Abstract Introduction: Complex structural remodelling of cells and extracellular matrix during cancer initiation and progression elicit substantial biomechanical alterations, which can be measured by Atomic Force Microscopy (AFM) at the nanoscale level. Clinical and translational evidence indicates that tissue nanomechanical signature (NS) can be a useful tool for rapid cancer diagnosis, and assessment of cancer aggressiveness. We demonstrated that the AFM-based Automated and Reliable Tissue Diagnostics (ARTIDIS) platform represents a valid method for rapid diagnosis, prognosis, and treatment response assessment in patients with breast cancer. Here we aimed to use this platform to examine tumour biopsies from non-small cell lung cancer (NSCLC) patients for the first time. Methods: This is an ongoing, single center study at the Hospital Clinic of Barcelona and University of Barcelona (UHB) Spain, aiming to enroll 75 patients by January 2024 in the first phase, followed by 200 patients in the expansion phase. To date, 54 matching tumor and non-tumor fresh tissue biopsies were taken by experienced pathologists from fresh surgical resection specimens from 27 patients with previously diagnosed NSCLC. Tissue biopsies were measured with the ARTIDIS device in a blinded manner, without knowing the malignancy status of the biopsy. Routine clinico-pathologic parameters have been collected. The multiparametric nanomechanical signature has been analyzed in an automated manner using the proprietary AI-based ARTIDISNET software platform together with available clinico-pathologic parameters. Results: In total, the NSCLC tissue samples included 16 squamous cell carcinoma (SCC), 6 Adenocarcinoma (ADC), 1 large cell carcinoma (LCC) and 4 other histological subtypes. Non-tumor tissues exhibited significantly varied composition, including normal lung parenchyma, bronchial tissues, fibrosis and inflammatory changes. Among the 27 patients, 5 patients developed distant progression within 12 months after ARTIDIS measurements. Results analysis showed that the ARTIDIS NS can reliably differentiate malignant NSCLC lesions from non-tumor lung tissue, with a sensitivity of 0.84, specificity of 0.81, positive predictive value (PPV) of 0.79, negative predictive value (NPV) of 0.86 and accuracy of 0.82. In addition, the ARTIDIS NS can differentiate patients with and without distant progression with a sensitivity of 0.62, specificity of 0.81, PPV of 0.42, NPV of 0.90 and accuracy of 0.77. Conclusions: Here we demonstrated first clinical evidence of the ARTIDIS tissue NS as a novel diagnostic and prognostic tool in patients with NSCLC. This study aims to establish the diagnostic, prognostic, and predictive NS in patients NSCLC. In addition to local expansion at the UHB, study results will be further validated in ARTIDIS clinical program at MD Anderson Cancer Centre, USA. Citation Format: Jordi Alcaraz, Héctor Sanz-Fraile, Elba Marin, Paula Gausa Busquets, Kate Neal, Marselina Arshakyan, Marc Rico, Marc Boada, David Sanchez, Reinier Oropesa Nunez, Gitika Srivastava, Ahmed Jizawi, Sara Nizzero, Tobias Appenzeller, Mariam Gachechiladze, Marko Loparic, Marija Plodinec, Noemi Reguart. First clinical evidence of the tissue nanomechanical signature as a novel diagnostic and prognostic tool in patients with non-small-cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3759.

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 medi-astinal 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.

El objetivo del estudio es valorar el rendimiento diagnóstico de la tomografía computarizada (TC) y la tomografía por emisión de positrones (PET) en la estadificación clínica mediastínica del cáncer pulmonar quirúrgico según los datos de la cohorte prospectiva del Grupo Español de Cirugía Torácica Videoasistida (GEVATS). Se han analizado 2.782 pacientes intervenidos por carcinoma pulmonar primario. Se ha estudiado el acierto diagnóstico en la estadificación mediastínica (cN2). Se ha realizado un análisis bivariante y multivariante de los factores que influyen en el acierto. Se ha estudiado el riesgo de pN2 inesperado en los factores con los que se recomienda una prueba invasiva de estadificación: cN1, tumor central o tamaño mayor de 3 cm. El acierto global de la TC y PET en conjunto es del 82,9% con VPP y VPN de 0,21 y 0,93. En tumores mayores de 3 cm y a mayor SUVmax del mediastino, el acierto es menor, OR de 0,59 (0,44 – 0,79) y 0,71 (0,66 – 0,75), respectivamente. En el abordaje VATS el acierto es mayor, OR de 2,04 (1,52 – 2,73). El riesgo de pN2 inesperado aumenta con el número de los factores cN1, tumor central o tamaño mayor de 3 cm: entre el 4,5% (0 factores) y 18,8% (3 factores), pero no hay diferencias significativas con la realización de prueba invasiva. La TC y PET en conjunto tienen un elevado valor predictivo negativo. Su acierto global es menor en tumores mayores de 3 cm y SUVmax del mediastino elevado, y mayor en el abordaje VATS. El riesgo de pN2 inesperado es mayor si cN1, tumor central o mayor de 3 cm y no varía significativamente con prueba invasiva. 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). 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. 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. 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.

