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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.

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

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.

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.

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.

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.

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.

Objectives We hypothesize that selected genetic and/or epigenetic changes associated with advanced tumours may help identifying early non-small cell lung cancers (NSCLCs) that recur after resection. Among epigenetic changes, long interspersed nuclear element-1 (LINE-1) hypomethylation is seen early during carcinogenesis and may act in concert with genetic alterations to cancer progression. LINE-1 hypomethylation and gene mutations frequently involved in lung cancer, were analysed to evaluate their prognostic role in resected stage I NSCLC. Methods Gene mutations and LINE-1 methylation were analysed in 167 Caucasian patients with stage I NSCLC, namely 100 adenocarcinomas (ADC) and 67 squamous-cell carcinomas (SqCC), using mass-spectrometry and pyrosequencing. We evaluated the correlation between molecular results and clinico-pathological data: age, gender, smoking status, period of surgery, histology, grading, pathological stage, p53 expression, LINE-1 hypomethylation. These variables have been assessed as possible predictors of cancer related survival by regression analysis. Results Frequency and spectrum of gene mutations were significantly different in ADCs compared with SqCCs. p53 positivity was more common in SqCC, while EGFR or KRAS mutations were mainly detected in ADC. LINE1 hypomethylation was associated with SqCC histology, p53 immunoreactivity and smoking habit. Stage IB, LINE-1 hypomethylation and PIK3CA mutation independently predicted a worse cancer-related survival. When combined into a scoring system, their prognostic power was strengthened. Conclusions In many stage I NSCLC a mutation pattern of advanced disease was observed. Stage IB, LINE-1 hypomethylation and PIK3CA mutation were associated to poor prognosis. Genetic and epigenetic events occurring in early carcinogenesis may help identifying stage I NSCLC patients who deserve adjuvant therapy.

Background: The optimal method for specimen preparation of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) is still controversial. This study aims to compare several techniques available for EBUS-TBNA specimen acquisition and processing, in order to identify the best performing technique. Methods: We retrospectively reviewed the data of 199 consecutive patients [male, 73%; median age, 64 years (IQR: 52–74 years)] undergoing EBUS-TBNA at our institution from 2012 through 2014 for diagnosis of hilar-mediastinal lymph node enlargement suspect of neoplastic (n=139) or granulomatous (n=60) disease. All procedures were performed by two experienced bronchoscopists, under conscious sedation and local anaesthesia, using 21/22-Gauge (G) needle, without rapid on-site evaluation (ROSE). Five specimen-processing techniques were used: cytology slides in 42 cases (21%); cell-block in 25 (13%); core-tissue in 60 (30%); combination of cytology slides and core-tissue in 51 (26%); combination of cytology slides and cell-block in 21 (10%). To assess the diagnostic accuracy of each tissue-processing technique we compared the EBUS-TBNA results to those obtained with surgical lymphadenectomy, or 1-year follow-up in non-operated patients. Results: Diagnostic yield, accuracy and area under the curve (AUC) were as follows. Cytology slides: 81%, 80%, 0.90; cell-block: 48%, 33%, 0.67; core-tissue: 87%, 99%, 0.96; cytology slides + core-tissue: 80%, 100%, 1.00; cytology slides + cell-block: 86%, 100%, 1.00. Cytology slides and core-tissue method showed non-significantly different diagnostic yield (P=0.435) and AUC (P=0.152). Conclusions: In our single-institution experience, cytology slides and core-tissue preparations demonstrated high and similar diagnostic performance. Cytology slides combination with core-tissue or cell-block showed the highest performance, however these combination methods were more resource-consuming.

The Society for Translational Medicine and The Chinese Society for Thoracic and Cardiovascular Surgery conducted a systematic review of the literature in an attempt to improve our understanding in the postoperative management of chest tubes of patients undergoing pulmonary lobectomy. Recommendations were produced and classified based on an internationally accepted GRADE system. The following recommendations were extracted in the present review: (I) chest tubes can be removed safely with daily pleural fluid of up to 450 mL (non-chylous and non-sanguinous), which may reduce chest tube duration and hospital length of stay (2B); (II) in rare instances, e.g., persistent abundant fluid production, the use of PrRP/B

