Characterization of the MicroRNA Cargo of Extracellular Vesicles Isolated from a Pulmonary Tumor-Draining Vein Identifies miR-203a-3p as a Relapse Biomarker for Resected Non-Small Cell Lung Cancer.

In resected non-small cell lung cancer (NSCLC), post-surgical recurrence occurs in around 40% of patients, highlighting the necessity to identify relapse biomarkers. An analysis of the extracellular vesicle (EV) cargo from a pulmonary tumor-draining vein (TDV) can grant biomarker identification. We studied the pulmonary TDV EV-miRNAome to identify relapse biomarkers in a two-phase study (screening and validation). In the screening phase, a 17-miRNA relapse signature was identified in 18 selected patients by small RNAseq. The most expressed miRNA from the signature (EV-miR-203a-3p) was chosen for further validation. Pulmonary TDV EV-miR-203a-3p was studied by qRT-PCR in a validation cohort of 70 patients, where it was found to be upregulated in relapsed patients (p = 0.0194) and in patients with cancer spread to nearby lymph nodes (N+ patients) (p = 0.0396). The ROC curve analysis showed that TDV EV-miR-203a-3p was able to predict relapses with a sensitivity of 88% (AUC: 0.67; p = 0.022). Moreover, patients with high TDV EV-miR-203a-3p had a shorter time to relapse than patients with low levels (43.6 vs. 97.6 months; p = 0.00703). The multivariate analysis showed that EV-miR-203a-3p was an independent, predictive and prognostic post-surgical relapse biomarker. In conclusion, pulmonary TDV EV-miR-203a-3p is a promising new relapse biomarker for resected NSCLC patients.

Role of a portable gamma-camera with optical view for margins assessment of pulmonary nodules resected by radioguided surgery.

PURPOSE: Radioguided occult lesion localization (ROLL) of pulmonary nodules is an alternative to hook-wire. Both required of a histological margin assessment. The activity emerging from the radiotracer allows to obtain an intraoperative scintigraphic image of the surgical specimen by a portable gamma-camera (PGC) fitted with an optical view, which provides information about the localization of the nodule in relation to the margins. The aim of this study was to evaluate the intraoperative use of a PGC for margin assessment of pulmonary nodules. METHODS: ROLL technique was used in 38 nodules (36 pulmonary, 1 chest wall, and 1 pleural nodules). A PGC intraoperative image of the surgical specimen was obtained in 32. Scintigraphic results were compared to the histological assessment. Other factors, such as nodule size, distance from the pleural surface, or distance covered by the needle, were considered as possible factors for non-centered lesions. RESULTS: PGC images showed that the lesion was in contact with the margins in 8/32 cases and centered in 24. In all cases in which the lesion was considered as centered by the PGC, the margins were free of involvement (NPV 100%), although the PPV is low. CONCLUSIONS: The use of a PGC for margin assessment after pulmonary nodule resection is feasible and provides a high NPV in our series. In addition, the short intraoperative time required for its use makes the PGC a useful tool for providing supplementary information to histopathologic results. Further studies from different surgical teams are required for an external validation.

Cost-effectiveness of a technology-supported multimodal prehabilitation program in moderate-to-high risk patients undergoing lung cancer resection: randomized controlled trial protocol.

BACKGROUND: Multimodal prehabilitation is a preoperative intervention with the objective to enhance cancer patients' functional status which has been showed to reduce both postoperative morbidity and hospital length of stay in digestive oncologic surgery. However, in lung cancer surgery patients further studies with higher methodological quality are needed to clarify the benefits of prehabilitation. The main aim of the current protocol is to evaluate the cost-effectiveness of a multimodal prehabilitation program supported by information and communication technologies in moderate-to-high risk lung cancer patients undergoing thoracic surgery. METHODS: A Quadruple Aim approach will be adopted, assessing the prehabilitation program at the following levels: i) Patients' and professionals' experience outcomes (by means of standardized questionnaires, focus groups and structured interviews); ii) Population health-based outcomes (e.g. hospital length of stay, number and severity of postoperative complications, peak oxygen uptake and levels of systemic inflammation); and, iii) Healthcare costs. DISCUSSION: This study protocol should contribute not only to increase the scientific basis on prehabilitation but also to detect the main factors modulating service adoption. TRIAL REGISTRATION: NCT04052100 (August 9, 2019).

