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IntroductionUnlike most malignancies, higher body mass index (BMI) is associated with a reduced risk of lung cancer and improved prognosis after surgery. However, it remains controversial whether height, one of determinants of BMI, is associated with survival independently of BMI and other confounders.MethodsWe extracted data on all consecutive patients with resectable non-small cell lung cancer included in Epithor, the French Society of Thoracic and Cardiovascular Surgery database, over a 16-year period. Height was analysed as a continuous variable, and then categorised into four or three categories, according to sex-specific quantiles. Cox proportional hazards regression was used to estimate the association of height with survival, adjusted for age, tobacco consumption, forced expiratory volume in one second (FEV1), WHO performance status (WHO PS), American Society of Anesthesiologists (ASA) score, extent of resection, histological type, stage of disease and centre as a random effect, as well as BMI in a further analysis.ResultsThe study included 61 379 patients. Higher height was significantly associated with better long-term survival after adjustment for other variables (adjusted HR 0.97 per 10 cm higher height, 95% CI 0.95 to 0.99); additional adjustment for BMI resulted in an identical HR. The prognostic impact of height was further confirmed by stratifying by age, ASA class, WHO PS and histological type. When stratifying by BMI class, there was no evidence of a differential association (p=0.93). When stratifying by stage of disease, the prognostic significance of height was maintained for all stages except IIIB-IV.ConclusionsOur study shows that height is an independent prognostic factor of resectable lung cancer.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jtcvs.2007.11.011 Byline: Rocco Trisolini (a), Carmine Tinelli (d), Alessandra Cancellieri (b), Daniela Paioli (a), Marco Alifano (c)(e), Maurizio Boaron (c), Marco Patelli (a) Abbreviations: CT, computed tomography; ROSE, rapid on-site cytopathologic examination; TBLB, transbronchial lung biopsy; TBNA, transbronchial needle aspiration Abstract: Transbronchial needle aspiration is a useful diagnostic procedure in sarcoidosis, but widely variable yields are reported. This study determined the diagnostic contribution of standard transbronchial needle aspiration in a large series of patients with sarcoidosis and evaluated predictor variables that might influence its results. Author Affiliation: (a) Unit of Thoracic Endoscopy and Pulmonology, Maggiore Hospital, Bologna, Italy (b) Unit of Pathology, Maggiore Hospital, Bologna, Italy (c) Unit of Thoracic Surgery, Maggiore Hospital, Bologna, Italy (d) Clinical Epidemiology and Biometry Service, IRCCS Policlinico San Matteo, Pavia, Italy (e) Thoracic Surgery Unit, HA[acute accent]tel-Dieu Hospital, AP-AH, Paris, France Article History: Received 28 July 2007; Revised 29 October 2007; Accepted 13 November 2007

Key words: low-molecular weight heparin; lung cancer; outcome; recurrence; surgery Abbreviations: LMWH = low-molecular-weight heparin; NSCLC non-small cell lung cancer; UH = unfractioned heparin; VTE = venous thromboembolism ********** N [...]

Objectives: To evaluate the incidence of catamenial pneumothorax (CP) among women who have been referred for the surgical treatment of spontaneous pneumothorax (SP) and to study its pathogenic mechanisms. Design: [...]

Objectives: To study the clinical characteristics, treatment modalities, and outcome of patients with superior sulcus tumors who underwent surgery over a 15-year period. Design: Retrospective clinical study. Methods: Clinical records [...]

Background: Serologic methods for diagnosis of tuberculosis have been widely investigated owing to their low cost and rapid technical execution. Sensitivity and specificity of different tests have been reported to be largely variable. Study objectives: To evaluate the IgA-mediated humoral immune response against the mycobacterial antigen P-90 as a tool for diagnosis of pulmonary tuberculosis. Participants: Eighty-eight patients with microbiologically confirmed diagnosis of pulmonary tuberculosis (32 with positive sputum smears and 56 with negative sputum smears), 28 patients with a definite nontuberculous lung disease, 12 subjects with healed tuberculosis, and 47 healthy volunteers (24 purified protein derivative negative and 23 positive). Measurements and results: Detection of anti-P-90 IgA was performed by enzyme-immunoassay. At a cutoff of 0.221 optical density, determined by a receiver operating characteristic curve, the overall sensitivity and specificity of the test were 70.4% and 91.9%, respectively. Patients with active tuberculosis showed significantly higher titers of anti-P-90 IgA compared with other groups (p [is less than] 0.05). Conclusions: The evaluation of IgA-mediated humoral immune response against the antigen P-90 might constitute a useful tool for presumptive diagnosis of pulmonary tuberculosis. (CHEST 1997;111:601-05) Key words: antigen P-90; IgA; serodiagnosis; tuberculosis Abbreviations: BCG = bacille Calmette-Guerin, EIA = enzyme-immunosorbent assay, OD = optical density; PPD = purified protein derivative; pTB = pulmonary tuberculosis; ROC = receiver operating characteristic; TB = tuerculosis, Tuberculosis (TB) is one of the most serious public health problems worldwide. It is estimated that 400,000 new cases occur in the industrialized world each year; in the underdeveloped world, [...]