Thyroidectomy associated to en bloc tracheal resection with end-to-end anastomosis is the treatment of choice of thyroid tumor invading the tracheal wall and is associated with a good prognosis. However, the postoperative morbidity is not irrelevant. The present review aims to discuss the complications occurring after this aggressive surgical procedure. The search was performed using PubMed through an overarching for the following terms: "complication of tracheal resection [AND] invasive thyroid cancer". Postoperative complications rate after tracheal sleeve resection with end-to-end anastomosis for thyroid cancer invading tracheal wall range from 15% to 39%. Postoperative mortality is about 1.2%. The most common postoperative complications are: anastomotic dehiscence, airway stenosis, infections and bleeding. Tumor local recurrence can be considered a late on set complication. To conclude, in locally invasive thyroid cancer, en bloc resection of the thyroid with the tracheal segment interested by the tumor provides a good prognosis despite the non-negligible postoperative morbidity rate. Patients' selection and accurate surgical technique performing a tracheal tension-free anastomosis are mandatory to reduce postoperative morbidity and mortality.

In the article that appeared on page 2061-2070, Vol 9, No 7 (July 2017) Issue of the Journal of Thoracic Disease (1), there are some mistakes in the presented authors information. In the list of collaborators of the Italian VATS Group are not included the following author names: Alessandro Bertani, Alessandro Gonfiotti, Mario Nosotti, Paolo Albino Ferrari, Lavinia De Monte, Emanuele Russo, Gioacchino Di Paola, Piergiorgio Solli, Andrea Droghetti, Luca Bertolaccini, Roberto Crisci. The correct list of collaborators of the Italian VATS Group should have been shown as below. Alessandro Bertani, MD (IRCCS ISMETT, Palermo); Alessandro Gonfiotti, MD (Careggi Hospital, Firenze); Mario Nosotti, MD (Policlinico Ca'Granda, Milano); Paolo Albino Ferrari, MD (IRCCS ISMETT, Palermo); Lavinia De Monte, MD (IRCCS ISMETT, Palermo); Emanuele Russo, MD (IRCCS ISMETT, Palermo); Gioacchino Di Paola, MD (IRCCS ISMETT, Palermo); Piergiorgio Solli, MD PhD (AUSL Romagna Teaching Hospital, Forlì); Andrea Droghetti, MD (ASST Mantova-Cremona, Mantova); Luca Bertolaccini, MD PhD (AUSL Romagna Teaching Hospital, Forlì); Roberto Crisci, MD PhD (Università dell'Aquila, L'Aquila); Carlo Curcio, MD (Monaldi Hospital, Napoli); Dario Amore, MD (Monaldi Hospital, Napoli); Giuseppe Marulli, MD (University of Padova); Samuele Nicotra, MD (University of Padova); Andrea De Negri, MD (San Martino Hospital, Genova); Paola Maineri, MD (San Martino Hospital, Genova); Gaetano di Rienzo (Vito Fazzi Hospital, Lecce); Camillo Lopez, MD (Vito Fazzi Hospital, Lecce); Angelo Morelli, MD (S. Maria delle Misericordia Hospital, Udine); Francesco Londero, MD (S. Maria delle Misericordia Hospital, Udine); Lorenzo Spaggiari, MD (IEO Hospital, Milano); Roberto Gasparri, MD (IEO Hospital, Milano); Guido Baietto, MD (Maggiore della Carità Hospital, Novara); Caterina Casadio, MD (Maggiore della Carità Hospital, Novara); Maurizio Infante, MD (Borgo Trento Hospital, Verona); Cristiano Benato, MD (Borgo Trento Hospital, Verona); Marco Alloisio, MD (IRCCS Humanitas, Milano); Edoardo Bottoni, MD (IRCCS Humanitas, Milano); Giuseppe Cardillo, MD (Forlanini Hospital, Roma); Francesco Carleo, MD (Forlanini Hospital, Roma); Franco Stella, MD (S. Orsola Hospital, Bologna); Giampiero Dolci, MD (S. Orsola Hospital, Bologna); Francesco Puma, MD (University of Perugia); Damiano Vinci, MD (University of Perugia); Giorgio Cavallesco, MD (University of Ferrara); Pio Maniscalco, MD (University of Ferrara); Luca Ampollini, MD (University of Parma); Paolo Carbognani, MD (University of Parma); Alberto Terzi, MD (Negrar Hospital, Verona); Andrea Viti, MD (Negrar Hospital, Verona); Giampiero Negri, MD (S. Raffaele Hospital, Milano); Alessandro Bandiera, MD (S. Raffaele Hospital, Milano); Reinhold Perkmann, MD (Bolzano Hospital, Bolzano); Francesco Zaraca, MD (Bolzano Hospital, Bolzano); Claudio Andretti, MD (S. Andrea Hospital, Roma); Camilla Poggi, MD (S. Andrea Hospital, Roma); Felice Mucilli, MD (S. Maria Annunziata Hospital, Chieti); Pierpaolo Camplese, MD (S. Maria Annunziata Hospital, Chieti); Luca Luzzi, MD (University of Siena); Marco Ghisalberti, MD (University of Siena); Andrea Imperatori, MD (University of Varese); Nicola Rotolo, MD (University of Varese); Luigi Bortolotti, MD (Humanitas Gavazzeni Hospital, Bergamo); Giovanna Rizzardi, MD (Humanitas Gavazzeni Hospital, Bergamo); Massimo Torre, MD (Niguarda Hospital, Milano); Alessandro Rinaldo, MD (Niguarda Hospital, Milano); Armando Sabbatini, MD (Ospedali Riuniti, Ancona); Majed Refai, MD (Ospedali Riuniti, Ancona); Mauro Roberto Benvenuti, MD (Spedali Civili, Brescia); Diego Benetti, MD (Spedali Civili, Brescia); Alessandro Stefani, MD (Ospedale Policlinico, Modena); Pamela Natali, MD (Ospedale Policlinico, Modena); Paolo Lausi, MD (Ospedale Molinette, Torino); Francesco Guerrera, MD (Ospedale Molinette, Torino).