N2 disease in non-small-cell lung cancer: straight to surgery?

The correct treatment for patients with non-small-cell lung cancer and ipsilateral mediastinal involvement (N2) remains a challenge. The heterogeneity of this group of patients has been shown, as well as many different prognostic factors, that will determine a specific management to each of them. Although the standard treatment is based on a multimodality therapy consisting of chemotherapy, radiotherapy and surgery, surgery is not always indicated. The selection of patients who are going to be operated, reminds being a key point of the treatment of this disease. Recent reports on operable N2 disease have been reviewed by our group in order to discuss surgery indications and when to bring it about, with the possibility to go straight to surgery.

Is it appropriate to perform video-assisted thoracoscopic surgery for advanced lung cancer?

Video-assisted thoracoscopic surgery (VATS) has showed benefits in terms of pain, hospital stay and accomplishment of adjuvancy therapy versus open surgery in early stage of non-small-cell lung cancer. Over the last years, the indication of VATS technique has been expanded to advanced lung cancer. In this article, we discuss the definition of VATS and advanced lung cancer, and the safety and feasibility of VATS technique for the resection of advanced tumors.

Steroids can reduce warm ischemic reperfusion injury in a porcine donation after circulatory death model with ex vivo lung perfusion evaluation.

Donation after circulatory death (DCD) is being used to increase the number of transplantable organs. The role and timing of steroids in DCD donation and ex vivo lung perfusion (EVLP) has not been thoroughly investigated. In this study, we investigated the effect of steroids on warm ischemic injury in a porcine model (n = 6/group). Following cardiac arrest, grafts were left untouched in the donor (90-min warm ischemia). Graft function was assessed after 6 h of EVLP. In the MP group, 500 mg methylprednisolone was given prior to cardiac arrest and during EVLP. In the CONTR group, no steroids were added. Median lung compliance (13 ml/cmH2 0) was significantly better preserved in the CONTR group than in the MP group (30.5 ml/cmH2 0). Also, median wet-to-dry weight (6.11 vs. 6.94) and CT density (182.5 vs. 352.9 g/l) were significantly better in the MP group than in the CONTR group, respectively. There was no difference in oxygenation and pulmonary vascular resistance. Perfusate cytokine analysis showed a significant reduction in IL-1ß, IL-8, IFN-α, IL-10, TNF-α, and IFN-γ in MP. Cytokines in bronchoalveolar lavage were not decreased except for IFN-gamma. We demonstrated that warm ischemic injury in DCD donation can be attenuated by steroids when given prior to warm ischemia and during EVLP. Ethical context of donor preconditioning should be discussed further.

Cardiorespiratory impact of transesophageal endoscopic mediastinoscopy compared with cervical mediastinoscopy: a randomized experimental study.

BACKGROUND: Transesophageal natural-orifice transluminal endoscopic surgery (NOTES) mediastinoscopy has been described as a feasible, less-invasive alternative to video-assisted mediastinoscopy (VAM). We aimed to investigate hemodynamic and respiratory effects during transesophageal NOTES mediastinoscopy compared with VAM. PATIENTS AND METHODS: This was a short-survival experiment in 20 female pigs randomized to NOTES (n = 10) or VAM (n = 10) mediastinoscopy. In the NOTES group, an endoscopist accessed the mediastinum through a 5-cm submucosal tunnel in the esophageal wall, and CO2 was used to create the pneumomediastinum. Conventional VAM was carried out by thoracic surgeons. A 30-minute systematic exploration of the mediastinum was then performed, including invasive monitoring for hemodynamic and respiratory data. Blood samples were drawn for gas analyses. RESULTS: All experiments except 2 in the NOTES group (one because of technical difficulties, the other because of thoracic lymphatic duct lesion) were completed as planned, and animals survived 24 hours. Also, 3 animals in the NOTES group presented a tension pneumothorax that was immediately recognized and percutaneously drained. VAM and NOTES animals showed similar pulmonary and systemic hemodynamic behavior during mediastinoscopy. Pulmonary gas exchange pattern was mildly impaired during the NOTES procedure, showing lower partial arterial oxygen pressure associated with higher airway pressures (more important in animals that presented with pneumothorax). CONCLUSIONS: NOTES mediastinoscopy induces minimal deleterious respiratory effects and hemodynamic changes similar to conventional cervical VAM and could be feasible when performed under strict hemodynamic and respiratory surveillance. Notably, serious complications caused by the injury of pleura are more frequent in NOTES, which mandates an improvement in technique and suitable equipment.

