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It is desirable to estimate the degree of the decrease in pulmonary function before lung stereotactic body radiation therapy (SBRT) especially for patients with poor pulmonary function. The purpose of this study was to investigate whether decreases in pulmonary function after SBRT may be predicted from radiation dose-volume parameters. A total of 70 patients undergoing SBRT were evaluated for changes in pulmonary function. Of these, 67 had primary lung cancer and 3 had lung metastasis. Twenty-six (37%) patients had chronic obstructive pulmonary disease. Pulmonary function tests (PFTs) were performed shortly before and at 18-24 months after SBRT. Radiation pneumonitis was Grade 2 in 10 patients and Grade 3 in 1. Mean forced vital capacity (FVC) decreased from 2.67 to 2.51 L (P < 0.01) and mean forced expiratory volume in 1 s (FEV1) decreased from 1.80 to 1.72 L (P < 0.01). Planning target volume (PTV) was correlated with changes in FVC. Changes in percent predicted FVC were correlated with %V5Gy (% of lung volume receiving > 5 Gy) and %V40Gy. Although the correlation was not significant, the %V20Gy value was the closest to the percent reduction in predicted FVC; %V20Gy of 10% tended to be associated with ~10% reduction in predicted FVC. Patients with poor pulmonary function did not necessarily show greater decreases in each PFT parameter. Decreases in FVC and FEV1 were within previously reported ranges. PTV was associated with decreases in FVC. The %V20Gy value was closest to the percentage decrease in predicted FVC., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objectives: Segmentectomies such as S1 + 2, S1 + 2+3 and S4 + 5 segmentectomy are used to treat patients with non-small-cell lung cancer (NSCLC) in the left upper lobe. However, the preservable lung volume and changes after such segmentectomies remain unknown. We compared the residual pulmonary function after thoracoscopic segmentectomy or lobectomy in the left upper lobe and examined the efficacy of S1 + 2 segmentectomy regarding postoperative pulmonary function., Methods: Patients with left upper lobe NSCLC who underwent thoracoscopic segmentectomy or lobectomy were included. Spirometry and computed tomography were performed before and 6 months after resection, and the ipsilateral preserved lobe volume was calculated using 3-dimensional computer tomography. The percentage of postoperative/preoperative forced expiratory volume in 1 s and actual/predicted regional forced expiratory volume in 1 s (preservation rate) in the residual lobe were compared., Results: Eighty-eight patients underwent lobectomy and 70 patients underwent segmentectomy (23 S1 + 2, 35 S1 + 2+3 and 12 S4 + 5 segmentectomies). The percentage of postoperative/preoperative forced expiratory volume in 1 s was 97 in S1 + 2, 82 in S1 + 2+3, 86 in S4 + 5 segmentectomy and 73 in left upper lobectomy, indicating that segmentectomy could be a meaningful approach to preserve pulmonary function. The preservation rate was 83% in S1 + 2 and 62% in S1 + 2+3 segmentectomy and was significantly higher in S1 + 2 than in S1 + 2+3 segmentectomy (P < 0.001)., Conclusions: Postoperative pulmonary function and the preservable lung volume of the residual lobe after thoracoscopic S1 + 2 segmentectomy were well-preserved among other segmentectomies and lobectomy. Thoracoscopic S1 + 2 segmentectomy is a good alternative for preserving postoperative function., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Context: Multiple endocrine neoplasia type 2B (MEN2B) is a rare cancer predisposition syndrome resulting from an autosomal-dominant germline mutation of the RET proto-oncogene. No prior studies have investigated pulmonary function in patients with MEN2B., Objective: This study characterized the pulmonary function of patients with MEN2B., Design: This is a retrospective analysis of pulmonary function tests (PFTs) and chest imaging of patients enrolled in the Natural History Study of Children and Adults with MEN2A or MEN2B at the National Institutes of Health., Results: Thirty-six patients with MEN2B (18 males, 18 females) were selected based on the availability of PFTs; 27 patients underwent at least 2 PFTs and imaging studies. Diffusion abnormalities were observed in 94% (33/35) of the patients, with 63% (22/35) having moderate to severe defects. A declining trend in diffusion capacity was seen over time, with an estimated slope of -2.9% per year (P = 0.0001). Restrictive and obstructive abnormalities were observed in 57% (20/35) and 39% (14/36), respectively. Computed tomography imaging revealed pulmonary thin-walled cavities (lung cysts) in 28% (9/32) of patients and metastatic lung disease in 34% (11/32) of patients; patients with metastatic lung lesions also tended to have thin-walled cavities (P = 0.035)., Conclusions: This study characterized pulmonary function within a MEN2B cohort. Diffusion, restrictive, and obstructive abnormalities were evident, and lung cysts were present in 28% of patients. Further research is required to determine the mechanism of the atypical pulmonary features observed in this cohort., (Published by Oxford University Press on behalf of the Endocrine Society 2020.)

Objectives: The objective of this retrospective multi-institutional study was to evaluate the postoperative outcomes of video-assisted thoracoscopic surgery (VATS)-lobectomy (VATS-L) for non-small-cell lung cancer (NSCLC) in patients with impaired lung function. The second end point was to illustrate the effective role of forced expiratory volume in 1 s (FEV1%) and the diffusing capacity of the lung for carbon monoxide (DLCO%) in predicting complications in this population., Methods: Data from patients who underwent VATS-L at participating centres were analysed and divided into 2 groups: group A comprised patients with FEV1% and/or DLCO% >60% and group B included patients with impaired lung function defined as FEV1% and/or DLCO% ≤60%. To define clinical predictors of death and complications, we performed univariate and multivariable regression analyses., Results: A total of 5562 patients underwent VATS-L, 809 (14.5%) of whom had impaired lung function. The postoperative mortality rate did not differ between the 2 groups (2.3% vs 3.2%; P = 0.77). The percentage of patients who had any complication (21.4% vs 34.2%; P ≤ 0.001), the complication rate (28% vs 49.8%; P ≤ 0.001) and the length of hospital stay (P ≤ 0.001) were higher for patients with limited pulmonary function. Impaired lung function was a strong predictor of overall and pulmonary complications at multivariable analysis., Conclusions: VATS-L for NSCLC can be performed in patients with impaired lung function without increased risk of postoperative death and with an acceptable incidence of overall and respiratory complications. Our analysis suggested that FEV1% and DLCO% play a substantial role in estimating the risk of complications after VATS-L, but their role was less reliable for estimating the mortality., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The American College of Chest Physicians guidelines recommend low-technology exercise tests in the functional evaluation of patients with lung cancer considered for resectional surgery. However, the 6-min walk test (6MWT) is not included, because the data on its clinical value are inconsistent. Our goal was to evaluate the 6MWT in assessing the risk of cardiopulmonary complications in candidates for lung resection., Methods: We performed a retrospective assessment of clinical data and pulmonary function test results in 947 patients, mean age 65.3 (standard deviation 9.5) years, who underwent a single lobectomy for lung cancer. In 555 patients with predicted postoperative values ≤60%, the 6MWT was performed. The 6-min walking distance (6MWD) and the distance-saturation product (DSP), which is the product of the 6MWD in metres, and the lowest oxygen saturation registered during the test were assessed., Results: A total of 363 patients with predicted postoperative values <60% and a 6MWT distance (6MWD) ≥400 m or DSP ≥ 350 m% had a lower rate of cardiopulmonary complications than patients with shorter 6MWD or lower DSP values [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.35-0.81] and 0.47 (95% CI 0.30-0.73), respectively. This result was also true for patients with predicted postoperative values <40%, ORs 0.33 (95% CI 0.14-0.79) and 0.25 (95% CI 0.10-0.61), respectively., Conclusions: The 6MWT is useful in the assessment of operative risk in patients undergoing a single lobectomy for lung cancer. It helps to stratify the operative risk, which is lower in patients with 6MWD ≥400 m or DSP ≥350 m% than in patients with a shorter 6MWD or lower DSP values., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Pathological tumour, node and metastasis (TNM) stage remains the most significant prognostic factor of non-small-cell lung cancer (NSCLC). Meanwhile, age, gender, pulmonary function tests, the extent of surgical resection and the presence of concomitant diseases are commonly used to complete the prognostic profile of the patient with early stage of NSCLC. The aim of this study is to assess how the result of a 6-min walk test (6MWT) further assists in predicting the prognosis of NSCLC surgical candidates., Methods: Six hundred and twenty-four patients who underwent surgical treatment for NSCLC between April 2009 and October 2011 were enrolled in this study. All patients were accepted for surgery on the basis of a standard evaluation protocol. Additionally, patients completed the 6MWT on the day before the surgery, and threshold values of the test were assessed based on both the Akaike information criterion and the coefficient of determination R2. Cox proportional hazards regression analysis was used to analyse the effect of important prognostic factors on the overall survival., Results: Three hundred and ninety men and 234 women with a mean age of 64 years underwent radical surgical treatment for primary lung cancer. Five hundred and twenty-five lobectomies (84%), 77 pneumonectomies (12%) and 24 (4%) lesser resections were performed. Three hundred and thirty-one patients (53%) were treated for stage I NSCLC, 191 patients (31%) for stage II and 102 patients (16%) for stages IIIA-IV. A distance of 525 m in the 6MWT [hazard ratio (HR) = 0.57, 95% confidence interval (CI) 0.41-0.78, P < 0.001] was the threshold value differentiating the patients' prognoses (P < 0.001). Using the Cox proportional hazards regression analysis, pathological TNM stage (IIA: HR = 1.87, 95% CI 1.95-2.92, P = 0.006; IIB: HR = 2.03, 95% CI 1.23-3.37, P = 0.006; IIIA-IV: HR = 2.37, 95% CI 1.49-3.75, P < 0.001), male gender (HR = 1.88, 95% CI 1.26-2.79, P = 0.001), pneumonectomy (HR = 1.78, 95% CI 1.17-2.70, P < 0.001) and the results of the 6MWT (HR = 0.50, 95% CI 0.36-0.70, P < 0.001) were considered as independent predictive factors of overall survival., Conclusions: The result of a 6MWT is an independent and convenient prognostic factor of surgically treated non-small-cell lung cancer., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Extended sleeve lobectomy (ESL), an atypical bronchoplasty with resection of more than 1 lobe, might be technically demanding but has certain theoretical advantages, including the avoidance of pneumonectomy. However, clinical outcomes after ESL are not well known., Methods: Between March 1995 and December 2015, 540 patients with centrally located non-small-cell lung cancer underwent sleeve resection. Among them, 63 patients underwent an ESL procedure. We retrospectively analysed those patients in terms of hospital mortality, postoperative complications and local recurrence and compared clinical outcomes with patients who underwent simple sleeve lobectomy in the same period., Results: The 63 patients were classified into 4 groups: anastomosis between the right main and lower bronchi (n = 14), anastomosis between the right main and upper bronchi (n = 37), anastomosis between the left main and basal segmental bronchi (n = 4) and anastomosis between the left main and upper divisional bronchi (n = 8). No operative deaths occurred within 30 days, but there were 2 in-hospital deaths from postoperative acute lung injury. Ten (16%) patients had anastomosis-related complications including 3 strictures, 5 bronchopleural fistulas and 2 pulmonary vein thromboses. There were no significant differences in in-hospital mortality (3% vs 3%, P = 0.67), anastomosis-related complications (16% vs 9%, P = 0.07) and loco-regional recurrence rate (8% vs 10%, P = 0.63) between ESL and simple sleeve lobectomy., Conclusions: According to our findings, ESL is a safe and feasible procedure that does not compromise oncological principles. It can be considered an appropriate alternative to pneumonectomy and should be considered in patients with centrally located tumours.