Background Selected microRNAs (miRNAs) that are abnormally expressed in the serum of patients with lung cancer have recently been proposed as biomarkers of this disease. The measurement of circulating miRNAs, however, requires a highly reliable quantification method. Quantitative real-time PCR (qPCR) is the most commonly used method, but it lacks reliable endogenous reference miRNAs for normalization of results in biofluids. When used in absolute quantification, it must rely on the use of external calibrators. Droplet digital PCR (ddPCR) is a recently introduced technology that overcomes the normalization issue and may facilitate miRNA measurement. Here we compared the performance of absolute qPCR and ddPCR techniques for quantifying selected miRNAs in the serum. Results In the first experiment, three miRNAs, proposed in the literature as lung cancer biomarkers (miR-21, miR-126 and let-7a), were analyzed in a set of 15 human serum samples. Four independent qPCR and four independent ddPCR amplifications were done on the same samples and used to estimate the precision and correlation of miRNA measurements obtained with the two techniques. The precision of the two methods was evaluated by calculating the Coefficient of Variation (CV) of the four independent measurements obtained with each technique. The CV was similar or smaller in ddPCR than in qPCR for all miRNAs tested, and was significantly smaller for let-7a (p = 0.028). Linear regression analysis of the miRNA values obtained with qPCR and ddPCR showed strong correlation (p

In a lung cancer survey in 2000 we showed significantly less favourable stage distribution and lower resection rate in Teesside (UK) than in the comparable industrialised area of Varese (Italy). Lung cancer services in Teesside were subsequently reorganised according to National Cancer Plan recommendations.For all new lung cancer cases diagnosed in Teesside (n=324) and Varese (n=260) during the 12 months October 2010 to September 2011 (hereafter 'the 2010 cohort'), demographic, clinico-pathological and disease management data were prospectively recorded using the same database and protocol as the 2000 survey. Findings were analysed focusing on resection rate.In the 2010 cohort compared with 2000, both in Teesside and Varese emergency referral decreased (p0.001), performance status improved (p0.001), but cancer stage shift was not seen; resection rate improved in Teesside, from 7% to 11% (p=0.054), and was unchanged in Varese (24%). Moreover, in Teesside compared with Varese the stage distribution remained less favourable, stage I-II non-small cell lung cancer (NSCLC) proportion being respectively 12% and 19% (p=0.040), and resection rate in all lung cancers remained lower (11% and 24%; p0.001). On multivariate analysis, resection predictors in Teesside were as follows: stage I-II NSCLC (OR 86.14; 95% CI 31.80 to 233.37), performance status 0-1 (OR 5.02; 95% CI 1.48 to 17.07), belonging to 2010 cohort (OR 2.85; 95% CI 1.06 to 7.64).In Teesside the main independent predictor of resection was disease stage; in 2010-2011 compared with 2000, lung cancer service improved but stage shift did not occur, and resection rate increased but remained significantly lower than in Varese.

