (log-lank test: p = 0.014). Among MPD patients, N0–1 disease was determined to be a favorable prognostic factor (p = 0.01). MPD status (MPE or MPN) was not prognostically significant (p = 0.40). MPE patients with N0–1 disease had a significantly better prognosis with a 5-year survival rate of 63.6% compared to MPE patients with N2–3 disease (p = 0.003). Twenty-seven percent of MPN patients with N0–1 disease achieved 5-year survival, whereas none of the MPD patients with N2–3 disease survived longer than 5 years after surgery. CONCLUSIONS The prognosis of patients with surgically detected MPD, who underwent resection, was better than that of M1b patients. MPE patients with N0–1 disease may be candidates for resection. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Removing or sampling lymph nodes from the bilateral paratracheal area through a left thoracotomy is not a standard procedure in patients with lung cancer. The aim of this study was to evaluate the feasibility of a technique without ductus arteriosus division and mobilization of the aortic arch and to compare the number of lymph nodes resected in left-sided dissections to the number of lymph nodes removed in right-sided mediastinal dissections that are routinely performed in clinical practice. Methods: A total of 93 patients with hilar lung cancer were evaluated. A prospective study was conducted on 51 patients with primary left-sided hilar lung cancer, who underwent left thoracotomy and paratracheal lymphadenectomy between January 2008 and January 2010. The number of nodes dissected in these patients was compared with the number of nodes dissected in 42 patients with right-sided hilar lung cancer by right-sided mediastinal dissection within the same period. Results: The mean number of resected nodes in the bilateral paratracheal area via left thoracotomy was 8.4 (2–18 nodes). The distribution from 4R–4L–2L–2R was as follows: 3.3–2.5–0.5–2.1, respectively. Six patients (11.7%) were diagnosed with occult N2, and two (3.9%) of these patients also had N3 disease concomitantly. The number of dissected nodes from the ipsilateral station 2 via right-sided versus left-sided thoracotomy was 1.6 versus 0.5 (p =0.000), whereas the number of dissected nodes from ipsilateral station 4 via right-sided versus left-sided thoracotomy was 3.3 versus 2.5, respectively (p =0.1). The number of dissected nodes from the contralateral station 2 via right-sided versus left-sided thoracotomy was 0.2 versus 2.1 (p =0.000), whereas those numbers from the contralateral station 4 via right-sided versus left-sided thoracotomy were 1.0 versus 3.3, respectively (p =0.000). Conclusions: Lymphadenectomy of the paratracheal area via left thoracotomy without ductus arteriosus division and mobilization of the aortic arch is technically feasible. From these data, regardless of approach, more lymph nodes are obtained from the right paratracheal space; this appears to be due to the fact that there are more right-sided paratracheal lymph nodes. [Copyright &y& Elsevier]

Abstract: Background: Lung cancer patients with chronic obstructive pulmonary disease (COPD) have a high risk of developing postoperative pneumonia (POP). This study aims to investigate the impact of COPD on POP and the trends for perioperative bronchial colonisation by micro-organisms. Methods: A retrospective chart review was made for 626 patients who underwent lung cancer surgeries at the Chiba University Hospital between 1996 and 2005. The patients were categorised as non-COPD (n =475) and COPD (forced expiratory volume in 1s/forced vital capacity (FEV1/FVC) <70%; n =151). All the patients had sputum and bronchial bacterial cultures examined for potentially pathogenic micro-organisms (PPMs). Risk factors for POP and mortality were analysed. Results: Patients with COPD had a significantly higher incidence of POP (23/151, 15.2%) than those without COPD (17/475, 3.6%) (p <0.0001). Preoperative bronchial bacterial examinations showed that 50 of 475 patients without COPD (10.5%) had positive cultures, while the results for 30 of 151 patients with COPD (19.9%) were positive (p =0.0111). Only 31 of 548 patients (5.7%) who did not show any preoperative PPMs had POP, while nine of 78 patients (11.5%) who presented preoperative PPMs had POP (p =0.0469). The PPMs that emerged postoperatively were primarily Staphylococcus aureus (and Gram-negative bacilli (94.4% of PPMs), while they were seen less frequently preoperatively (46.5% of PPMs). Multivariate analysis demonstrated that advanced age and FEV1/FVC were independent risk factors for POP. Patients with POP had significantly worse long-term survivals than those without POP (p =0.0004). Conclusion: COPD was a risk factor for POP. Staphylococcus aureus and Gram-negative bacilli should be targets for postoperative prophylactic antibiotic selection. Patients with POP had poor long-term survivals. [Copyright &y& Elsevier]