Robotic Lobectomy Learning Curve Has Better Clinical Outcomes than Videothoracoscopic Lobectomy.

Introduction: The robotic-assisted (RATS) lobectomy learning curve is usually measured compared to an established videothoracoscopic (VATS) surgery program. The objective of our study is to compare the learning curves of both techniques. Methods: We performed an intention-to-treat analysis comparing the RATS vs. VATS lobectomies. Surgical time, conversions, complications, number of lymph nodes (LNs) and lymph node stations harvested, chest drainage duration, length of stay, readmissions, and 90-day mortality were compared between both groups. The learning curve was assessed using the CUSUM method. Results: RATS cases (30) and VATS cases (35) displayed no significant differences. The RATS learning curve was completed after 23 procedures while the VATS curve required 28 interventions. Complications appeared in four RATS procedures and in eight VATS patients. No differences in the number of LNs and harvested LN stations were reported. Four patients were readmitted in the RATS group, and eight in the VATS group. No 90-day postoperative mortality was observed in either group. The RATS group reported fewer chest tube days (3 (2-5) vs. 5 (4-5.8), p = 0.005) and hospital days (4 (3-6) vs. 5 (4-6), p = 0.023). Conclusions: The RATS curve appears shorter than the VATS curve. RATS lobectomies resulted in reduced chest tube duration and length of stay during the learning time period.

A look ahead to promote the early detection of lung cancer: technical and cost implications of a confirmed diagnosis before surgery.

OBJECTIVE: To compare the costs and length of hospital stay among patients with a confirmed diagnosis of lung cancer (LC) prior to surgery versus those without confirmation. METHODS: This retrospective, single-center study was conducted in patients who underwent a surgical procedure for LC, with or without a pathologically confirmed LC diagnosis prior to surgery, between March 2017 and December 2019. The main outcomes were costs and length of hospital stay (LOS). RESULTS: Among the 269 patients who underwent surgery for lung cancer between March 2017 and December 2019, 203 (75.5%) patients underwent surgery due to a histopathological diagnosis, and 66 (24.5%) because of a Multidisciplinary Cancer Committee indication. The unadjusted mean cost was significantly lower in Group II (patients with surgery based on Multidisciplinary Cancer Committee criteria) (Є2,581.80 ± Є1,002.50) than in Group I (patients with histopathological diagnosis) (Є4,244.60 ± Є2,008.80), P < 0.0001. Once adjusted for covariables, there was a mean difference of -Є1,437.20 in the costs of Group II, P < 0.0001. Unadjusted mean hospital stay was significantly longer in Group I (5.6 days) than in Group II (3.5 days). CONCLUSIONS: The results suggest that indicating surgical resection of lung cancer based on Multidisciplinary Cancer Committee criteria, rather than performing CT-guided percutaneous lung biopsy, may result in a significant decrease in cost and length of hospital stay.

Starting a robotic thoracic surgery program: From wedge resection to sleeve lobectomy in six months. Initial conclusions.

