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The purpose of this bicentric case series was to report the safety, efficacy, and clinical outcome of transcatheter embolization in pulmonary artery pseudoaneurysms (PAPAs). Between January 2016 and June 2021, eight patients with PAPA were subjected to transcatheter embolization. The total number of patients was eight, of which five were female, with a mean age of 62 ± 14 years (average ± standard deviation). Etiology was traumatic in 2/8 cases and iatrogenic in 6/8 cases (after positioning a Swan-Ganz catheter in 5/6 cases and a temporary pacemaker in the latter case). In a single case, the PAPA was incidentally discovered during a routine X-ray, in the remaining 7 cases, the procedure was performed in emergency settings. PAPA embolization was performed using detachable coils alone in 3 cases; coils and glue in 1 case; coils, glue, and vascular plug in 1 case; coils and non-adhesive liquid embolic agents (Onyx and Squid respectively) in 2 cases; and non-adhesive liquid embolic agent alone (Onyx) in 1 case. No peri-procedural or post-procedural complications were recorded. Both the technical and clinical success rates were 100.0%. In conclusion, endovascular embolization is a technically feasible and safe therapeutic option for patients with PAPAs.

Introduction: The purpose of this study is to evaluate the diagnostic value of positron emission computed tomography-cone beam computed tomography (PET/CT-CBCT) fusion guided percutaneous biopsy, targeted to the maximum standardized uptake value (SUVmax) and minimum standardized uptake value (SUVmin) of large lung lesions. Materials and Methods: Inside a larger cohort of PET/CT-CBCT guided percutaneous lung biopsies, 10 patients with large pulmonary lesions (diameter > 30 mm) were selected retrospectively. These patients have been subjected to double biopsy sampling respectively in the SUVmax area and in the SUVmin area of the lesion. Technical success has been calculated. For each sample, the percentage of neoplastic, inflammatory, and fibrotic cells was reported. Furthermore, the possibility of performing immunohistochemical or molecular biology investigations to specifically define the biomolecular tumor profile was analyzed. Results: Nine lesions were found to be malignant, one benign (inflammation). Technical success was 100% (10/10) in the SUVmax samples and 70% (7/10) in the SUVmin samples ( P-value: .21). In the first group, higher percentages of neoplastic cells were found at pathologic evaluation, while in the second group areas of inflammation and fibrosis were more represented. The biomolecular profile was obtained in 100% of cases (9/9) of the first group, while in the second group only in 33.3% of cases (2/6), with a statistically significant difference between the 2 groups ( P-value: .011). Conclusion: A correlation between the standardized uptake value value and the technical success of the biopsy sample has been identified. PET/CT-CBCT guidance allows to target the biopsy in the areas of the tumor which are richer in neoplastic cells, thus obtaining more useful information for the planning of patient-tailored cancer treatments.

Purpose of the report This article aims to explore the prognostic role of 18F-FDG PET/CT metabolic parameters in stage I lung adenocarcinoma patients. Patients and methods One hundred eighty pathological stage I lung adenocarcinoma patients were retrospectively reviewed. Semiquantitative analysis of FDG tumor uptake was performed with TrueD software on the Siemens Leonardo workstation. SUVmean and MTV were calculated using SUV threshold of 41% of SUVmax; the total lesion glycolysis (TLG) was calculated as the product of SUVmean and MTV. Correlation was evaluated using Spearman correlation coefficient. Maximally selected rank statistics was performed to detect the optimal cutoff used for dichotomizing each PET parameter (6.5 for SUVmean, 9.6 for SUVmax, and 19.1 for TLG). Results Our main finding was the significant correlation between 18F-FDG PET/CT parameters (SUVmean, SUVmax, and TLG) and disease-free survival in pathologic stage I non-small cell lung cancer. SUVmean has the greatest accuracy in recurrence prediction (integrated area under the curve, 0.803; 95% confidence interval, 0.689-0.918). We run the maximally selected rank statistics to provide the classification of observations in 2 groups by a continuous predictor parameter; the free from recurrence rate was significantly greater in patients with SUVmean ≤6.5, SUVmax ≤9.6, and TLG ≤19.1. Conclusions Our research supports the hypothesis that SUVmean, SUVmax, and TLG are well correlated with free from recurrence rate in stage I adenocarcinoma patients, subjected to pulmonary lobectomy. Our findings also indicate these markers as promising prognostic indicators.

OBJECTIVES Digital chest drainage systems allow real-time and continuous monitoring and recording of air leak flow rate and intrapleural pressure (IPP) from the immediate postoperative period to the chest drainage removal. A multicentre retrospective observational analysis of consecutive patients undergoing pulmonary lobectomy for lung cancer was performed to evaluate the association between the airflow and IPP digitally recorded during the immediate postoperative period after video-assisted thoracic surgery (VATS) lobectomy for lung cancer. Here, we present a work in progress report. METHODS All patients treated with VATS lobectomies for lung cancer were included. Multiple airflow measurements and minimum and maximum IPP through the chest tubes were digitally monitored and recorded using microelectronic mechanical sensor technology. The PALs were defined as an air leak lasting >5 days from the conclusion of the surgical procedure. The cessation of air leaks was defined as an airflow RESULTS This analysis comprised 76 patients who underwent VATS lobectomy for lung cancer. Nineteen patients (25%) showed prolonged air leaks (PAL) (≥5 days). The operative time was higher in the PAL group (mean difference = 44 min) without a statistically significant difference. Before the 7th postoperative hours, there were no statistically significant differences in IPPs. CONCLUSIONS Patients with PAL showed less negative IPP in the first 24 postoperative hours. Therefore, the 7th—24th postoperative hours were critical in PAL prediction since the mechanism for PAL seems to develop after the 7th postoperative hour.

