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OBJECTIVES Only few studies compared the surgical morbidity and mortality of thoracoscopic segmentectomy versus lobectomy for non-small-cell lung cancer, in particular, by relating the segmental resections with the corresponding anatomical lobes. METHODS We enrolled a total of 7487 patients who underwent VATS lobectomy (7269) or segmentectomy (218) from January 2014 to July 2019. A propensity score matching approach was used to account for potential confounding factors between the 2 groups. After matching, 349 lobectomies and 208 segmentectomies were included in the analysis. We analysed the operative and postoperative outcomes of video-assisted anatomical segmentectomy compared with video-assisted lobectomy and, in details, the results of segmentectomy with its corresponding lobectomy in a large cohort of patients from the Italian VATS Group Registry. RESULTS The overall conversion rate to thoracotomy was not statistically different between the groups (27 patients 8% vs 7 patients 3%, P = 0.1). The lobectomy group had a greater number of resected lymph nodes (median 11 vs 8, P = 0.006). No significant differences were detected in 30-day mortality (1.4%, 5 patients vs 0.9%, 2 patients), overall complications (18%, 62 patients vs 14%, 29 patients) and prolonged air leakage (31 patients, 9% vs 12 patients, 6%) between lobectomy and segmentectomy, respectively. No statistical differences were found regarding the median duration of drainage (3.2 days, P = 1) and the overall median length of hospital stay (6.4 days, P = 0.1) between the 2 groups. In the context of segmentectomy versus corresponding lobectomy, the right upper lobectomy compared with right upper segmentectomy showed a higher number of resected lymph nodes (P = 0.027). No statistical differences were reported in terms of conversion rate and postoperative complication and mortality. CONCLUSIONS Segmentectomy could be considered a safe procedure without significant differences compared to thoracoscopic lobectomy in terms of postoperative morbidity and mortality.

OBJECTIVES This study compares the uniportal with the 3-portal video-assisted thoracic surgery (VATS) by examining the data collected in the Italian VATS Group Database. The primary end point was early postoperative pain; secondary end points were intraoperative and postoperative complications, surgical time, number of dissected lymph nodes and length of stay. METHODS This was an observational, retrospective, cohort, multicentre study on data collected by 49 Italian thoracic units. Inclusion criteria were clinical stage I–II non-small-cell lung cancer, uniportal or 3-portal VATS lobectomy and R0 resection. Exclusion criteria were cT3 disease, previous thoracic malignancy, induction therapy, significant comorbidities and conversion to other techniques. The pain parameter was dichotomized: the numeric rating scale ≤3 described mild pain, whereas the numeric rating scale score >3 described moderate/severe pain. The propensity score-adjusted generalized estimating equation was used to compare the uniportal with 3-portal lobectomy. RESULTS Among 4338 patients enrolled from January 2014 to July 2017, 1980 met the inclusion criteria; 1808 patients underwent 3-portal lobectomy and 172 uniportal surgery. The adjusted generalized estimating equation regression model using the propensity score showed that over time pain decreased in both groups (P CONCLUSIONS Data from the Italian VATS Group Database showed that in clinical practice uniportal lobectomy seems to entail a higher risk of moderate/severe pain on second and third postoperative days.

OBJECTIVESInherent technical aspects of pulmonary lobectomy by video-assisted thoracoscopic surgery (VATS) may limit surgeons’ ability to deal with factors predisposing to complications. We analysed complication rates after VATS lobectomy in a prospectively maintained nationwide registry.METHODSThe registry was queried for all consecutive VATS lobectomy procedures from 49 Italian Thoracic Units. Baseline condition, tumour features, surgical techniques, devices, postoperative care, complications, conversions and the reasons thereof were detailed. Univariable and multivariable regressions were used to assess factors potentially linked to complications.RESULTSFour thousand one hundred and ninety-one VATS lobectomies in 4156 patients (2480 men, 1676 women) were analysed. The median age-adjusted Charlson index of the patients was 4 (interquartile range 3–6). Grade 1 and 2 and Grade 3–5 complications were observed in 20.1% and in 5.8%, respectively. Ninety-day mortality was 0.55%. The overall conversion rate was 9.2% and significantly higher in low-volume centres (CONCLUSIONSVATS lobectomy is a safe procedure even in medically compromised patients. An improved classification system for conversions is proposed and prevention strategies are suggested to reduce conversion rates and possibly complications in less-experienced centres.

Accurate staging of early non-small cell lung cancer is fundamental for selecting the best treatment. The aim of this study was to identify risk factors for nodal upstaging after video-assisted thoracoscopic lobectomy for clinical T1-3N0 tumors.From 2014 to 2017, 3276 thoracoscopic lobectomies were recorded in the prospective database "Italian VATS Group". Linear and multiple logistic regression models were adapted to identify independent predictors of nodal upstaging and factors associated with progression in postoperative N status.Nodal upstaging was found in 417 cases (12.7%), including 206 cases (6.2%) of N1-positive nodes, 81 cases of N2 nodes (2.4%), and 130 cases (4%) of involvement of both N1 + N2 nodes. A total of 241 (7.3%) patients had single-station nodal involvement, whereas 176 (5.3%) had multiple-station involvement. In the final regression model, the tumor grade, histology, pathologic T status, and 12 resected nodes were independent predictors of nodal upstaging.The number of resected lymph nodes seems to predict nodal upstaging better than the type of intraoperative lymph node management. Other preoperative risk factors correspond to those for which the current guidelines of the European Society of Thoracic Surgery recommend more extensive preoperative mediastinal staging.

