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Early detection of lung cancer is the key to improving treatment and prognosis of this disease, and the advent of advances in computed tomography (CT) imaging and national screening programs have improved the detection rate of very small pulmonary lesions. As such, the management of this sub-centimetric and often sub-solid lesions has become quite challenging for clinicians, especially for choosing the most suitable diagnostic method. In clinical practice, to fulfill this diagnostic yield, transthoracic needle biopsy (TTNB) is often the first choice especially for peripheral nodules. For lesions for which TTNB could present technical difficulties or failed, other diagnostic strategies are needed. In this case, video-assisted thoracic surgery (VATS) is the gold standard to reach the diagnosis of lung nodules suspect of being malignant. Nonetheless it's often not easy the identification of such lesions during VATS because of their little dimensions, non-firm consistency, deep localization. In literature various marking techniques have been described, in order to improve intraoperative nodules detection and to reduce conversion rate to thoracotomy: CT-guided hookwire positioning, methylene blue staining, intra-operative ultrasound and electromagnetic navigation bronchoscopy are the most used. The scientific evidence on this matter is weak because there are no randomized clinical trials but only case series on single techniques with no comparison on efficacy, so there are no guidelines to refer. From this standing, in this article we conducted a narrative review of the existing literature on the subject, with the aim of outlining a framework as complete as possible. We analyzed strengths and weaknesses of the main techniques reported, so as to allow the clinician to orient himself with greater ease., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1712). IR, and LR served as the unpaid Guest Editors of the series. The other authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Pulmonary oligo-metastases and oligo-recurrences are terms used to define a set of clinical conditions consisting of limited metastatic malignant disease characterized by an intermediate aggressive behavior compared to diffuse metastatic conditions. If the primary tumor has been controlled and extra-thoracic lesions are excluded, there is a suggestion in the medical literature that removal of such lesions could potentially prolong survival. The lungs are a common metastatic spreading site, especially from epithelial malignancies and sarcomas; pulmonary surgical or interventional metastasectomy have been proposed with curative intent in case of limited tumor load (usually less than 5 lesions). There are many series reporting data about colorectal, renal or breast lung metastasectomy, but the absence of multi centric prospective trials determines a lack of definitive evidence, especially for less common tumors such as metastatic germ cell and prostate cancer. They rarely present in the oligo-metastatic form and their management is often based on personal experience. The aim of our article is to review the latest evidence in the treatment of pulmonary metastatic germ cell and prostate tumors. We cover the full range of treatments: from surgery to ablative radiotherapy and combination of local and systemic therapy. Despite the absence of evidence based guidelines, it emerges that pulmonary metastasectomy should always be considered when general criteria for resection have been met. In germ cell tumors surgery should be mainly reserved for residual disease after chemotherapy, whereas in prostate cancer, pulmonary metastasectomy should be preferred to avoid or delay hormonal deprivation therapy and its side effects., Competing Interests: Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.04.51). The series “Pulmonary Metastases” was commissioned by the editorial office without any funding or sponsorship. MC serves as an unpaid editorial board member of Journal of Thoracic Disease from Mar 2020 to Feb 2022. The authors have no other conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Background: In rapidly lung deteriorating patients, urgent lung transplantation (ULT) seems the only definitive therapy. Few publications on this topic report conflicting results, putting a word of caution about ULT programs., Methods: A national ULT program was introduced in 2010: patients on mechanical support may be transplanted with the first available graft. We reviewed the experience of three national center, focusing on post-operative outcomes after ULT., Results: Ten patients (17.5%) died awaiting transplantation, while 47 underwent LT with a median urgent waiting list time of 6 days. Pre-operatively, 4.3% of patients were supported only by mechanical ventilation (MV), 55.3% by extracorporeal membrane oxygenation (ECMO) and the remaining 40.4% by both. The main indication was cystic fibrosis (64%). Median recipient lung allocation score was 72. In-hospital mortality was 19%. MV and ECMO median duration of 7 and 3 days, respectively while intensive care unit (ICU) and hospital stay were 20 and 46 days, respectively. At long-term, 1- and 3-year survival rate were 74% and 70%, respectively. Highly impact risk factors for in-hospital mortality were both presence and duration of preoperative veno-arterial ECMO and pre-transplant C-reactive protein level., Conclusions: ULT program allows transplantation in a significant percentage of patients with acceptable results. Pre-operative recipient selection is mandatory to improve clinical outcomes., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Journal of Thoracic Disease. All rights reserved.)

