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1.
ERJ Open Res ; 10(1)2024 Jan.
Article in English | MEDLINE | ID: mdl-38259816

ABSTRACT

Introduction: Non-small cell lung cancer (NSCLC) is often associated with compromised lung function. Real-world data on the impact of surgical approach in NSCLC patients with compromised lung function are still lacking. The objective of this study is to assess the potential impact of minimally invasive surgery (MIS) on 90-day post-operative mortality after anatomic lung resection in high-risk operable NSCLC patients. Methods: We conducted a retrospective multicentre study including all patients who underwent anatomic lung resection between January 2010 and October 2021 and registered in the Epithor database. High-risk patients were defined as those with a forced expiratory volume in 1 s (FEV1) or diffusing capacity of the lung for carbon monoxide (DLCO) value below 50%. Co-primary end-points were the impact of risk status on 90-day mortality and the impact of MIS on 90-day mortality in high-risk patients. Results: Of the 46 909 patients who met the inclusion criteria, 42 214 patients (90%) with both preoperative FEV1 and DLCO above 50% were included in the low-risk group, and 4695 patients (10%) with preoperative FEV1 and/or preoperative DLCO below 50% were included in the high-risk group. The 90-day mortality rate was significantly higher in the high-risk group compared to the low-risk group (280 (5.96%) versus 1301 (3.18%); p<0.0001). In high-risk patients, MIS was associated with lower 90-day mortality compared to open surgery in univariate analysis (OR=0.04 (0.02-0.05), p<0.001) and in multivariable analysis after propensity score matching (OR=0.46 (0.30-0.69), p<0.001). High-risk patients operated through MIS had a similar 90-day mortality rate compared to low-risk patients in general (3.10% versus 3.18% respectively). Conclusion: By examining the impact of surgical approaches on 90-day mortality using a nationwide database, we found that either preoperative FEV1 or DLCO below 50% is associated with higher 90-day mortality, which can be reduced by using minimally invasive surgical approaches. High-risk patients operated through MIS have a similar 90-day mortality rate as low-risk patients.

2.
JTCVS Tech ; 21: 227-236, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37854807

ABSTRACT

Objective: Recent studies have demonstrated the feasibility and favorable long-term results of tracheobronchial replacement using stented cryopreserved aortic allografts. We propose to investigate the outcomes of this emerging technique in the subgroup of patients with extensive tracheal cancer. Methods: This study was based on 13 patients with primary extensive tracheal cancer extracted from the prospective registry TRITON-01 (ClinicalTrials.gov Identifier: NCT04263129), which included 40 patients in total. We analyzed early and late outcomes in this subset of patients. Results: From March 2019 to September 2022, 13 patients were included in the study. There were 9 female and 4 male patients, with a mean age of 53.9 years [36-71 years]. They had tracheal replacement for extended adenoid cystic carcinoma (n = 11), squamous cell carcinoma (n = 1), and mucoepidermoid carcinoma (n = 1). A venovenous extracorporeal membrane oxygenation was used in the 6 last cases. The mean length of resection was 81 mm [50-120 mm]. There was no 30-day postoperative mortality. A complete resection (R0) was achieved in 11 patients. The main late complications consisted of tracheal granulomas related to the stent and requiring repeated bronchoscopies (n = 9), pneumonia (n = 3), airway infection (n = 1), bronchoesophageal fistula (n = 1), mechanical stent obstruction requiring change (n = 2), and mediastinitis treated by antibiotics, drainage, and omentoplasty (n = 1). With a maximal follow-up of 3 years and 7 months, cancer recurrence was observed in 2 patients. All patients were alive at last follow-up except 2 (84.6%). Conclusions: Airway replacement using stented CAA represents a feasible and promising solution for extensive tracheal cancer.

