Genome-wide expression of the residual lung reacting to experimental Pneumonectomy.

BACKGROUND: Acute or chronic irreversible respiratory failure may occur in patients undergoing pneumonectomy. Aim of this study was to determine transcriptome expression changes after experimental pneumonectomy in swine model. Experimental left pneumonectomy was performed in five pigs under general anaesthesia. Both the resected and the remaining lung, after 60 post-operative completely uneventful days, underwent genome-wide bulk RNA-Sequencing (RNA-Seq). RESULTS: Histological analysis showed dilation of air spaces and rupture of interalveolar septa. In addition, mild inflammation, no fibrosis, radial stretch of the bronchus, strong enlargement of airspaces and thinning of the blood supply were observed. Bioinformatic analyses of bulk RNA-Seq data identified 553 Differentially Expressed Genes (DEGs) at adjusted P-value below 0.001, between pre- and post-pneumonectomy. The top 10 up-regulated DEGs were Edn1, Areg, Havcr2, Gadd45g, Depp1, Cldn4, Atf3, Myc, Gadd45b, Socs3; the top 10 down-regulated DEGs were Obscn, Cdkn2b, ENSSSCG00000015738, Prrt2, Amer1, Flrt3, Efnb2, Tox3, Znf793, Znf365. Leveraging digital cytometry tools, no difference in cellular abundance was found between the two experimental groups, while the analysis of cell type-specific gene expression patterns highlighted a striking predominance of macrophage-specific genes among the DEGs. DAVID-based gene ontology analysis showed a significant enrichment of "Extrinsic apoptotic signaling pathway" (FDR q = 7.60 × 10- 3) and "Response to insulin" (FDR q = 7.60 × 10- 3) genes, along with an enrichment of genes involved as "Negative regulators of DDX58/IFIH1 signaling" (FDR q = 7.50 × 10- 4) found by querying the REACTOME pathway database. Gene network analyses indicated a general dysregulation of gene inter-connections. CONCLUSION: This translational genomics study highlighted the existence both of individual genes, mostly dysregulated in certain cellular populations (e.g., macrophages), and gene-networks involved in pulmonary reaction after left pneumonectomy. Their involvement in lung homeostasis is largely supported by previous studies, carried out both in humans and in other animal models (under homeostatic or disease-related conditions), that adopted candidate-gene approaches. Overall, the present findings represent a preliminary assessment for future, more focused, studies on compensatory lung adaptation, pulmonary regeneration and functional reload.

Sublobar resection versus lobectomy for stage I non-small cell lung cancer: an appropriate choice in elderly patients?

PURPOSES: The aim of this study was to evaluate whether sublobar resection could achieve recurrence and survival rates equivalent to lobectomy in high-risk elderly patients. METHODS: We conducted a retrospective multicenter study that including all consecutive patients (aged >75 years) who underwent operation for clinical stage I non-small cell lung cancer (NSCLC). The clinicopathological data, postoperative morbidity and mortality, recurrence rate and vital status were retrieved. The overall survival, cancer-specific survival and disease-free survival were also assessed. RESULTS: Two hundred and thirty-nine patients (median age 78 years) were enrolled. Lobectomies were performed in 149 (62.3 %) patients and sublobar resections in 90 (39 segmentectomies, 51 wedge resections). There were no differences in the recurrence rates following lobar versus sublobar resections (19 versus 23 %, respectively; p = 0.5) or the overall survival (p = 0.1), cancer-specific survival (p = 0.3) or disease-free survival (p = 0.1). After adjusting for 1:1 propensity score matching and a matched pair analysis, the results remained unchanged. A tumor size >2 cm and pN2 disease were independent negative prognostic factors in unmatched (p = 0.01 and p = 0.0003, respectively) and matched (p = 0.02 and p = 0.005, respectively) analyses. CONCLUSIONS: High-risk elderly patients may benefit from sublobar resection, which provides an equivalent long-term survival compared to lobectomy.