Background: The expertise curve of video-assisted thoracoscopic surgery (VATS) lobectomies still stirs debate and controversy both because of the number of procedures to carry out and of the evaluation of the learning threshold. The purpose of our study was the examination of the variables related to the learning curve of the video-assisted approach, to establish what may be an expression of the technical maturity of the surgeon. Methods: The National Register for VATS lobectomy built in 2013 was used to collect data from 65 Thoracic Surgery Units. Out of more than 3,700 patients enrolled, only information from Units with ≥100 VATS lobectomies were retrospectively analysed. Unpaired Student’s t-tests, Fisher’s exact tests, Pearson’s χ 2 were applied as needed. Cumulative summative analysis and one-way ANOVA were used to identify the expertise curve of VATS lobectomy. Results: Ten institutions contributed a total of 1,679 patients, who were divided into three uniform groups according to the chronological sequence of surgery. The length of utility incision, the number of dissected lymph nodes and the operative time were not statistically significant (P=0.999, P=0.972 and P=0.307, respectively) among groups. Conversion to thoracotomy and postoperative air leaks occurred in 125 (7.44%) and 109 (6.49%) patients, gradually declined in Group 3 with statistical signi cance (P=0.048 and P=0.00086). Conclusions: The conversion rate and the percentage of air leaks seem to de ne the expertise of VATS lobectomy, being linked to the ability to manage more complicated surgical cases or intraoperative adverse events.

Background: the case of an oldest-old woman with severe hypercalcemia and hyperparathyroidism due to left parathyroid adenoma. Case presentation: An 85-year-old woman, hospitalized for rapid loss of functional abilities, mental confusion, worsening of depression, anorexia and incontinence. In the medical history, she had depression, hypertension, osteopenia and osteoarthritis. Blood examinations showed high levels of calcium and intact parathyroid hormone (PTHi), severe renal failure with hyperphosphoremia. After hydration and loop diuretic administration, renal function improved and pamidronate and calcimimetic treatments were followed by reduction of calcium levels. The ultrasound of neck identified a possible parathyroid adenoma; 99Tc-sestamibi scintigraphy and CT scan with contrast confirmed the diagnosis. The surgical left hemithyroidectomy was the treatment of choice and the PTHi and calcium reached normal circulating levels immediately post-surgery. At the 3-month clinical follow-up from surgery, the functional, psychological and cognitive functions improved substantially, although mood disorder secondary to disability persisted. Conclusions: Hypercalcemia due to primary hyperparathyroidism is a low prevalence condition among older adults. However, we should keep in mind whenever we find ourselves facing a sudden and unjustified physical, psychological and cognitive deterioration in such a clinical condition old and oldest-old persons.

OBJECTIVES: Inherent technical aspects of pulmonary lobectomy by video-assisted thoracoscopic surgery (VATS) may limit surgeons’ ability to deal with factors predisposing to complications. We analysed complication rates after VATS lobectomy in a prospectively maintained nationwide registry. METHODS: The registry was queried for all consecutive VATS lobectomy procedures from 49 Italian Thoracic Units. Baseline condition, tumour features, surgical techniques, devices, postoperative care, complications, conversions and the reasons thereof were detailed. Univariable and multivariable regressions were used to assess factors potentially linked to complications. RESULTS: Four thousand one hundred and ninety-one VATS lobectomies in 4156 patients (2480 men, 1676 women) were analysed. The median age-adjusted Charlson index of the patients was 4 (interquartile range 3–6). Grade 1 and 2 and Grade 3–5 complications were observed in 20.1% and in 5.8%, respectively. Ninety-day mortality was 0.55%. The overall conversion rate was 9.2% and significantly higher in low-volume centres (

Purpose Video-assisted thoracoscopic surgery (VATS) lobectomy has become an accepted procedure for the treatment of selected cases of lung cancer. The aim of this project was to establish national practical recommendations for the management of patients suitable for VATS lobectomy. Methods The Scientific Committee of the VATS Lobectomy Group (a branch of the Italian Society of Thoracic Surgery) identified the consensus conference as an appropriate tool for a national debate. The consensus conference was organized following indications of the Italian Department of Health: a panel of experts reviewed the literature, the jury board revised the experts’ reports, and the national conference discussed and voted on statements. The strength of recommendation for a statement was classified as weak, fair, or high when the total score ranged between 51% and 67%, 68% and 84%, or 85% and 100%, respectively. Results Eighty-six Italian thoracic surgeons attended the 1st Italian Consensus Conference on VATS lobectomy in Giulianova, Italy, on October 29-30, 2015. Thirty-three topics were discussed: indications, surgical strategy, perioperative management, and training were the main topics. Consensus was reached on 24 statements that were consequently recommended. Conclusions The Italian Consensus Conference is the first attempt to discuss VATS lobectomy-related issues in a national scientific community. Such experience determined an improvement in epistemic knowledge among the Italian thoracic surgeons and could be a suggestion for other national communities.