Background: Endothelin (ET) is an endothelium-derived multifunctional peptide involved in the local regulation of the vascular tone. Study objectives: To assess changes of endogenous ET production/excretion in the acute phase (36 h from the event) of pulmonary embolism (PE). Participants: Ten patients with acute PE, nine patients with acute lung injury (ALI), and 12 healthy volunteers (HVs). Measurements and results: ET was detected by radioimmunoassay in venous and arterial blood as well as in 24-h urine specimens. For each subject, arterial/venous immunoreactive ET (ir-ET) ratio was evaluated as an index of its pulmonary extraction/synthesis. Creatinine clearance was employed in each case to obtain a corrected renal ir-ET clearance. Renal ir-ET clearance was comparable in all three groups. Arterial/venous ir-ET ratio was comparable in PE and in ALI patients (1.31 ± 0.25 vs 1.24 ± 0.20; p=0.7), while it was significantly higher in PE patients than in HV subjects (0.85 ± 0.07; p=0.0001). Accordingly, 24-h urine ir-ET excretion was higher in PE (120.50 ± 27.36 ng/24 h) and ALI patients (135.80 ± 21.60 ng/24 h) than in HV subjects (68.33 ± 9.31 ng/24 h; p=0.0001). Conclusions: Abnormalities of ET metabolism--mainly related to increased synthesis and/or defective pulmonary handling--occur in the acute phase of PE. The relevance of this finding with respect to the pathogenesis and/or management of pulmonary thromboembolism remains to be elucidated. (CHEST 1997;111:544-49) Key words: Endothelin; endothelium; pulmonary embolism Abbreviations: ALI =acute lung injury; ET=endothelin; ET-1 endothelin l; ET-2=endothelin 2; ET-3=endothelin 3; HV=healthy volunteers; ET=immunoreactive endothelin; ETart=immunoreactive arsenal endothelin irETur=immunoreactive urinary endothelin; ETven=immunoreactive venous endothelin; PE=pulmonary embolism, Pulmonary embolism (PE) is an important cause of morbidity and mortality.[1] Little information is available on the role of endothelium damage with respect to the pulmonary abnormalities taking place during [...]

The tumor microenvironment is a complex mix of cancerous and noncancerous cells (especially immune cells and fibroblasts) with distinct metabolisms. These cells interact with each other and are influenced by the metabolic disorders of the host. In this review, we discuss how metabolic pathways that sustain biosynthesis in cancer cells could be targeted to increase the effectiveness of cancer therapies by limiting the nutrient uptake of the cell, inactivating metabolic enzymes (key regulatory ones or those linked to cell cycle progression), and inhibiting ATP production to induce cell death. Furthermore, we describe how the microenvironment could be targeted to activate the immune response by redirecting nutrients toward cytotoxic immune cells or inhibiting the release of waste products by cancer cells that stimulate immunosuppressive cells. We also examine metabolic disorders in the host that could be targeted to inhibit cancer development. To create future personalized therapies for targeting each cancer tumor, novel techniques must be developed, such as new tracers for positron emission tomography/computed tomography scan and immunohistochemical markers to characterize the metabolic phenotype of cancer cells and their microenvironment. Pending personalized strategies that specifically target all metabolic components of cancer development in a patient, simple metabolic interventions could be tested in clinical trials in combination with standard cancer therapies, such as short cycles of fasting or the administration of sodium citrate or weakly toxic compounds (such as curcumin, metformin, lipoic acid) that target autophagy and biosynthetic or signaling pathways.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jtcvs.2007.03.052 Byline: Alessando Stefani (a), Edouard Boulenger (b), Sylvie Mehaut (c), Adrian Ciupea (c), Marco Alifano (a) Author Affiliation: (a) Department of Thoracic Surgery, HA[acute accent]tel-Dieu University Hospital, Paris, France (b) Department of Thoracic Surgery, Hospital of Troyes, Troyes, France (c) Department of Pathology, Hospital of Troyes, Troyes, France. Article History: Received 24 February 2007; Accepted 29 March 2007