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) ((sic)2,581.80 +/- (sic)1,002.50) than in Group I (patients with histopathological diagnosis) ((sic)4,244.60 +/- (sic)2,008.80), P < 0.0001. Once adjusted for covariables, there was a mean difference of -(sic)1,437.20 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. (C) 2023 AEC. Published by Elsevier Espana, S.L.U. All rights reserved.

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. (C) 2022 AEC. Published by Elsevier Espani a, S.L.U. All rights reserved.

OBJECTIVES:Unplanned readmission is defined as the return to inpatient hospitalization within 30 days after discharge. Worldwide, its incidence after lung resection ranges between 8% and 50%, and it has been shown to impact both patient recovery and healthcare resources. Our goal was to identify the risk factors to prioritize early follow-ups. METHODS:We analysed data from the database of the Grupo Español de Cirugía Torácica Video-Asistida from 33 thoracic surgery departments over 15 months. Standard tests were used to compare the different risk groups. Our goal was to present the most relevant explanatory variables for readmission. RESULTS:A total of 174 of 2808 patients (6%) underwent unplanned readmission after a lobectomy. Of all the preoperative individual characteristics, only lung function was found to be a risk factor for readmission [forced expiratory volume in 1 s < 80%, risk ratio (RR) 1.78, P < 0.001; diffusing capacity of carbon monoxide <60%, RR 1.6, P = 0.02; and VO2 < 20 ml/kg/min, RR 1.59, P = 0.02]. The tumour's characteristics and the stage of the disease did not have an influence on the readmission rates. In the readmitted cohort, an open approach or thoracotomy was associated with more frequent readmissions (RR 1.77; P < 0.001). Strong adhesions (RR 1.81; P < 0.001) or adhesions occupying more than half of the hemithorax (RR 1.73, P < 0.001) were also found to be risk factors for readmission and for longer operative times. A length of stay of >10 days after a lobectomy was found to be a risk factor for readmission (RR 1.9). CONCLUSIONS:We identified preoperative, intraoperative and postoperative risk factors for readmission. This information can be a useful tool to help with the prioritization of early follow-ups, especially in centres with high workloads.

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.

OBJECTIVES: Resection of thymic tumours including the removal of both the tumour and the thymus gland (thymothymectomy; TT) is the procedure of choice and is recommended in most relevant articles in the literature. Nevertheless, in recent years, some authors have suggested that resection of the tumour (simple thymomectomy; ST) may suffice from an oncological standpoint in patients with early-stage thymoma who do not have myasthenia gravis (MG) (non-MG). The goal of our study was to compare the short- and long-term outcomes of ST versus TT in non-MG early-stage thymomas using the European Society of Thoracic Surgeons thymic database. METHODS: A total of 498 non-MG patients with pathological stage I thymoma were included in the study. TT was performed in 466 (93.6%) of 498 patients who had surgery with curative intent; ST was done in 32 (6.4%). The completeness of resection, the rate of complications, the 30-day mortality, the overall recurrence and the freedom from recurrence were compared. We performed crude and propensity score-adjusted comparisons by surgical approach (ST vs TT). RESULTS: TT showed the same rate of postoperative complications, 30-day mortality and postoperative length of stay as ST. The 5-year overall survival rate was 89% in the TT group and 55% in the ST group. The 5-year freedom from recurrence was 96% in the TT group and 79% in the ST group. CONCLUSION: Patients with early-stage thymoma without MG who have a TT show significantly better freedom from recurrence than those who have an ST, without an increase in postoperative morbidity rate.

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.