Concomitant Intubation with Minimal Cuffed Tube and Rigid Bronchoscopy for Severe Tracheo-Carinal Obstruction.

BACKGROUND: Our aim was to report on the use of an innovative technique for airway management utilizing a small diameter, short-cuffed, long orotracheal tube for assisting operative rigid bronchoscopy in critical airway obstruction. METHODS: We retrospectively reviewed the clinical data of 36 patients with life-threatening critical airway stenosis submitted for rigid bronchoscopy between January 2008 and July 2021. The supporting ventilatory tube, part of the Translaryngeal Tracheostomy KIT (Fantoni method), was utilized in tandem with the rigid bronchoscope during endoscopic airway reopening. RESULTS: Indications for collateral intubation were either tumors of the trachea with near-total airway obstruction (13), or tumors of the main carina with total obstruction of one main bronchus and possible contralateral involvement (23). Preliminary dilation was necessary before tube placement in only 2/13 patients with tracheal-obstructing tumors (15.4%). No postoperative complications were reported. There was one case of an intraoperative cuff tear, with no further technical problems. CONCLUSIONS: In our experience, this innovative method proved to be safe, allowing for continuous airway control. It enabled anesthesia inhalation, use of neuromuscular blockage and reliable end-tidal CO2 monitoring, along with protection of the distal airway from blood flooding. The shorter time of the procedure was due to the lack of need for pauses to ventilate the patient.

A New Medium (HistoCold) for Surgical Specimens Preserving to Improve the Preanalytic Issues in Histopathological Samples Handling: Morphologic and Antigenic Analysis.

Introduction: The onset of precision medicine has led to the integration of traditional morphologic tissues evaluation with biochemical and molecular data for a more appropriate pathological diagnosis. The preanalytic phase and, particularly, timing of cold ischemia are crucial to guarantee high-quality biorepositories of formalin-fixed paraffin-embedded (FFPE) tissues for patients' needs and scientific research. However, delayed fixation using the gold-standard and carcinogenic fixative neutral-buffered formalin (NBF) can be a significant limitation to diagnosis and biopathological characterization. HistoCold (patented; Bio-Optica Milano S.p.A., Milano, Italy) is a nontoxic, stable, and refrigerated preservative solution for tissue handling. This study examined HistoCold's potential role in improving the preanalytic phase of the pathological diagnostic process. Materials and Methods: Breast, lung, or colorectal cancers (20, 25, and 10 cases, respectively) that were to be surgically resected were recruited between 2019 and 2021. Once specimens were surgically removed, three residual samples for each patient were first promptly immersed into HistoCold for 24, 48, and 72 hours and then FFPE. These were compared with routine specimens regarding morphologic features (hematoxylin and eosin) and tissue antigenicity (immunohistochemical stains). Results: Good concordance regarding both the morphologic characteristics of the neoplasms and their proteins expression between the routine and HistoCold handled tissues were found. The tissue handling with the solution never affected the histopathological diagnosis. Conclusions: The use of HistoCold for samples transporting is easy, allows for improving the management of cold ischemia time, and monitoring the fixation times in NBF, resulting in good quality tissue blocks for biobanking. Moreover, it could be a candidate to eliminate formalin from operating theaters. HistoCold looks very promising for the preanalytic phase of human tissues handling in the era of precision medicine, to provide the best service to patients, and to scientific research.

Prognostic Significance of Pulmonary Multifocal Neuroendocrine Proliferation With Typical Carcinoid.