BackgroundInfection of the pleural cavity invariably leads to hospitalisation, and a fatal outcome is not uncommon. Our aim was to study the epidemiology of pleural empyema on a nationwide basis in the whole population and in three subgroups of patients, namely post-lung resection, associated cancer and those with no surgery and no cancer.MethodsData from patients aged ≥18 years hospitalised with a diagnosis of pleural infection in France between January 2013 and December 2017 were retrieved from the medical-administrative national hospitalisation database and retrospectively analysed. Mortality, length of stay and costs were assessed.ResultsThere were 25 512 hospitalisations for pleural empyema. The annual rate was 7.15 cases per 100 000 habitants in 2013 and increased to 7.75 cases per 100 000 inhabitants in 2017. The mean age of patients was 62.4±15.6 years and 71.7% were men. Post-lung resection, associated cancer and no surgery–no cancer cases accounted for 9.8%, 30.1% and 60.1% of patients, respectively. These groups were significantly different in terms of clinical characteristics, mortality and risk factors for length of stay, costs and mortality. Mortality was 17.1% in the whole population, 29.5% in the associated cancer group, 17.7% in the post-lung resection group and 10.7% in the no surgery–no cancer group. In the whole population, age, presence of fistula, higher Charlson Comorbidity Index (>3), alcohol abuse, arterial hypertension, hyperlipidaemia, atheroma, atrial fibrillation, performance status >3 and three subgroups of pleural empyema independently predicted mortality.ConclusionsEmpyema is increasing in incidence. Factors associated with mortality are recent lung resection and associated diagnosis of cancer.

Les adénocarcinomes du poumon présentent des réarrangements chromosomiques touchant les gènes ALK, ROS1, NTRKet RETdans 5 à 10 % des cas. Ces réarrangements sont associés à la production de transcrits de fusion, aboutissant à la synthèse de protéines chimériques ayant une activité kinase constitutive. Ces protéines anormales induisent une dépendance oncogénique pouvant être ciblée par des inhibiteurs de tyrosine kinase. Dans cette revue, nous ferons le point sur l’épidémiologie clinique et moléculaire des réarrangements chromosomiques touchant les gènes ALK, ROS1, NTRK, et RET. Nous décrirons les mécanismes de résistance aux inhibiteurs de tyrosine kinase qui ont été observés. Nous présenterons les techniques de détection pouvant être utilisées pour détecter ces réarrangements et les stratégies mises en place dans les plateformes de génétique moléculaire des cancers pour mettre en évidence ces altérations génétiques.

Caloric starvation, as well as various diets, has been proposed to increase the oxidative DNA damage induced by radiotherapy (RT). However, some diets could have dual effects, sometimes promoting cancer growth, whereas proposing caloric restriction may appear counterproductive during RT considering that the maintenance of weight is a major factor for the success of this therapy. A systematic review was performed via a PubMed search on RT and fasting, or caloric restriction, ketogenic diet (>75% of fat-derived energy intake), protein starvation, amino acid restriction, as well as the Warburg effect. Twenty-six eligible original articles (17 preclinical studies and 9 clinical noncontrolled studies on low-carbohydrate, high-fat diets popularized as ketogenic diets, representing a total of 77 patients) were included. Preclinical experiments suggest that a short period of fasting prior to radiation, and/or transient caloric restriction during treatment course, can increase tumor responsiveness. These regimens promote accumulation of oxidative lesions and insufficient repair, subsequently leading to cancer cell death. Due to their more flexible metabolism, healthy cells should be less sensitive, shifting their metabolism to support survival and repair. Interestingly, these regimens might stimulate an acute anticancer immune response, and may be of particular interest in tumors with high glucose uptake on positron emission tomography scan, a phenotype associated with poor survival and resistance to RT. Preclinical studies with ketogenic diets yielded more conflicting results, perhaps because cancer cells can sometimes metabolize fatty acids and/or ketone bodies. Randomized trials are awaited to specify the role of each strategy according to the clinical setting, although more stringent definitions of proposed diet, nutritional status, and consensual criteria for tumor response assessment are needed. In conclusion, dietary interventions during RT could be a simple and medically economical and inexpensive method that may deserve to be tested to improve efficiency of radiation.