Objectives: Accurate risk assessments are particularly important for elderly patients being considered for lobectomy. Considering the positive effects of the thoracoscopic approach on postoperative outcomes, we sought to review the reliability of the established risk factors for elderly patients undergoing thoracoscopic lobectomy., Methods: From January 2009 to March 2016, 441 patients in our institution underwent thoracoscopic lobectomy for early-stage lung cancer. Clinical outcomes were compared between elderly (>70 years, n = 176) and younger patients (n = 265)., Results: There was no significant difference in postoperative mortality and morbidity between elderly and younger patients. In the regression analyses restricted to elderly patients, American Society of Anesthesiologists physical status (ASA-PS) was the single strong predictor of postoperative morbidity. The odds of pulmonary and cardiopulmonary complications increased nearly 6- and 3-fold, respectively, in those with ASA-PS Grade 3 compared with patients with ASA-PS Grade <3. Additionally, male gender was found to have a possible causal effect of pulmonary complication in elderly patients. After confounder adjustment using propensity score matching, the generalized linear mixed model revealed more than an 8-fold increase in the odds of pulmonary complications in elderly men compared with elderly women. To check the robustness of the above-mentioned finding, inverse probability of treatment weighting was used as an alternative analysis indicating a weaker but still substantively significant effect of male gender, with an odds ratio >3., Conclusions: Our results suggest that ASA-PS is a strong predictor of morbidity among elderly patients considered for thoracoscopic lobectomy. Compared with elderly women, elderly men are particularly prone to postoperative pulmonary complications.