INTRODUCTION: Robot-assisted thoracic surgery (RATS) is a rapidly expanding technique. In our study, we aimed to analyze the results of the process to adopt robotic surgery in our Department of Thoracic Surgery. METHODS: This is an intention-to-treat analysis of a series of consecutive patients operated on using the RATS approach in our hospital from January 2021 to March 2022. Data were registered for patient characteristics, type of surgery, operative times, conversion rate, chest tube duration, length of hospital stay and complications. The IBM SPSS® statistical software was used for the statistical analysis. A cumulative sum analysis of the operating time was performed to define the learning curve. RESULTS: During the study period, 51 patients underwent robotic surgery, including pulmonary and non-pulmonary interventions. In addition, 15 patients (29.4%) underwent non-pulmonary interventions: one pleural (2%), 2 diaphragmatic (3.9%), and 12 mediastinal (23.5%). Among the mediastinal surgeries, one conversion was necessary (8.3%) for a complex vascular malformation, and 11 were completed by RATS, including 7 (58.3%) thymomas, 3 (25%) pleuro-pericardial cysts, and one (8.3%) neurogenic tumor. Mean operative time was 141 min (104-178), mean chest tube duration was 0.9 days (0-2), and mean length of stay was 1.45 days (1-2). Thirty-six patients underwent lung surgery (70.6%). The complete RATS resections (34; 94.4%) included: 3 wedge resections (11.1%), 2 segmentectomies (3.7%), 28 lobectomies (81.5%), and one sleeve lobectomy (3.7%). Mean surgery time was 194.56 min (141-247), chest tube duration was 3.92 days (1-8), and length of stay was 4.6 days (1-8). Complications occurred in 4 patients (11.1%). No 90-day mortalities were registered. CONCLUSIONS: The implementation of RATS was achieved with good clinical results and operative times for all indications. A rapid learning curve was accomplished in short time. Previous VATS experience, patient selection, team training and program continuity are fundamental to successfully develop a RATS program.

Integral mediastinal staging in patients with NON-SMALL cell lung cancer and risk factors for occult N2 disease.

BACKGROUND: In patients with non-small cell lung cancer (NSCLC), the presence of abnormal hiliar lymph nodes (clinical N1; cN1), central tumor location and/or tumor size (diameter >3 cm) increases the risk of occult mediastinal metastasis (OMM). This study investigates prospectively the diagnostic value of an integral mediastinal staging (IMS) strategy that combines EndoBronchial Ultrasound-TransBronchial Needle Aspiration (EBUS-TBNA) and Video-Assisted Mediastinoscopy (VAM) in patients with NSCLC at risk of OMM. METHODS: Patients with NSCLC and radiologically normal mediastinum assessed non-invasively by positron emission tomography and computed tomography of the chest (PET-CT), and OMM risk factors (cN1, central tumor and/or >3 cm) underwent EBUS-TBNA followed by VAM if the former was negative. Those with negative IMS underwent resection surgery of the tumor. RESULTS: EBUS-TBNA identified OMM in 2 out of the 49 patients evaluated (4%) and VAM in 1 of the 47 patients with negative EBUS (2%). Two patients with a negative IMS had OMM at surgery. Overall, the prevalence of OMM was 10%. EBUS-TBNA has a sensitivity of 40%, a negative predictive value (NPV) of 93.6%, and negative likelihood ratio of 0.60 (95%CI:0.30-1.16). The risk of not diagnosing OMM after EBUS was 6% and after IMS was 4.4%. CONCLUSION: Integral mediastinal staging in patients with NSCLC and clinical risk factors for OMM, does not seem to provide added diagnostic value to that of EBUS-TBNA, except perhaps in patients with cN1 disease who deserve further research.

Results in mediastinal lymph node staging of surgical lung cancer: Data from the prospective cohort of the Spanish Video-Assisted Thoracic Surgery Group.

OBJECTIVES: The objective of this study was to assess the diagnostic performance of combined computerised tomography (CT) and positron emission tomography (PET) in mediastinal staging of surgical lung cancer based on data obtained from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS). METHODS: A total of 2782 patients underwent surgery for primary lung carcinoma. We analysed diagnostic success in mediastinal lymph node staging (cN2) using CT and PET. Bivariate and multivariate analyses were performed of the factors involved in this success. The risk of unexpected pN2 disease was analysed for cases in which an invasive testing is recommended: cN1, the tumour centrally located or the tumour diameter >3 cm. RESULTS: The overall success of CT together with PET was 82.9% with a positive predictive value of 0.21 and negative predictive value of 0.93. If the tumour was larger than 3 cm and for each unit increase in mediastinal SUVmax, the probability of success was lower with OR 0.59 (0.44-0.79) and 0.71 (0.66-0.75), respectively. In the video-assisted thoracic surgery (VATS) approach, the probability of success was higher with OR 2.04 (1.52-2.73). The risk of unexpected pN2 increased with the risk factors cN1, the tumour centrally located or the tumour diameter >3 cm: from 4.5% (0 factors) to 18.8% (3 factors) but did not differ significantly as a function of whether invasive testing was performed. CONCLUSIONS: CT and PET together have a high negative predictive value. The overall success of the staging is lower in the case of tumours >3 cm and high mediastinal SUVmax, and it is higher when VATS is performed. The risk of unexpected pN2 is higher if the disease is cN1, the tumour centrally located or the tumour diameter >3 cm but does not vary significantly as a function of whether patients have undergone invasive testing.