Une adaptation des thérapeutiques et une prise en charge personnalisée des patients atteints d’un cancer bronchique non à petites cellules opérable représentent ces dernières années un enjeu majeur. Ceci passe par une intégration de plusieurs paramètres dans la prise en charge du patient, pas uniquement les résultats histologiques, mais également par une meilleure compréhension des mécanismes impliqués dans la progression tumorale. Ainsi, de nombreuses études se sont intéressées à l’impact des caractéristiques de l’hôte, de la tumeur et des interactions de ces derniers. Le rôle des processus inflammatoires et l’environnement immunitaire tumoral y jouent une place centrale. Ainsi, au-delà du stade tumoral, la dénutrition, la sarcopénie et l’état inflammatoire ont pu être identifiés comme facteurs indépendants pouvant impacter directement les suites postopératoires. Le développement de programmes de récupération améliorés après chirurgie (RAAC), où le patient devient acteur principal de sa prise en charge, semble une réponse intéressante puisqu’elle permet une diminution des complications postopératoires, une diminution de la durée de séjour et indirectement une diminution des coûts. Une vision plus large et plus complète comprenant l’évaluation morphométrique du patient, ses performances physiques, son état inflammatoire et son état nutritionnel fourniraient des informations discriminantes supplémentaires pouvant permettre de prédire l’issue postopératoire et ainsi adapter les thérapeutiques de façon personnalisée.

De nombreuses études suggèrent un rôle suppresseur de tumeur du complexe de remodelage de la chromatine SWI/SNF. Des altérations de ce complexe ont été observées dans de nombreuses tumeurs de différentes origines, morphologiquement et phénotypiquement diverses. Notamment, elles définissent deux entités de tumeurs thoraciques : les sarcomes et les carcinomes SMARCA4 déficients. Certaines caractéristiques cliniques semblent communes à ces deux entités, comme le tabagisme, la prédominance masculine et le pronostic sombre. En revanche, la distinction histologique entre ces deux entités est parfois difficile et il n’est pas exclu que ces entités appartiennent au même spectre tumoral à des degrés de différenciation différents. La thérapie de ces tumeurs n’est pas encore codifiée. Ces tumeurs ne semblent pas associées à la présence de mutations driversoncogéniques permettant la prescription de thérapie ciblée, néanmoins l’immunothérapie a montré une efficacité dans de rares cas rapportés. Des traitements plus spécifiques utilisant des inhibiteurs d’EZH2 semblent également prometteurs dans les sarcomes SMARCA4 déficients.

L’examen macroscopique est une des étapes essentielles de l’examen anatomopathologique d’un prélèvement de chirurgie thoracique. Il comprend la description de la pièce opératoire et des lésions et l’échantillonnage précis et exhaustif des territoires tumoraux et adjacents à la tumeur. Cet examen nécessite une bonne connaissance de la classification pTNM actualisée. Les pathologistes du groupe PATTERN se sont associés à des chirurgiens thoraciques, sous l’égide de la Société française de pathologie, pour proposer des recommandations sur la prise en charge macroscopique des pièces opératoires pulmonaires pour carcinome. Cette démarche s’inscrit dans le contexte de la réédition du compte rendu d’anatomie pathologique structuré des carcinomes pulmonaires, recommandé par la société française de pathologie et nécessaire à une prise en charge standardisée des patients.

Reprogramming of energy metabolism is a well-established hallmark of cancer, with aerobic glycolysis classically considered a prominent feature. We investigate the heterogeneity in glucose metabolism pathways within resectable primary lung adenocarcinoma and its clinical significance.

Multiple nodules in the lung are being diagnosed with an increasing frequency thanks to high-quality computed tomography imaging. In patients with lung cancer, this situation represents up to 10% of patients who have an operation. For clinical management, it is important to classify the disease as intrapulmonary metastasis or multiple primary lung carcinoma to define TNM classification and optimize therapeutic options. In the present study, we evaluated the respective and combined input of histological and molecular classification to propose a classification algorithm for multiple nodules.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jtcvs.2006.03.020 Byline: Marco Alifano (a), Mohamed Sadok Boudaya (a), Carmen Dinu (b), Habiba Kadiri (b), Jean-Francois Regnard (a) Author Affiliation: (a) Unite de Chirurgie Thoracique, HA[acute accent]pital HA[acute accent]tel-Dieu, AP-HP, Universite Paris V, Paris, France (b) Service d'Anatomie et de Cytologie Pathologiques, HA[acute accent]pital HA[acute accent]tel-Dieu, AP-HP, Universite Paris V, Paris, France Article History: Received 6 February 2006; Accepted 15 March 2006

To the Editor: Conceptually, the suggestion by Alifano et al (1) (August 2004) is especially compelling from both the scientific and clinical observational standpoints. However, one needs to carefully consider [...]