Recent studies suggested that human CD56brightCD16− NK cells may play a role in the regulation of the immune response. Since the mechanism(s) involved have not yet been elucidated, in the present study we have investigated the role of nucleotide-metabolizing enzymes that regulate the extracellular balance of nucleotides/nucleosides and produce the immunosuppressive molecule adenosine (ADO). Peripheral blood CD56dimCD16+ and CD56brightCD16− NK cells expressed similar levels of CD38. CD39, CD73, and CD157 expression was higher in CD56brightCD16− than in CD56dimCD16+ NK cells. CD57 was mostly expressed by CD56dimCD16+ NK cells. CD203a/PC-1 expression was restricted to CD56brightCD16− NK cells. CD56brightCD16− NK cells produce ADO and inhibit autologous CD4+ T cell proliferation. Such inhibition was 1) reverted pretreating CD56brightCD16− NK cells with a CD38 inhibitor and 2) increased pretreating CD56brightCD16− NK cells with a nucleoside transporter inhibitor, which increase extracellular ADO concentration. CD56brightCD16− NK cells isolated from the synovial fluid of juvenile idiopathic arthritis patients failed to inhibit autologous CD4+ T cell proliferation. Such functional impairment could be related to 1) the observed reduced CD38/CD73 expression, 2) a peculiar ADO production kinetics, and 3) a different expression of ADO receptors. In contrast, CD56brightCD16− NK cells isolated from inflammatory pleural effusions display a potent regulatory activity. In conclusion, CD56brightCD16− NK cells act as “regulatory cells” through ADO produced by an ectoenzymes network, with a pivotal role of CD38. This function may be relevant for the modulation of the immune response in physiological and pathological conditions, and it could be impaired during autoimmune/inflammatory diseases.

Background Treatment of pulmonary recurrence from colorectal cancer involving the main bronchus usually entails palliation using interventional bronchoscopy, because the prognosis is generally very poor. Surgical experience has clarified that in this setting pneumonectomy should only be performed in carefully selected patients showing favorable prognostic profiles (defined by low carcinoembryonic antigen serum levels pre-thoracotomy), solitary and completely resectable pulmonary metastasis, and long disease-free intervals. In the few long-term survivors after pneumonectomy for late-recurrent colorectal cancer, the disease has a relatively indolent metastatic course and genetic and epigenetic profiling may provide further insight regarding tumor evolution. Case presentation We describe a rare case of late hilar-endobronchial and lymph nodal recurrence of rectal cancer, sequential to hepatic metastasectomy, that we successfully treated with pneumonectomy and chemotherapy (leucovorin, 5-fluorouracil and oxaliplatin regimen); the patient achieved 7-year relapse-free survival after lung metastasectomy and 24-year overall survival after primary rectal cancer resection. To our knowledge, this is the longest survival reported after sequential liver resection and pneumonectomy for recurrent colorectal cancer. In our case the primary rectal cancer and its recurrences showed identical immunohistochemical patterns. The primary rectal cancer and the matched metastases (hepatic, pulmonary and lymph nodal) demonstrated no KRAS, NRAS, BRAF and PIK3CA mutations, a microsatellite stable phenotype, and no tumor protein p53 alterations or recurrent copy number alterations on chromosome 8. High genetic concordances between the paired primary tumor and metastases suggest that the key tumor biological traits remained relatively conserved in the three metastatic sites. Minor differences in gene specific hypermethylation were observed between the primary tumor and lung and nodal metastases. These differences suggest that epigenetic mechanisms may be causally involved in the microenvironmental regulation of cancer metastasis. Conclusion The exceptionally long survival of the patient in our case study involving favorable clinical features was related to an excellent response to surgery and adjuvant chemotherapy; however, genetic or epigenetic factors that remain unidentified cannot be excluded as contributory factors. Our findings support the concept of a common clonal origin of the primary cancer and synchronous and late metastases, and suggest that aberrant DNA methylation may regulate tumor dormancy mechanisms.