Abstract: Objective: Mediastinal lymph node metastasis (N2) is a key prognostic factor for lung carcinoma. This study was undertaken to investigate the relationship between vascular endothelial growth factor C (VEGF-C) expression and postoperative early recurrence in patients with N2 non-small-cell lung cancer. Methods: Cancer tissue samples from 92 patients with pN2 non-small-cell lung cancer and benign lung disease tissues samples from 30 patients were examined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry assays to detect VEGF-C expression. The difference of VEGF-C expression was compared by χ 2 test. All patients with N2 disease were evaluated within 1 year after surgery to detect early tumour recurrence. Cox regression analysis was performed to determine the risk factors of postoperative early recurrence of N2 lung cancer. Results: VEGF-C mRNA expression was observed in 64 (70%) pN2 lung cancer tissues, but was not found in benign lung disease tissues. Early recurrence occurred in 43 patients (47%) at 1 year after operation. The main pattern was distant recurrence, and the most frequent sites were the brain and lung. The early recurrence rate in patients with positive VEGF-C expression was significantly higher than that of those with negative VEGF-C expression (P =0.006, log-rank test). Cox regression analysis revealed that positive VEGF-C expression in tumours (hazard ratio (HR)=2.523, P =0.037) was an independent risk factor of postoperative early recurrence of N2 lung cancer. Conclusions: VEGF-C expression was high in N2 lung cancer, with significant correlation to postoperative early recurrence. About one-half of the patients with N2 non-small-cell lung cancer would develop recurrence disease within 1 year after surgery, frequently with mediastinal nodes, brain or lung metastases. VEGF-C might be a predictor of postoperative early recurrence in patients with N2 non-small-cell lung cancer. [Copyright &y& Elsevier]

Abstract: Objective: Alpha-B-crystallin, a small heat-shock protein, recently gained major interest because of its differential expression during tumourigenesis and metastasis in various epithelial tumours. The purpose of this study was to investigate the expression of alpha-B-crystallin and its biologic and prognostic significance in non-small-cell lung cancer (NSCLC). Methods: Immunohistochemical analysis was performed on a tissue microarray slide containing samples from 146 NSCLC patients who were operated on between 2004 and 2005. Results: Cytoplasmic and nuclear staining was detected. Squamous cell carcinomas and adenocarcinomas had a distinctive profile of expression. The cytoplasmic staining of the tumours, however, is related to the local invasion – T-factor (p =0.044). Nuclear staining was more commonly detected in advanced stages, and was a biomarker of an aggressive tumour biology (p =0.042). Kaplan–Meier analysis showed that patients with positive nuclear staining had shorter overall survival (log-rank p =0.002). Using Cox''s proportional hazards model, we performed multivariate analyses to assess the independent prognostic value of nuclear staining. The variables used included age, histology, gender and stage. Alpha-B-crystallin was an independent negative prognostic factor of survival in addition to clinical stage. Conclusions: Alpha-B-crystallin plays an essential role in NSCLC biology and its nuclear staining is an independent factor of poor survival. Its clinical application in molecular biologic substaging of NSCLC patients needs further validation. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the diagnostic yield, the learning curve and the safety of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) in mediastinal staging of patients with lung cancer. Methods: Mediastinal staging was performed with EBUS-TBNA according to the Danish national guidelines in patients fulfilling one or more of the following criteria: (1) central tumour; (2) enlarged (>10mm) mediastinal lymph nodes on computed tomography; or (3) positron emission tomography (PET)-positive mediastinal lymph nodes. The study period began in January 2006 when EBUS-TBNA was introduced in the department and ended in December 2007. All records were reviewed retrospectively. None of the four examiners had any previous experience with EBUS-TBNA or ultrasound when the study began. All examinations were performed under general anaesthesia. Patients without useful cytological material from the EBUS-TBNA were subjected to a supplementary standard cervical mediastinoscopy if the mediastinal lymph nodes were found to be enlarged (>10mm), PET positive or if the examiner was insecure of the result of the EBUS-TBNA. Patients with mediastinal lymph node involvement, detected by EBUS-TBNA or standard cervical mediastinoscopy, were referred to oncological treatment, while those without mediastinal lymph node involvement underwent – if they were otherwise eligible for surgery – resection and systematic lymph node sampling either by thoracotomy or by video-assisted thoracoscopy. Final mediastinal staging was defined as positive if mediastinal lymph node involvement was detected by EBUS-TBNA, standard cervical mediastinoscopy or surgery, or defined as negative otherwise. Results: A total of 157 patients were included in the study. N2/N3 disease was found in 67 patients (42.6%). EBUS-TBNA missed the mediastinal spread in 10 patients. Five of the ten patients had lymph node metastases in station 5, 6 or 8 – out of reach of EBUS-TBNA or standard cervical mediastinoscopy. EBUS-TBNA had a sensitivity of 0.85 (0.74–0.93) and a negative predictive value of 0.90 (0.82–0.95). No complications occurred from EBUS-TBNA. The number of supplementary standard cervical mediastinoscopies decreased significantly in the study period. Conclusion: The results of this study suggest that staging of the mediastinum with EBUS-TBNA is safe and easy to learn – even without previous experience with ultrasound. The diagnostic yield of EBUS-TBNA is in accordance with the yield of standard cervical mediastinoscopy reported in the literature. We do not find any indications in the present study of the recommended necessity for mediastinoscopy in all EBUS-TBNA-negative patients. [Copyright &y& Elsevier]