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.

Background Tracheal chondrosarcoma is an extremely rare, slow-growing, malignant tumour. This study aims to analyze the cases of tracheal chondrosarcoma published in the literature and our case report, in order to better define tracheal chondrosarcoma management. Methods A systematic review of the English literature was carried out for fully described tracheal chondrosarcoma cases. Additionally, we reported a new case of a 58-year-old man undergoing tracheal resection and reconstruction for tracheal chondrosarcoma. Results To date, 30 cases were published. This tumour predominantly involved male patients (93%; median age: 65 years), generally conditioning dyspnoea and cough. Most of the patients underwent tracheal resection with end-to-end anastomosis, without recurrence (median follow-up: 2 years). Tumour endoscopically treated recurred in half cases. Conclusion Tracheal resection is the treatment of choice for chondrosarcoma, with an excellent prognosis. Endoscopic treatment and/or radiotherapy should be indicated for patients unfit for surgery.

The incidence, severity and associated risk factors of acute pain after preoperative needle localization of pulmonary nodules are poorly characterized. We therefore conducted a cross-sectional study to quantify the acute pain induced by preoperative needle localization of small pulmonary nodules before video-assisted thoracoscopic surgery (VATS).We conducted this study at Shanghai Chest Hospital from September 2021 through December 2021. Eligible patients were between 18 and 75 years old and had small pulmonary nodules requiring preoperative CT-guided needle localization. The intensity of acute pain was assessed using the visual analogue scale (VAS) after preoperative needle localization. A VAS score ≥4 cm indicated moderate to severe pain. Patient demographics and CT-guided localization factors were collected to identify significant predictors associated with moderate to severe pain.A total of 300 patients were included in the final analysis, with a mean (SD) age of 51 (SD =12) years old; 63% were female. Moderate to severe pain occurred in 50.8% of patients during deep breathing and 45.7% of patients during movement. Multivariate logistic regression analysis showed that multiple localization needles [multiple needle localizationsIn adult patients receiving hookwire CT-guided localization, moderate to severe pain was common. Avoiding the localization route through lateral chest wall may be helpful and pharmacological medications or regional blockade is necessitated in high-risk population.

The aim of this study was to assess the impact of BMI on perioperative outcomes in patients undergoing VATS lobectomy or segmentectomy. Data from 5088 patients undergoing VATS lobectomy or segmentectomy, included in the VATS Group Italian Registry, were collected. BMI (kg/m

The purpose of this study was to develop a score to predict the complexity of video-assisted thoracoscopic surgery (VATS) lobectomies preoperatively.One hundred and thirty-nine consecutive patients undergoing VATS lobectomy operated on by a single surgeon as the first operator were included. Complex operations were defined as: operation time180 min (corresponding to the 75th percentile) or a conversion to thoracotomy. Several patient-related baseline and radiological variables were tested for a possible association with surgical complexity by logistic regression analysis. An aggregate score was created by weighing the regression estimates of the significant predictors. Patients were then grouped in classes of risk according to their scores. Finally, the score was validated in an external population of 154 VATS lobectomy patients.Twenty-nine VATS lobectomies (21%) were classified as complex. The following variables were found to be significantly associated with a complex operation and were used to calculate the risk score in each patient (1 point each): male (P = 0.006), presence of thick pleura (P = 0.003), presence of emphysema (P = 0.001), enlarged hilar nodes (P = 0.003). Patients were grouped in 4 classes showing an incremental incidence of complex operations (P 0.0001): score 0, 7.4%; score 1, 18%; score 2, 27%; score2, 67%. In the external validation set, the score confirmed its association with the incidence of complex operations (P 0.001): score 0, 7.3%; score 1, 10%; score 2, 16%; score2 50%.The complexity score appeared to be reproducible in an external setting and can be used to preoperatively identify appropriate candidates for VATS lobectomies to improve the efficiency and safety of the training phase.

Purpose Neuroendocrine neoplasia (NEN) has been displaying an incremental trend along the last two decades. This phenomenon is poorly understood, and little information is available on risk factor for neuroendocrine neoplasia development. Aim of this work is to elucidate the role of potentially modifiable risk factors for pancreatic and pulmonary NEN. Methods We conducted a case–control study on 184 patients with NEN (100 pancreas and 84 lung) and 248 controls. The structured questionnaire included 84 queries on socio-demographic, behavioral, dietary and clinical information. Results Increased risk was associated with history of cancer (“other tumor”, lung OR = 7.18; 95% CI: 2.55–20.20 and pancreas OR = 5.88; 95% CI: 2.43–14.22; “family history of tumor”, lung OR = 2.66; 95% CI: 1.53–4.64 and pancreas OR = 1.94; 95% CI: 1.19–3.17; “family history of lung tumor”, lung OR = 2.56; 95% CI: 1.05–6.24 and pancreas OR = 2.60; 95% CI: 1.13–5.95). Type 2 diabetes mellitus associated with an increased risk of pancreatic NEN (OR = 3.01; 95% CI: 1.15–7.89). Conclusions Besides site-specific risk factors, there is a significant link between neuroendocrine neoplasia and cancer in general, pointing to a shared cancer predisposition.