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Aspergillus fumigatusis a ubiquitous mold that can cause severe infections in immunocompromised patients, typically manifesting as invasive pulmonary aspergillosis (IPA). Adaptive and innate immune cells that respond to A. fumigatusare present in the endogenous repertoire of patients with IPA but are infrequent and cannot be consistently isolated and expanded for adoptive immunotherapy. Therefore, we gene-engineered A. fumigatus–specific chimeric antigen receptor (Af-CAR) T cells and demonstrate their ability to confer antifungal reactivity in preclinical models in vitro and in vivo. We generated a CAR targeting domain AB90-E8 that recognizes a conserved protein antigen in the cell wall of A. fumigatushyphae. T cells expressing the Af-CAR recognized A. fumigatusstrains and clinical isolates and exerted a direct antifungal effect against A. fumigatushyphae. In particular, CD8+Af-CAR T cells released perforin and granzyme B and damaged A. fumigatushyphae. CD8+and CD4+Af-CAR T cells produced cytokines that activated macrophages to potentiate the antifungal effect. In an in vivo model of IPA in immunodeficient mice, CD8+Af-CAR T cells localized to the site of infection, engaged innate immune cells, and reduced fungal burden in the lung. Adoptive transfer of CD8+Af-CAR T cells conferred greater antifungal efficacy compared to CD4+Af-CAR T cells and an improvement in overall survival. Together, our study illustrates the potential of gene-engineered T cells to treat aggressive infectious diseases that are difficult to control with conventional antimicrobial therapy and support the clinical development of Af-CAR T cell therapy to treat IPA.

The aim of the study was to evaluate the effect of 2-(18F)-fluoro-2-deoxy-D-glucose (18F-FDG)-PETcomputed tomography (CT) respiratory-gated imaging four-dimensional (4D) in the metabolic evaluation of small solitary pulmonary nodules and analyze the cutoff maximum standardized uptake value (SUVmax) of 2.5 in classifying and distinguishing benignmalignant pulmonary pathologies in 4D studies.

Histologic classification of lung adenocarcinoma subtype has a prognostic value in most studies. However, lung adenocarcinoma characteristics differ across countries. Here, we aimed at validating the prognostic value of this classification in a large French series of lung adenocarcinoma.

A significant percentage of pneumothorax in women is due to thoracic endometriosis. Pathophysiologic mechanisms continue to be debated, and pathologic aspects are poorly known.

Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct types of physical and chemical stress, including multiple chemotherapeutics. This effect requires pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. In line with a general role of vitamin B6 in stress responses, low PDXK expression levels were found to be associated with poor disease outcome in two independent cohorts of patients with NSCLC. These results indicate that PDXK expression levels constitute a biomarker for risk stratification among patients with NSCLC.

Although known for several decades, catamenial pneumothorax has been considered until recently as an extremely rare entity. The condition is now more easily recognized and several studies have been published, with somewhat relevant discrepancies with respect to etiologic, epidemiologic, and management features. In the present review, I will provide a synthesis of available knowledge on the subject.

Management of bronchiectasis remains controversial and information on long-term results of surgical treatment is poor. Clinical records of 45 patients, who underwent surgery for bronchiectasis in an 8-year period, were retrospectively reviewed. Bronchiectasis focus was isolated in 24 cases, associated with a limited homolateral or controlateral focus in 9 and 11, respectively; two patients had bilateral evident foci. Bronchiectasis was responsible for lobe destruction in 23 cases. All patients had symptoms: haemoptysis (n=7), recurrent pneumonia (n=7), persistent bronchorrea with recurrent infection (n=15), hemoptysis and recurrent infection (n=16). A total of 23 lobectomies, 11 lobectomies+segmentectomies, 2 bi-lobectomies, 9 segmentectomies and 1 pneumonectomy were carried out. There were no perioperative deaths; complications occurred in 5 patients (postoperative pneumonia in 2, prolonged air-leak, residual air-space and bronchial infection 1 each). Symptoms disappeared in 32 patients, 10 patients experienced a significant improvement. Exercise tolerance remained stable or improved in 33 and 2 cases, respectively, a slight impairment was observed in 9. Out of 32 evaluable patients 11 had an unchanged FEV(1), 15 had a limited FEV(1) lowering (<15%), and 9 had a more important functional loss. Surgical treatment of bronchiectasis obtains satisfactory long-term results, with acceptable morbidity rates.