Background: The clinical significance of lymph-node metastases, multicentric forms, and tumorlets in bronchial carcinoids is still a matter of debate. Aim of this study was to analyze their prevalence and clinical significance in a series of 123 bronchial carcinoids. Patients and Methods: Nodal dissection and serial sections of resected lung parenchima for research of multicentric forms and tumorlets were performed in most patients. Survival curve was produced using the Kaplan-Meyer method and multivariate analysis by the Cox proportional hazard model. Results: Lymph-node involvement was present in 14% of typical (14 of 100) and 13.04% of atypical carcinoids (3 of 23). Multicentric forms (syncronous carcinoids or tumorlets) were found in 11.3% of the total with a negative impact on survival (p = 0.021). Multiple tumorlets were found in 7.3% of all cases at the standard pathologic examination, but whenever accurate palpation and serial sections of the surgical specimen were performed, the percentage reached 24% of the cases. Overall survival was 98.2%, 95.8%, and 83.9% for typical and 71.6%, 57.3%, and 24% for atypical carcinoid respectively at 5, 10, and 15 years. Time from surgery was significantly directly correlated with recurrences (p < 0.0001) and disease related death (p = 0.0002). Conclusions: A high prevalence of tumorlets, multiple carcinoids, and lymph-nodal involvement was found in our series. On the basis of these observations bronchial carcinoids always require major surgical procedures with systematic nodal dissection, and a careful search for multifocal lesions should always be performed. Follow-up should always be accurate and protracted, due to the frequency of very long-term relapses (often more than 10 years after surgery). © 2009 by the International Association for the Study of Lung Cancer

Objectives Tumor angiogenesis is an essential and complex process necessary for the growth of all tumors which represents a potential therapeutic target. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) or their receptor tyrosine kinases have been approved by the FDA. In thymic epithelial tumors (TET), targeted therapies have been sporadically applied due to their rarity. To ascertain the presence of potential therapeutic targets, we analyzed by immunohistochemistry the expression of angiogenesis-related biomarkers in a large series of TET arranged in Tissue Micro Arrays (TMA). Materials and methods We assessed by immunohistochemistry the expression of the possible molecular target of anti-angiogenic therapy, i.e. VEGFA, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, and PDGFRβ, in a TMA series of 200 TET collected in the framework of a multi-institutional collaborative project for Rare Diseases. Results When compared to the low-risk tumors, high-risk TET (B2, B3, carcinomas) contained higher proportion of cancer cells expressing VEGFA, VEGFC and VEGFD ( P P P P =0.002), VEGFR2 ( P =0.013), and VEGFR3 ( P =0.041). No differences were observed in terms of PDGFRβ expression. Conclusions According to our data, it is possible to hypothesize the existence of multiple paracrine and/or autocrine loops in TET, particularly in the high-risk ones, involved in TET growth and progression. Anti-angiogenic agents, directed to inhibit these loops, are therefore to be considered as potential tools in advanced TET therapy.

Background: Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment. Methods: This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival. Results: Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58-85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P

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.

Most patients with undifferentiated thyroid cancer have unresectable disease with a very high rate of airway compromise. Tracheostomy typically entails technical issues in these cases. In fact, it can be very difficult to expose or simply locate the trachea beneath the mass, and the extensive soft tissue involvement can force the surgeon to cut the tumor to place the tracheostomy tube. The combined use of rigid bronchoscopy and percutaneous tracheostomy techniques, applied in an open surgical procedure, can greatly simplify the procedure. Furthermore, by this method, the airways are quickly secured and the risk of intraoperative bleeding is reduced.

Introduction: Microalbuminuria (MA) is considered a reflection of systemic capillary leak and an early marker of acute stress reaction to the surgical insult, proportional to the severity of the initiating condition and predictive of the individual response to surgical stress. Objectives: We conducted a prospective study to assess for the variation of MA within 4 days after thoracic surgery. We correlated observed MA levels with both their respective PaO2/FiO2 respiratory ratio and the onset of postoperative complications. Methods: This single-centre study enrolled 255 consecutive patients having an American Society of Anaesthesiologists (ASA)score≤3. The mean age was 62 years with 67% male. All patients were scheduled for elective pulmonary resection. MA was measured in urine samples as the albumin-to-creatinine ratio (A/C), prior to, at and after extubation up to 96 hours. PaO2/FiO2 was measured at extubation and on the first postoperative day. Results: Overall, preoperative A/C levels resulted normal, with a significant average increase at extubation which peaked 6 hours later (P 61mg/g (P=0.0003) was associated with postoperative cardio-pulmonary complications (OR 3.85; P=0.003). Conclusion: Within 6 hours after extubation, MA assessment may be a rapid and relatively inexpensive method for better predicting perioperative risk in an ASA score ≤3 population.