Objective: To evaluate the influence of lung adenocarcinoma second predominant pattern on the maximal standard uptake value (SUVmax) and its prognostic effect in different histologic groups. Methods: We retrospectively collected surgically resected pathologic stage I and II lung adenocarcinoma from nine European institutions. Only patients who underwent preoperative PET-CT and with available information regarding SUVmax of T (SUVmaxT) and N1 (SUVmaxN1) component were included. Results: We enrolled 344 patients with lung adenocarcinoma. SUVmaxT did not show any significant relation according to the second predominant pattern ( p = 0.139); this relationship remained nonsignificant in patients with similar predominant pattern. SUVmaxT influenced the disease-free survival in the whole cohort ( p = 0.002) and in low- and intermediate-grade predominant pattern groups ( p = 0.040 and p = 0.008, respectively). In the high-grade predominant pattern cohort and in the pathologic N1 cases, SUVmaxT lost its prognostic power. SUVmaxN1 did not show any significant correlation with predominant and second predominant patterns and did not have any prognostic impact on DFS. Conclusions: SUVmaxT is influenced only by the adenocarcinoma predominant pattern, but not by second predominant pattern. Concurrently, in high-grade predominant pattern and pN1 group the prognostic power of SUVmaxT becomes nonsignificant.

Thoracoscopic lobectomy (VATS-L) for non-small-cell lung cancer (NSCLC) is a well-established option for early stage NSCLC, but the evidences are limited for octogenarians.The objectives of this multi-institutional study were to evaluate the post-operative outcomes of VATS-L in octogenarians and to estimate the post-operative quality of life (QoL) using a validated questionnaire (EuroQoL5D).Data from patients underwent VATS-L between 2014 and 2019 were analysed and divided into two groups: Group A (younger patients) and Group B (octogenarians). To define predictors for complications, univariate and multivariable logistic regression analysis were performed.7023 patients underwent VATS-L and 329 (4.6%) were octogenarians. 30-day and 90-day post-operative mortality were similar (0.95% vs 0.91%, p = 0.84 and 1.3% vs 1.2%, p = 0.58), whereas the percentage of patients who suffered from any complication (25.5% vs 31.9%, p = 0.012) and the complication rate (31.6% vs 45.2%, p=0.01) were higher for octogenarians. At discharge, the values of EuroQoL5D were worse in group B, but after one month these levels became similar. Age80 years had a significant influence on morbidity on both univariate and multivariable analyses (p = 0.025).VATS-L for NSCLC can be performed in selected octogenarians without increased risk of post-operative death, acceptable not-life-threatening complications and a moderate impact on QoL.

Background and objectives Adenocarcinoma patterns could be grouped based on clinical behaviors: low- (lepidic), intermediate- (papillary or acinar), and high-grade (micropapillary and solid). We analyzed the impact of the second predominant pattern (SPP) on disease-free survival (DFS). Methods We retrospectively collected data of surgically resected stage I and II adenocarcinoma. Selection criteria anatomical resection with lymphadenectomy and pathological N0. Pure adenocarcinomas and mucinous subtypes were excluded. Recurrence rate and factors affecting DFS were analyzed according to the SPP focusing on intermediate-grade predominant pattern adenocarcinomas. Results Among 270 patients, 55% were male. The mean age was 68.3 years. SPP pattern appeared as follows: lepidic 43.0%, papillary 23.0%, solid 14.4%, acinar 11.9%, and micropapillary 7.8%. The recurrence rate was 21.5% and 5-year DFS was 71.1%. No difference in DFS was found according to SPP (p = .522). In patients with high-grade SPP, the percentage of SPP, age, and tumor size significantly influenced DFS (p = .016). In patients with lepidic SPP, size, male gender, and lymph-node sampling (p = .005; p = .014; p = .038, respectively) significantly influenced DFS. Conclusions The impact of SPP on DFS is not homogeneous in a subset of patients with the intermediate-grade predominant patterns. The influence of high-grade SPP on DFS is related to its proportion in the tumor.

To establish the feasibility of performing percutaneous biopsy of lung lesions guided by fusion PET/CT-CBCT and to evaluate whether the metabolic information provided by a prior PET/CT scan add incremental benefits for diagnosis. We retrospectively reviewed data from 180 patients who underwent CBCT-guided lung biopsy (group 1—90 cases) or PET/CT-CBCT fusion-guided lung biopsy (group 2—90 cases). Technical and clinical success was calculated. We also evaluated the agreement between biopsy and definitive histology and the possibility to carrying out immunehistochemical and molecular biology analyses. Technical success was achieved in 84/90 (93.3%) cases for group 1 and 89/90 (98.9%) for group 2 cases (p 0.054). Clinical success was achieved in 80/94 (95.2%) cases for group 1 and 88/89 (98.9%) cases for group 2. Sensitivity, specificity, positive and negative predictive values and accuracy rate were, respectively, 94.5%, 100.0%, 100.0%, 73.3% and 95.2% for group 1 and 98.6%, 100.0%, 100.0%, 94.4% and 98.9% for group 2 (p 0.167). Agreement between biopsy and definitive histology was reached in 85.7% for group 1 and in 96.2% for group 2 (p 0.211). Immunohistochemical and molecular biology investigations were possible in 66.7% for group 1 and in 77.0% for group 2 (p 0.297). No major complication occurred. PET/CT-CBCT-guided lung biopsy is a feasible technique. In our retrospective case series, we found a higher clinical success rate, but no statistical difference was found.

Studies investigating microRNAs as potential biomarkers for cancer, immune-related diseases, or cardiac pathogenic diseases, among others, have exponentially increased in the last years. In particular, altered expression of specific miRNAs correlates with the occurrence of several diseases, making these molecules potential molecular tools for non-invasive diagnosis, prognosis, and response to therapy. Nonetheless, microRNAs are not in clinical use yet, due to inconsistencies in the literature regarding the specific miRNAs identified as biomarkers for a specific disease, which in turn can be attributed to several reasons, including lack of assay standardization and reproducibility. Technological limitations in circulating microRNAs measurement have been, to date, the biggest challenge for using these molecules in clinical settings. In this review we will discuss pre-analytical, analytical, and post-analytical challenges to address the potential technical biases and patient-related parameters that can have an influence and should be improved to translate miRNA biomarkers to the clinical stage. Moreover, we will describe the currently available methods for circulating miRNA expression profiling and measurement, underlining their advantages and potential pitfalls.