Objectives: To clarify differences in postoperative changes in systemic and regional pulmonary functions between segmentectomy and lobectomy in patients with lung cancer, we compared the 2 procedures using lung perfusion scintigraphy with a fusion image of single-photon emission computed tomography and computed tomography., Methods: This study is a retrospective matched cohort study of consecutively acquired data. Pulmonary function tests and perfusion single-photon emission computed tomography/computed tomography were conducted before surgery and 6 months after surgery to measure changes in forced expiratory volume in 1 s of a whole lung, contralateral lung and a lobe. After exactly matching the site of the resected lobe between the 2 procedures, propensity scores for age, sex, smoking status and pulmonary function were used to match them., Results: Of the 184 patients treated with segmentectomy and the 208 patients treated with lobectomy between 2013 and 2016, 103 patients were selected from each group after the matching. Whole lung function was significantly more preserved after segmentectomy than after lobectomy (P < 0.001). Segmentectomy preserved the function of the operated lobe with 48 ± 21% of the preoperative function. The function of the ipsilateral non-operated lobe increased after segmentectomy (P = 0.003) but not after lobectomy (P = 0.97). Contralateral lung function increased after both procedures (P < 0.001)., Conclusions: Our data suggest that segmentectomy preserved whole lung function better than lobectomy, because it not only preserved the lobe but also increased the function of the ipsilateral non-operated lobe. Lobectomy did not result in an increase of ipsilateral non-operated lobe function. Contralateral lung function increased after both procedures. The postoperative increase in regional functions could be the result of compensatory lung growth., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Radiologically small-sized adenocarcinomas are special entities of lung cancer, as their radiological and pathological invasiveness determines the surgical procedures applied; however, the clinicopathological features of small-sized lung adenocarcinoma adjoining cystic airspaces (Ca-ADJ) have yet to be fully clarified. The aim of this study was to elucidate the clinicopathological characteristics, including the programmed death ligand 1 (PD-L1) expression, in patients with Ca-ADJ ≤3.0 cm., Methods: A total of 283 patients with resected adenocarcinoma, whose radiological tumour size was ≤3.0 cm without lymph node or distant metastases on preoperative high-resolution computed tomography, were analysed for their clinicopathological and radiological features. Furthermore, the PD-L1 expression was evaluated by immunohistochemistry using an anti-human PD-L1 rabbit monoclonal antibody (clone SP142)., Results: Among the 283 patients, 31 (11.0%) patients were reported to have Ca-ADJ. The Fisher's exact test demonstrated that Ca-ADJ was significantly associated with male gender (P < 0.001), a history of smoking (P < 0.001), a high consolidation/tumour ratio (P = 0.026), advanced pathological stage (P < 0.001), the presence of pleural (P < 0.001) and vessel invasion (P < 0.001), histological invasive subtypes (P < 0.001) and wild-type epidermal growth factor receptor (P = 0.001). The patients with Ca-ADJ had a significantly higher maximum standardized uptake value than those without Ca-ADJ (8.4 vs 4.1, P < 0.001). Furthermore, Ca-ADJ was significantly associated with the PD-L1 expression (P < 0.001). Log-rank test showed that patients with Ca-ADJ had a significantly shorter disease-free survival than those without Ca-ADJ (P = 0.001)., Conclusions: This study showed that patients with radiologically small-sized Ca-ADJ might exhibit radiologically and pathologically invasive features., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Little is known about the relationship between preoperative physical fitness and postoperative pneumonia after lung resection. We examined the association between preoperative 6-min walk distance (6MWD) and postoperative pneumonia., Methods: A retrospective study was conducted on patients with malignant lung tumours who were scheduled to undergo lung resection at Nagoya University Hospital from January 2014 to December 2015. Preoperative pulmonary function tests and the 6-min walk test were assessed. A logistic regression model and receiver operating characteristic curves were used to analyse clinical variables and compare the performance on 6MWD, forced expiratory volume in 1 s and diffusion capacity of the lung for carbon monoxide., Results: The data from a total of 321 patients including 283 with primary lung cancer and 38 with metastatic lung tumours were analysed. Pneumonia developed in 13 patients and caused longer hospital stays after surgery. The preoperative 6MWD of patients with pneumonia was significantly lower than that without pneumonia (425 vs 500 m, P = 0.002). In receiver operating characteristic analysis, 6MWD ≤ 450 m was a threshold for predicting postoperative pneumonia with 69.2% sensitivity and 71.1% specificity. A 6MWD ≤ 450 m, forced expiratory volume in 1 s <80% of the predicted value, diffusion capacity of the lung for carbon monoxide <80% of the predicted value, serum albumin <3.5 g/dl and blood loss during surgery ≥200 g were significantly associated with postoperative pneumonia in a logistic model., Conclusions: Preoperative 6MWD was significantly associated with postoperative pneumonia in patients who underwent lung resection for malignancies., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The goal of this study was to assess the impact of a preoperative 1-week, systematic, high-intensity inpatient exercise regimen on patients with lung cancer who had risk factors for postoperative pulmonary complications (PPCs)., Methods: We conducted a randomized controlled trial with 101 subjects of a preoperative, 7-day systematic, integrated, high-intensity pulmonary exercise regimen. The control group received standard preoperative care. We analysed the occurrence of PPCs in both groups as the primary outcome; other outcomes included changes in blood gas, quality of life, peak expiratory flow rate, the 6-min walk distance and others., Results: The 6-min walk distance showed an increase of 22.9 ± 25.9 m in the intervention group compared with 4.2 ± 9.2 m in the control group, giving a between-group difference of 18.7 m (95% confidence interval: 8.8-28.6; P < 0.001); the peak expiratory flow increased by 25.2 ± 24.6 l/min, compared with 4.2 ± 7.7 l/min (between-group difference: 21.0 m, 95% confidence interval: 7.2-34.8; P = 0.003). The intervention group had a shorter average total (15.6 ± 3.6 vs 17.7 ± 5.3 days, P = 0.023) and postoperative length of stay (6.1 ± 3.0 vs 8.7 ± 4.6 days, P = 0.001) than the control group; the incidence of PPCs (9.8%, 5/51 vs 28.0%, 14/50, P = 0.019) was significantly lower. A multivariable analysis of the risk of PPCs identified short-term rehabilitation intervention to be an independent risk factor (odds ratio = 0.156, 95% confidence interval: 0.037-0.649, P = 0.011)., Conclusions: The study results suggested that a systematic, high-intensity pulmonary exercise programme was a practical strategy when performed preoperatively in patients with lung cancer with risk factors for PPCs., Clinical Trial Registration: ChiCTR-IOR-16008109., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The aim of this study was to investigate gender differences in the relationship between preoperative body mass index (BMI), postoperative body weight change and prognosis in patients with non-small cell lung cancer (NSCLC)., Methods: Two hundred and sixty-three patients with NSCLC were enrolled in this study. Preoperative BMI was categorized based on WHO definition as follows: underweight (BMI <18.5): 21 patients (8.0%), normal (18.5 ≦ BMI <25): 179 patients (68%), overweight and obese (BMI ≧25): 63 patients (24%). Several factors such as age, sex, cancer stage, body weight change and BMI were recorded and correlated to the postoperative overall survival (OS)., Results: For male patients, those in the low-BMI group had the worst prognosis (P < 0.05) whereas female patients with low BMI did not. Male patients with low BMI had statistically significant poorer prognosis compared to corresponding female patients (P < 0.05). Male patients with more than 5% body weight loss within 1 year after operation when compared to preoperative body weight had poorer prognosis than those with less than 5% body weight loss (P < 0.001). Furthermore, these male patients had statistically significant worse prognosis than the corresponding female patients (P < 0.05). In multivariable analysis, gender, more than 5% of body weight loss compared to preoperative body weight, and pathological stage were independent prognostic factors in NSCLC., Conclusions: This study illustrates significant gender differences in the relationship between prognosis and BMI or body weight change in patients with postoperative NSCLC., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The goal of this study was to describe non-supervised daily physical activity in patients during the period immediately following anatomical lung resection., Methods: The study was an observational study on 50 consecutive patients (33 men) admitted for anatomical lung resection over a 4-month period. All cases were approached using a minimally invasive technique. Patients were instructed by nursing and physiotherapy staff and asked to wear a portable pedometer (Omron HJ-720 T-E2) from admission until hospital discharge, excluding the day of the operation and the first hours in the recovery room. The variables collected included sex, age, body mass index, type of lung resection, cardiopulmonary postoperative complications, percentage forced expiratory volume in 1 s, percentage single-breath carbon monoxide diffusing capacity, predicted postoperative forced expiratory volume in 1 s calculated according to functional segments removed at surgery, predicted postoperative single-breath carbon monoxide diffusing capacity calculated according to functional segments removed at surgery, total steps, aerobic steps and daily total strolled distance in metres. Comparison of activity was analysed using the paired t-test for individual data evolution and the unpaired t-test for patients showing complications or not. Body mass index and exercise capacity were analysed using the Spearman correlation analysis., Results: A total of 34 patients underwent lobectomy or bilobectomy. All patients could walk on the first postoperative day. The average walked distance on the first and fourth postoperative days was 6100 m and 7400 m, respectively. Compared with the preoperative day, patients walked significantly fewer total steps on Day 1 and Day 2 (Day 1, P = 0.0001; Day 2, P = 0.049). The rate of aerobic to total daily steps was comparable after the second postoperative day. Patients having any postoperative cardiopulmonary complication showed a significantly inferior walking capacity (P < 0.001), both preoperatively and postoperatively, than their peers without complications., Conclusions: After anatomical lung resection, patients could perform a relevant amount of physical activity. These data could be useful for designing physical recovery programmes to be implemented postoperatively., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Poor aerobic fitness is a potential modifiable risk factor for long-term survival and quality of life in patients with lung cancer. This randomized trial evaluates the impact of adding rehabilitation (Rehab) with high-intensity interval training (HIIT) before lung cancer surgery to enhance cardiorespiratory fitness and improve long-term postoperative outcome., Methods: Patients with operable lung cancer were randomly assigned to usual care (UC, n  = 77) or to intervention group (Rehab, n  = 74) that entailed HIIT that was implemented only preoperatively. Cardiopulmonary exercise testing (CPET) and pulmonary functional tests (PFTs) including forced vital capacity (FVC), forced expiratory volume (FEV 1 ) and carbon monoxide transfer factor (KCO) were performed before and 1 year after surgery., Results: During the preoperative waiting time (median 25 days), Rehab patients participated to a median of 8 HIIT sessions (interquartile [IQ] 25-75%, 7-10). At 1 year follow-up, 91% UC patients and 93% Rehab patients were still alive ( P  = 0.506). Pulmonary functional changes were non-significant and comparable in both groups (FEV 1 mean -7.5%, 95% CI, -3.6 to -12.9 and in KCO mean 5.8% 95% CI 0.8-11.8) Compared with preoperative CPET results, both groups demonstrated similar reduction in peak oxygen uptake (mean -12.2% 95% CI -4.8 to -18.2) and in peak work rate (mean -11.1% 95% CI -4.2 to -17.4)., Conclusions: Short-term preoperative rehabilitation with HIIT does not improve pulmonary function and aerobic capacity measured at 1 year after lung cancer resection., Trial Registry: ClinicalTrials.gov; No. NCT01258478; www.clinicaltrials.gov ., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Stair climbing is considered the first step for functional evaluation of patients requiring anatomical lung resection who have low-predicted postoperative forced expiratory volume in the first second of expiration (FEV1) or diffusing capacity of the lungs for carbon monoxide (DLCO) values. Nevertheless, stair climbing is not performed in many centres because of structural issues or patient safety concerns. We hypothesized that comparable exercise can be obtained on an ergometric bicycle in a safer environment where any adverse event can be treated. We tried to correlate the amount of exercise performed by stair climbing and by using an ergometric bicycle in a series of patients with non-small-cell lung cancer (NSCLC) evaluated prospectively., Methods: Thirty-four consecutive patients with NSCLC who were scheduled for lung resection were prospectively enrolled to complete two low-technology exercise tests: The first one was stair climbing, and the second was a ramp test on an ergometric bicycle. For most patients (85%), both tests were performed on the same day, separated with at least 2 h of rest. The amount of exercise on the stair-climbing test (in watts: Watt 1) was calculated per patient weight, height reached on stairs and time spent. The bicycle test was performed on a Lode Corival ergometer with automatic calculation of the total work load (Watt 2). No estimation of VO 2 max was attempted. The bicycle test was conducted in an ad-hoc room fully equipped with oxygen, cardiac and blood pressure and PO 2 monitoring and resuscitation equipment. The Bland-Altman plot was used to evaluate the agreement between both tests. A linear regression model was constructed in which the power developed on the stairs was the dependent variable and the watts generated on the bicycle and patient age were the covariates., Results: All patients (median age: 65.5 years; range: 41-84), completed both tests without any adverse events. The number of watts was greater on the stairs tests (mean 227 vs 64 on the ergometric bicycle). The Bland-Altman plot showed agreement between tests in most cases (Pitman-Morgan test: 0.96). Work load was more dependent on age in the stairs tests (Pearson coefficient -0.72 on stairs; -0.52 on ergometric bicycle). The logistic model was highly predictive when the workload on the bicycle was corrected by the patient's age ( R 2  =   0.80; Wald test <0.001)., Conclusions: This simple test on an ergometric bicycle shows a high correlation with the widely accepted stair-climbing test when workload results are corrected using the patient's age. It could replace the stair-climbing test and has the advantage of being conducted in an environment that is safer for the patient. Nevertheless, its reliability for risk prediction needs to be adequately evaluated., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Many patients with lung cancer have been cured by surgical intervention. However, the long-term effects of lung resection on pulmonary function are unclear. Therefore, we investigated long-term pulmonary function after surgery., Methods: We retrospectively reviewed the medical records of patients who underwent surgery for lung cancer between 2001 and 2009. A total of 445 patients who had survived more than 5 years since the surgery were included. The patients were divided into lobectomy, segmentectomy and partial resection groups. The time-dependent changes in pulmonary function were investigated., Results: The percentages of the vital capacity and forced expiratory volume in 1 second (FEV 1 ) at postoperative year (POY) 1 vs preoperative values were 92.9 ± 11.1% and 91.3 ± 13.0% in the lobectomy group, 95.9 ± 9.0% and 93.8 ± 10.5% in the segmentectomy group and 97.8 ± 7.3% and 98.1 ± 8.3% in the partial resection group, respectively. The values in the lobectomy group were significantly lower than those in the segmentectomy and partial resection groups. The percentages of vital capacity and FEV 1 at POY 5 vs preoperative values were 90.0 ± 11.5% and 86.2 ± 11.9% in the lobectomy group, 93.4 ± 9.8% and 91.1 ± 9.8% in the segmentectomy group and 94.3 ± 8.8% and 94.0 ± 8.0% in the partial resection group, respectively. The decrease in the rates from POY 1 to POY 5 were not significantly different among the procedures., Conclusions: Pulmonary function declined with pulmonary resection. After the patient recovered from the operation, pulmonary function decreased with time regardless of the surgical procedure., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: To assess whether quality of life (QOL) was associated with cardiopulmonary complications following pulmonary lobectomy for lung cancer., Methods: Retrospective analysis of 200 consecutive patients who had pulmonary lobectomy for lung cancer (September 2014-October 2015). QOL was assessed by the self-administration of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire within 2 weeks before the operation. The individual QOL scales were tested for a possible association with cardiopulmonary complications along with other objective baseline and surgical parameters by univariable and multivariable analyses., Results: Forty-three patients (21.5%) developed postoperative cardiopulmonary complications; 4 of them died within 30 days (2%). Univariable analysis showed that, compared to patients without complications, those with complications reported a lower global health status (GHS) [59.1; standard deviation (SD) 27.2 vs 69.6; SD 20.6, P  =   0.02], were older (71.2; SD 8.4 vs 67.7; SD 9.4, P  =   0.03), had lower values of forced expiratory volume in one second (FEV1) (83.9; SD 27.2 vs 91.4; SD 20.9), P  =   0.06) and carbon monoxide lung diffusion capacity (DLCO) (67.9; SD 20.9 vs 74.2; SD 17.6, P  =   0.02) and higher performance score (0.76; SD 0.63 vs 0.53; SD 0.64, P  =   0.02). Stepwise logistic regression analysis showed that factors independently associated with cardiopulmonary complications were age [odds ratio (OR) 1.04, 95% CI 1.0-1.09, P  =   0.02] and patient-reported GHS [OR 0.98, 95% confidence interval (CI) 0.96-0.99, P  =   0.006], whereas other objective parameters (i.e. FEV1, DLCO) were not. The best cut-off value for GHS to discriminate patients with complications after surgery was 50 (c-index 0.65, 95% CI 0.58-0.72)., Conclusions: A poor GHS perceived by the patient was associated with postoperative cardiopulmonary morbidity. Patient perceptions and values should be included in the risk stratification process to tailor cancer treatment., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: Exclusion of patients with a history of other cancer treatment except in situ situation has been considered to be inevitable for clinical trials investigating survival outcome. However, there have been few reports confirming these influences on surgical outcome of lung cancer patients ever., Methods: Multi-institutional, individual data from patients with non–small cell lung cancer resected between 2000 and 2013 were collected. The patients were divided into two groups: those with a history of gastrointestinal tract cancer (GI group) and those without any history (non-GI group). We compared the outcomes with well-matched groups using propensity scoring to minimize bias related to the nonrandomness. The influence of gastrointestinal tract cancer stage, disease-free interval, and treatment method for gastrointestinal tract cancer on the surgical outcome of non–small cell lung cancer was examined., Results: We analyzed 196 patients in the GI group and 3732 in the non-GI group. In unmatched cohort, multivariate analyses showed that a history of gastrointestinal tract cancer did not affect overall survival or recurrence-free survival. Independent predictors of poor prognosis included older age, male sex, high carcinoembryonic antigen levels and advanced clinical stage of non–small cell lung cancer. The two groups in the matched cohort demonstrated equivalent overall survival and recurrence-free survival, even in patients with clinical stage I. Gastrointestinal tract cancer stage, disease-free interval and treatment method for gastrointestinal tract cancer were not associated with outcomes., Conclusions: History of early gastrointestinal tract cancer completely resected is not always necessary for exclusion criteria in clinical trial of lung cancer.