To evaluate the incidence of catamenial pneumothorax (CP) among women who have been referred for the surgical treatment of spontaneous pneumothorax (SP) and to study its pathogenic mechanisms.

Circulating and urinary levels of endothelin (ET), an endothelium-derived vasoconstrictive and mitogenic peptide have been reported to increase in patients with chronic obstructive pulmonary disease (COPD), but the mechanisms of these abnormalities are not fully understood. Our study objectives were to evaluate pulmonary and renal ET clearance in COPD patients during an acute exacerbation. Our participants included nine consecutive patients with moderate to severe COPD without signs of right heart failure admitted for acute exacerbation and ten healthy volunteers (HV) as controls. ET was detected by radioimmunoassay in venous and arterial blood as well as in a timed urine specimen. For each subject, arterial/venous immunoreactive ET ratio (ir-ETart/ir-ETven) was evaluated as an index of its pulmonary clearance. Creatinine clearance was employed in each case to obtain a corrected renal ir-ET clearance. Glomerular filtration rate (GFR) was also assessed by dynamic99mTc-diethylenetriamine pentaacetic acid renal scintigraphy in six COPD patients during acute exacerbation and at recovery. The ratio ir-ETart/ir-ETven was comparable in COPD patients (0.75±0.12) and in HV (0.82±0.09). A significant difference was found with respect to 24 h ir-ET urinary excretion between COPD patients during exacerbation as well as at recovery (respectively 142.1±12.8 ng/24 h and 89.0±15.1 ng/24 h) and HV (65.1±10.1 ng/24 h). ET renal clearance was higher in COPD patients than in HV (29.2±5.2 ml min−1in COPD during exacerbation; 17.5±3.9 ml min−1at recovery and 13.6±2.4 ml min−1in HV, P<0.001). GFR was 69.4±10.0 ml min−1in COPD patients during exacerbation and it significantly increased at the recovery (95.5±20.9 ml min−1P<0.001). Corrected renal clearance of the peptide was significantly correlated to GFR values during the exacerbation (r=−0.81, P<0.05). Furthermore change in renal ET production resulted associated with changes in paCO2(r=0.83, P<0.001) and in paO2(r=−0.73 , P<0.05). Acute exacerbation in COPD patients causes an increase in renal ET production which is partially reversible at the recovery, in the absence of significant changes in ET-1 circulating levels. ET might contribute to the renal response to hypoxaemia and hypercapnia in COPD.

Objective:Successful treatment of postoperative empyema remains a challenge for thoracic surgeons. We report herein our 12-year experience in the management of this condition by means of open window thoracostomy. Methods:Open window thoracostomy was used in the treatment of 46 patients with empyema complicating pulmonary resection. A bronchopleural fistula was associated in 39 of 46 cases. Previous operations included pneumonectomy (n = 30), bilobectomy (n = 5), lobectomy (n = 9), and wedge resection (n = 2) performed for benign (n = 10) or malignant (n = 36) disease. In 10 patients open window thoracostomy was definitive because of patient death (n = 2), concomitant major illness (n = 2), tumor recurrence (n = 4), spontaneous closure (n = 1), or patient choice (n = 1). In 36 cases intrathoracic flap transposition was eventually performed. Muscular (n = 29), omental (n = 5), or combined muscular and omental (n = 2) flaps were used to obliterate the thoracostomy cavity and to close a possibly associated bronchopleural fistula. In 9 patients with postpneumonectomy cavities too wide to be filled by the available flaps, a limited thoracoplasty represented an intermediate step. Results:Among patients treated with definitive open window thoracostomy, local control of the infection was achieved in all the survivors (8/8). After open window thoracostomy and subsequent flap transposition, success (definitive closure of the thoracostomy and, if present, of the bronchopleural fistula) was achieved in 27 (75.0%) of 36 patients. Four initial failures could be salvaged by means of reoperation (initial reopening of thoracostomy and subsequent muscular or omental transposition). Conclusion:Open window thoracostomy followed by intrathoracic muscle or omental transposition represents a valid therapeutic option in patients with empyema complicating pulmonary resections. (J Thorac Cardiovasc Surg 2000;120:270-5)