Background: Regional analysis by computed tomography (CT) is an attractive technique to interpret lung patterns after transplantation (LTx). We evaluated the application of CT functional mask derived parameters to determine whether development of primary graft dysfunction (PGD) is associated with short and/or long-term postoperative evidences of pulmonary function alterations., Methods: A total of 38 patients who underwent bilateral LTx were evaluated at 24, 48 and 72 hours after the end of surgery to establish PGD occurrence and grading. CT scans at 3 and 12 months after LTx were analyzed to measure specific gas volume (SV g ) changes normalized on expiratory SVgEXP of the whole lung (ΔSV g /SV gEXP ) and to obtain functional masks of density variation, namely maps of low ventilation (LV), consolidation (C), air trapping (AT) and healthy parenchyma (H)., Results: Our main result was the evidence of a marked decrease in ΔSV g /SV gEXP in all subjects, irrespectively on PGD, at each time point after LTx, indicating a high degree of ventilation defects versus healthy. High percentages of LV were found in all subjects while percentages of AT and C were negligible., Conclusions: We demonstrate that quantification of ventilation defects by CT functional mask offers insights into the correlation between PGD and pulmonary function after LTx at short and mid-term., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Many studies on fine-needle aspiration biopsy (FNAB) for undetermined pulmonary nodules reported that diagnostic accuracy tended to decline, whereas complication prevalence raised as the size of nodule decreased. Reconsideration on the effectiveness of FNAB would be appropriate considering the dramatic increase in the identification of small nodules with screening programs and new demands of target therapies. The aim of this study was to verify the efficacy of FNAB in pulmonary nodules smaller than 15 mm., Methods: A retrospective, cohort study was conducted on patients with undetermined solitary pulmonary nodules (SPNs) who underwent computer tomography (CT) guided FNAB at our Institution from January 2012 to December 2014. Patients with SPNs with diameter up to 15 mm were considered; inclusion criteria comprised ASA 3, FEV1 <70% of predicted, cardiac comorbidity or previous chest surgery. FNAB diagnostic performance and clinical efficacy were calculated., Results: Out of 225 patients referred for FNAB, 68 covered inclusion criteria. Forty-nine out of 68 smears (72%) were adequate for diagnosis. Specificity was 100% (95% CI: 77-100%), sensitivity was 100% (95% CI: 90-100%). Positive and negative predictive values were 1.0 (95% CI: 0.9-1.0) and 1.0 (95% CI: 0.77-1.0) respectively. A post-biopsy pneumothorax was detected in 27 cases (39%); the pneumothorax rate was significantly affected by the number of passages (P=0.01)., Conclusions: The satisfactory results of our study lead to reconsidering FNAB in patients with pulmonary nodules below 15 mm in diameter, especially in order to avoid unnecessary surgery., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Lung transplantation is the only therapeutic option for end-stage pulmonary failure. Nevertheless, the shortage of donor pool available for transplantation does not allow to satisfy the requests, thus the mortality on the waiting list remains high. One of the tools to overcome the donor pool shortage is the use of ex-vivo lung perfusion (EVLP) to preserve, evaluate and recondition selected lung grafts not otherwise suitable for transplantation. EVLP is nowadays a clinical reality and have several destinations of use. After a narrative review of the literature and looking at our experience we can assume that one of the chances to improve the outcome of lung transplantation and to overcome the donor pool shortage could be the tissue regeneration of the graft during EVLP and the immunomodulation of the recipient. Both these strategies are performed using mesenchymal stem cells (MSC). The results of the models of lung perfusion with MSC-based cell therapy open the way to a new innovative approach that further increases the potential for using of the lung perfusion platform., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Despite advances in perioperative care and surgical techniques, patients undergoing pulmonary lobectomy are still at high risk for postoperative complications. Among interventions expected to reduce complications, continuous positive airway pressure (CPAP) is a discussed option. This trial aims to test the hypothesis whether prophylactic application of CPAP following pulmonary lobectomy can reduce postoperative complications., Methods: The study was designed as a prospective, randomized, controlled trial. Patients with clinical stage I non-small cell lung cancer scheduled for pulmonary lobectomy were eligible and were trained for the use of CPAP interface. The control group received standard postoperative pain management and physiotherapy; in addition, the study group received CPAP (PEEP 8-12 cmH 2 O, 2 hours thrice daily for three days)., Results: After the appropriate selection, 163 patients were considered for the analysis: 82 patients constituted the control group, 81 the study group. The two groups were substantially comparable for preoperative parameters. The rate of postoperative complications was lower in the study group (24.7% vs. 43.9%; P=0.015) as well as the hospital stay (6 vs. 7 days; P=0.031). The stepwise logistic regression model identified: CPAP [odd ratio (OR): 0.3026, CI: 0.1389-0.6591], smoke habits [OR: 2.5835, confidence interval (CI): 1.0331-6.4610] and length of surgery in minutes (OR: 1.0102, CI: 1.0042-1.0163) as regressors on postoperative complications., Conclusions: The present trial demonstrated that prophylactic application of CPAP during the postoperative period after pulmonary lobectomy for stage I non-small cell lung cancer was effective in prevent postoperative complications., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is commonly used for the pathological diagnosis in patients with mediastinal lymphadenopathy. Even though the accuracy of EBUS-TBNA is considered high, several authors have tried to outline characteristic ultrasound criteria for malignant mediastinal lymph-node identification to maximize this accuracy. Recently, a color-Doppler patterns classification has been proposed by Nakajima to target suspected mediastinal lymph-nodes. The aim of this study was to assess such classification., Methods: Clinical, sonographic and pathological data of patients with suspected malignant mediastinal lymph-nodes on computed tomography (CT) and/or on positron emission tomography (PET) were prospectively recorded. On the basis of color-Doppler patterns, mediastinal lymph-nodes were classified in four grades and the bronchial-artery inflow sign was noted according to the Nakajima classification. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predicted value (NPV) and accuracy were calculated using standard definitions., Results: Seventy-five patients were enrolled in this prospective study, median age 66 years; 85% of patients had primary lung cancer and 15% had extra-thoracic malignancy. EBUS-TBNA was performed in 87 lymph-nodes (rate 1.16 per patient); 6 lymph-nodes had inadequate samples and were excluded from the analysis; 64 nodes were confirmed as malignant and 17 nodes as benign. Color-Doppler patterns classification was as follow: grade 0-I, 14 lymph-nodes; grade II-III, 67 lymph-nodes; bronchial-artery inflow sign, 8 lymph-nodes. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy of the classification were 0.93, 0.64, 0.84, 0.6 and 0.81 respectively., Conclusions: The color-Doppler sonography is a fast, reproducible and effective tool that could help in targeting suspected malignant lymph-nodes during EBUS-TBNA. The current study validates the efficacy of the color-Doppler patterns classification proposed by Nakajima., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Multi-institutional studies of endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) for mediastinal staging in lung cancer are scarce. It is unclear if the high diagnostic performance of EBUS-TBNA reported by experts' guidelines can be generally achieved., Methods: This is a retrospective study performed in five tertiary referral centers of thoracic surgery in Italy, to assess the EBUS-TBNA diagnostic performance in patients with non-small cell lung cancer (NSCLC). Patient inclusion criteria were: both genders; >18 years old; with suspect/confirmed NSCLC; undergoing EBUS-TBNA for mediastinal node enlargement at computed tomography (size >1 cm, ≤3 cm) and/or pathological uptake at positron emission tomography. Altogether we included 485 patients [male, 366; female, 119; median age, 68 years (IQR, 61-74 years)] undergoing mediastinal staging between January 2011 and July 2016. All EBUS-TBNAs were performed by experienced bronchoscopists, without pre-defined quality standards. Depending on usual practice in each center, EBUS-TBNA was done under conscious sedation, with 21- or 22-Gauge (G) needle, and specimen preparation was cell-block, or cytology slides, or core-tissue. Sampling was classified inadequate in absence of lymphocytes, or when sample was insufficient. We analyzed the EBUS-TBNA procedural steps likely to influence the rate of adequate samplings (diagnostic yield)., Results: EBUS-TBNA sensitivity, negative predictive value (NPV) and accuracy respectively were 90%, 78% and 93% in the whole cohort. At multivariate analysis, use of 21-G needle was associated with better diagnostic yield (P<0.001). Center and specimen processing technique were not independent factors affecting EBUS-TBNA diagnostic yield., Conclusions: In this multicentric study, EBUS-TBNA was a highly sensitive and accurate method for NSCLC mediastinal node staging. Results indicate better performance of EBUS-TBNA with 21-G needle, and suggest that specimen processing technique could be chosen according to the local practice preference., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Endobronchial ultrasonography with transbronchial needle aspiration (EBUS-TBNA) is recognized as an accurate and minimal invasive procedure for diagnosis and staging of lung cancer and lymph nodal malignancies. EBUS is recommended as the first choice procedure for mediastinal staging in lung cancer in international guidelines., Methods: A retrospective evaluation was performed on single center experience with EBUS-TBNA in our thoracic surgery department in a 10-year time frame. Main indication for the procedure was suspected non-lymphomatous malignancy in intrathoracic lymph-nodes on computed tomography (CT) or positron emission tomography (PET) scan. All procedures were performed under conscious sedation in a day-hospital setting. All the aspirated specimens were obtained with a 22-gauge needle and were fixed in 10% formalin and paraffin embedded. Sections of 3 micron in thickness were cut and hematoxylin-eosin stained., Results: From October 2005 to August 2016, 496 patients were submitted to EBUS-TBNA. Number of nodal stations punctured was 592 with a mean of 2.25 punctures per patient. Diagnosis of malignancy was obtained in 291 patients (58.6%). In 25 cases a nodal metastasis from an extrathoracic primary tumor was diagnosed. Sensitivity, specificity and diagnostic accuracy were 95%, 100% and 96% respectively. Negative predictive value was 90% and positive predictive value (PPV) was 100%. When molecular tests were requested, mutational analysis was successfully performed on cell block derived material in 55 out of 56 cases (98.2%), and fluorescence in situ hybridization (FISH) analysis in 26 out of 27 cases (96.2%)., Conclusions: EBUS-TBNA in our setting was an accurate and safe tool to diagnose non-lymphomatous nodal malignancies. Interestingly, in our series EBUS-TBNA has demonstrated to yield sufficient tissue for molecular analysis., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.