Objectives: Pulmonary assessment before major lung resections is used to determine patient's operability. In marginal cases, extensive pulmonary assessment is additionally important under the fear of a more radical parenchymal removal. This study investigates the outcome of wider lung parenchymal resections in patients with low lung functional status undergoing video-assisted thoracic surgery (VATS) major lung resection., Methods: The medical records of patients who underwent VATS major lung resection for cancer, over a period of 5 years (August 2009-August 2014), were retrospectively reviewed. Patients with postoperative forced expiratory volume in first second (ppoFEV1) or postoperative diffusional capacity for carbon monoxide (ppoDLCO) <40% who underwent wider lung resection than preoperatively planned (Group A) were compared with patients with ppoFEV1 or ppoDLCO <40% who underwent the planned operation (Group B) and patients with ppoFEV1 and ppoDLCO >40% who underwent wider resection than preoperatively planned (Group C). Data analysed included demographics, past medical history, the surgery planned and performed, the reason for higher parenchymal resection, the clinical and pathological stage, the length of stay (LOS), the morbidity, the 30-day mortality and the survival., Results: Overall, 73 patients were analysed (15 patients in Group A, 50 patients in Group B and 8 patients in Group C). The mean age was 68.5 years and 31.5% were males. The wider lung resection regarded 7 patients who underwent bilobectomy instead of lobectomy and 16 patients who underwent pneumonectomy instead of lobectomy. The main reason for higher resection was the wider invasion of the mass (21 patients). The age, gender and body mass index between three groups were similar, whereas ppoFEV1 and ppoDLCO were different (P < 0.001 and P < 0.001 respectively). Conversions, pulmonary morbidity and the 30-day mortality between groups were similar (P = 0.67, P = 0.88 and P = 0.33, respectively). LOS between groups was not different (P = 0.46). Survival rate between groups was also similar (log-rank, P = 0.79)., Conclusions: Wider lung parenchymal resection than preoperatively anticipated may be performed, even in patients with low lung functional status, without increased adverse outcome when compared with patients with good lung function. This finding indicates that the preoperative risk stratification based on lung function tests is questionable., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Dividing the intersegmental planes with a stapler during pulmonary segmentectomy leads to volume loss in the remnant segment. The aim of this study was to assess the influence of segment division methods on preserved lung volume and pulmonary function after segmentectomy., Methods: Using image analysis software on computed tomography (CT) images of 41 patients, the ratio of remnant segment and ipsilateral lung volume to their preoperative values (R-seg and R-ips) was calculated. The ratio of postoperative actual forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) per those predicted values based on three-dimensional volumetry (R-FEV1 and R-FVC) was also calculated. Differences in actual/predicted ratios of lung volume and pulmonary function for each of the division methods were analysed. We also investigated the correlations of the actual/predicted ratio of remnant lung volume with that of postoperative pulmonary function., Results: The intersegmental planes were divided by either electrocautery or with a stapler in 22 patients and with a stapler alone in 19 patients. Mean values of R-seg and R-ips were 82.7 (37.9-140.2) and 104.9 (77.5-129.2)%, respectively. The mean values of R-FEV1 and R-FVC were 103.9 (83.7-135.1) and 103.4 (82.2-125.1)%, respectively. There were no correlations between the actual/predicted ratio of remnant lung volume and pulmonary function based on the division method. Both R-FEV1 and R-FVC were correlated not with R-seg, but with R-ips., Conclusions: Stapling does not lead to less preserved volume or function than electrocautery in the division of the intersegmental planes., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Patients with poor lung function usually undergo cardiopulmonary exercise testing (CPET) and those with a predicted postoperative maximal oxygen consumption (VO 2 max) of >10 ml/kg/min undergo lung resection surgery and still some complications are observed. We aimed to determine other parameters beyond VO 2 able to predict postoperative complications in patients undergoing lung resection surgery., Methods: This is an observational study with longitudinal follow-up. Patients with forced expiratory volume in 1 second (FEV 1 ) or diffusing capacity for carbon monoxide of <40% underwent CPET and those with VO 2 max of >10 ml/kg/min were considered fit for surgery. Patients were followed up prospectively for 12 months and postoperative complications and survival were recorded. Physiological parameters obtained during CPET and pulmonary function tests were analysed., Results: Eighty-three chronic obstructive pulmonary disease (COPD) patients were evaluated for surgery between 2010 and 2015. Twenty-four patients were considered unfit for surgery and received an alternative therapy. Fifty-five patients had a VO 2 max of >10 ml/kg/min and underwent lung surgery. Among them, 4% died and 41% developed complications postoperatively. Baseline minute ventilation to carbon dioxide output (VE/VCO 2 ) slope was significantly higher among those who developed postoperative complications or died (P = 0.047). Furthermore, VE/VCO 2 slope of >35 (at maximal exercise) was the single parameter most strongly associated with the probability of mortality and postoperative complications (hazard ratio 5.14) with a survival probability of 40% after 1 year of follow-up. In a multivariable model, VO 2 , VE/VCO 2 slope of >35 and work load were independently associated with the probability of having an event., Conclusions: VO 2 is not the unique parameter to consider when CPET is performed to evaluate the postoperative risk of lung cancer surgery in COPD patients. The signs of ventilatory inefficiency such as VE/VCO 2 slope predict complications better than VO 2 does., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Lung cancer is the leading cause of cancer-related death worldwide. For early stages of the disease, lung resection surgery remains the best treatment with curative intent, but significant morbidity is associated, especially among patients with poor pulmonary function and cardiorespiratory fitness. In those cases, the implementation of a preoperative exercise-based intervention could optimize patient's functional status before surgery and improve postoperative outcomes and enhance recovery. The aim of this systematic review is to provide the current body of knowledge regarding the effectiveness of a preoperative exercise-based intervention on postoperative and functional outcomes in patients with lung cancer submitted to lung resection surgery. A systematic review of the literature using CINAHL, EMBASE, MEDLINE, Pubmed, PEDro and SCOPUS was undertaken in September 2015 yielding a total of 1656 references. Two independent reviewers performed the assessment of the potentially eligible records against the inclusion criteria and finally, 21 articles were included in the review. Articles were included if they examined the effects of an exercise-based intervention on at least one of the selected outcomes: pulmonary function, (functional) exercise capacity, health-related quality of life (HRQoL) and postoperative outcomes (length of stay and postoperative complications). Fourteen studies were further selected for a meta-analysis to quantify the mean effect of the intervention and generate 95% confidence intervals (CIs) using the Cochrane Review Manager 5.0.25. For two of the outcomes included (exercise capacity and HRQoL), studies showed large heterogeneity and thus, a meta-analysis was considered inappropriate. Pulmonary function (forced vital capacity and forced expiratory volume in 1 s) was significantly enhanced after the intervention [standardized mean difference (SMD) = 0.38; 95% CI 0.14, 0.63 and SMD = 0.27, 95% CI 0.11, 0.42, respectively]. In comparison with the patients in the control groups, patients in the experimental groups spent less days in the hospital (mean difference = -4.83, 95% CI -5.9, -3.76) and had a significantly reduced risk for developing postoperative complications (risk ratios = 0.45; 95% CI 0.28, 0.74). In conclusion, preoperative exercise-based training improves pulmonary function before surgery and reduces in-hospital length of stay and postoperative complications after lung resection surgery for lung cancer., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Prolonged air leak (PAL) after major lung resections is a common postoperative complication that leads to extended length of hospital stay (LOS) and increased hospital costs. Dissection of the lung tissue through the fissure may increase the incidence of PAL especially in the patients with incomplete fissures. The objective of this study was to evaluate the impact of the fissureless fissure-last technique in VATS lobectomy on immediate outcome, especially relating to air leak and LOS., Methods: This is an observational analysis on prospectively collected data of a single thoracic surgery unit. A total of 54 consecutive patients underwent VATS lobectomy and mediastinal lymphadenectomy-in 24 patients conventional VATS lobectomy (Group 1), in 30 patients fissureless VATS lobectomy (Group 2) was performed. The two groups were compared according to preoperative, operative and postoperative parameters., Results: No differences were found when comparing patient characteristics, operation time (M1 = 185 min; M2 = 176 min; P = 0.52) and number of staplers used (M1 = 6.2; M2 = 7.7; P = 0.088). The presence of air leak (P = 0.004; RR = 3.5), PAL (P = 0.003; RR = 10), in days with chest tube (M1 = 7.2; M2 = 4.2; P = 0.028) and LOS (M1 = 12.7; M2 = 8.9; P = 0.020) was significantly more frequent in patients that underwent conventional VATS lobectomy. Focusing on the air leak, significance was present in male gender (P = 0.034; RR = 2.41), higher ASA (M1 = 3.04; M2 = 2.67; P = 0.012), postoperative complications other than air leak (P = 0.001; RR = 5.78) and age between groups with and without air leak (M1 = 63.9; M2 = 74.1; P < 0.001)., Conclusions: Fissureless fissure-last VATS lobectomy is a feasible and equivalent to conventional VATS lobectomy in terms of operation time, stapler use and complications. Fissureless fissure-last VATS lobectomy, however, appears to be a superior technique to conventional VATS lobectomy in terms of preventing PAL and reducing the LOS., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The aim was to investigate whether 2 weeks of inspiratory muscle training (IMT) could preserve respiratory muscle strength in high-risk patients referred for pulmonary resection on the suspicion of or confirmed lung cancer. Secondarily, we investigated the effect of the intervention on the incidence of postoperative pulmonary complications., Methods: The study was a single-centre, parallel-group, randomized trial with assessor blinding and intention-to-treat analysis. The intervention group (IG, n = 34) underwent 2 weeks of postoperative IMT twice daily with 2 × 30 breaths on a target intensity of 30% of maximal inspiratory pressure, in addition to standard postoperative physiotherapy. Standard physiotherapy in the control group (CG, n = 34) consisted of breathing exercises, coughing techniques and early mobilization. We measured respiratory muscle strength (maximal inspiratory/expiratory pressure, MIP/MEP), functional performance (6-min walk test), spirometry and peripheral oxygen saturation (SpO2), assessed the day before surgery and again 3-5 days and 2 weeks postoperatively. Postoperative pulmonary complications were evaluated 2 weeks after surgery., Results: The mean age was 70 ± 8 years and 57.5% were males. Thoracotomy was performed in 48.5% (n = 33) of cases. No effect of the intervention was found regarding MIP, MEP, lung volumes or functional performance at any time point. The overall incidence of pneumonia was 13% (n = 9), with no significant difference between groups [IG 6% (n = 2), CG 21% (n = 7), P = 0.14]. An improved SpO2 was found in the IG on the third and fourth postoperative days (Day 3: IG 93.8 ± 3.4 vs CG 91.9 ± 4.1%, P = 0.058; Day 4: IG 93.5 ± 3.5 vs CG 91 ± 3.9%, P = 0.02). We found no association between surgical procedure (thoracotomy versus thoracoscopy) and respiratory muscle strength, which was recovered in both groups 2 weeks after surgery., Conclusions: Two weeks of additional postoperative IMT, compared with standard physiotherapy alone, did not preserve respiratory muscle strength but improved oxygenation in high-risk patients after lung cancer surgery. Respiratory muscle strength recovered in both groups 2 weeks after surgery., Clinical Trialsgov Id: NCT01793155., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: In lung cancer preoperative evaluation, functional lung imaging is commonly used to assess lobar function. Computed tomography ventilation (CT-V) imaging is an emerging lung function imaging modality. We compared CT-V imaging assessment of lobar function and its prediction of postoperative lung function to that achieved by (i) positron emission tomography ventilation (PET-V) imaging and (ii) the standard anatomical segment counting (ASC) method. We hypothesized (i) that CT-V and PET-V have similar relative lobar function and (ii) that functional imaging and anatomic assessment (ASC) yield different predicted postoperative (ppo) lung function and therefore could change clinical management., Methods: In this proof-of-concept study, 11 patients were subjected to pulmonary function tests, CT-V and PET-V imaging. The Bland-Altman plot, Pearson's correlation and linear regression analysis were used to assess the agreement between the CT-V-, PET-V- and ASC-based quantification of lobar function and in the ppo lung function., Results: CT-V and PET-V imaging demonstrated strong correlations in quantifying relative lobar function (r = 0.96; P < 0.001). A Wilcoxon-signed rank test showed no significant difference in the lobar function estimates between the two imaging modalities (P = 0.83). The Bland-Altman plot also showed no significant differences. The correlation between ASC-based lobar function estimates with ventilation imaging was low, r < 0.45; however, the predictions of postoperative lung function correlated strongly between all three methods., Conclusions: The assessment of lobar function from CT-V imaging correlated strongly with PET-V imaging, but had low correlations with ASC. CT-V imaging may be a useful alternative method in preoperative evaluation for lung cancer patients., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Micro-sized lung adenocarcinoma with a tumour of 1.0 cm or less could help identify the patients who would undergo the surgery treatment with limited resection; however, its clinical characteristics and survival rates remain unclear and are to be tested further., Methods: Histology, lymphatic metastasis, surgical procedure and survival rates of 366 lung adenocarcinoma patients (from January 2007 to December 2013) with a tumour of 2.0 cm or less were analysed retrospectively. Among these patients, 175 had a primary tumour with a diameter of 1.0 cm or less and 191 had a tumour of 1.1-2.0 cm. The survival of 366 patients was evaluated by the restricted mean survival time (RMST) test, and the risk factors were assessed by multivariable analysis., Results: Larger lesion had a significant relation to old age, male sex, preoperatively carcinoembryonic antigen (CEA) positive, invasive adenocarcinoma (IAC) and advanced-stage disease (P < 0.0001, P = 0.001, P = 0.001, P < 0.0001 and P < 0.0001, respectively). Patients with adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma obtained a better prognosis than those with IAC (5-year overall survival rate: 98.5 vs 84.3%, P = 0.001; disease-related survival rate: 98.5 versus 85.2%, P = 0.001). The 5-year overall survival rates of patients with a tumour less than 1.0 cm in comparison with 1.1-2.0 cm were 100.0 and 88.4% (P < 0.001), whereas the 5-year lung adenocarcinoma-specific survival rates were 100.0 and 89.0% (P < 0.001), respectively. Multivariable analysis for prognosis of lung adenocarcinoma patients with a tumour 2.0 cm or less in diameter revealed that histology, lymphatic metastasis and advanced pathological stage affected the 5-year overall and disease-related survival rates unfavourably (P < 0.0001, 0.002, 0.001; and P < 0.0001, 0.005, 0.001, respectively), whereas tumour size did not have an obvious influence on survival., Conclusions: Micro-sized lung adenocarcinoma (1.0 cm or less) had specific clinical characteristics and more favourable survival rates. These tumours and a subtype of AIS evaluated by computed tomography images or intraoperative frozen section may be appropriate candidates for a limited resection without mediastinal lymph node dissection., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: To implement internal monitoring using a risk-adjusted model specific for video-assisted thoracoscopic surgery (VATS) lobectomy., Methods: Retrospective analysis on prospectively collected data of 348 patients submitted to VATS lobectomy (August 2012-August 2014). Baseline and surgical variables were tested for a possible association with postoperative cardiopulmonary complications. Logistic regression and bootstrap resampling analyses were used to develop the risk-adjusted model to obtain the predicted morbidity of 50 consecutive patients (September 2014-November 2014). A risk-adjusted control chart was constructed to track down practice variation during this period. Patients were ordered by date of operation and assigned a score represented by the individual predicted morbidity: the plotted line goes up in case of absence of complications and goes down by the predicted morbidity minus 1 in case of complications. Over time, if outcomes are as expected based on the risk-adjusted model, the plotted line will tend to be close to zero., Results: Cardiopulmonary complications and in-hospital/30-day mortality rates were 14% (47 cases) and 1.8% (6 cases), respectively. Age (P = 0.006, coefficient 0.55, bootstrap frequency 76%) and predicted postoperative forced expiratory volume in 1 s (ppoFEV1) (P < 0.001, coefficient -0.38, bootstrap frequency 98%) remained independently associated with cardiopulmonary morbidity after logistic regression and bootstrap analyses. The following risk logit model for cardiopulmonary morbidity after VATS lobectomy was generated: -3.17 -0.038XppoFEV1 +0.55Xage. The risk-adjusted control chart showed a downward trend indicating a worse than expected performance in the audited period., Conclusion: The present analysis offers a methodological template for VATS lobectomy that helps to evaluate the surgical programme. It aims to give a real-time monitoring with the possibility to confront the performance of the centre with the population-specific expectancies. Moreover, being reactive with time, this method allows early detection of underperformance and implementation of critical change in clinical practice., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Previous studies have demonstrated that the rising mortality due to mesothelioma and asbestosis can be predicted from historic asbestos usage. Mortality due to idiopathic pulmonary fibrosis (IPF) is also rising, without any apparent explanation., Aims: To compare mortality due to these conditions and examine the relationship between mortality and national asbestos imports., Methods: Mortality data for IPF and asbestosis in England and Wales were available from the Office for National Statistics. Data for mesothelioma deaths in England and Wales and historic UK asbestos import data were available from the Health & Safety Executive. The numbers of annual deaths due to each condition were plotted separately by gender, against UK asbestos imports 48 years earlier. Linear regression models were constructed., Results: For mesothelioma and IPF, there was a significant linear relationship between the number of male and female deaths each year and historic UK asbestos imports. For asbestosis mortality, a similar relationship was found for male but not female deaths. The annual numbers of deaths due to asbestosis in both sexes were lower than for IPF and mesothelioma., Conclusions: The strength of the association between IPF mortality and historic asbestos imports was similar to that seen in an established asbestos-related disease, i.e. mesothelioma. This finding could in part be explained by diagnostic difficulties in separating asbestosis from IPF and highlights the need for a more accurate method of assessing lifetime occupational asbestos exposure., (© Crown copyright 2015.)