BACKGROUND: The clinical significance of multifocal pulmonary neuroendocrine proliferation (MNEP), including tumorlets and pulmonary neuroendocrine cell hyperplasia, in association with typical carcinoid (TC), is still debated. METHODS: We evaluated a retrospective series of TC with long-term follow-up data prospectively collected from 2 institutions and compared the outcome between TC alone and MNEP plus TC. Several baseline covariates were imbalanced between the MNEP plus TC and TC groups; therefore, we conducted 1:1 propensity score matching and inverse probability of treatment weighting in the full sample. In the matched group, the association of clinical, respiratory, and work-related factors with the group was determined through univariable and multivariable conditional logistic regression analysis. RESULTS: A total of 234 TC patients underwent surgery: 41 MNEP plus TC (17.5%) and 193 TC alone (82.5%). In the MNEP plus TC group, older age (P < .001), peripheral tumors (P = .0032), smaller tumor size (P = .011), and lymph node spread (P = .02) were observed compared with the TC group. Relapses occurred in 8 patients in the MNEP plus TC group (19.5%) and 7 in the TC group (3.6%). After matching, in 36 pairs of patients, a significantly higher 5-year progression-free rate was observed for the TC group (P < .01). Similar results were observed using inverse probability of treatment weighting in the full sample. The odds of being in the MNEP plus TC group was higher for those with work-related exposure to inhalant agents (P = .008), asthma or bronchitis (P = .002), emphysema, fibrosis, and inflammatory status (P = .032), or micronodules on the chest computed tomography scan and respiratory insufficiency (P = .036). CONCLUSIONS: The association with MNEP seems to represent a clinically and prognostic relevant factor in TC. Hence, careful preoperative workup, systematic pathologic evaluation, including nontumorous lung parenchyma, and long-term postoperative follow-up should be recommended in these patients.

Rescue Tracheostomy for Patients With Unresectable Large Growing Neck Masses.

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.

Identification of the intersegmental plane during thoracoscopic segmentectomy: state of the art.

During thoracoscopic segmentectomy, where direct palpation of the tumour is not always possible, achieving adequate margins from the cancer is of crucial importance. It is thus mandatory to accurately identify the intersegmental plane (ISP). Indeed, inadequate determination and division of the ISP can lead to unsatisfactory oncological results. Our systematic review focused on the effectiveness of the different techniques for identifying the ISP, highlighting the fact that a 1-size-fits-all method is not feasible. Based on the published evidence, 6 main methods were reported, each with its pros and cons: inflation-deflation technique, selective resected segmental inflation, systemic injection of indocyanine green, injection of endobronchial dye, 3-dimensional simulation using multidetector computed tomography and virtual-assisted lung mapping. In conclusion, ISP demarcation is mandatory to achieve a high rate of success of thoracoscopic segmentectomy, and it is very helpful in surgical planning, especially when preoperative multidetector computed tomography and 3-dimensional reconstructions are routinely performed.

Dynamic titanium prosthesis based on 3D-printed replica for chest wall resection and reconstruction.

3D-printing technologies can assist the surgical planning and prosthesis engineering for the management of extended chest wall resection. Different types of prosthesis have been utilized over time, but some concerns remain about their impact on the respiratory function. Here we present a new kind of 3D-printed titanium prosthesis designed to be either strong and flexible. The prosthesis was created on a 1:1 3D-printed anatomic replica of the chest, used to delineate surgical margins and to define the reconstructive requirements.

Microalbuminuria assessment after thoracic surgery: Early identification of complication risks.

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 < 0.001). Larger postoperative A/C increases were observed in patients who developed postoperative complications, compared to those without these complications (P < 0.019). Moreover, patients undergoing major open pulmonary resections had larger postoperative A/C increases, compared to those undergoing minor video-assisted thoracic surgery resections (P < 0.006). At the time of extubation, A/C was inversely related to the PaO2 /FiO2 ratio (r = -0.25; P = 0.038). Peak A/C > 61 mg/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.

Prognostic factors of lung cancer in lymphoma survivors (the LuCiLyS study).

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<0.0001); incidental diagnosis of lung cancer (HR: 1.71; P<0.0001); and lung cancer resection (HR: 2.79; P<0.0001) were favorable prognostic factors. At multivariable analysis, no-active lymphoma (HR: 2.68; P=0.004); early lung cancer stage (HR: 2.37; P<0.0001); incidental diagnosis of lung cancer (HR: 2.00; P<0.0001); and lung cancer resection (HR: 2.07; P<0.0001) remained favorable prognostic factors. Patients with non-active lymphoma (n=146) versus those with active lymphoma (n=18) at lung cancer diagnosis presented better median survival (64 vs. 37 months; HR: 2.4; P=0.02), but median lung cancer specific survival showed no significant difference (27 vs. 19 months; HR: 0.3; P=0.17). CONCLUSIONS: The presence and/or a history of lymphoma should not be a contraindication to resection of lung cancer. Inclusion of lymphoma survivors in a lung cancer-screening program may lead to early detection of lung cancer, and improve the survival.