OBJECTIVES Risk factors for pneumothorax recurrence after videothoracoscopy for primary spontaneous pneumothorax are still being debated. The goal of this study was to assess whether the pleurodesis technique and other variables are possibly associated with the postoperative ipsilateral recurrence of pneumothorax. METHODS We retrospectively collected data of 1178 consecutive ≤40-year-old patients who underwent videothoracoscopy for primary spontaneous pneumothorax in 9 centres between 2007 and 2017. We excluded patients with hybrid pleurodesis and/or incomplete follow-up, leaving for analysis 843 cases [80% men; median age (interquartile range) 22 (18–28) years]. Univariable and multivariable analyses were performed by logistic regression and tested by Cox regression model to assess factors related to ipsilateral pneumothorax recurrence including age, gender, body mass index, smoking habit, cannabis smoking, respiratory comorbidity, dystrophic severity score, surgical indication, videothoracoscopy port number and side, lung resection, pleurodesis technique and postoperative prolonged air leak (>5 days). RESULTS Blebs/bullae resection was performed in 664 (79%) patients. Pleurodesis was achieved by partial pleurectomy in 228 (27%) cases; by pleural electrocauterization in 176 (21%); by pleural abrasion in 121 (14%); and by talc poudrage in 318 (38%). During a median follow-up period of 70.0 months (95% confidence interval 66.6–73.4), pneumothorax recurred in 79 patients (9.4%); among these, 29 underwent redo surgery; 34, chest drain/talc slurry; and 16, clinicoradiological observation. The only independent risk factor for recurrence was postoperative prolonged air leak (P CONCLUSIONS In this multicentric series, postoperative ipsilateral pneumothorax recurrence was remarkable and independently related to prolonged postoperative air leak; besides the retrospective study setting, the pleurodesis method did not have an impact on recurrence. To prevent prolonged air leak, blebs/bullae treatment should be accurate and performed only if indicated.

Validation of predictive risk models for prolonged air leak (PAL) is essential to understand if they can help to reduce its incidence and complications. This study aimed to evaluate both the clinical and statistical performances of 4 existing models. We selected 4 predictive PAL risk models based on their scientific relevance. We referred to these models as Chicago, Bordeaux, Leeds and Pittsburgh model, respectively, according to the affiliation place of the first author. These predicting risk models were retrospectively applied to patients recorded on the second edition of the Italian Video-Assisted Thoracoscopic Surgery Group registry. Predictions for each patient were calculated based on the logistic regression coefficient values provided in the original manuscripts. All models were tested for their overall performance, discrimination, and calibration. We recalibrated the original models with the re-estimation of the model intercept and slope. We used curve decision analysis to describe and compare the clinical effects of the studied risk models. Better statistical metrics characterize the models developed on larger populations (Chicago and Bordeaux models). However, no model has a valid benefit for threshold probability greater than 0.30. The Net benefit of the most performing model (Bordeaux model) at the threshold probability of 0.11 is 23 of 1000 patients, burdened by 333 false positive cases. One of 1000 is the Net benefit at the threshold probability of 0.3. The use of PAL scores based on preoperative predictive factors cannot be currently used in a clinical setting because of a high false positive rate and low positive predictive value.

Introduction We tested the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) summary score (SumSC) to detect changes in the HRQOL after Non-small-cell lung cancer (NSCLC) surgery and compared its performance to the traditional scales. Method EORTC QLQ-C30 data was obtained from 326 consecutive pre-operative patients submitted for anatomical lung resections for NSCLC.66 patients completed post-operative assessments 3 months after surgery. The data was analysed to evaluate the ability of the SumSC compared to the traditional scales to [1] preoperatively differentiate between clinical groups [2]; detect post-op changes and to [3] compare pre and post-op changes in clinically different groups.The importance of perioperative changes was measured by calculating the effect size (ES). Results Of the 326 patients, those older than 70 years, with higher DLCO value and Performance Status (PS) ≤1 had a significantly better preoperative SumScore. Physical function (PF) showed a large and significant decline (ES 0.91). Role and social function also showed a significant and medium decline (ES 0.62 and 0.41). Postoperatively some symptoms scales showed significant increases in the values, implying worse symptoms with the largest increase in dyspnoea (ES -0.88). The change in General Health score (GH) was not significant after surgery (ES 0.26, p = 0.062). The SumSc, decreased significantly postoperatively. In particular, medium or large postoperative declines of SumSc were observed in both males and females, in patients with lower FEV1, lower performance score, and in those older than 70 years. Interestingly the decline of SumSc was observed irrespective of the preoperative DLCO level. Discussion The Summary Score was more sensitive to changes in subjects' HRQOL, than the GH score. The SumSc can be used as a parsimonious and easy to interpreted patient-reported-outcome measure in multi-institutional database and future clinical trials.

Adrenocorticotropic hormone (ACTH)-secreting lung carcinoids represent the principal cause of ectopic Cushing syndrome, but the prevalence of ACTH expression and the association between ACTH production and Cushing syndrome in lung carcinoids have scarcely been investigated. In addition, available information on the prognostic meaning of ACTH production is controversial. The aims of this multicentric retrospective study, also including a review of the literature, were to describe the clinico-pathologic features of ACTH-producing lung carcinoids, to assess recurrence and specific survival rates, and to evaluate potential prognostic factors. To identify ACTH production in 254 unselected and radically resected lung carcinoids, we used a double approach including RT-PCR (mRNA encoding for pro-opiomelanocortin) and immunohistochemistry (antibodies against ACTH and β-endorphin). Sixty-three (24.8%) tumors produced ACTH and 11 of them (17.4%), representing 4.3% of the whole series, were associated with Cushing syndrome. The median follow-up time was 71 months. The 10-year overall and specific survival rates were 88.5% and 98.2%, respectively, with difference neither between functioning and nonfunctioning tumors nor between ACTH-positive and ACTH-negative carcinoids. At univariate analysis, histological type (typical or atypical) and Ki67 index significantly correlated with tumor recurrence. The literature review identified 172 previously reported patients with functioning ACTH-secreting lung carcinoids, and the meta-analysis of survival showed that 92% of them were alive after a mean follow-up time of 50 months. Our results demonstrate that ACTH-producing lung carcinoids are not rare, are not always associated with Cushing syndrome, and do not represent an aggressive variant of lung carcinoid.