Objectives: Thoracoscopic lobectomy has been widely performed on patients with early-stage lung cancer; meanwhile indications of thoracoscopic segmentectomy have not been clearly defined due to technical difficulties and unclear oncological outcomes. The aim of this study was to compare early and late outcomes between thoracoscopic segmentectomy and thoracoscopic lobectomy., Methods: Between January 2005 and December 2013, 100 thoracoscopic segmentectomies and 1049 thoracoscopic lobectomies were performed on patients with lung cancer in our institute. Preoperative clinical parameters including gender, age, tumour size, pathological stage, histology and forced expiratory volume in 1 s (FEV1) were used for propensity score matching. After propensity score matching, 94 thoracoscopic segmentectomies and 94 lobectomies were selected and compared., Results: Thoracoscopic segmentectomies were performed on patients with normal lung function (mean FEV1 = 101.6 ± 24.1%), small-sized tumour (mean diameter 1.7 ± 1.0 cm), early-stage cancer (Stage I 93.7%) and predominant adenocarcinoma (81.9%). The lobectomy group had similar clinical features with the segmentectomy group. Most commonly performed procedures were left upper lobe upper division segmentectomy (19%) and right lower lobe superior segmentectomy (17%). Segmentectomies were performed in all lobes except the right middle lobe. There were no differences between segmentectomy and lobectomy in terms of operation time (166.3 ± 54.7 min vs 181.1 ± 85.2 min, P = 0.47) and hospital stay (6.2 ± 5.2 days vs 7.1 ± 7.1 days, P = 0.31). Incidence of postoperative complications was non-significantly higher in the lobectomy group (17.2 vs 10.6%, P = 0.1), and postoperative mortality rates were also non-significantly higher in the segmentectomy group (1.1 vs 2.1%, P = 0.56). Postoperative FEV1 decrease was non-significantly lower in the segmentectomy group (8.9 ± 10.8 vs 11.0 ± 13.1, P = 0.36). The 3-year overall survival and recurrence-free survival was not different between the two groups (94 and 87% in the segmentectomy group and 96 and 94% in the lobectomy group, P = 0.62 and P = 0.69, respectively)., Conclusions: Thoracoscopic segmentectomy could achieve equal short-term surgical results and long-term oncological outcomes compared with thoracoscopic lobectomy., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