Tunnel technique for robotic-assisted left upper lobectomy.

Robotic-assisted thoracoscopy is a procedure that allows certain improvements over the traditionally used thoracoscopic procedures but still has disadvantages. Its association with dissection techniques such as the tunnel technique allows an approach to lungs with incomplete or fused fissures. We present the case of a 65-year-old female smoker with a 33-mm mass with a 13.7 SUVmax on positron emission tomography-computed tomography scans accompanied by biopsies that confirmed the diagnosis of small-cell lung cancer. After confirming that it was stage N0 and M0, surgical treatment was chosen. We performed a left upper lobectomy and thoracoscopic lymphadenectomy with robotic assistance; due to the presence of incomplete fissures, we used the fissure tunneling technique. This procedure ensured a safe dissection technique with the correct identification of the vascular and bronchial structures and reduced the risk of air leakage.

Preoperative localization of lung nodules: a comparative analysis of hookwire and radio-guided procedures.

Background: Histological diagnosis of pulmonary nodules requires surgical resection on many occasions. There are multiple localization strategies each with their own benefits and complications. The objective of this study is to compare preoperative lung nodule localization with hookwire and radiotracer injection (radioguided occult lesion localization, ROLL). To compare results, complications, and volume of the sample resected with both techniques. Methods: Patients undergoing resection of pulmonary nodules with video-assisted thoracoscopy and pre-surgical localization with hookwire or ROLL were studied. Eighty-eight pulmonary nodules were resected in 76 patients: 52 with a hook wire and 36 with a radiotracer. The localization rate, the shortest distance between the nodule and the pleura, the intrapulmonary distance of the locator, the complications, the volume of the resection piece, and the histological result were all assessed. In addition, the factors that influence the volume of the surgical piece were analyzed. Results: All the nodules were resected with both techniques. The intrapulmonary path of the locator is longer for the ROLL group (23.91 vs. 16.28 mm; P=0.04), with no differences in the distance from the nodule to the pleura. The rate of pneumothorax was significantly higher after the placement of a hook wire (69.2% vs. 24.2%; P<0.0001), while there were no differences in the presence of hemorrhage. The volume of the pieces resected using ROLL was more minor than with hookwire, although not statistically significant (20.19 vs. 34.26 cc; P=0.07). Conclusions: Preoperative localization with the ROLL technique is safer than the placement of hookwire. In addition, the ROLL technique shows a tendency to obtain a smaller volume of resected tissue since the marking is not affected by the intrapulmonary route used during marker placement. ROLL technique allows to locate lung nodules with fewer complications than hookwire and probably gets smaller resection samples.

Surgical Risk Following Anatomic Lung Resection in Thoracic Surgery: A Prediction Model Derived from a Spanish Multicenter Database. / Riesgo quirúrgico tras resección pulmonar anatómica en cirugía torácica. Modelo predictivo a partir de una base de datos nacional multicéntrica.

INTRODUCTION: The aim of this study was to develop a surgical risk prediction model in patients undergoing anatomic lung resections from the registry of the Spanish Video-Assisted Thoracic Surgery Group (GEVATS). METHODS: Data were collected from 3,533 patients undergoing anatomic lung resection for any diagnosis between December 20, 2016 and March 20, 2018. We defined a combined outcome variable: death or Clavien Dindo grade IV complication at 90 days after surgery. Univariate and multivariate analyses were performed by logistic regression. Internal validation of the model was performed using resampling techniques. RESULTS: The incidence of the outcome variable was 4.29% (95% CI 3.6-4.9). The variables remaining in the final logistic model were: age, sex, previous lung cancer resection, dyspnea (mMRC), right pneumonectomy, and ppo DLCO. The performance parameters of the model adjusted by resampling were: C-statistic 0.712 (95% CI 0.648-0.750), Brier score 0.042 and bootstrap shrinkage 0.854. CONCLUSIONS: The risk prediction model obtained from the GEVATS database is a simple, valid, and reliable model that is a useful tool for establishing the risk of a patient undergoing anatomic lung resection.