Abstract: Background: Video-assisted thoracoscopic surgery (VATS) is an increasingly used technique to treat patients with pulmonary metastases, but it does not usually afford lung palpation. Methods: A retrospective study on patients with lesions defined as ‘VATA-able’ who underwent open metastasectomy via thoracotomy. All patients underwent 64-slice helical CT scan with intravenous contrast using 5mm cuts and integrated FDG-PET/CT. Unsuspected malignant pulmonary nodules that were palpitated and removed, and were not imaged pre operatively were defined as ‘malignant nodules’ and would have been missed by VATS metastasectomy. Results: From January 2004 to December 2005, 57 patients had ‘VAT-able’ metastatic pulmonary lesions that were resected via thoracotomy by one thoracic surgeon. Twenty-one (37%) patients had non-imaged pulmonary nodules that were discovered only by bi-manual palpation and would have been missed by VATS metastasectomy, but these nodules were only malignant in 10 (18%) patients. The median size of the non-imaged pulmonary nodule was 0.7cm (range, 0.4–0.8cm). Colorectal carcinoma was the most common tumor requiring metastasectomy. Non-imaged malignant pulmonary nodules were most frequently found in patients with leiyomyosarcoma and osteosarcoma (three of eight patients in both). Conclusion: Metastasectomy via open thoracotomy, which affords bi-manual lung palpation of the entire ipsilateral lung, may discover non-imaged malignant pulmonary metastases in 18% of patients who have had a previously treated solid organ cancer and have at least one imaged metastatic lesion in the lung. The clinical impact of these findings is unknown. A prospective study to further examine this issue is underway. [Copyright &y& Elsevier]