In vitro 3D growth of tumors is a new cell culture model that more closely mimics the features of the in vivo environment and is being used increasingly in the field of biological and medical research. It has been demonstrated that cancer cells cultured in 3D matrices are more radio-resistant compared with cells in monolayers. However, the mechanisms causing this difference remain unclear. Here we show that cancer cells cultured in a 3D microenvironment demonstrated an increase in cells with stem cell properties. This was confirmed by the finding that cells in 3D cultures upregulated the gene and protein expression of the stem cell reprogramming factors such as OCT4, SOX2, NANOG, LIN28 and miR-302a, compared with cells in monolayers. Moreover, the expression of β-catenin, a regulating molecule of reprogramming factors, also increased in 3D-grown cancer cells. These findings suggest that cancer cells were reprogrammed to become stem cell-like cancer cells in a 3D growth culture microenvironment. Since cancer stem cell-like cells demonstrate an increased radio-resistance and chemo-resistance, our results offer a new perspective as to why. Our findings shed new light on understanding the features of the 3D growth cell model and its application in basic research into clinical radiotherapy and medicine., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Objectives: Uniportal approaches to video-assisted thoracoscopic surgery (VATS) lobectomy have been described in significant series. Few comparison studies between the two techniques exist. The aim was to determine whether the uniportal technique had more favourable postoperative outcomes than the multiport technique., Methods: All VATS lobectomies undertaken at a single university hospital during August 2012 to December 2013 were studied. Patients with preoperative opiate use or chronic pain were excluded. Patients were divided into those with uniportal and multiport approaches for analysis. All continuous data were assessed for normality, and analysed with the Mann-Whitney U-tests or t-tests as appropriate. Categorical data were analysed by Fisher's exact or χ(2) test for trend as appropriate., Results: One hundred and twenty-nine VATS lobectomies were completed. Six were excluded and data were incomplete for 13, leaving 110 (15 uniportal, 95 multiport) for analysis. The demographics of the two groups were similar. There was no significant difference in the Thoracoscore or American Society of Anesthesiologists grades. The median morphine use in the first 24 postoperative hours was 19 mg in the uniportal group and 23 mg in the multiport group, P = 0.84. The median visual analogue pain score in the first 24 h was 0 in the uniportal group and 0 in the multiport group, P = 0.65. There was no difference in the duration of patient-controlled analgesia (P = 0.97), chest drain duration (P = 0.67) or hospital length of stay (P = 0.54). There was no inpatient mortality and no unplanned admission to critical care in either group., Conclusions: Uniportal VATS lobectomy is safe, and there is no appreciable negative impact on the hospital stay or morbidity. Patient-reported pain and morphine use in the first 24 h was low with either technique. Larger prospective studies are needed to quantify any benefit to a particular approach for VATS lobectomy., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The purpose of this study was to investigate the relationship between tumor size and blood volume for patients with lung tumors, using dual-energy computed tomography (DECT) and a gemstone spectral imaging (GSI) viewer. During the period from March 2011 to March 2013, 50 patients with 57 medically inoperable lung tumors underwent DECT before stereotactic body radiotherapy (SBRT) of 50-60 Gy in 5-6 fractions. DECT was taken for pretreatment evaluation. The region-of-interest for a given spatial placement of the tumors was set, and averages for CT value, water density and iodine density were compared with tumor size. The average values for iodine density in tumors of ≤ 2 cm, 2-3 cm, and >3 cm maximum diameter were 24.7, 19.6 and 16.0 (100 µg/cm(3)), respectively. The average value of the iodine density was significantly lower in larger tumors. No significant correlation was detected between tumor size and average CT value or between tumor size and average water density. Both the average water density and the average CT value were affected by the amount of air in the tumor, but the average iodine density was not affected by air in the tumor. The average water density and the average CT value were significantly correlated, but the average iodine density and the average CT value showed no significant correlation. The blood volume of tumors can be indicated by the average iodine density more accurately than it can by the average CT value. The average iodine density as assessed by DECT might be a non-invasive and quantitative assessment of the radio-resistance ascribable to the hypoxic cell population in a tumor., (© The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Physiotherapy is considered an important component of the perioperative period of lung resection surgery. A systematic review was conducted to assess evidence for the effectiveness of different physiotherapy interventions in patients undergoing lung cancer resection surgery. Online literature databases [Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, SCOPUS, PEDro and CINAHL] were searched up until June 2013. Studies were included if they were randomized controlled trials, compared 2 or more perioperative physiotherapy interventions or compared one intervention with no intervention, included only patients undergoing pulmonary resection for lung cancer and assessed at least 2 or more of the following variables: functional capacity parameters, postoperative pulmonary complications or length of hospital stay. Reviews and meta-analyses were excluded. Eight studies were selected for inclusion in this review. They included a total of 599 patients. Seven of the studies were identified as having a low risk of bias. Two studies assessed preoperative interventions, 4 postoperative interventions and the remaining 2 investigated the efficacy of interventions that were started preoperatively and then continued after surgery. The substantial heterogeneity in the interventions across the studies meant that it was not possible to conduct a meta-analysis. The most important finding of this systematic review is that presurgical interventions based on moderate-intense aerobic exercise in patients undergoing lung resection for lung cancer improve functional capacity and reduce postoperative morbidity, whereas interventions performed only during the postoperative period do not seem to reduce postoperative pulmonary complications or length of hospital stay. Nevertheless, no firm conclusions can be drawn because of the heterogeneity of the studies included. Further research into the efficacy and effectiveness of perioperative respiratory physiotherapy in this patient population is needed., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Survival from lung cancer remains poor in Scotland, UK. Although the presence of comorbidities is known to influence outcomes, detailed quantification of comorbidities is not available in routinely collected audit or cancer registry data. The aim of the present study was to assess the prevalence and severity of comorbidities in patients with newly diagnosed lung cancer across four centres throughout Scotland using validated criteria., Methods: Between 2005 and 2008, all patients with newly diagnosed lung cancer coming through the multidisciplinary teams in four Scottish centres were included in the study. Patient demographics, WHO/Eastern Cooperative Oncology Group performance status, clinicopathological features and primary treatment modality were recorded., Results: Details of 882 patients were collected prospectively. The majority of patients (87.3%) had at least one comorbidity, the most common being weight loss (53%), chronic obstructive pulmonary disease (43%), renal impairment (28%) and ischaemic heart disease (27%). A composite score was produced that included both number and severity of comorbidities. One in seven patients (15.3%) had severe comorbidity scores. There were statistically significant variations in comorbidity scores between treatment centres and between non-small cell lung carcinoma treatment groups. Disease stage was not associated with comorbidity score., Conclusions: There is a high prevalence of multiple, severe comorbidities in Scottish patients with lung cancer, and these vary by site and treatment group. Further research is needed to determine the relationship between comorbidity scores and survival in these patients., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: There are few reports on optimal surgical approaches to bilateral pulmonary metastasis and the sequences used in the operation. The aim of this study was to evaluate the feasibility of the thoracoscopic bilateral approach to pulmonary metastasis., Methods: From June 2006 to February 2013, 61 patients underwent a planned bilateral pulmonary metastasectomy with one- (n = 52) or two-stage (n = 9) thoracoscopic surgery. We retrospectively analysed the outcomes of this group of patients to define the role and limitation of thoracoscopic surgery in bilateral disease., Results: In 17 patients with bilateral single lesions on the computed tomography (CT) scans, we were able to resect more nodules than initially imaged in 7 patients (41.2%), and there were 2 patients (11.8%) who had more true metastatic lesions than expected. Among 44 patients who showed more than two bilateral multiple lesions on the CT scan, we were able to resect more than 10 nodules in 2 patients (4.5%). The overall accuracy rate for resected malignant nodules was 76.6%, and 9 patients (14.8%) actually had the disease confined to the unilateral thorax, with solitary (n = 8) and multiple (n = 1) metastases after bilateral exploration. The prognostic factors for unilateral disease were unilateral lesion on the positron emission tomography (PET) scan (P = 0.024). The values of FVC and FEV1 were, respectively, 14.4 and 15.4% reduction at 6 months postoperatively in patients who had three or more nodules resected. Sarcomatous histology (P = 0.039), a diameter larger than 3 cm (P = 0.042) and bilateral lesion on PET (P = 0.035) were the prognostic factors for intrathoracic recurrences., Conclusions: Bilateral pulmonary metastasectomy was performed safely with thoracoscopy in patients with bilateral oligo-metastatic sub-pleural lesions and the one-stage approach was a feasible option in bilateral single lesions. Preoperative PET scan could help predict intrathoracic recurrence after thoracoscopic metastasectomy.