The tumor microenvironment can polarize innate immune cells to a proangiogenic phenotype. Decidual natural killer (dNK) cells show an angiogenic phenotype, yet the role for NK innate lymphoid cells in tumor angiogenesis remains to be defined. We investigated NK cells from patients with surgically resected non-small cell lung cancer (NSCLC) and controls using flow cytometric and functional analyses. The CD56(+)CD16(-) NK subset in NSCLC patients, which represents the predominant NK subset in tumors and a minor subset in adjacent lung and peripheral blood, was associated with vascular endothelial growth factor (VEGF), placental growth factor (PIGF), and interleukin-8 (IL-8)/CXCL8 production. Peripheral blood CD56(+)CD16(-) NK cells from patients with the squamous cell carcinoma (SCC) subtype showed higher VEGF and PlGF production compared to those from patients with adenocarcinoma (AdC) and controls. Higher IL-8 production was found for both SCC and AdC compared to controls. Supernatants derived from NSCLC CD56(+)CD16(-) NK cells induced endothelial cell chemotaxis and formation of capillary-like structures in vitro, particularly evident in SCC patients and absent from controls. Finally, exposure to transforming growth factor-β(1) (TGFβ(1)), a cytokine associated with dNK polarization, upregulated VEGF and PlGF in peripheral blood CD56(+)CD16(-) NK cells from healthy subjects. Our data suggest that NK cells in NSCLC act as proangiogenic cells, particularly evident for SCC and in part mediated by TGFβ(1).

Background Atrial fibrillation (AF) after thoracic surgery is a continuing source of morbidity and mortality. The effect of postoperative AF on long-term survival however has not been studied. Our aim was to evaluate the impact of AF on early outcome and on survival > 5 years after pulmonary lobectomy for lung cancer. Methods From 1996 to June 2009, 454 consecutive patients undergoing lobectomy for lung cancer were enrolled and followed-up until death or study end (October 2010). Patients with postoperative AF were identified; AF was investigated with reference to its predictors and to short- and long-term survival (> 5 years). Results Hospital mortality accounted for 7 patients (1.5%), while postoperative AF occurred in 45 (9.9%). Independent AF predictors were: preoperative paroxysmal AF (odds ratio [OR] 5.91; 95%CI 2.07 to 16.88), postoperative blood transfusion (OR 3.61; 95%CI 1.67 to 7.82) and postoperative fibro-bronchoscopy (OR 3.39; 95%CI 1.48 to 7.79). Patients with AF experienced higher hospital mortality (6.7% vs. 1.0%, p = 0.024), longer hospitalization (15.3 ± 10.1 vs. 12.2 ± 5.2 days, p = 0.001) and higher intensive care unit admission rate (13.3% vs. 3.9%, p = 0.015). The median follow-up was 36 months (maximum: 179 months). Among the 445 discharged subjects with complete follow-up, postoperative AF was not an independent predictor of mortality; however, among the 151 5-year survivors, postoperative AF independently predicted poorer long-term survival (HR 3.75; 95%CI 1.44 to 9.08). Conclusion AF after pulmonary lobectomy for lung cancer, in addition to causing higher hospital morbidity and mortality, predicts poorer long-term outcome in 5-year survivors.

International audience; It has been confirmed recently that the volunteer effect in lung cancer screening is characterized by higher lung cancer mortality risk in self-selected screening participants. The Mayo Lung Project, the most influential trial of screening for lung cancer ever completed, was conducted in Mayo Clinic outpatients, with a peculiar study design that rendered the randomization vulnerable to the volunteer effect. Of all nonvolunteers randomized in the Mayo Lung Project, only those allocated in the screened group were asked consent to participate in the trial. The final Mayo Lung Project report stated that 655 randomized nonvolunteers refused screening and were excluded from the study, thus documenting violation of the rule that no selection should occur after randomization. The long-term follow-up of the Mayo Lung Project showed an enigmatic result which has never been explained: the lung cancer mortality was 13% higher in the screening intervention group than in the control group [4.4 (95% CI 3.9-4.9) vs. 3.9 (95% CI 3.5-4.4) per 1,000 person-years; = 0.09]. Such overrepresented mortality is consistent with the volunteer effect and supports the concept that the Mayo Lung Project randomization was compromised by the post-randomization self-selection of participant nonvolunteers.