Abstract: Objective: Due to recent advances in imaging, the incidence of patients presenting with bilateral lung lesions is increasing. A single contralateral lung lesion can be an isolated metastasis or a synchronous second primary lung cancer. For the revision of the TNM in 2009, the International Association for the Study of Lung Cancer Staging Committee proposes that patients with contralateral lung nodules remain classified as M1 disease. In this retrospective study, the survival after resection of synchronous bilateral lung cancer is evaluated. Methods: From our database of bronchial carcinoma, all patients with bilateral synchronous lung lesions between 1990 and 2007 were retrieved. We analysed 57 patients in which, after functional assessment and thorough staging, the decision was taken to treat the disease with bilateral resection. All these files were retrospectively reviewed. Twenty-one patients were excluded from this analysis because only one side was resected (n =15) or one of the lesions was non-neoplastic on final pathology (n =6). Results: Thirty-six patients underwent bilateral resection for synchronous multiple primary lung cancer. All resections were performed as sequential procedures. In 23 patients, one side was anatomically resected (2 pneumonectomies) and the contralateral side was resected by limited resection. In 10 patients a bilateral lobectomy was performed, and 3 patients had bilateral limited resections. Postoperative mortality was 2.8%. Eighteen patients had a tumour with a different histological pattern, confirmed by comparing both specimens by an experienced senior pathologist. The median survival after resection of synchronous bilateral lung cancer in our series was 25.4 months with a 5-year survival rate of 38%. There was no significant difference in survival between patients with different versus same histology. This survival is much higher compared to the survival of assumed stage IV disease. Conclusions: Our study shows that selected patients with bilateral lung cancer may benefit from an aggressive approach, with acceptable morbidity and mortality, and rewarding long-term survival. Patients with a single contralateral lung lesion should not be treated as disseminated disease (stage IV). After extensive searching for metastatic spread, bilateral surgical resection should be considered in fit patients. [Copyright &y& Elsevier]

Abstract: Objective: Diagnosis of multiple independent primary cancers is increasing in many settings. Objectives of this study were to analyze clinical characteristics, organ location, and prognosis associated with the presentation of multiple independent primaries when a lung cancer is involved. Methods: We analyzed all patients with a histology-proven diagnosis of lung cancer registered from January 1990 to December 2004 at the Tumor Registry of the Hospital del Mar, Barcelona. We compared 1686 patients presenting a lung cancer as unique primary versus 228 patients presenting a lung cancer and another independent primary. Cofactors included age, sex, smoking habit, lung cancer histology and stage, type and intention of treatment, organ location of the other cancer, and survival from the date of lung cancer diagnosis. Results: Seventy percent of the other cancers were tobacco-related. Independent risk factors of cancer multiplicity were smoking (OR: 3.99; 95% CI: 1.4–11.2), lung cancer stages I (OR: 1.84; 95% CI: 1.2–2.9) and II (OR: 3.25; 95% CI: 1.7–6.3), and older age (OR: 3.11; 95% CI: 1.9–5.1). Once adjusted by age and sex, the main determinant of survival was lung cancer stage rather than cancer multiplicity. However, patients with multiple cancers presented a slightly better survival than patients with a lung cancer as unique primary. When analyzed by subgroups, survival was higher in patients with the lung cancer first (HR: 0.44; 95% CI: 0.24–0.80), and in patients with the other cancer first (HR: 0.80; 95% CI: 0.65–0.99), but it was not different in the patients with a lung cancer and a synchronous other cancer (HR: 0.80; 95% CI: 0.52–1.15). Conclusions: The risk of developing a second independent cancer was strongly associated with tobacco smoking. Cancer multiplicity was not associated with a worse prognosis. As a consequence, when a first primary tobacco-related cancer is treated with curative intention, patients should be closely followed up for an early diagnosis of a possible new independent cancer; and if diagnosed, treatment to cure should be considered as the first option. [Copyright &y& Elsevier]

Abstract: Background: This prospective study was undertaken to establish a novel management algorithm using new indicators to decide the type of lung resection for small peripheral lung lesions. Methods: Inclusion criteria were: (1) ≤20mm peripheral lung lesion(s) and (2) absence of significant lymph node swelling on preoperative CT. Along with the conventional criteria, the percentage of ground-glass opacity (GGO) (≥50% as GGO type and <50% as solid type) on high-resolution CT scan was employed. In accordance with such indicators, a wide wedge resection (WWR), segmentectomy or lobectomy was planned for individual patients. The primary endpoint was to estimate the effectiveness of limited resection in patients with lung cancer by analyzing their locally disease-free survival rates at 5 and 10 years. Results: Of 179 patients enrolled between 1997 and 2002, 90 were male and 89 female. They were divided into 77 GGO types and 102 solid types. During surgery, conversions from limited resections to standard operations were performed on six patients to avoid the risk of local-regional recurrence. Finally, WWR was performed on 73 patients, segmentectomy on 26 and lobectomy on 80, respectively. There were 138 lung cancers and 41 non-cancers. Of 138 cancer patients, 114 patients are alive and 24 died. There were no local-regional recurrences among the 58 cancer patients who underwent limited resection. Conclusions: This intermediate-term outcome suggests that the selection of the type for lung resection using this management algorithm for small peripheral lung lesions was effective for preventing both local-regional recurrences and the excessive resection of normal lung tissue. [Copyright &y& Elsevier]