Objectives: Preoperative lung function is an independent predictor of long-term survival after lung resection for non-small-cell lung cancer (NSCLC). The extent of resection has an impact on operative mortality, determines postoperative lung function and may influence both overall- and cancer-specific survival. We sought to determine the impact of predicted postoperative (ppo) lung function on long-term survival after lung cancer resection., Methods: We previously reported long-term survival analyses for patients who underwent major lung resection for NSCLC 1980-2006. For this study, we calculated ppo spirometry (forced expiratory volume in the first second, FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) in the same cohort using the functional segment technique or quantitative perfusion scans when available, and updated survival data; missing data were imputed. We assessed the relationship of ppoFEV1 and ppoDLCO to long-term survival using Cox regression., Results: Of 854 patients, 471 (55%) were men, the mean age was 63 years and median survival was 42 months. At the time of analysis, 70% of patients had died. On regression analysis, all-cause mortality was related to age, stage, performance status, renal function and prior myocardial infarction. Preoperative lung function was marginally associated with mortality [DLCO (10-percentage point decrease): HR (hazard ratio) 1.04, 95% confidence interval (95% CI) 1.00-1.08, P = 0.056; FEV1 (10-percentage point decrease): HR 1.04, 95% CI 1.00-1.09, P = 0.067]. In contrast, ppo lung function was strongly associated with mortality (ppoDLCO: HR 1.06, 95% CI 1.01-1.12, P = 0.024; ppoFEV1: HR 1.06, 95% CI 1.01-1.12, P = 0.031)., Conclusions: Ppo lung function is strongly associated with long-term survival after major lung resection and is more strongly related to survival than preoperative lung function. Surgeons struggle with challenging decisions about the appropriate extent of resection for early-stage cancer, balancing factors such as operative morbidity/mortality, local recurrence and postoperative quality of life. Ppo lung function and its relation to survival also should be taken into consideration during such deliberations.

Background: Lung cancer (LC) is often diagnosed late when curative intervention is no longer viable. However, current referral guidelines (e.g. UK National Institute for Health and Care Excellence guidelines) for suspected LC are based on a weak evidence base. Aim. The purpose of this systematic review is to identify symptoms that are independently associated with LC and to identify the key methodological issues relating to symptomatic diagnosis research in LC., Methods: Medline, Ovid and Cumulative Index to Nursing and Allied Health Literature were searched for the period between 1946 and 2012 using the MeSH terms 'lung cancer' and 'symptom*'. Quality of each paper was assessed using Scottish Intercollegiate Guidelines Network and Consolidated Criteria for Reporting Qualitative Research Checklists and checked by a second and third reviewer., Results: Evidence regarding the diagnostic values of most symptoms was inconclusive; haemoptysis was the only symptom consistently indicated as a predictor of LC. Generally, evidence was weakened by methodological issues such as the lack of standardized data collection (recording bias) and the lack of comparability of findings across the different studies that extend beyond the spectrum of disease. Qualitative studies indicated that patients with LC experienced symptoms months before diagnosis but did not interpret them as serious enough to seek health care. Therefore, early LC symptoms might be under-represented in primary care clinical notes., Conclusion: Current evidence is insufficient to suggest a symptom profile for LC across the disease stages, nor can it be concluded that classical LC symptoms are predictors of LC apart from, perhaps, haemoptysis. Prospective studies are now needed that systematically record symptoms and explore their predictive values for LC diagnosis.

Objectives: Upper lobectomy inevitably leads to an upward displacement of the remaining lower lobe. Such displacement may result in bronchial angulation, thereby narrowing the airway. We hypothesized that the degree of displacement of the bronchus is associated with the degree of exacerbation of postoperative pulmonary dysfunction. This study investigated whether bronchial angulation affects postoperative pulmonary function., Methods: Patients undergoing upper lobectomy for lung cancer were retrospectively evaluated. A check for the presence of dyspnoea, pulmonary function test, chest X-ray and chest computed tomography (CT) were performed at 3 and 12 months postoperatively in these patients. The angle formed by the main bronchus and the bronchus intermedius on the right side and that by the main bronchus and the lower lobar bronchus were measured using the coronal view of the chest CT. We analysed the relationship between the change in bronchial angle and pulmonary function., Results: Ninety-nine patients were enrolled in this study. Among these patients, 50 underwent left upper lobectomy (LUL) and 49 underwent right upper lobectomy (RUL). Nine patients who underwent LUL showed worsening symptoms, and among them, 8 presented an increase in the angle. However, among the 9 patients with worsening symptoms after RUL, only 4 presented an increase in the angle. Decreased forced expiratory volume in 1 s (FEV1) from 3 to 12 months after surgery was observed in 16 patients in the LUL group and 14 in the RUL group. Exacerbation of pulmonary dysfunction was associated with an increase in the bronchial angle (P = 0.04 for LUL and P = 0.02 for RUL). The degree of angle change was also associated with the extent of FEV1 reduction (P = 0.02 for LUL and P = 0.02 for RUL)., Conclusions: Although the change in the bronchial angle is a physiological condition, it can reduce postoperative pulmonary function. The measurement of the change in the angle using the coronal view of a chest CT is a useful screening tool for predicting the postoperative reduction in FEV1.

Objective: Herein, inhibition of hepatocyte growth factor receptor, c-Met, significantly increased cytochrome c release and Bax/Bcl-2 ratio, indicating that c-Met played an anti-apoptotic role. The following experiments are to elucidate this anti-apoptotic mechanism, then the effect of c-Met on autophagy has also been discussed., Methods: Investigated was the influence of c-Met on apoptosis, autophagy and loss of mitochondrial transmembrane potential (Δψm), and the relevant proteins were examined., Key Findings: First, we found that activation of extracellular signal-regulated kinase (ERK), p53 was promoted by c-Met interference. Subsequent studies indicated that ERK was the upstream effector of p53, and this ERK-p53 pathway mediated release of cytochrome c and up-regulation of Bax/Bcl-2 ratio. Secondly, the inhibition of c-Met augmented oridonin-induced loss of mitochondrial transmembrane potential (Δψm), resulting apoptosis. Finally, the inhibition of c-Met increased oridonin-induced A549 cell autophagy accompanied by Beclin-1 activation and conversion from microtubule-associated protein light chain 3 (LC3)-I to LC3-II. Activation of ERK-p53 was also detected in autophagy process and could be augmented by inhibition of c-Met. Moreover, suppression of autophagy by 3-methyladenine (3-MA) or small interfering RNA against Beclin-1 or Atg5 decreased oridonin-induced apoptosis. Inhibition of apoptosis by pan-caspase inhibitor (z-VAD-fmk) decreased oridonin-induced autophagy as well and Loss of Δψm also occurred during autophagic process., Conclusion: Thus, inhibiting c-Met enhanced oridonin-induced apoptosis, autophagy and loss of Δψm in A549 cells., (© 2013 Royal Pharmaceutical Society.)

Objectives: Peak VO2, as measure of physical performance is central to a correct preoperative evaluation in patients with both non-small-cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) because it is closely related both to operability criteria and the rate of postoperative complications. Strategies to improve peak VO2, as a preoperative pulmonary rehabilitation programme (PRP), should be considered favourably in these patients. In order to clarify the role of pulmonary rehabilitation, we have evaluated the effects of 3-week preoperative high-intensity training on physical performance and respiratory function in a group of patients with both NSCLC and COPD who underwent lobectomy., Methods: We studied 40 patients with both NSCLC and COPD, age < 75 years, TNM stages I-II, who underwent lobectomy. Patients were randomly divided into two groups (R and S): Group R underwent an intensive preoperative PRP, while Group S underwent only lobectomy. We evaluated peak VO2 in all patients at Time 0 (T0), after PRP/before surgery in Group R/S (T1) and 60 days after surgery, respectively, in both groups (T2)., Results: There was no difference between groups in peak VO2 at T0, while a significant difference was observed both at T1 and T2. In Group R, peak VO2 improves significantly from T0 to T1: 14.9 ± 2.3-17.8 ± 2.1 ml/kg/min ± standard deviation (SD), P < 0.001 (64.5 ± 16.5-76.1 ± 14.9% predicted ± SD, P < 0.05) and deteriorates from T1 to T2: 17.8 ± 2.1-15.1 ± 2.4, P < 0.001 (76.1 ± 14.9-64.6 ± 15.5, P < 0.05), reverting to a similar value to that at T0, while in Group S peak VO2 did not change from T0 to T1 and significantly deteriorates from T1 to T2: 14.5 ± 1.2-11.4 ± 1.2 ml/kg/min ± SD, P < 0.00001 (60.6 ± 8.4-47.4 ± 6.9% predicted ± SD, P < 0.00001)., Conclusions: PRP was a valid preoperative strategy to improve physical performance in patients with both NSCLC and COPD and this advantage was also maintained after surgery.