Objectives Preoperative chemotherapy may play a role in postoperative respiratory complications due to subclinical parenchymal damage. We investigated the gene expression of lung tissue components after neoadjuvant chemotherapy of alveolar-capillary membrane, extracellular matrix and membrane proteins. Methods The study group included 14 patients submitted to pulmonary resection for lung cancer after 3 cycles of gemcitabine-cisplatin, while the control group included 14 naive-treatment patients. RNA was extracted from frozen tissue obtained by healthy lung specimens using EZ1 RNA Universal Tissue kit and automatically purified by BioRobot EZ1 instrument. Three hundred nanograms of total RNA was reverse transcribed to complementary DNA and used to evaluate the gene expression of type I and III collagen, elastin, syndecan, metalloproteinase 13 and aquaporins (AQPs) in real-time polymerase chain reaction. Results were expressed as the mean ± standard deviation of 3 independent experiments. Analysis of variance followed by Sheffe's F-test was performed. Results Among the alveolar-capillary membrane and extracellular matrix genes, type I-III collagens and syndecan were significantly up-regulated (+645%, +327% and +261%, respectively), while elastin and metalloproteinase 13 were down-regulated in the study group versus control group (-46% and -77%, respectively). Furthermore, chemotherapy was associated with a significant up-regulation of AQP expressions (AQP1:+51% and AQP5:+36%). Conclusions We observed, in the treated group, increases in the mean values of gene expressions for macromolecules involved in the remodelling of both the alveolar septa and parenchyma scaffold, thereby supporting the hypothesis that induction chemotherapy may foster a fibrosing effect on the pulmonary parenchyma and lead to altering the alveolar-capillary membrane.

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.

Lung cancer is the leading cause of cancer-related deaths worldwide with an overall 5-year survival rate of 17% after diagnoses. Indeed many patients tend to have a very poor prognosis, due to being diagnosed at an advanced stage. Conversely patients who are diagnosed at an early stage have a 5-year survival >70%, indicating that early detection of lung cancer is crucial to improve survival. Although flexible bronchoscopy is a relatively non-invasive procedure for patients suspected of having lung cancer, only 29% of carcinoma in situ (CIS) and 69% of microinvasive tumors were detectable using white light bronchoscopy (WLB) alone. As a result, in the past two decades, new bronchoscopic techniques have been developed to increase the yield and diagnostic accuracy, such as autofluorescence bronchoscopy (AFB), narrow band imaging (NBI) and high magnification bronchovideoscopy (HMB). However, due to the low specificity and the limitation to detect only proximal bronchial tree, new probe-based technologies have been introduced: radial endobronchial ultrasound (R-EBUS), optical coherence tomography (OCT), confocal laser endomicroscopy (CLE) and laser Raman spectroscopy (LRS). To date, although tissue biopsy remains the gold standard for diagnosing malignant/premalignant airway disease and some techniques are still investigational, bronchoscopic technologies can be considered the safest and most accurate tools to evaluate both central and distal airway mucosa.

Lobectomies with bronchial and/or vascular reconstruction are conservative procedures aimed at managing locally advanced lung cancer, avoiding a pneumonectomy. Considering morbidity, mortality and the functional consequences of a pneumonectomy, such procedures must be in the technical armamentarium of every thoracic surgeon. Vascular reconstruction of the pulmonary artery (PA) is seldom performed with or without the bronchial sleeve resection. Both functional and oncologic outcomes have been reported to be better than after a pneumonectomy. Different technical options are now available but some aspects and technical details are not standardized. Indications, possible complications, planning and even definitions need to be more solid to allow for definitive improvement in such procedures. This analysis is aimed at assessing the acquired technical data with special emphasis on the PA reconstruction with autologous tissues.

Background To evaluate the incidence, predictors, and survival of unexpected pN2 disease in patients with clinical stage I non-small cell lung cancer. Methods This is a retrospective observational multicenter study on all consecutive patients operated for clinical stage I non-small cell lung cancer from January 2006 to December 2012. Medical records were reviewed to investigate the incidence and risk factors for unexpected pN2 disease. Then, the survival of patients with unexpected pN2 disease was statistically compared with that of patients with clinical N2 disease operated after induction therapy in the same period. Results Our study population counted 901 patients. An incidence of 12% (108/901) unexpected pN2 disease was found. Among 3,389 lymph nodes sampled, 124 distinct metastases were found. Of the 108 patients, 92 (85%) had metastases in single N2 station and 16 (15%) patients had disease in multiple N2 stations; 47 (44%) had pN2 disease without pN1 involvement (skip metastases) and 61/108 (56%) had also pN1 metastases. Factors associated with unexpected pN2 disease were central tumor location (p 4.0 (0.007). Patients with pN2 disease compared with patients with cN2 disease presented a better median overall survival (56 versus 20 months; p = 0.001) and disease-free survival (46 versus 11 months; p

Background The intraoperative localization of small and deep pulmonary nodules is often difficult during minimally invasive thoracic surgery. We compared the performance of three miniaturized ultrasound (US) convex probes, one of which is currently used for thoracic endoscopic diagnostic procedures, for the detection of lung nodules in an ex vivo lung perfusion model. Methods Three porcine cardiopulmonary blocks were perfused, preserved at 4°C for 6 h and reconditioned. Lungs were randomly seeded with different patterns of echogenicity target nodules (9 water balls, 10 fat, and 11 muscles; total n = 30). Three micro-convex US probes were assessed in an open setting on the pleural surface: PROBE 1, endobronchial US 5–10 MHz; PROBE 2, laparoscopic 4–13 MHz; PROBE 3, fingertip micro-convex probe 5–10 MHz. US probes were evaluated regarding the number of nodules localized/not localized, the correlation between US and open specimen measurements, and imaging quality. Results For detecting target nodules, the sensitivity was 100% for PROBE 1, 86.6% for PROBE 2, and 78.1% for PROBE 3. A closer correlation between US and open specimen measurements of target diameter (r = 0.87; P = 0.0001) and intrapulmonary depth (r = 0.97; P = 0.0001) was calculated for PROBE 1 than for PROBES 2 and 3. The imaging quality was significantly higher for PROBE 1 than for PROBES 2 and 3 (P Conclusions US examination with micro-convex probes to detect pulmonary nodules is feasible in an ex vivo lung perfusion model. PROBE 1 achieved the best performance. Clinical research with the endobronchial US micro-convex probe during minimally invasive thoracic surgery is advisable.