Objective: To determine whether patient gender affects the outlook following lung resection for non-small cell lung cancer (NSCLC). Patients and methods: Prospectively collected data on 833 patients undergoing lung resection for NSCLC between 1990 and 2000 in a single unit were analysed. Results: 581 patients were male (mean age 64.7±7 years) and 252 were female (mean age 62.6±7.8 years) (P=0.006). Male patients were more likely to have a history of ischaemic heart disease (P=0.03), to have poorer preoperative spirometry as demonstrated by their % predicted FEV1 (P=0.02) and to need pneumonectomy (P=0.0001) than their female counterparts. Squamous cell carcinoma was the predominant histological cell type in men and adenocarcinoma in women (P<0.0001). There was a trend towards a lower pathological stage among women, but this was not significant. Operative mortality for men was 4.6 and 1.2% for women (P=0.01). Overall 5-year survival for men was 34.2±2.65% and 47.5±4.2% for women (P=0.001) and, for the hospital survivors, was 36.5±2.7% and 48.1±4.2%, respectively (P=0.01). On univariate analysis, older age, the need for pneumonectomy and higher pathological stage were significant adverse factors whereas squamous cell type and female gender were significant favourable factors for survival (P<0.05). On Cox proportional hazards model (with and without hospital deaths), pathological stage (P<0.0001), female gender (P=0.0006) and squamous cell type (P=0.001) were independent predictors of survival. The survival was significantly better for women having squamous cell (P=0.01) or non-squamous cell cancers (adenocarcinoma and other) (P=0.002). Regarding the stage, women had a significant survival advantage at pathological stage I (P=0.01) and a relatively better survival at stage II and stage III disease (P=0.3). Conclusions: This study suggests that female gender exerts a significant positive effect on survival following lung resection for NSCLC. This effect is pronounced at early disease stage and persists after adjusting for important differences in the clinical, histo-pathological features and extent of pulmonary resection between male and female patients. [Copyright &y& Elsevier]

We treated two lung cancer patients with metastatic hilar lymph node at the left lower lobe, involving the bifurcation of the left upper- and lower lobar bronchi and the lingular pulmonary artery. After induction chemoradiotherapy, we performed a bronchial sleeve resection of the left lower lobe and lingular division. In these cases, anastomosis of the left superior divisional and main bronchial stumps was necessary, which required correction of an orifice size mismatch. For this purpose, we performed different procedures on each patient. In Procedure 1, we edged the larger superior divisional bronchial stump with the partially excised walls of the upper lobar and the lingular divisional bronchi. In Procedure 2, we reefed the membranous portion of the main bronchus with adjusting stitches. Our procedure is useful for adjusting mismatch of the bronchial stump in anastomosis in a bronchial sleeve resection of the left lower lobe and lingular division. [ABSTRACT FROM AUTHOR]

Abstract: The standard method of bronchoscopic guidance used to identify a bronchial or tracheal tumour during surgery has some disadvantages: (1) it is impossible to identify the incision site in a distal bronchus; (2) bronchoscopy must be performed by a skilled physician; and (3) time and effort are wasted during the operation. We report a new and simple technique to locate endobronchial tumours. Our technique uses a butterfly needle connected to a syringe kept half-full of normal saline solution via an extension tube. The bronchus is punctured using the needle, keeping the syringe under negative pressure. We found that a tumour could be detected through simple observation of the saline solution within the syringe upon bronchial puncture, whereby the tumour is positively detected through the absence of bubble production and ruled out through the production of bubbles. This technique will locate a bronchial or tracheal tumour without bronchoscopy. In addition, it saves time, which benefits the patient. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Time to refine N2 staging? cN2α and cN2β based on local regional involvement provide a more accurate prognosis in surgically treated IIIA non-small-cell lung cancer than N2 alone or the number of node stations involved," by T. Matsunaga and colleagues in the 2014 issue.