A quarter of patients with clinical N1 (cN1) non-small cell lung cancer (NSCLC) based on positron emission tomography-computed tomography (PET-CT) imaging have occult mediastinal nodal involvement (N2 disease). In a prospective study, endosonography alone had an unsatisfactory sensitivity (38%) in detecting N2 disease. The current prospective multicentre trial investigated the sensitivity of preoperative mediastinal staging by video-assisted mediastinoscopy (VAM) or VAM-lymphadenectomy (VAMLA).Consecutive patients with operable and resectable (suspected) NSCLC and cN1 after PET-CT imaging underwent VAM(LA). The primary study outcome was sensitivity to detect N2 disease. Secondary endpoints were the prevalence of N2 disease, negative predictive value (NPV) and accuracy of VAM(LA).Out of 105 patients with cN1 on imaging, 26% eventually developed N2 disease. Invasive mediastinal staging with VAM(LA) had a sensitivity of 73% to detect N2 disease. The NPV was 92% and accuracy 93%. Median number of assessed lymph node stations during VAM(LA) was 4 (IQR 3-5), and in 96%, at least three stations were assessed.VAM(LA) has a satisfactory sensitivity of 73% to detect mediastinal nodal disease in cN1 lung cancer, and could be the technique of choice for pre-resection mediastinal lymph node assessment in this patient group with a one in four chance of occult-positive mediastinal nodes after negative PET-CT.

Background. The purpose of this study was to evaluate the long-term clinical and immunologic outcome of cryopreserved arterial allograft (CAA) revascularization of intrathoracic vessels invaded by malignancies.Methods. Since January 2002, consecutive patients whose intrathoracic vessels were invaded by malignancies were operated on and revascularizion made using human lymphocyte antigen (HLA)- and ABO-mismatched CAAs. Immunologic studies were performed preoperatively, and 1, 3, 6, 12, and 24 months postoperatively. Postoperative oral anticoagulation therapy was not given.Results. Twenty-six patients aged 53.1 +/- 15 years with a nonsmall-cell lung cancer (n = 10), invasive mediastinal tumors (n = 7), pulmonary artery sarcoma (n = 3), laryngeal (n = 2), or other rare lung neoplasms (n = 4) underwent operation. Cardiopulmonary bypass was used in 10 cases (38%), and all resections were pathologically complete. Revascularization was either for venous (n = 12) or arterial (n = 14) vessels, and a total of 30 allografts revascularized the superior vena cava (n = 6), pulmonary artery (n = 7), innominate vein (n = 3) or artery (n = 2), ascendent (n = 4) or descending (n = 1) aorta, and subclavian vein (n = 3) or artery (n = 4). Hospital morbidity and mortality were 50% (n = 13) and3.8% (n = 1), respectively, all CAA unrelated. With a median follow-up of 18 months (range, 3 to 60 +), 5-year survival and allograft patency were 84% and 95%, respectively. Preoperative anti-HLA antibodies were detected in 2 patients (7.7%) and a postoperative anti-HLA antibody response, clinically irrelevant, in 1 of 24 patients (4%).Conclusions. Revascularization of intrathoracic venous and arterial vessels in patients with malignancies using HLA- and ABO-mismatched CAA is technically feasible and clinically attractive because of no infection risk and postoperative anticoagulation, and excellent long-term survival, patency, and nonimmunogeneicity.

A 17-year-old man underwent a high-speed motorbike collision and was admitted into our intensive care unit. A chest computed tomographic scan showed a complete bronchial disruption at the level of the intermediate bronchus contained by mediastinal structures (Fig 1A,arrows), pneumothorax, and pneumomediastinum, and a right-sided upper and lower lobe parenchymal contusion, but no rib fractures. The transection followed an oblique path starting in front of the right upper lobe takeoff on its membranous face and reaching the middle lobe bronchus on its cartilaginous aspects (Fig 1B, arrows). The pneumothorax was treated with the placement of a chest tube, and a rigid bronchoscopy confirmed the total disruption of the intermediate bronchus and showed mediastinal structures protruding into the airway. Surgical repair was made by resecting the disrupted stumps and performing an end-to-end anastomosis between the right lower and middle lobe takeoff and the short residual intermediate bronchus [1Macchiarini P. Altmayer M. Go T. et al.Technical innovations of carinal resection for nonsmall-cell lung cancer.Ann Thorac Surg. 2006; 82: 1989-1997Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar]. The anastomosis was wrapped with a pleural flap. The patient was extubated on postoperative day 5 and was discharged after an uneventful course.