Cervical mediastinoscopy is widely employed for biopsy of mediastinal lymph nodes and staging of lung cancer. The application of video-assisted technology to mediastinoscopy in a series of patients with lung cancer has not been reported. Preliminary experience with the use of video-mediastinoscopy in diagnosis and staging of lung cancer is presented. Fifteen patients with lung cancer were studied. Results of previous computed tomography scans had shown the presence of enlarged mediastinal lymph nodes in the retrovascular plane in all of the cases. Video-mediastinoscopy was performed under general anesthesia using a specifically designed rigid scope connected to a mono–charged-coupled device video camera (model INH 002756; Karl Storz-Endoskope, Tuttlingen, Germany). Neither fatalities nor major complications related to the procedure were observed. In all cases, video-mediastinoscopy proved useful for diagnosis or staging of lung cancer, therefore contributing to clinical decision making. The optimal visualization of mediastinal structure and the possibility for the surgeon to operate with both hands are appreciable characteristics of this technique.

Influenza virus infection leads to severe and complicated disease, particularly in patients with lung cancer. It alters the tumor microenvironment (TME), which may potentiate lung cancer progression and disrupt responses to antitumoral treatments. Consequently, influenza vaccination and antiviral treatments should be recommended to all patients with lung cancer.

Scimitar syndrome is one of the large congenital pulmonary venolobar syndromes and is defined as hypogenetic lung associated with partial anomalous pulmonary venous return. We report the case of a 25-year-old man with complex and exceptional variant scimitar syndrome. A chest CT scan with three-dimensional (3-D) reconstruction led us to identify hypoplastic right lung with homolateral hemidiaphragm agenesis and hypogenetic right pulmonary artery. There was a large and sinuous systemic arterial supply and anomalous venous return directed into the left atrium (venous return being usually directed into the right atrium or inferior vena cava in scimitar syndrome). Hyperoxia test showed no shunt. This variant scimitar syndrome has been previously reported and anomalous venous return called “meandering” pulmonary vein. Diagnosis and management of these patients with complex congenital anomalies are difficult because of their exceptional condition. Chest CT scan with 3-D reconstruction offers an accurate noninvasive diagnosis.

Non-traumatic, spontaneous diaphragmatic rupture is a rare event whose pathophysiology is not known. We report the case of endometriosis-related spontaneous rupture of the right diaphragm with intrathoracic herniation of the liver, gallbladder and colon. We hypothesize that the invasiveness of endometriotic tissue caused diaphragm fragility, which finally lead to its complete rupture without traumatic event. The treatment consisted of a classical management of diaphragmatic rupture, with excision of the endometriotic nodule followed by medical ovarian suppression for six months.

Abstract.: The intrathoracic rupture of a splenic hydatid cyst is very unusual. We report herein the case of a 29-year-old man who presented with a left-sided pleural effusion associated with fever and chest pain. The patient underwent laparotomy and splenectomy en bloc with a portion of gastric wall and diaphragm, followed by irrigation of the pleural cavity with a hypertonic solution through a phrenotomy. His outcome was favorable and there was no recurrence at 2-year follow-up.

ABSTRACTIn non-small cell lung carcinoma (NSCLC), stimulation of toll-like receptor 7 (TLR7), a receptor for single stranded RNA, is linked to tumor progression and resistance to anticancer chemotherapy. However, the mechanism of this effect has been elusive. Here, using a murine model of lung adenocarcinoma, we demonstrate a key role for TLR7 expressed by malignant (rather than by stromal and immune) cells, in the recruitment of myeloid derived suppressor cells (MDSCs), induced after TLR7 stimulation, resulting in accelerated tumor growth and metastasis. In adenocarcinoma patients, high TLR7 expression on malignant cells was associated with poor clinical outcome, as well as with a gene expression signature linked to aggressiveness and metastastic dissemination with high abundance of mRNA encoding intercellular adhesion molecule 1 (ICAM-1), cytokeratins 7 and 19 (KRT-7 and 19), syndecan 4 (SDC4), and p53. In addition, lung tumors expressing high levels of TLR7 have a phenotype of epithelial mesenchymal transition with high expression of vimentin and low abundance of E-cadherin. These data reveal a crucial role for cancer cell-intrinsic TLR7 expression in lung adenocarcinoma progression.