OBJECTIVES: The human fibrinogen/thrombin surgical patch is proposed for videothoracoscopic pleurodesis after recurrent observation in routine clinical practice of site-specific pleuro-pulmonary adhesions. METHODS: A total of 36 experimental videothoracoscopies were performed on 18 pigs, all of which underwent a bilateral sequential procedure. The right or left side was casually approached and two 4.8 × 4.8 cm Tachosil® patches were placed over the dorsal lung surface in the highest antigravitary position through a double-port thoracoscopy. The contralateral side was subsequently entered by a single-port thoracoscopy to perform talc poudrage in accordance with current recommendations (1 g/18 kg). Thoracoscopy and autopsy were performed after 60 days to evaluate the outcome. Pleurodesis was graded on a predefined three-tier scale (none-moderate-firm); specimens were then submitted to the pathologist. The statistical analyses performed were: frequencies distribution, variables association test and hypothesis testing using binomial distribution. RESULTS: Pleurodesis was firm in 15/18 cases (P = 0.004), moderate in 2/18, and none in 1/18 cases with the sealant matrix. Talc pleurodesis was firm in 7/18 cases and moderate in 11/18. No surgical, medical, behavioural or growth disorders were recorded. There was complete correspondence between lung surface covered by the sealant patch and pleural adhesion topography (P < 0.001) and no other sites of adhesion were found at autopsy, whereas talc effect was commonly found to produce random pleural cavity obliteration, most frequently in declivous places, with inhomogeneous pleural adhesion for tissue density and rough/smooth outline (P < 0.001). The pathologist disclosed that talc creates a variable and unpredictable inflammatory background, sometimes severe, with the development of many granulomas. Fibrin sealant patch pleurodesis is caused by connective tissue irrespective of the pleural and pulmonary anatomy. CONCLUSIONS: The fibrin sealant patch is effective in producing localized pleurodesis in swine. The morphology and topography of the adhesions, 2 months after the patch placement, are consistent and more predictable than after talc poudrage. The latter causes a diffuse pleurodesis which is not predictable, with a predominantly gravitational location and produces a much more serious inflammatory response.

OBJECTIVES: Endothelial progenitor cells are capable of contributing to neovascularization in tumours. In patients with either malignant or transudative pleural effusion, we tested the presence of pleural endothelial progenitor cells. We also measured the number of endothelial progenitor cells in post-surgery pleural drainage of either patients with early non-small-cell lung cancer or control patients with benign lung disease undergoing pulmonary resection. The prospective influence of post-surgery pleural-drainage endothelial progenitor cells on cancer recurrence/survival was investigated. METHODS: Pleural endothelial progenitor cell levels were quantified by fluorescence-activated cell sorting analysis in pleural effusion of 15 patients with late-stage non-small-cell lung cancer with pleural involvement and in 15 control patients with congestive heart failure. Also, pleural-drainage endothelial progenitor cells were measured in pleural-drainage fluid 48 h after surgery in 64 patients with earlystage non-small-cell lung cancer and 20 benign lung disease patients undergoing pulmonary resection. Cancer recurrence and survival was evaluated in patients with high pleural-drainage endothelial progenitor cell levels. RESULTS: The number of pleural endothelial progenitor cells was higher in non-small-cell lung cancer pleural effusion than in transudative pleural effusion. Also, pleural-drainage endothelial progenitor cell levels were higher in patients with non-small-cell lung cancer than in patients with benign lung disease undergoing pulmonary resection (P < 0.05). Non-small-cell lung cancer patients with high pleural-drainage endothelial progenitor cell levels had a significantly 4.9 higher rate of cancer recurrence/death than patients with lower pleural-drainage endothelial progenitor cell levels, irrespective of confounders. CONCLUSIONS: Endothelial progenitor cells are present in the pleural effusion and are higher in patients with late-stage non-small-cell lung cancer with pleural involvement than in congestive heart failure patients. Endothelial progenitor cell levels are higher in the postsurgery pleural drainage of patients with non-small-cell lung cancer than in non-neoplastic pleural-drainage fluid. High pleural-drainage endothelial progenitor cell levels in patients undergoing pulmonary resection for early non-small-cell lung cancer predict an increased risk of cancer recurrence and death.