Combined neoplasms of the lung are defined by the WHO classification as an admixture of a small or large cell neuroendocrine carcinoma and a non-neuroendocrine component. However, rare cases of carcinoids combined with a non-neuroendocrine component have been described. These tumor types are not included as a specific entity in the WHO classification of pulmonary neoplasms and their pathogenesis is still unknown. We describe the clinico-pathologic and molecular features of a mixed (combined) lung neoplasm composed of adenocarcinoma and atypical carcinoid. The NGS analysis of the two different tumor components shows a similar molecular profile suggesting their monoclonal origin from a transformed stem/progenitor tumor cell which acquires a divergent differentiation during its development and progression. We also suggest the use of the recently proposed term of mixed neuroendocrine/non-neuroendocrine neoplasm (MiNEN) to define mixed (combined) neoplasms of the lung, because it seems to better cover the wide spectrum of different possible combinations of neuroendocrine and non-neuroendocrine components.

Background This study aimed to assess the reliability and the validity of a prognostic model of survival recently developed by the European Society of Thoracic Surgery Neuroendocrine Tumor Working Group to predict 5-year overall survival after surgical resection of pulmonary typical carcinoid. Methods We retrospectively collected data on 240 consecutive patients (164 men, 76 women; median age, 58 years [interquartile range, 47 to 68]) who underwent curative lung resection for pulmonary typical carcinoid in seven centers between 2000 and 2015. For each patient, we calculated the corresponding risk class (A, B, C, D) using the following variables: male, age, previous malignancy, Eastern Cooperative Oncology Group performance status, peripheral tumor, TNM stage. Kaplan-Meier method, and Cox proportional hazards model were used for the statistical analysis. Results During a median follow-up of 42 months (interquartile range, 11 to 84), the 5-year overall survival was 94.2% (95% confidence interval [CI]: 90.2% to 98.2%); 15 of 240 patients died. A significantly decreasing rate of survival was observed from class A to class D ( p = 0.004) with rates of 100% (95% CI: 100% to 100%), 96.3% (95% CI: 88.6% to 98.8%), 86.7% (95% CI: 63.0% to 95.7%), and 33.3% (95% CI: 0.9% to 77.4%), respectively, for class A, B, C, and D. This difference persisted also using clinical stage as a variable in the risk class calculation ( p = 0.006). No differences were observed in term of overall survival among TNM stage I, II, and III patients ( p = 0.94). Conclusions This prognostic model of survival is easily applicable, it is validated by our independent cohort, and it appears to stratify better than the traditional TNM staging. Therefore, it may be useful in counseling patients about their outcomes from surgical treatment and in tailoring treatment for high-risk patients.

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.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 (size1 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).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 (P0.001). Center and specimen processing technique were not independent factors affecting EBUS-TBNA diagnostic yield.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.

Assessment of Beta-AR protein expression on tumour tissues might be a plausible strategy to select cancer patients who can benefit from Beta-blockers therapy. The aim of this study is to evaluate the differences between resected tissue specimens from primary lung cancer (adenocarcinoma (ADC) and squamous cell carcinoma (SCC)) in terms of expression pattern of Beta1- and Beta2-AR in both tumour and adjacent surrounding non-tumour tissue. This retrospective study was based on the analysis of 80 patients with histologically confirmed diagnosis of primary Non-Small Cell Lung Cancer (NSCLC) who received surgical treatment. The cases were carefully selected in order to obtain the most homogeneous sample in terms of histologic subtype (40 ADCs and 40 SCCs) and clinical stage (10 each). Beta1- and Beta2-AR expression was determined by immunohistochemistry and the staining evaluated by semi-quantitative scoring using the H-score method. In our NSCLC series, Beta1- and Beta2-AR are differentially expressed. Beta1-AR expression is present at low levels in both SCC and ADC. Likewise, when compared with the matched surrounding non-tumour tissues, Beta1-AR expression level was significantly lower in both histologic subtypes. Conversely, Beta2-AR is highly expressed in both histologic subtypes, but clearly highly expressed in ADC when compared with SCC and with their matched surrounding non-tumour tissue. Overall, this clinicopathological study highlights the differential expression of Beta1- and Beta2-AR in ADC and SCC. Repurposing non-selective Beta-blockers in oncologic setting might be a suitable therapeutic strategy for lung ADC. Graphical abstract.