Les tumeurs pulmonaires multiples (TPM) représentent jusqu’à près de 15 % des cancers pulmonaires [1]. Leur prise en charge thérapeutique est complexe car elle dépend de leur nature métastatique (ME) ou multi-primitive (MP) [2], avec tantôt de la chirurgie à visée curative, ou des traitements systémiques à visée palliative.

ABSTRACTCo-stimulatory and inhibitory receptors expressed by immune cells in the tumor microenvironment modulate the immune response and cancer progression. Their expression and regulation are still not fully characterized and a better understanding of these mechanisms is needed to improve current immunotherapies. Our previous work has identified a novel ligand/receptor pair, LLT1/CD161, that modulates immune responses. Here, we extensively characterize its expression in non-small cell lung cancer (NSCLC). We show that LLT1 expression is restricted to germinal center (GC) B cells within tertiary lymphoid structures (TLS), representing a new hallmark of the presence of active TLS in the tumor microenvironment. CD161-expressing immune cells are found at the vicinity of these structures, with a global enrichment of NSCLC tumors in CD161+CD4+and CD8+T cells as compared to normal distant lung and peripheral blood. CD161+CD4+T cells are more activated and produce Th1-cytokines at a higher frequency than their matched CD161-negative counterparts. Interestingly, CD161+CD4+T cells highly express OX40 co-stimulatory receptor, less frequently 4-1BB, and display an activated but not completely exhausted PD-1-positive Tim-3-negative phenotype. Finally, a meta-analysis revealed a positive association of CLEC2D(coding for LLT1) and KLRB1(coding for CD161) gene expression with favorable outcome in NSCLC, independently of the size of T and B cell infiltrates. These data are consistent with a positive impact of LLT1/CD161 on NSCLC patient survival, and make CD161-expressing CD4+T cells ideal candidates for efficient anti-tumor recall responses.

ABSTRACTThere is now growing evidence that the immune contexture influences cancer progression and clinical outcome of patients with non-small cell lung cancer (NSCLC). If chemotherapy is widely used to treat patients with advanced-stage NSCLC, it remains unclear how it could modify the immune contexture and impact its prognostic value. Here, we analyzed two retrospective cohorts, respectively composed of 122 stage III-N2 NSCLC patients treated with chemotherapy before surgery and 39 stage-matched patients treated by surgery only. In patients treated with neoadjuvant chemotherapy, the histological characteristics, the expression of PD-L1 protein, and the tumor immune microenvironment (CD8+T cells, DC-LAMP+mature dendritic cells, and CD68+macrophages) were evaluated and their prognostic value assessed together with standard clinical parameters. By analyzing pre- and post-treatment specimens, we did not find any changes in the PD-L1 expression. We also found that the tumor immune contexture in patients treated with neoadjuvant chemotherapy exhibited a similar pattern that the one found in chemotherapy-naive patients, with comparable densities of tumor-infiltrating CD8+and DC-LAMP+cells and a similar spatial organization. The percentage of residual viable tumor cells and the immune pattern (CD8+and DC-LAMP+cell densities) were significantly associated with the clinical outcome and allowed the identification of short- and long-term survivors, respectively. In multivariate analysis, the immune pattern was found to be the strongest independent prognostic factor. In conclusion, this study decrypts the complex interplay between cancer and immune cells in patients undergoing chemotherapy and supports potential beneficial synergistic effect of immunotherapy and chemotherapy.

Endobronchial localization of sclerosing hemangioma is extremely rare. Exact localization of lesion at preoperative work-up allows parenchymal-sparing procedures. We report a case of endobronchial sclerosing hemangioma diagnosed preoperatively and treated by lingular-sparing upper lobectomy with nodal dissection.

A 31-year-old patient is described with thrombophlebitis of the right jugular vein, and anerobic septicemia (Lemierre’s syndrome). Multiple pulmonary abscesses and bilateral fibrinopurulent empyema were also present. Treatment included intravenous antibiotics, heparin, and video-assisted thoracoscopic debridement of pleural cavities. A favorable outcome was observed.

We report a case of staghorn nephrolithiasis that evolved into xanthogranulomatous pyelonephritis with perinephric abscess, nephrobronchial fistula, and lung abscess. The patient was an intravenous drug abuser who tested positive for human immunodeficiency virus, without evidence of acquired immunodeficiency syndrome. He presented with a 2-month history of untreated repeated episodes of left flank pain and hyperpyrexia. Treatment involved left nephrectomy, debridement of abscess, tube drainage, and intravenous antibiotics. The patient illustrates the need to consider untreated nephrolitiasis as a predisposing factor for pulmonary complications.