The article presents a case study of 52-year old female lung cancer patient who was diagnosed with pulmonary varix associated with an anomalous unilateral single pulmonary vein.

OBJECTIVES We hypothesized that postoperative cardiorespiratory morbidity and/or 30-day death rates decreased after implementing the new European ERS/ESTS guidelines for functional evaluation before lung resection and tested the hypothesis by means of a case–control study. METHODS The analysis included a series of 916 consecutive patients who underwent an anatomical pulmonary resection for non-small-cell lung cancer in our centre. Patients were divided into cases (September 2009–August 2012) and controls (December 2002–August 2009). We reviewed the records from a prospective computerized database; the final dataset included no missing data. The primary studied outcomes were the occurrence of cardiorespiratory morbidity or 30-day death after surgery. The patients were 1:1 propensity score matched according to the following variables age, ppoFEV1% and the need of pneumonectomy. RESULTS After the matching process, 670 cases (335 cases and 335 controls) entered into the study. The rates of pneumonectomy in cases and controls were 5.7 and 13.2%, respectively, (P < 0.0001) in the whole series and 5.7 and 6.9% after matching (P = 0.52). Cardiorespiratory morbidity was 8.1% (27 of 308) in cases and 9.8% (33 of 335) in controls [odds ratio (OR): 0.8; 95% confidence interval (CI): 0.4–1.4]. Thirty-day mortality was 0.90% (3/335) in cases and 1, 2% (4 of 335) in controls (OR: 0.7; 95% CI: 0.1–4.4). CONCLUSIONS Although we have observed a trend towards lower cardiorespiratory morbidity and 30-day mortality after implementing ERS/ESTS guidelines, the benefit of the guidelines remains unclear. Multicentric analysis including a very large number of cases is needed to demonstrate statistically the effectiveness of the guidelines to reduce operative mortality and cardiorespiratory morbidity. Maybe the effect could be easier demonstrated in series with higher operative mortality or morbidity. [ABSTRACT FROM AUTHOR]

OBJECTIVES The aim of the study was to develop a multistranded pragmatic rehabilitation programme for operable lung cancer patients, that looks into feasibility, process indicators, outcome measures, local adaptability, compliance and potential cost benefit. METHODS An outpatient-based complex intervention, rehabilitation for operated lung cancer (ROC) programme, was developed to optimize physical status, prepare for the inpatient journey and support through recovery after surgery. It includes exercise classes, smoking cessation, dietary advice and patient education and was tested in an enriched cohort study within a regional thoracic unit over 18 months. RESULTS A multistranded pragmatic rehabilitation programme pre- and post-surgery is feasible. Fifty-eight patients received the intervention and 305 received standard care. Both groups were matched for age, lung function comorbidity and type of surgery. Patients in the intervention group attended exercise classes twice a week until surgery, which was not delayed. Patients attended four sessions presurgery (range 1–15), resulting in an improvement of 20 m (range −73–195, P = 0.001) in a 6-min walk test and 0.66 l in forced expiratory volume in 1 s (range −1.85 from 1.11, P = 0.009) from baseline to presurgery. Fifty-four percentage of smokers in the intervention group stopped smoking. Sixteen percentage of patients were identified as being at risk of malnourishment and received nutritional intervention. There was a trend in patients in the intervention group towards experiencing fewer postoperative pulmonary complications than those in the non-intervention group (9 vs 16%, respectively, P = 0.21) and fewer readmissions to hospital because of complications (5 vs 14% respectively, P = 0.12). CONCLUSION Chronic obstructive pulmonary disease-type pulmonary rehabilitation before and after lung cancer surgery is viable, and preliminary results suggest improvement in physical measures. A multicentre, randomized controlled trial is warranted to confirm clinical efficacy. ISRCTN registration number ISRCTN00061628. [ABSTRACT FROM AUTHOR]