Monitoring HOTTIP levels on extracellular vesicles for predicting recurrence in surgical non-small cell lung cancer patients.

In resected non-small cell lung cancer (NSCLC), postsurgical recurrence is the major factor affecting long-term survival. The identification of biomarkers in extracellular vesicles (EV) obtained from serial blood samples after surgery could enhance early detection of relapse and improve NSCLC outcome. Since EV cargo contains long non-coding RNAs (lncRNAs), we aimed to analyze whether the oncogenic lncRNA HOTTIP, which higher expression in tumor tissue was related to worse outcome in NSCLC, could be detected in EV from NSCLC patients and serve as recurrence biomarker. After purification of EVs by ultracentrifugation in 52 serial samples from 18 NSCLC patients, RNA was isolated and HOTTIP was quantified by Real time PCR. We observed that patients that relapsed after surgery displayed increased postsurgical EV HOTTIP levels in comparison with presurgical levels. In the relapsed patients with several samples available between surgery and relapse, we observed an increment in the EV HOTTIP levels when approaching to relapse, which indicated its potential utility for monitoring disease recurrence. When we focused in EV HOTTIP levels in the first post-surgical sample, we observed that the detection of an increment of the expression levels in comparison to presurgical sample, predicted recurrence with high sensitivity (85.7%) and specificity (90.9%) and that patients had shorter time to relapse and shorter overall survival. In conclusion, our pilot study showed that EV HOTTIP is a potential biomarker for monitoring disease recurrence after surgery in NSCLC.

Pathological response to neoadjuvant therapy with chemotherapy vs chemoradiotherapy in stage III NSCLC-contribution of IASLC recommendations.

BACKGROUND: Neoadjuvant treatment (NT) with chemotherapy (Ch) is a standard option for resectable stage III (N2) NSCLC. Several studies have suggested benefits with the addition of radiotherapy (RT) to NT Ch. The International Association for the Study of Lung Cancer (IASLC) published recommendations for the pathological response (PHR) of NSCLC resection specimens after NT. AIM: To contribute to the IASLC recommendations showing our results of PHR to NT Ch vs NT chemoradiotherapy (ChRT). METHODS: We analyzed 67 consecutive patients with resectable stage III NSCLC with positive mediastinal nodes treated with surgery after NT Ch or NT ChRT between 2013 and 2020. After NT, all patients were evaluated for radiological response (RR) according to Response Evaluation Criteria in Solid Tumours criteria and evaluated for surgery by a specialized group of thoracic surgeons. All histological samples were examined by the same two pathologists. PHR was evaluated by the percentage of viable cells in the tumor and the resected lymph nodes. RESULTS: Forty patients underwent NT ChRT and 27 NT Ch. Fifty-six (83.6%) patients underwent surgery (35 ChRT and 21 Ch). The median time from ChRT to surgery was 6 wk (3-19) and 8 wk (3-21) for Ch patients. We observed significant differences in RR, with disease progression in 2.5% and 14.8% of patients with ChRT and Ch, respectively, and partial response in 62.5% ChRT vs 29.6% Ch (P = 0.025). In PHR we observed ≤ 10% viable cells in the tumor in 19 (54.4%) and 2 cases (9.5%), and in the resected lymph nodes (RLN) 30 (85.7%) and 7 (33.3%) in ChRT and Ch, respectively (P = 0.001). Downstaging was greater in the ChRT compared to the Ch group (80% vs 33.3%; P = 0.002). In the univariate analysis, NT ChRT had a significant impact on partial RR [odds ratio (OR) 12.5; 95% confidence interval (CI): 1.21 - 128.61; P = 0.034], a decreased risk of persistence of cancer cells in the tumor and RLN and an 87.5% increased probability for achieving downstaging (OR 8; 95%CI: 2.34-27.32; P = 0.001). CONCLUSION: We found significant benefits in RR and PHR by adding RT to Ch as NT. A longer follow-up is necessary to assess the impact on clinical outcomes.

Is invasive mediastinal staging necessary in intermediate risk patients with negative PET/CT?