Minimal knowledge exists regarding the outcome, prognosis and optimal treatment strategy for patients with pulmonary large cell neuroendocrine carcinomas (LCNEC) due to their rarity. We aimed to identify factors affecting survival and recurrence after resection to inform current treatment strategies.We retrospectively reviewed 72 patients who had undergone a curative resection for LCNEC in 8 centers between 2000 and 2015. Univariable and multivariable analyses were performed to identify the factors influencing recurrence, disease-specific survival and overall survival. These included age, gender, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, additional chemo- and/or radiotherapy, tumor location, tumor size, pT, pleural invasion, pN and pStage.Median follow-up was 47 (95%CI 41-79) months; 5-year disease-specific and overall survival rates were 57.6% (95%CI 41.3-70.9) and 47.4% (95%CI 32.3-61.1). There were 22 systemic recurrences and 12 loco-regional recurrences. Tumor size was an independent prognostic factor for systemic recurrence [HR: 1.20 (95%CI 1.01-1.41); p = 0.03] with a threshold value of 3 cm (AUC = 0.71). For tumors ≤3 cm and3 cm, 5-year freedom from systemic recurrence was 79.2% (95%CI 43.6-93.6) and 38.2% (95%CI 20.6-55.6) (p 0.001) and 5-year disease-specific survival was 60.7% (95%CI 35.1-78.8) and 54.2% (95%CI 32.6-71.6) (p = 0.31), respectively.A large proportion of patients with surgically resected LCNEC will develop systemic recurrence after resection. Patients with tumors3 cm have a significantly higher rate of systemic recurrence suggesting that adjuvant chemotherapy should be considered after complete resection of LCNEC3 cm, even in the absence of nodal involvement.

Background The role of sublobar resection in the treatment of pulmonary typical carcinoids is controversial. This study aims to compare long-term outcomes between sublobar and lobar resections in patients with peripheral typical carcinoid. Methods We retrospectively compared consecutive patients who underwent curative sublobar resection with patients who underwent lobectomy for cT1-3 N0 M0 peripheral pulmonary typical carcinoid in eight centers between 2000 and 2015. Primary outcomes were rates and patterns of recurrence and overall survival. Cox regression modeling was performed to identify factors influencing overall survival and recurrence. Propensity score analysis was done, and overall survival was compared between the two groups. Results In all, 177 patients were analyzed, consisting of 74 sublobar resections and 103 lobectomies, with a total of 857 person-years of follow-up. The R1 resection rates were 7% and 1% after sublobar resection and lobectomy, respectively (P = .08). One of 5 patients with sublobar R1 resection had recurrence. Recurrence rate was 0.02 (95% confidence interval [CI]: 0.009 to 0.044) per person-year of follow-up after sublobar resection and 0.008 (95% CI: 0.003 to 0.02) after lobectomy (P = .15). Five-year survival rates were 91.7% (95% CI: 78.5% to 96.9%) and 97.4% (95% CI: 90.1% to 99.4%) after sublobar and lobar resection, respectively (P = .08). Extent of resection was not a predictor of recurrence or survival. Propensity score analysis confirmed a similar survival and freedom from recurrence between the two groups. Conclusions Sublobar resection of peripheral cT1-3 N0 M0 pulmonary typical carcinoid was not associated with worse short- or long-term outcomes compared with lobectomy. In select patients, sublobar resection may be considered for treatment of peripheral typical carcinoids if an R0 resection is obtained.

Objectives Vascular injuries are among the most severe causes of unplanned conversion during VATS lobectomies. The study aimed to analyse the incidence of vascular injuries and their risk factors during VATS lobectomy. Methods The Italian VATS lobectomy Registry was used to collect data from 66 Thoracic Surgery Units. From 2013 to October 2016 (out of more than 3,700 patients enrolled) only information from Units with an enrollment >100 VATS lobectomies were retrospectively analysed. Logistic regression analysis was performed on selected variables of the univariate analysis. Results Ten institutions contributed a total of 1,679 patients. Vascular injuries leading to conversion occurred in 44 (2.6%) patients. Years of experiences were inversely related to the risk of vascular injuries. Univariate analysis showed age, gender, surgical activity, Charlson Index Score and number of resected lymph nodes like significantly associated variables. Multivariate analysis revealed that number of resected lymph nodes, VATS experience ratio (number of VATS lobectomies/total lobectomies performed in the same year at same centre), and surgical activity of the centre were significantly associated with the risk of conversion. Unplanned thoracotomy was correlated with postoperative morbidity. Conclusion Vascular injuries in VATS lobectomies represented a rare complication which could directly affect the postoperative outcomes. The predictive factors for conversion were multifactorial and depended on characteristics of centres and surgeons’ seniority. Minimally invasive VATS lobectomy approaches did not influence the risk of vascular damages.

Objectives Computed tomography (CT)-guided hydrogel plug deployment was recently proposed for lung nodule preoperative localization and simultaneous prevention of pneumothorax. We analysed our initial experience with CT-guided hydrogel plug localization of lung nodules in patients undergoing video-assisted thoracoscopic (VATS) resection. Methods We retrospectively evaluated the medical notes from 27 consecutive patients (mean age 68 ± 11 SD years; men 74%) undergoing VATS lung wedge resection for biopsy or definitive treatment of 28 small pulmonary nodules (malignant 82%) at a single institution between October 2017 and July 2018. Difficult intraoperative nodule localization was anticipated with a lesion 1, ground-glass opacity or the judgement of the operating surgeon. All lesions were preoperatively marked by deployment of a CT-guided hydrogel plug. Study end points were frequency of postlocalization pneumothorax; feasibility of delayed surgery; rate of localization of intraoperative nodule and rate of successful VATS resection. Results The mean sizes of the solid nodules (n = 24) and of the ground-glass opacities (n = 4) were, respectively, 10.4 ± 3.4 mm and 16.0 ± 6.2 mm. One (4%) hydrogel plug marking procedure caused a clinically relevant pneumothorax. Nodule resection was scheduled flexibly as required by patient management/operating room scheduling: same day (11 nodules) or delayed [median 6 days (range 1-60 days)]; (17 nodules). All nodules were localized intraoperatively: 25 (89%) by hydrogel plug; 3 (11%) by palpation and pleural puncture hole visible after plug displacement. All nodules were completely excised by VATS, without complications. Conclusions CT-guided hydrogel plug marking was valuable for VATS localization and resection of challenging lung nodules. The plug minimized clinically relevant pneumothoraxes and allowed flexible surgical schedules.