Introduction Aim of this study is to analyze outcome and the decision making process to approach airway invasion by thyroid tumors. Methods Retrospective study of 30 years experience in thyroid surgery for cancer invading airway. Clinical records, surgical and pathology reports have been analyzed to assess which principles and procedural details are significant to facilitate efficient diagnosis, staging and treatment. Medical therapy was not evaluated. Results Out of a consecutive series of 2165 thyroid cancer patients, T4a cancers are 303 (14%). Airway invasion was found in 141 (6.5%) cases. Well-differentiated pattern was determined in 110 (78%) while other histology was reported in 31 (22%). Airway-related symptoms have been recorded in 111 (78%) patients. Flexible bronchoscopy was performed in all patients. Rapidly evolving disease or non-resectable airway was found in 105 (74.5%) cases. Permanent tracheotomy was performed in 43 (30.5%) cases, airway lumen restoration with or without stenting in 39 (27.7%), laryngectomy in 8 (5.7%), segmental airway resection and reconstruction in 28 (19.9%). Perioperative mortality was recorded after palliative treatment only. In resected patients, completely radical surgery was not always achievable. All patients with positive margin after resection underwent adjuvant treatment and showed comparable survival to radical surgery patients after 5 years. Tumor relapse occurred in 8 (28.6%) cases (distant or locoregional). Patients with unresectable disease require treatment for symptoms relief but survival is poor. Conclusion Although some patients are currently referred with a severely advanced disease, the indication for tracheotomy, salvage procedures or supportive care has decreased over time. Resection is feasible for differentiated tumors with an overall good outcome.

OBJECTIVES: B-type natriuretic peptides (BNPs) are secreted by the human heart in response to ventricular wall stretch or myocardial ischaemia, and predict adverse cardiovascular events and death in the general population. Following non-cardiac surgical procedures, there is growing evidence supporting BNP measurement as a powerful independent predictor of death and perioperative complications. However, the clinical implication of elevated BNP measurements after pulmonary resection has not been completely defined. This study aimed to evaluate the role of BNP in predicting adverse cardiopulmonary events after thoracic surgery. METHODS: A prospective, short-term, observational cohort study was conducted in a tertiary care hospital, including consecutive patients undergoing scheduled pulmonary resection between April 2012 and October 2013. Baseline clinical details were obtained; serum BNP levels were measured at baseline and on postoperative days 1 and 4. RESULTS: We enrolled 294 consecutive patients, median age 66 [interquartile range (IQR): 57-73], 67% male. There were 2 perioperative deaths, and 52 patients experienced one or more cardiopulmonary complications. The baseline median BNP value was normal (29.5 pg/ ml, IQR: 16-57.2), and showed significant postoperative increase, peaking on day 1. Patients who developed postoperative complications had a significantly greater BNP increase (P < 0.0001) when compared with those without complications. A postoperative day 1 BNP measurement of ≥118.5 [receiver operating characteristic area: 0.654; 95% confidence interval (CI): 0.57-0.74; P = 0.001] was associated with a 3-fold risk of developing postoperative cardiopulmonary complications [odds ratio (OR): 2.94; 95% CI: 1.32-6.57; P = 0.008]. Logistic regression analysis showed major pulmonary resections (lobectomies or pneumonectomies), BNP ≥ 118.5 and age ≥ 65 to be the only independent predictive variables. In the subset of patients undergoing lobectomy or pneumonectomy (n = 226), BNP was the strongest independent predictor of complications (OR: 3.49; 95% CI: 1.51-8.04). CONCLUSIONS: Our results show that BNP elevation, measured in the first days after thoracic surgery, is independently associated with postoperative adverse events. In patients undergoing major pulmonary resections, a postoperative BNP elevation is the strongest independent predictor of cardiopulmonary complications.

OBJECTIVES: To analyse clinical and biomolecular prognostic factors associated with the surgical approach and the outcome of 247 patients affected by primary atypical carcinoids (ACs) of the lung in a multi-institutional experience. METHODS: We retrospectively evaluated clinical data and pathological tissue samples collected from 247 patients of 10 Thoracic Surgery Units from different geographical areas of our country. All patients were divided into four groups according to surgical procedure: sub-lobar resections (SURG1), lobar resections (SURG2), tracheobronchoplastic procedures (SURG3) and pneumonectomies (SURG4). Overall survival analysis was performed using the Kaplan-Meier method and log-rank test. Survival was calculated from the date of surgery to the last date of follow-up or death. The parameters evaluated included age, gender, smoking habits, laterality, type of surgery, 7th edition of TNM staging, mitosis Ki-67 (MIB1), multifocal forms, tumourlets, type of lymphadenectomy and neo/adjuvant therapy. For multivariate analysis, a Cox regression model was used with a forward stepwise selection of covariates. RESULTS: Two hundred and forty-seven patients (124 females and 123 males; range 10-84, median 60 years) underwent surgical resection for AC in the last 30 years as follows: n = 38 patients in SURG1, 181 in SURG2, 15 in SURG3 and 14 in SURG4. A smoking history was present in 136 of 247 (55%) patients. The median follow-up period was 98.7 (range 11.2-369.9) months. The overall survival probability analysis of the AC was 86.7% at 5 years, 72.4% at 10 years, 64.4% at 15 years and 58.1% at 20 years. Neuroendocrine multicentric forms were detected in 12 of 247 patients (4.8%; 1 of 12 pts) during the follow-up (range 11.2-200.4, median 98.7 months) and 33.4% had recurrence of disease. There were no significant differences between gender, tumour location and type of surgery at the multivariate analysis. Age [P < 0.001, hazard ratio (HR) 0.60; confidence interval (CI) 0.32-1.12], smoking habits (P = 0.002; HR 0.43, 95% CI 0.23-0.80) and lymph nodal metastatic involvement (P = 0.008; HR 0.46, 95% CI 0.26-0.82) were all significant at multivariate analysis. CONCLUSIONS: ACs of the lung are malignant neuroendocrine tumours with a worst outcome in patients over 70 years and in smokers. With the exception of pneumonectomy, the extent of resection does not seem to affect survival and should be accompanied preferably by lymphadenectomy. Pathological staging, along with a mitotic index more than Ki-67 (MIB1), appears to be the most significant prognostic factor at the univariate analysis.