3.
J Pers Med ; 13(7)2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37511690

ABSTRACT

Several therapies to improve the management of lymphoma are currently being investigated, necessitating the development of new biomarkers. However, this requires high-quality and clinically annotated biological material. Therefore, we established a lymphoma biobank including all available biological material (tissue specimens and matched biological resources) along with associated clinical data for lymphoma patients diagnosed, according to the WHO classification, between 2005 and 2022 in the Laboratory of Clinical and Experimental Pathology, Nice, France. We retrospectively included selected cases in a new collection at the Côte d'Azur Biobank, which contains 2150 samples from 363 cases (351 patients). The male/female ratio was 1.3, and the median age at diagnosis was 58 years. The most common lymphoma types were classical Hodgkin lymphoma, diffuse large B-cell lymphoma, and extra-nodal marginal zone lymphoma of MALT tissue. The main sites of lymphoma were the mediastinum, lymph node, Waldeyer's ring, and lung. The Côte d'Azur Biobank is ISO 9001 and ISO 20387 certified and aims to provide high quality and diverse biological material to support translational research projects into lymphoma. The clinico-pathological data generated by this collection should aid the development of new biomarkers to enhance the survival of patients with lymphoid malignancies.

4.
Radiat Oncol ; 18(1): 97, 2023 Jun 07.
Article in English | MEDLINE | ID: mdl-37287020

ABSTRACT

BACKGROUND: Early-stage lung cancer, primarily treated with surgery, often occur in poor surgical candidates (impaired respiratory function, prior thoracic surgery, severe comorbidities). Stereotactic ablative radiotherapy (SABR) is a non-invasive alternative that provides comparable local control. This technique is particularly relevant for surgically resectable metachronous lung cancer, in patients unable to undergo surgery.. The objective of this study is to evaluate the clinical outcome of patients treated with SABR for stage I metachronous lung cancer (MLC) versus stage I primary lung cancer (PLC). PATIENTS AND METHODS: 137 patients treated with SABR for stage I non-small cell lung cancer were retrospectively reviewed, of which 28 (20.4%) were MLC and 109 (79.6%) were PLC. Cohorts were evaluated for differences in overall survival (OS), progression-free survival (PFS), metastasis-free survival, local control (LC), and toxicity. RESULTS: After SABR, patients treated for MLC have comparable median age (76.6 vs 78.6, p = 0.2), 3-year LC (83.6% vs. 72.6%, p = 0.2), PFS (68.7% vs. 50.9%, p = 0.9), and OS (78.6% vs. 52.1%, p = 0.9) as PLC, along with similar rates of total (54.1% vs. 42.9%, p = 0.6) and grade 3 + toxicity (3.7% vs. 3.6%, p = 0.9). Previous treatment of MLC patients was either surgery (21/28, 75%) or SABR (7/28, 25%). The median follow-up was 53 months. CONCLUSION: SABR is a safe and effective approach for localized metachronous lung cancer.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Radiosurgery , Humans , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Retrospective Studies , Treatment Outcome , Radiosurgery/methods , Lung
5.
Lung Cancer ; 181: 107230, 2023 07.
Article in English | MEDLINE | ID: mdl-37150140

ABSTRACT

INTRODUCTION: Both MET expression and the PD-L1 tumor proportion score (TPS) are companion diagnostics for treatment of advanced non-small cell lung carcinoma (aNSCLC) patients. We evaluated the rate of correlation between MET expression and the PD-L1 TPS in matched biopsies and surgically resected specimens from NSCLC patients. PATIENTS AND METHODS: This retrospective analysis assessed the prevalence and correlation between MET expression (SP44 clone) and the PD-L1 TPS (22C3 clone) by immunohistochemistry together with molecular alterations determined by targeted next-generation sequencing in matched lung biopsy and surgically lung resected specimens from 70 patients with NSCLC. RESULTS: The study found a significant correlation between the MET H-score in surgical samples and matched biopsies (P-value < 0.0001), as well as between the PD-L1 TPS in paired biopsies and surgical samples (P-value < 0.0001). However, there was no significant correlation between the MET H-score or expression subgroups and the PD-L1 TPS in both types of paired samples (P-value = 0.47, and P-value = 0.90). The MET H-score was significantly higher in adenocarcinoma compared to squamous cell carcinoma (P-value < 0.0001). A mutational analysis showed that the MET H-score was significantly higher in NSCLC cases with targetable molecular alterations (P-value = 0.0095), while no significant correlation was found for the PD-L1 TPS. CONCLUSIONS: Our study found no significant correlation between PD-L1 and MET expression in samples from NSCLC patients, highlighting the importance of personalized treatment strategies based on individual expression profiles. These findings provide valuable insight into the development of effective immunotherapy and targeted therapy for NSCLC patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , B7-H1 Antigen/metabolism , Biomarkers, Tumor/metabolism , Biopsy , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Retrospective Studies
7.
Cancers (Basel) ; 14(7)2022 Mar 29.
Article in English | MEDLINE | ID: mdl-35406511