BACKGROUND: Tumor involvement of mediastinal lymph nodes is of high importance in non-small cell lung cancer (NSCLC). Invasive mediastinal staging is recommended in selected patients without evidence of mediastinal involvement on staging by imaging. In the present study we aimed to evaluate the effectiveness of invasive mediastinal staging in reducing pN2, its impact on survival and the risk factors for occult pN2. METHODS: Patients with NSCLC tumors larger than 3 cm, central tumors or cN1 cases treated in our institution between 2013 and 2018 were prospectively included in the study. Incidence of pN2 and overall survival was compared among invasively staged (IS) and non-invasively staged groups (NIS). Multivariate analysis was performed to identify risk factors of pN2. RESULTS: A total of 201 patients were included in the study, 79 (39.3%) of whom were not invasively staged (NIS group) and 122 (60.7%) were invasively staged (IS group). Incidence of cN1 and mean PET/CT uptake was different among both groups. Prevalence of pN2 was similar in both groups (7.6% in NIS vs. 12.6% in IS; P>0.05). Median survival in IS-pN2 patients was 11 months longer than in NIS-pN2 group (33.6 vs. 22.5 months; P=0.245). cN1 emerged as the only a risk factor for pN2. CONCLUSIONS: Invasive staging does not reduce the incidence of pN2. However, this finding could be biased because in our series cN1 patients were more often staged and cN1 has been detected as a risk factor for pN2. In addition patient better selection after invasive staging might have an impact on overall survival. To conclude, invasive mediastinal staging in intermediate risk patients for positive mediastinal nodes is justified.

Spanish Video-Assisted Thoracic Surgery Group: Method, Auditing, and Initial Results From a National Prospective Cohort of Patients Receiving Anatomical Lung Resections.

INTRODUCTION: Our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS). METHODS: We conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for "90-day mortality" and "Grade IIIb-V complications". RESULTS: The series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres' median recruitment rate was 99% (25-75th:76-100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95-100% rates as reference): grade IIIb-V OR=0.61 (p=0.081), 90-day mortality OR=0.46 (p=0.051). CONCLUSIONS: More than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort.

Perioperative outcome of lung cancer surgery in women: results from a Spanish nationwide prospective cohort study.

BACKGROUND: To assess possible differences in the perioperative profile between men and women in lung cancer surgery. METHODS: A prospective cohort multicenter study was design, in which consecutive patients undergoing curative intent surgery for lung cancer in 24 Thoracic Services throughout Spain were included. Clinical features, tumor- and surgery-related data, postoperative complications, and mortality were recorded. RESULTS: There were 2,566 men and 741 women. Women were younger than men [mean (SD) age, 61.8 (10.8) vs. 66.5 (9.1) years, P<0.0001] and showed a more favorable preoperative characteristics, with significantly higher percentages of ECOG grade 0 and lower percentages of active smokers (28.4% vs. 33.9%; pack-years 18.8 vs. 26.9) and comorbidities [chronic obstructive pulmonary disease (COPD), diabetes, hypertension, cardiac disorders]. There were significant differences (P<0.001) in histological types and TNM stages with adenocarcinoma (70.1% vs. 46.4%) and IA stage (41.5% vs. 33.6%) more frequent in women. The use of VATS or thoracotomy was similar. The rate of pneumonectomy was higher in men (10.9%) than in women (5.1%) (P<0.001) but the distributions of other procedures were similar. Postoperative complications (pneumonitis, atelectasis, air leak, hemorrhage, fistula, empyema, wound dehiscence, and need of reintubation) were lower in women. Significant differences (P<0.0001) in the severity of postoperative complications (Clavien-Dindo classification) were also found, with higher percentages of grades I (51.6% vs. 43%) and II (37.5% vs. 33%) and lower percentages of grades III and IV among women. The mean length of hospital stay was 7.8 (7.1) days in men versus 6.3 (5.0) days in women, and the 30-day mortality rate 0.3% in women versus 2.9% in men (P<0.0001). The percentage of readmissions within 30 days after surgery was also higher in men (8.6% vs. 2.8%). CONCLUSIONS: This multicenter nationwide study of lung cancer surgery with curative intent shows that the perioperative profile is better in women than in men.