Objectives: The following study presents a special independent atrial fibrillation (AF) risk factor-preoperative fluctuation of heart rate variability (HRV), as well as other perioperative AF risk factors in patients qualified for pneumonectomy and undergoing pneumonectomy or lobectomy for lung cancer., Methods: The prospective study was performed in patients who had undergone anatomical resection for non-small-cell lung cancer. A total of 117 patients (92 men and 25 women) qualified for statistical research. In order to determine the risk factors, all patients were divided into two groups: Group A-98 patients without AF and Group B-19 patients with AF during the perioperative time. A number of different risk factors of AF have been analysed and further divided into preoperative, operative and postoperative., Results: Postoperative AF occurred in 19 patients (16%), all of them were male. The patients with higher short-term HRV parameters (SD1, RMSSD), slower mean heart rate and those with a lower fluctuation of HRV-related parameters (HRV Afternoon, Night, Day (A/N/D)) before the operation, were more prone to AF. Postoperative risk of AF was higher in patients with a higher number of ventricular ectopic beats before the operation, a higher number of supraventricular and ventricular ectopic beats and a higher maximal heart rate after the operation. Statistical analysis revealed that male gender and the extent of pulmonary resection, particularly left pneumonectomy, constituted significant risk factors. AF was more often observed in patients who had ASA physical status score of III, in comparison with ASAI and ASAII patients., Conclusions: Along with other concomitant AF risk factors presented in this work, the evaluation of the fluctuation tendencies of HRV parameters should be taken into consideration before any major lung resection. The balance disturbance between the sympathetic and parasympathetic nervous systems is responsible for AF.

Objectives: Response to chemotherapy in malignant pleural mesothelioma (MPM) is usually evaluated by radiological criteria, but no common agreement exists on their validity, yet. The cytoreductive effect of chemotherapy on pleural thickening may make the lung more expansible, reducing the restrictive ventilatory impairment. The aim of this study was to evaluate the changes in pulmonary function following chemotherapy in patients with MPM and to correlate these findings with radiological changes., Methods: Between 2004 and 2011, 62 consecutive patients (74% males, median age 63 years) were prospectively investigated. Modified RECIST criteria were used for radiological evaluation of response to chemotherapy. All patients underwent pulmonary function tests before and after three cycles of platinum-based chemotherapy. Changes between baseline and post-chemotherapy pulmonary function values (Δ) and their differences were assessed by means of Student's paired and unpaired t-test, respectively. Receiver operating characteristic (ROC) curve analysis was performed on spirometric parameters significantly associated with response., Results: Thirty (48.4%) patients had a radiological stable disease (S), 23 (37.1%) a partial response (R) and 9 (14.5%) a progressive disease (P). ΔFEV1%pred (R: 18.1 ± 18.5%; S: 0.5 ± 9.3%; P: -11 ± 13.5%; P < 0.0001), ΔFVC%pred (R: 16.1 ± 11.8%; S: 0.4 ± 11.2%; P: -9.2 ± 14.6%; P < 0.0001) and ΔVC%pred (R: 12.9 ± 15.7%; S: 1.5 ± 12.1%; P: -6.1 ± 13.2%; P = 0.001) were significantly associated with radiological response. A significant correlation was observed between ΔFEV1%pred (r = 0.46, P = 0.01), ΔFVC%pred (r = 0.43, P = 0.02) and % change in linear tumour measurement. ROC curve analysis using dichotomized radiological response (P/S vs R) as classification variables showed AUC = 0.88 (95%CI: 0.77-0.95) for ΔFEV1%pred (optimal cut-off value: +7%, sensitivity: 83%, specificity: 82%, PPV: 73%, NPV: 89%) and AUC = 0.86 (95%CI: 0.75-0.94) for ΔFVC%pred (optimal cut-off value: +6%, sensitivity: 82%, specificity: 74%, PPV: 64%, NPV: 88%)., Conclusions: Dynamic lung volumes and radiological changes after chemotherapy seem directly related. Lung function changes could be an additional tool to better evaluate the response to chemotherapy in MPM.

Objectives: Patients undergoing thoracotomy were studied to compare the effects of cryoanalgesia, combined with intravenous patient-controlled analgesia (IVPCA), against IVPCA alone during the four days following surgery., Methods: Fifty patients were randomized into two groups: an IVPCA group (n = 25) and an IVPCA-cryo group (n = 25). Subjective pain intensity was assessed on a verbal analogue scale at rest and during coughing. The intensity and the incidence of post-thoracotomy pain, numbness, epigastric distension and/or back pain, the analgesic requirements, as well as the blood gas values and respiratory function tests were evaluated up to the second postoperative (postop) month. Haemodynamic data and episodes of nausea and/or vomiting were recorded over the four postop days., Results: In the cryo group there was a statistically significant improvement in postop pain scores (P = 10(-4)), reduction in consumption of morphine (P = 10(-4)) and other analgesics (P = 10(-4)), optimization (less acidosis) of the pH values of blood gases (P < 0.015 over 72 hours postop and P < 0.03 on the first and second postop months), increase in systolic blood pressure (P < 0.05 over 96 hours postop), reduction in heart rate (P < 0.05 over 96 hours postop), increase in values of FEV1 (P < 0.02) and FVC (P < 0.05) at the first and second postop months, reduction in the incidence of nausea (0.05 < P < 0.1 over 18 hours postop), numbness, epigastric distension and back pain (P < 0.05 at days 5, 6, 7, 14, 30 and 60 following surgery)., Conclusions: We suggest that cryoanalgesia be considered as a simple, safe, inexpensive, long-term form of post-thoracotomy pain relief. Cryoanalgesia effectively restores FEV1 values at the second postop month.

Intensity-modulated radiation therapy, when used in the clinic, prolongs fraction delivery time. Here we investigated both the in vivoand in vitroradiobiological effects on the A549 cell line, including the effect of different delivery times with the same dose on A549 tumor growth in nude mice. The in vitroeffects were studied with clonogenic assays, using linear-quadratic and incomplete repair models to fit the dose-survival curves. Fractionated irradiation of different doses was given at one fraction per day, simulating a clinical dose-time-fractionation pattern. The longer the interval between the exposures, the more cells survived. To investigate the in vivoeffect, we used sixty-four nude mice implanted with A549 cells in the back legs, randomly assigned into eight groups. A 15 Gy radiation dose was divided into different subfractions. The maximum and minimum tumor diameters were recorded to determine tumor growth. Tumor growth was delayed for groups with prolonged delivery time (40 min) compared to the group receiving a single dose of 15 Gy (P< 0.05), and tumors with a 20 min delivery time had delayed growth compared to those with a 40 min delivery time [20' (7.5 Gy × 2 F) vs 40' (7.5 Gy × 2 F), P= 0.035; 20' (3 Gy × 5 F) vs 40' (3 Gy × 5 F); P= 0.054; 20' (1.67 Gy × 9 F) vs 40' (1.67 Gy × 9 F), P= 0.028]. A prolonged delivery time decreased the radiobiological effects, so we strongly recommend keeping the delivery time as short as possible.

Dyskerin is one of the three subunits of the telomerase ribonucleoprotein (RNP) complex. Very little is known about the role of dyskerin in the biology of the telomeres in cancer cells. In this study, we use a quantitative, multiscale 3D image-based in situ method and several molecular techniques to show that dyskerin is overexpressed in lung cancer cell lines. Furthermore, we show that dyskerin expression correlates with telomere length both at the cell population level--cells with higher dyskerin expression have short telomeres--and at the single cell level--the shortest telomeres of the cell are spatially associated with areas of concentration of dyskerin proteins. Using this in vitro model, we also show that exogenous increase in dyskerin expression confers resistance to telomere shortening caused by a telomerase inactivating drug. Finally, we show that resistance is achieved by the recovery of telomerase activity associated with dyskerin. In summary, using a novel multiscale image-based in situ method, we show that, in lung cancer cell lines, dyskerin responds to continuous telomere attrition by increasing the telomerase RNP activity, which in turn provides resistance to telomere shortening.

Epithelial-mesenchymal transition (EMT) plays a critical role in the early stages of dissemination of carcinoma leading to metastatic tumors, which are responsible for over 90% of all cancer-related deaths. Current therapeutic regimens, however, have been ineffective in the cure of metastatic cancer, thus an urgent need exists to revisit existing protocols and to improve the efficacy of newly developed therapeutics. Strategies based on preventing EMT could potentially contribute to improving the outcome of advanced stage cancers. To achieve this goal new assays are needed to identify targeted drugs capable of interfering with EMT or to revert the mesenchymal-like phenotype of carcinoma to an epithelial-like state. Current assays are limited to examining the dispersion of carcinoma cells in isolation in conventional 2-dimensional (2D) microwell systems, an approach that fails to account for the 3-dimensional (3D) environment of the tumor or the essential interactions that occur with other nearby cell types in the tumor microenvironment. Here we present a microfluidic system that integrates tumor cell spheroids in a 3D hydrogel scaffold, in close co-culture with an endothelial monolayer. Drug candidates inhibiting receptor activation or signal transduction pathways implicated in EMT have been tested using dispersion of A549 lung adenocarcinoma cell spheroids as a metric of effectiveness. We demonstrate significant differences in response to drugs between 2D and 3D, and between monoculture and co-culture.