ABSTRACT

The histological distinction of lung neuroendocrine carcinoma, including small cell lung carcinoma (SCLC), large cell neuroendocrine carcinoma (LCNEC) and atypical carcinoid (AC), can be challenging in some cases, while bearing prognostic and therapeutic significance. To assist pathologists with the differentiation of histologic subtyping, we applied a deep learning classifier equipped with a convolutional neural network (CNN) to recognize lung neuroendocrine neoplasms. Slides of primary lung SCLC, LCNEC and AC were obtained from the Laboratory of Clinical and Experimental Pathology (University Hospital Nice, France). Three thoracic pathologists blindly established gold standard diagnoses. The HALO-AI module (Indica Labs, UK) trained with 18,752 image tiles extracted from 60 slides (SCLC = 20, LCNEC = 20, AC = 20 cases) was then tested on 90 slides (SCLC = 26, LCNEC = 22, AC = 13 and combined SCLC with LCNEC = 4 cases; NSCLC = 25 cases) by F1-score and accuracy. A HALO-AI correct area distribution (AD) cutoff of 50% or more was required to credit the CNN with the correct diagnosis. The tumor maps were false colored and displayed side by side to original hematoxylin and eosin slides with superimposed pathologist annotations. The trained HALO-AI yielded a mean F1-score of 0.99 (95% CI, 0.939-0.999) on the testing set. Our CNN model, providing further larger validation, has the potential to work side by side with the pathologist to accurately differentiate between the different lung neuroendocrine carcinoma in challenging cases.

8.
Lung Cancer ; 166: 1-8, 2022 04.
Article in English | MEDLINE | ID: mdl-35134710

ABSTRACT

OBJECTIVES: The evaluation of an increasing number of diagnostic and predictive markers is playing a central role in precision thoracic oncology. Multiplex immunohistochemistry (mIHC), alongside next-generation sequencing, is ideally situated for this purpose and maximizes tumor tissue preservation for molecular analyses that use increasingly large panels. However, the standardization and validation of mIHC that supports routine clinical laboratory processes are mandatory. After a previous proof-of-concept study, we now (i) optimized two automated four-plex assays on a commercially available IHC autostainer for use in daily practices worldwide and (ii) evaluated the repeatability and concordance of the assessment of the cell density. PATIENTS AND METHODS: Two four-plex mIHC assays [i) TTF1, p40, PD-L1, CD8; and, ii) ALK, ROS1, BRAFV600E, NTRK] were optimized on the BenchMark ULTRA autostainer (Ventana Medical Systems, Inc.), as determined in comparison to conventional IHC chromogenic assays. Intra-site repeatability was evaluated on serial tumor sections from non-small cell lung carcinomas (NSCLC). The concordance was assessed by linear fit to plots of the percentage staining evaluated on tumor sections from 89 NSCLC patients. RESULTS: Following optimization, an average concordance for a staining rate of 95.4% was achieved between conventional IHC and mIHC across all selected markers. Assessment of intra-site repeatability showed strong concordance for all these markers (average, R2 = 0.96; P-value < 0.001). CONCLUSIONS: Our optimized mIHC assay gave a sensitive and repeatable assessment of two panels of eight diagnostic and predictive biomarkers for NSCLC. The availability of standardized protocols to determine these biomarkers on a widely available IHC platform will expand the number of pathology laboratories able to determine the eligibility of patients with NSCLC for targeted treatment or immunotherapy in a reliable and concordant manner, thus providing a unique sample-sparing tool to characterize limited tissue samples in thoracic oncology.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antibodies, Monoclonal/therapeutic use , B7-H1 Antigen/analysis , Biomarkers, Tumor/analysis , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Immunohistochemistry , Lung Neoplasms/pathology , Protein-Tyrosine Kinases , Proto-Oncogene Proteins/therapeutic use
9.
Article in English | MEDLINE | ID: mdl-34143577