Background Left main bronchus resection and reconstruction (LMBRR) is a complex surgical procedure indicated for management of inflammatory, benign and low grade malignant lesions. Its application provides maximal parenchymal sparing. Methods Out of 98 bronchoplastic procedures performed at the Authors' Institution in the 1995-2011 period, 4 were LMBRR. Indications were bronchial carcinoid in 2 cases, inflammatory pseudotumor in 1 case, TBC stricture in 1 case. All patients underwent preoperatively a rigid bronchoscopy to restore the airway lumen patency. At surgery a negative resection margin was confirmed by frozen section in the neoplastic patients. In all patients an end-to-end bronchial anastomosis was constructed according to Grillo. Results There were neither mortality nor major complications. Airway lumen was optimal in 3 patients, good in 1. Conclusion LMBRR is a valuable option for the thoracic surgeon. It maximizes the parenchyma-sparing philosophy, broadening the spectrum of potential candidates for cure. It remains a technically demanding procedure, to be carried out by an experienced surgical team. Correct surgical planning affords excellent results, both in the short and long term.

Background We investigated whether tigecycline (TIGE) is more effective than talc in inducing pleurodesis in rabbits. Methods Fifty-six New Zealand rabbits were utilized in a two-phase study: Effects at 14 d (phase I) and at 28 d (phase II) were assessed. Saline solution (SAL n = 3), talc slurry (TALC 200 mg/kg, n = 5), and TIGE at different concentrations (mg/kg): TIGE0.5 (n = 5); TIGE1 (n = 5); TIGE3 (n = 5); TIGE25 (n = 5); TIGE50 (n = 5) were randomly injected, for each phase, through a right chest drainage. TIGE0.5 and TIGE1 were ineffective during phase I and were thus excluded from further investigation. At post mortem examination, pleurodesis was graded grossly and microscopically by three observers blinded to treatment groups. Results Phase I: pleurodesis was more effective in TIGE25 and TIGE50 (P < 0.001); TALC was better than TIGE0.5 (P < 0.001), and TIGE1 (P = 0.49), macroscopically. Pleural thickness was significantly higher in TIGE25 compared with SAL, TALC, TIGE0.5, TIGE1, and TIGE3 (P < 0.01). No significant differences were evident between TALC and TIGE3, both macroscopically (P = 0.90) and microscopically (inflammation P = 0.99, fibrosis P = 0.96, pleural thickness P = 0.99). Phase II: better effectiveness of TIGE50 compared with all other groups (P < 0.001) except TIGE 25 (P = 0.29); results similar to phase I for TALC and TIGE3 (P = 0.99), macroscopically. Microscopically greater inflammation in TALC compared with TIGE3 (P < 0.05) and in TIGE50 to TIGE3 (P = 0.05). Significant complications occurred in all TIGE50 group. One of TIGE25 and one of TIGE50 died of respiratory distress and of right hemothorax+ascites, respectively. Conclusions Intrapleural TIGE3 mg/kg is as effective as talc in inducing pleurodesis in rabbits. The intrapleural TIGE toxicity threshold was reached at TIGE25 mg/kg concentration.

Ovarian cancer is the most lethal gynaecologic malignancy. It usually spreads out of the abdomen involving thoraco-abdominal organs and serosal surface. This disease is poorly curable and surgery, at early stage, is supposed to achieve the best survival outcome. In systemic dissemination, chemiotherapy is indicated, sometimes with neoadjuvant aim. The most common clinical expressions of advanced ovarian carcinoma are multiple adenopathy, neoplastic pleuritis, peritoneal seeding and distant metastasis, mainly hepatic and pulmonary. Isolated adenopathy of the mediastinum is rare and isolated bilateral have never been described before. We report two cases of isolated bilateral cardiophrenic angle lymphnode metastasis from ovarian carcinoma, without peritoneal and pleural involvement. Both patients were successfully resected through minimally invasive thoracic surgery. About the role of surgery, few data are available but survival seems to be longer after resection thus, more investigation is required to make the indication to surgery more appropriate in advanced cases.