Lobectomy with angioplasty: which is the best technique for pulmonary artery reconstruction?

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.

Surgery and perioperative management for post-intubation tracheoesophageal fistula: case series analysis.

BACKGROUND: Post-intubation tracheoesophageal fistula (PITEF) is an often mistreated, severe condition. This case series reviewed for both the choice and timing of surgical technique and outcome PITEF patients. METHODS: This case series reviewed ten consecutive patients who had undergone esophageal defect repair and airway resection/reconstruction between 2000 and 2014. All cases were examined for patients: general condition, medical history, preparation to surgery, diagnostic work-up, timing of surgery and procedure, fistula size and site, ventilation type, nutrition, post-operative course and complications. RESULTS: All patients were treated according to Grillo's technique. Overall, 6/10 patients had undergone a preliminary period of medical preparation. Additionally, 3 patients had already had a tracheostomy, one had had a gastrostomy and 4 had both. One patient had a Dumon stent with enlargement of the fistula. Concomitant tracheal stenosis had been found in 7 patients. The mean length of the fistulas was 20.5 mm (median 17.5 mm; range, 8-45 mm), at a median distance from the glottis of 43 mm (range, 20-68 mm). Tracheal resection was performed in all ten cases. The fistula was included in the resection in 6 patients, while it was excluded in the remaining 4 due to their distance. Post-repair tracheotomy was performed in 3 patients. The procedure was performed in 2 ventilated patients. Morbidity related to fistula and anastomosis was recorded in 3 patients (30%), with one postoperative death (10%); T-Tube placement was necessary in 3 patients, with 2/3 decannulations after long-stenting. Definitive PITEF closure was obtained for all patients. At 5-year follow-up, the 9 surviving patients had no fistula-related morbidity. CONCLUSIONS: Primary esophageal closure with tracheal resection/reconstruction seemed to be effective treatment both short and long-term. Systemic conditions, mechanical ventilation, detailed preoperative assessment and appropriate preparation were associated with outcome. Indeed, the 3 patients who had received T-Tube recovered from anastomotic complications.

Variations in gene expression of lung macromolecules after induction chemotherapy for lung cancer.

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.

The role of bronchoscopy in the diagnosis of early lung cancer: a review.

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.

Reduced survival in patients with early-stage non-small-cell lung cancer is associated with high pleural endothelial progenitor cell levels.

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 early-stage 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 post-surgery 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.

Malignant giant solitary fibrous tumor of the pleura metastatic to the thyroid gland.

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.

Thyroid cancer invading the airway: diagnosis and management.

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.

Expression of OP4 (ORL1, NOP1) receptors in vascular endothelium.

Endothelial cells from rat brain microvessels, human aortic artery and human umbilical vein were examined, together with ex vivo rat brain capillaries and rat aortic ring sections, for the expression of opioid receptor-like OP-4 mRNA and protein. High levels of mRNA expression and an immunopositive reaction for the receptor protein were detected in the endothelial cells from primary and from established in vitro cultures, as well as in the intima of ex vivo rat aortic rings, where the signal was limited to the endothelial layer. Interaction of the OP4 receptor with its physiological ligand nociceptin caused, in cultured endothelial cells, the activation of a mitogen-activated protein (MAP) kinase cascade. Taken together, these results show that the OP4 receptor is synthesised and functionally expressed in endothelial cells, presumably as a starting point for some vasoactive mechanism(s).

B-type natriuretic peptide following thoracic surgery: a predictor of postoperative cardiopulmonary complications.

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.