ABSTRACT

Complex chest and lung infections with bronchial fistula are life-threatening situations with a mortality rate of up to 20%. If medical treatment fails, these patients require aggressive procedures to heal. Transposition of the omentum is a valuable, nonstandard option in these complex cases with aggressive infection involving the pleural space, with or without a bronchial fistula, when medical treatment is unsuccessful. We present a 29-year-old female patient diagnosed with primary immunodeficiency and invasive fungal infection with involvement of the left upper lobe and mediastinal and vertebral bodies treated with a lobectomy and intrathoracic transposition of the omentum.


Subject(s)
Lung Diseases, Fungal/surgery , Omentum/transplantation , Adult , Ascomycota , Female , Humans , Pneumonectomy
11.
Front Immunol ; 12: 630096, 2021.
Article in English | MEDLINE | ID: mdl-33717159

ABSTRACT

Background: Distal airway metaplasia may precede honeycombing in progressive fibrosing interstitial lung disease (ILD). The SCGB1A1+ bronchiolar-specific club cell may play a role in this aberrant regenerative process. Objective: To assess the presence of club cells in the small airways of patients suffering from ILD. Methods: Small airways (internal diameter <2 mm) in lung samples [surgical lung biopsy (SLB) and/or transbronchial lung cryobiopsy (TBLC)] from 14 patients suffering from ILD and 10 controls were morphologically assessed and stained for SCGB1A1. SCGB1A1 was weighted by epithelial height as a marker of airway generation (SCGB1A1/EH). Correlations between clinical, functional, and high-resolution CT (HRCT) prognostic factors and histomorphometry were assessed. Results: Small airways from samples with ILD patterns were significantly less dense in terms of SCGB1A1+ cells [0.064 (0.020-0.172)] as compared to controls' sample's small airways [0.393 (0.082-0.698), p < 0.0001]. Usual interstitial pneumonia (UIP) patterns most frequently contained small airways with limited or absent SCGB1A1 expression (SCGB1A1/EH <0.025): UIP (18/33; 55%) as compared with non-UIP patterns (4/31; 13%) or controls (0/29; 0%): p < 0.0001. In addition, correlations with HRCT indicated a significant negative relationship between SCGB1A1 and bronchiectasis as a feature of bronchiolization (Rho -0.63, p < 0.001) and a positive relationship with both forced vital capacity (FVC) and Hounsfield unit (HU)-distribution pattern in kurtosis (Rho 0.38 and 0.50, respectively, both p < 0.001) as markers of fibrotic changes. Conclusion: Compared with controls, the small airways of patients with ILD more often lack SCGB1A1, especially so in UIP. Low densities of SCGB1A1-marked cells correlate with bronchiectasis and fibrotic changes. Further research investigating SCGB1A1 staining as a pathological feature of the bronchiolization process is merited.


Subject(s)
Lung Diseases, Interstitial/metabolism , Lung Diseases, Interstitial/pathology , Metaplasia/pathology , Adult , Aged , Bronchiectasis/pathology , Bronchioles/pathology , Epithelial Cells/pathology , Female , Humans , Lung/pathology , Male , Metaplasia/physiopathology , Middle Aged , Prospective Studies , Smoking , Uteroglobin/metabolism
12.
Theranostics ; 10(24): 10849-10860, 2020.
Article in English | MEDLINE | ID: mdl-33042257