Introduction Anatomical segmentectomy is again under evaluation for the cure of T1a N0 non-small cell lung cancer and carcinoid tumors. Whether anatomical segmentectomy does permit or not, an adequate resection of nodal stations for staging or cure is still pending. Methods A case-matched study was ruled on patients with peripheral cT1a N0 M0 tumors that underwent anatomical segmentectomy or lobectomy. Dissection of lymph node stations 4, 5, 6, and 7 was identical in anatomical segmentectomy and lobectomy; stations 10, 11, 12, and 13 were also dissected carefully during anatomical segmentectomy. Results We individually matched 46 (69% men) anatomical segmentectomy with 46 (71% men) lobectomy for age, anatomical segment, and size of the tumor. The median (interquartile range) size of the resected lesions was 1.7 cm (1.35–1.95 cm) in anatomical segmentectomy and 1.6 cm (1.3–1.9 cm) ( p = 0.96) in lobectomy. The anatomical segmentectomy and lobectomy resection margins were free of cancer. The median number (interquartile range) of total dissected lymph nodes was 12 (8–5–14) in anatomical segmentectomy compared with 13 (12–14.5) in lobectomy ( p = 0.68), with a number of N1 nodes being 6 (4–7.5) and 7 (4.5–9.5) ( p = 0.43), respectively, and N2 nodes 5.5 (4–7.7) and 5 (4–6.5) ( p = 0.88). Only 1 patient of 46 (2%) anatomical segmentectomy was N1, whereas in lobectomy, 4% had N1 (2 patients). Freedom from recurrence at 36 months was 100% for anatomical segmentectomy and 93.5% for lobectomy ( p = 0.33). Conclusions Anatomical segmentectomy for cT1a tumors compared with lobectomy procures an adequate number of N1 and N2 nodes for pathological examination. Cancer-specific survival was equivalent at 36 months.

Objective: Lobectomy with pulmonary artery resection and reconstruction is seldom performed in order to avoid pneumonectomy in selected cases. The aim of this study is to determine how safe and effective the graft reconstruction of the pulmonary artery is, using autologous tissue taken from the pulmonary vein. Methods: Eight patients with diagnosed non-small-cell lung cancer were treated by lobectomy with pulmonary artery reconstruction with curative intent. All patients could have tolerated pneumonectomy. Patch or conduit angioplasty was performed by usingatailoredgraft,harvestedfromtheautologouspulmonaryveinoftheresectedlobe.Patientswerefollowedupandtheclinicalrecordswere analyzed retrospectively. Long-term patency of the reconstructed pulmonary artery was investigated by computed tomographic pulmonary angiogram. Results: No procedure-related complications and no perioperative mortality were observed. No blood transfusion was required. Follow-up varied from 10 to 64 months. No local recurrences were found next to the angioplasty. Ideal long-term patency of the pulmonary artery was demonstrated in all cases. Two patients are alive with evidence of extrathoracic metastatic disease and four patients are apparently healthy. Two patients died of progressive disease. Conclusions: The use of pulmonary vein tissue as a graft to repair the pulmonary artery is feasible, reproducible, and seems to be oncologically correct. Pulmonary vein tissue can be easily harvested during surgery and offers a high-quality vascular tissue for pulmonary angioplasty. # 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Neuroendocrine tumors may occur in the setting of multiple endocrine neoplasia type 1 (MEN1) syndrome. Among these, a probably underestimated prevalence of well differentiated neuroendocrine thymic carcinoma (carcinoid), a neoplasm characterized by very aggressive behavior, has been described. We report characterization of the seven Italian cases in which this association occurred among a series of 221 MEN1 patients (41 sporadic and 180 familial cases; prevalence, 3.1%). All of the patients were male, and six of seven (85%) were heavy smokers. No associated hormonal hypersecretion was detected. The first diagnosis was between the second and fifth decades. Familial clusters were present in three of seven (42.8%). No genotype-phenotype correlation was found. All seven cases were associated with hyperparathyroidism. In one patient, prophylactic thymectomy revealed a small nodular lesion suggestive of a thymic carcinoid, providing evidence that preventive thymectomy might prevent additional growth of an occult thymic carcinoid. These findings confirm that thymic carcinoids are associated with a very high lethality, with a near-total prevalence in smoker males. Therefore, prophylactic thymectomy should be considered at neck surgery for primary hyperparathyroidism in MEN1 male patients, especially for smokers, and, due to the frequent familial clusters distribution of this pathology, in subjects with affected relatives presenting this feature. Thus, we recommend screening every patient affected with a neuroendocrine thymic neoplasm for MEN1 syndrome.

Purpose Solitary fibrous tumor (SFT) of the pleura is a rare mesenchymal neoplasm arising from mesenchymal cells in the areolar tissue subjacent to the mesothelial-lined pleura and accounting for less than 5% of primary pleural tumors. SFTs are generally benign and asymptomatic, with 10-year survival rates of up to 98%. Unfortunately, approximately 10% have malignant potential, leading to local recurrence after radical surgery and/or metastatic spread. Of note, giant pleural SFT, which consists of a tumor occupying at least 40% of the affected hemithorax, is even less common with only anecdotal cases reported in the medical literature. Methods We describe a unique case of giant SFT of the pleura that metastasized to the thyroid gland 1 year after complete resection, focusing on its clinical and pathological features of presentation. Results En bloc resection remains the mainstay of therapy with curative intent. Patients with large tumors may undergo preoperative angiography with percutaneous embolization of the tumor, which allows to reduce perioperative bleeding. In case of local recurrence, surgery still remains the best treatment option. However, surgery can also be considered in patients with isolated metastatic spread. Conclusions Every suspected and proven SFT of the pleura should undergo surgical resection, as clinical and radiological criteria cannot accurately distinguish benign from malignant forms. Moreover, the peculiar histological features of SFT should not be neglected when planning clinicoradiological follow-up. Additionally, suspicious clinical findings during follow-up should always be thoroughly investigated in order to exclude or confirm the diagnosis of recurrent disease.