Objective: The objective of the study is to analyse the causes and impact of conversion from VATS to thoracotomy identifying any possible pre-operative risk factors and related consequences. Methods: Data from patient who underwent VATS lobectomy (VATS-L) for NSCLC at VATS Group participating centres were retrospectively analysed and divided in two groups: patients treated with VATS-L and patients who suffered from conversion. Predictors of conversion were assessed with univariate and multivariable exact logistic regression. Complications were evaluated as dependent variables of conversion in a Cox multivariable logistic regression model. Results: A total of 4629 patients underwent planned VATS-L for NSCLC and of these, 432 (9.3%) required conversion; the most frequent causes were bleeding (30.4%) and fibro-calcified hilar lymph nodes (23.9%). The independent risk factors at multivariable analysis model were sex male (OR 1.458, p < 0.01), age older than 70years (OR 1.248, p = 0.036) and the clinically node-positive disease (OR 2.258, p < 0.01). The mortality rate was similar, but the percentage of patients who suffered from any complication (41.7% vs 24.4%, p < 0.01), the complication rate (65% vs 32.2%, p < 0.01), chest tube duration (p < 0.01) and the hospitalisation rate (p < 0.01) were higher for patients converted. Atrial fibrillation (OR 1.471, p = 0.019), prolonged air leak (OR 1.403, p = 0.043), blood transfusions (OR 4.820, p < 0.01), sputum retention (OR 1.80, p = 0.027) and acute kidney failure (OR 2.758, p = 0.03) were significantly associated with conversion at multivariable analysis. Conclusions: Conversion is associated with increased surgical morbidity, blood loss and hospital stay. Sex male, old age and the clinical involvement of lymph nodes were the strongest predictors of conversion.

Background: The published circulating miRNA signatures proposed for early-stage non–small cell lung cancer (NSCLC) detection are inconsistent and difficult to replicate. Reproducibility and validation of an miRNA simple signature of NSCLC are prerequisites for translation to clinical application. Methods: The serum level of miR-223 and miR-29c, emerging from published studies, respectively, as a highly sensitive and a highly specific biomarker of early-stage NSCLC, was measured with droplet digital PCR (ddPCR) technique in an Italian cohort of 75 patients with stage I–II NSCLC and 111 tumor-free controls. By ROC curve analysis we evaluated the miR-223 and miR-29c performance in discerning NSCLC cases from healthy controls. Results: Reproducibility and robust measurability of the two miRNAs using ddPCR were documented. In a training set (40 stage I–II NSCLCs and 56 controls), miR-223 and miR-29c, respectively, showed an AUC of 0.753 [95% confidence interval (CI), 0.655–0.836] and 0.632 (95% CI, 0.527–0.729) in identifying NSCLC. Combination of miR-223 with miR-29c yielded an AUC of 0.750, not improved over that of miR-223 alone. Furthermore, in an independent blind set (35 stage I–II NSCLCs and 55 controls), we validated serum miR-223 as an effective biomarker of stage I–II NSCLC (AUC = 0.808; 95% CI, 0.712–0.884), confirming the miR-223 diagnostic performance reported by others in Chinese cohorts. Conclusions: Using ddPCR technology, miR-223 was externally validated as a reproducible, effective serum biomarker of early-stage NSCLC in ethnically different subjects. Combination with miR-29c did not improve the miR-223 diagnostic performance. Impact: Serum miR-223 determination may be proposed as a tool for refining NSCLC risk stratification, independent of smoking habit and age.

We review the clinical and pathologic features of seven cases of papillary carcinoma of the thyroid that invaded the trachea and were treated by thyroidectomy, airway resection with reconstructive surgery over an interval of 15 years. We depicted the peculiarity of invasion of well differentiated papillary thyroid carcinoma (PTC) cells is perpendicularly oriented to the tracheal lumen, in between cartilaginous rings, along blood vessels and collagen fibers. Tracheal rings appear non-infiltrated in all histological sections of well differentiated PTC infiltrating the trachea. Similar description of inter-cartilage PTC infiltration into the trachea was first provided by Shin et al. in 1993. Interestingly, our pathological revision support the estimation by Shin et al., though that cartilage rings infiltration did occur in poorly differentiated thyroid cancers with exiguous prognosis.

OBJECTIVES Kinesiology taping (KT) is a rehabilitative technique performed by the cutaneous application of a special elastic tape. We tested the safety and efficacy of KT in reducing postoperative chest pain after lung lobectomy. METHODS One-hundred and seventeen consecutive patients, both genders, age 18-85, undergoing lobectomy for lung cancer between January 2013 and July 2015 were initially considered. Lobectomies were performed by the same surgical team, with thoracotomy or video-assisted thoracoscopic surgery (VATS) access. Exclusion criteria (n = 25 patients) were: previous KT exposure, recent trauma, pre-existing chest pain, lack of informed consent, >24-h postoperative intensive care unit treatment. After surgery, the 92 eligible patients were randomized to KT experimental group (n = 46) or placebo control group (n = 46). Standard postoperative analgesia was administered in both groups (paracetamol/non-steroidal anti-inflammatory drugs, epidural analgesia including opioids), with supplemental analgesia boluses at patient request. On postoperative day 1 in addition, in experimental group patients a specialized physiotherapist applied KT, with standardized tape length, tension and shape, over three defined skin areas: at the chest access site pain trigger point; over the ipsilateral deltoid/trapezius; lower anterior chest. In control group, usual dressing tape mimicking KT was applied over the same areas, as placebo. Thoracic pain severity score [visual analogue scale (VAS) ranging 0-10] was self-assessed by all patients on postoperative days 1, 2, 5, 8, 9 and 30. RESULTS The KT group and the control group had similar demographics, lung cancer clinico-pathological features and thoracotomy/VATS ratio. Postoperatively, the two groups also resulted similar in supplemental analgesia, complication rate, mean duration of chest drainage and length of stay. There were no adverse events with KT application. After tape application, KT patients reported overall less thoracic pain than the control group, the difference being significant on postoperative day 5 [median VAS, 2 (interquartile range, 1-3) vs 3 (2-5), P < 0.01] and day 8 [median VAS, 1 (0-2) vs 2 (1-3), P < 0.05]. Moreover, on postoperative day 30 persistence of chest pain (VAS ≥3) was reported less frequently by the KT group than by the control group (7 vs 24%; P = 0.03). CONCLUSIONS KT after lung lobectomy is a safe and effective auxiliary technique for chest pain control. ISRCTN REGISTRY ISRCTN37253470.