To the Editor: Paracardiac paragangliomas are very rare. A catecholamine-producing intrapericardial paraganglioma has never been described previously in the context of multiple endocrine neoplasia (MEN) IIA syndrome.1,2 We report the case of a patient with MEN IIA syndrome and secondary hypertension caused by functioning paraganglioma exceptionally located intrapericardially. A 34-year–old woman presented with recent episodes of headache, palpitation, and flushing. For several months she had arterial hypertension controlled by ramipril; however, she reported high blood pressure spikes (180/90 mm Hg). Moreover, her sister was diagnosed with medullary thyroid cancer. Examination of the patient's neck demonstrated a small lump in the left thyroid lobe. Aspiration cytology of the nodule (1 cm) revealed a medullary thyroid carcinoma cell pattern. Thyrocalcitonin serum level was high (217.6 pg/mL; normal

In recent years, there has been increased interest in the vascular component of airway remodelling in chronic bronchial inflammation, such as asthma and COPD, and in its role in the progression of disease. In particular, the bronchial mucosa in asthmatics is more vascularised, showing a higher number and dimension of vessels and vascular area. Recently, insight has been obtained regarding the pivotal role of vascular endothelial growth factor (VEGF) in promoting vascular remodelling and angiogenesis. Many studies, conducted on biopsies, induced sputum or BAL, have shown the involvement of VEGF and its receptors in the vascular remodelling processes. Presumably, the vascular component of airway remodelling is a complex multi-step phenomenon involving several mediators. Among the common asthma and COPD medications, only inhaled corticosteroids have demonstrated a real ability to reverse all aspects of vascular remodelling. The aim of this review was to analyze the morphological aspects of the vascular component of airway remodelling and the possible mechanisms involved in asthma and COPD. We also focused on the functional and therapeutic implications of the bronchial microvascular changes in asthma and COPD.

During recent years there has been a growing interest in using non-invasive biomarkers to understand and monitor the airway inflammation in subjects with respiratory tract disorders. To date, the best validated and performing non-invasive biomarkers are measures of inflammation in induced sputum in both cellular and fluid phase, which can provide biological insights into the pathogenesis of respiratory diseases such as asthma and chronic obstructive pulmonary disease. The purpose of this review is to examine the principal literature on the different markers of inflammation in pulmonary diseases assessed by induced sputum analysis in either cellular or fluid phase.

Surgical resection is the treatment of choice of pulmonary metastases from colorectal cancer. We retrospectively reviewed our experience of pulmonary resections of single metastases from colorectal cancer, in order to document postoperative clinical outcome and survival.In the years 1997-2007, in 23 patients we performed 26 curative resections of pulmonary metastases from colorectal cancer (19 rectal and 7 colon; 12 males and 11 females; mean age 64.5 years). All patients had single lung metastasis. Three of the 23 patients underwent re-resection of the lung for treatment of a subsequent lung metastasis. Interval between resection of primary tumor and diagnosis of lung metastasis (disease-free interval (DFI)) was36 months in 19 patients (73%) and was36 months in 7 patients (27%). In 21 patients the metastases were metachronous; in 2 patients metastases were synchronous with primary colorectal cancer. The type of lung resection was wedge resection in 18 cases (70%); lobectomy in 6 cases (23%); pneumonectomy in 2 cases (7%). Of the 18 wedge resections, 12 (66%) were done thoracoscopically. After lung metastasectomy patients were followed up for 5-121 months (median: 61 months).We had 1 early postoperative mortality (after re-resection) from cardiac complication (3.8%). Postoperative morbidity (within 30 days) was observed in 7 cases (27%): 1 pneumonia, 1 empyema, 1 arrhythmia and 4 prolonged air leaks requiring chest drainage7 days. Median survival was 74 months (Kaplan-Meier).Resection of single metachronous lung metastases from colorectal cancer has low mortality and morbidity and in our experience it correlated with prolonged postoperative survival. Re-resection of the lung for treatment of subsequent metachronous metastases carries higher risk.

The effects of different marine derived agents were studied in A549 cell growth. These drugs induced cell cycle arrest at the G2-M phase associated with the up-regulation of GADD45alpha-gamma and down-regulation of c-Myc. In treated cells, GADD45alpha-gamma and c-Myc were up- and down-regulated, respectively. A cascade of events leading to apoptotic mitochondrial 'intrinsic' pathway was observed in treated cells: (1) dephosphorylation of BAD serine136; (2) BAD dissociation from 14-3-3 followed by its association with BCL-XL; (3) cytochrome c release; (4) caspase-3 activation, and (5) cleavage of vimentin. Caspase(s) inhibitor prevented the formation of cleavage products and, in turn, apoptosis was inhibited through a p53-independent mechanism. Moreover, these compounds did not activate NF-kappaB. Our findings may offer new insights into the mechanisms of action of these agents in A549 cells. The better understanding of their effects might be important to fully exploit the potential of these new drugs.