OBJECTIVES Endothelial progenitor cells (EPCs) are believed to play a role in promoting abnormal vascularization in neoplastic sites. We measured the number of circulating EPCs in treatment-naïve patients with early non-small-cell lung cancer (NSCLC) and healthy controls. The prospective influence of baseline and post-surgery EPC levels on cancer recurrence and survival was investigated. METHODS Circulating EPCs were quantified by FACS analysis in 34 patients with Stage I–II NSCLC and 68 healthy age- and sex-matched controls. Measurement of EPCs was repeated 48 h after thoracic surgery and at the hospital discharge. Cancer recurrence and survival was evaluated after 446 ± 106 days of follow-up (range 182–580 days). RESULTS The base 10 logarithmic [log] number of circulating EPCs was comparable between patients with NSCLC and controls [mean ± standard deviation (SD): 2.3 ± 0.32 vs 2.3 ± 0.26 n/ml, P = 0.776]. In regression analysis, smoking status [standardized coefficient beta (β) = −0.26, 95% confidence interval (CI) for B −0.29/−0.03, P = 0.014] and systolic blood pressure [β = −0.23, 95% CI for B −0.011/−0.001, P = 0.018] were independent predictors of the number of EPCs, irrespective of the NSCLC status. The mean number of EPCs did not change after surgical treatment. However, a post-surgery EPC increase was observed in 44% patients. Patients with a 48 h post-surgery EPC increase had a higher rate of cancer recurrence/death than patients with either stable or decreased post-surgery EPC levels [hazard ratio (HR) 4.4, 95% CI 1.1–17.3; P = 0.032], irrespective of confounders. CONCLUSIONS Circulating EPC levels are comparable between patients with early-stage NSCLC and healthy controls. Overall, surgical cancer resection was not associated with a significant early EPC change. However, an early post-surgery EPC increase is able to predict an increased risk of cancer recurrence and death. [ABSTRACT FROM AUTHOR]

In this article, the author discusses several clinical studies related to resections in lung cancer surgery, lymphatic system spread and systematic nodal dissection. He focuses on the study conducted by T. Maniwa which shows the complication rates associated with patients having SND and L-SND. He mentions that patient-related factors and tumour-related factors are responsible to indicate L-SND, according to Maniwa.

OBJECTIVES In a previous study, we found that a standardized-uptake value (SUV) index obtained from positron emission tomography (PET)/computed tomography (CT) data was significantly correlated with prognosis in patients with pathological Stage I lung adenocarcinoma. However, this value has not been studied in early stage lung cancer patients undergoing limited resection. In this study, we investigated if an SUV index could be used to identify patients with clinical Stage IA lung cancers that were appropriate for limited resection. METHODS This was a retrospective study of prospectively collected data from 183 patients with clinical Stage IA non-small-cell lung cancer undergoing both PET–CT examinations and surgery from May 2004 to December 2010. A corrected SUV was defined as the SUV index, which was calculated from the ratio of the tumour SUVmax to the liver SUVmean. The associations between survival, recurrence and several clinical factors, including the SUV index, were evaluated. RESULTS The following pathological stages were identified: Stage IA (n = 133; 72.7%), Stage IB (n = 31; 16.9%), Stage IIA (n = 11; 6.0%), Stage IIB (n = 1; 0.5%) and Stage IIIA (n = 7; 3.8%). There were 50 upstaged cases (27.3%). The 5-year overall survival, 5-year cancer-specific survival and 5-year freedom from recurrence (FFR) rates after surgery were 83.5, 91.6 and 83.1%, respectively. Twenty-six (14.2%) patients developed recurrences. Multivariate analysis showed that an SUV index was a significant predictive factor for recurrence (P = 0.01). The 5-year FFR rates in patients with an SUV indices <1.0 and ≥1.0 were 100 and 77.1%, respectively (P < 0.01). The 5-year cancer-specific survival rates in patients with an SUV indices <1.0 and ≥1.0 were 100 and 88.7%, respectively (P = 0.04). CONCLUSIONS In clinical Stage IA lung cancer patients, the SUV index was a significant predictive marker for recurrence. Patients with SUV indices <1.0 were less likely to have a recurrence. Thus, clinical Stage IA patients with SUV indices <1.0 should be candidates for limited resection. [ABSTRACT FROM AUTHOR]