Natural killer (NK) cells are crucial in tumor recognition and eradication, but their activity is impaired in cancer patients, becoming poorly cytotoxic. A particular type of NK cells, from the decidua, has low cytotoxicity and shows proangiogenic functions. We investigated whether NK cells from peripheral blood (PB) and pleural effusions of patients develop decidual-like NK phenotype and whether exposure to IL-2 can restore their killing ability in the presence of pleural fluids. NK cells from pleural effusion of patients with inflammatory conditions (iPE, n = 18), primary tumor (ptPE, n = 18), and metastatic tumor (tmPE, n = 27) acquired the CD56brightCD16− phenotype. NK cells from both ptPE and tmPE showed increased expression for the CD49a and CD69 decidual-like (dNK) markers and decreased levels of the CD57 maturation marker. NK from all the PE analyzed showed impaired degranulation capability and reduced perforin release. PE-NK cells efficiently responded to IL-2 stimulation in vitro. Addition of TGFβ or cell-free pleural fluid to IL-2 in the culture medium abrogated NK cell CD107a and IFNγ expression even in healthy donors (n = 14) NK. We found that tmPE-NK cells produce VEGF and support the formation of capillary-like structures in endothelial cells. Our results suggest that the PE tumor microenvironment can shape NK cell polarization towards a low cytotoxic, decidual-like, highly proangiogenic phenotype and that IL-2 treatment is not sufficient to limit this process.

Objective Neuroendocrine tumors of the lung are currently staged with the 7th edition TNM non–small cell lung cancer staging system. This decision, based on data analysis without data on histology or disease-specific survival, makes its applicability limited. This study proposes a specific staging system for these tumors. Methods We retrospectively analyzed 510 consecutive patients (female/male, 313/197; median age, 61 years; interquartile range, 51-70) undergoing lung resection for a primary neuroendocrine tumor between 2000 and 2015 in 8 centers. Multivariable analysis was performed using a Cox proportional hazard model to identify factors associated with disease-specific survival. A new staging system was proposed on the basis of the results of this analysis. Kaplan–Meier disease-specific survival was analyzed by stage using the proposed and the 7th TNM staging system. Results Follow-up was completed in 490 of 510 patients at a median of 51 months (interquartile range, 18-99). Histology (G1-typical carcinoid vs G2-atypical carcinoid vs G3-large-cell neuroendocrine carcinoma) and pT were independently associated with survival, but pN was not. After regrouping histology and pT, we proposed the following staging system: IA (pT1-2G1), IB (pT3G1, pT1G2), IIA (pT4G1, pT2-3G2, pT1G3), IIB (pT4G2, pT2-3G3), and III (pT4G3). The 5-year survivals were 97.9%, 81.0%, 69.1%, 51.8%, and 0%, respectively. By using the 7th TNM, 5-year survivals were 95.0%, 92.3%, 67.7%, 70.9%, and 65.1% for stage IA, IB, IIA, IIB, and III, respectively. Conclusions Incorporating histology and regrouping tumor stage create a unique neuroendocrine tumor staging system that seems to predict survival better than the 7th TNM classification.

Background: The presence of air leak following lung resection remains a frequent problem, which may prolong hospital stay and increase hospital costs. In the past, some studies documented the efficacy of soft and flexible chest tube in patients who underwent thoracic surgery. Nevertheless, safety in case of post-operative large air or liquid leak remains questionable. The objective of this study was to verify through a multicentre study the safety and the effectiveness of the coaxial chest tube in a consecutive series of selected patients who underwent anatomical pulmonary resection and with an active and large air leak. Methods: Between October 2016 and September 2017, data from patients submitted to anatomical lung resection with curative intent and operated in two Department of Thoracic Surgery of two different were prospectively collected. The inclusion criteria consisted in the presence of an air leak greater than 50 mL/min measured with a digital drainage system during the 3 postoperative hours. A descriptive statistic was used to report the incidence of complications assumed to be associated with the use of the coaxial drain. Results: Forty-eight consecutive patients (27 males) submitted to lobectomy (37 patients: 77%) or anatomic segmentectomies (11 patients) were included in the analyses. Thirty-four operations (71%) were performed by video-assisted thoracic surgery (VATS). The median duration of chest tubes was 13 days [interquartile range (IQR), 4–19] and the median duration of air leak was 9 days (IQR, 2–17.5). No patient had undrained postoperative pleural effusion judged to require an additional chest tube placement. There were 12 (25%) cases of clinically or radiologically significant surgical emphysema; in none of these patients any additional procedure or re-operation was required, and they were treated conservatively by increasing the level of suction. Conclusions: Our experience with this novel Coaxial Drain was satisfactory with no clinically relevant complication caused using this drain, no need to insert additional drain or replace the existing one with another drain a duration of air leak and chest tubes as well as the incidence of subcutaneous emphysema that was in line with what observed in the daily practice in similar highly selected patients with large air leak.