ABSTRACT

Rationale: The characterization of new theranostic biomarkers is crucial to improving the clinical outcome of patients with advanced lung cancer. Here, we aimed at characterizing the P2RX7 receptor, a positive modulator of the anti-tumor immune response, in patients with lung adenocarcinoma. Methods: The expression of P2RX7 and its splice variants was analyzed by RT-qPCR using areas of tumor and non-tumor lung adenocarcinoma (LUAD) tissues on both immune and non-immune cells. The biological activity of P2RX7 was studied by flow cytometry using fluorescent dyes. Bi-molecular fluorescence complementation and confocal microscopy were used to assess the oligomerization of P2RX7. Tumor immune infiltrates were characterized by immunohistochemistry. Results: Fifty-three patients with LUAD were evaluated. P2RX7A, and 3 alternative splice variants were expressed in LUAD tissues and expression was down regulated in tumor versus adjacent non-tumor tissues. The protein retained biological activity only in immune cells. The P2RX7B splice variant was differentially upregulated in immune cells (P < 0.001) of the tumor and strong evidence of oligomerization of P2RX7A and B was observed in the HEK expression model, which correlated with a default in the activity of P2RX7. Finally, LUAD patients with a high level of P2RX7B had non-inflamed tumors (P = 0.001). Conclusion: Our findings identified P2RX7B as a new theranostic tool to restore functional P2RX7 activity and open alternative therapeutic opportunities to improve LUAD patient outcome.


Subject(s)
Adenocarcinoma of Lung/genetics , Biomarkers, Tumor/genetics , Lung Neoplasms/genetics , Neoplasm Recurrence, Local/ethnology , Receptors, Purinergic P2X7/genetics , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/therapy , Adult , Aged , Aged, 80 and over , Alternative Splicing , Biomarkers, Tumor/metabolism , Chemotherapy, Adjuvant , Female , Gene Expression Regulation, Neoplastic/immunology , HEK293 Cells , Humans , Lung/immunology , Lung/pathology , Lung/surgery , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Male , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/immunology , Pneumonectomy , Prospective Studies , Protein Isoforms/genetics , Protein Isoforms/metabolism , Protein Multimerization/genetics , Protein Multimerization/immunology , Receptors, Purinergic P2X7/metabolism , Retrospective Studies , Signal Transduction/genetics , Signal Transduction/immunology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Up-Regulation
13.
Bull Cancer ; 107(9): 946-958, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32646604

ABSTRACT

It has been found that occurrence of immune-related adverse events (irAEs) is associated with outcome in the treatment of advanced non-small-cell lung cancer (NSCLC) with anti-programmed cell death (PD)-1 or anti-PDL1 agents. Independent correlation with survival was not consistently demonstrated and correlation with the number of toxicities was also not previously described. All patients treated with nivolumab for advanced NSCLC, in the second line setting, were retrospectively reviewed in a single-center from March 2015 to March 2017. Sixty-nine patients were identified. After a median follow-up of 13 months (95% CI: 10.8; 15.3), there were 46 tumor progressions and 37 deaths. The 6-month and one-year progression-free survival (PFS) and overall survival (OS) rates were 29%/61% and 24%/49%, respectively. Thirty-one patients (44.9%) presented irAEs. Patients presenting tumor response to previous chemotherapy had a higher rate of irAEs (P=0.01) and a better OS (HR=2, P=0.04). Occurrence of irAEs correlated with OS in multivariate analysis (HR=0.4, 95% CI [0.19; 0.8], P=0.02). The number of irAEs correlated with tumor response, PFS and OS in univariate analysis. Having≥2 irAEs correlated with better outcome compared with one irAE, which correlated with better tumor response and PFS in comparison with 0 irAE, in multivariate analysis. In this study, irAEs was associated with a better outcome in patients treated with nivolumab for advanced NSCLC in the second line setting. Interestingly, the number of irAEs correlated with tumor response and PFS.


Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Nivolumab/adverse effects , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Nivolumab/therapeutic use , Progression-Free Survival , Retrospective Studies , Survival Rate
15.
Clin Lung Cancer ; 21(1): 56-65.e8, 2020 01.
Article in English | MEDLINE | ID: mdl-31519454

ABSTRACT

BACKGROUND: The introduction of liquid biopsy using PCR-based assays into routine practice has had a strong impact on the treatment of EGFR-mutated lung adenocarcinoma and is now commonly used for routine testing of EGFR mutations in certain clinical settings. To assess whether the claimed benefits of PCR-based assays hold true in daily practice at a multicenter clinical institution, we assessed how treatment decisions are affected by PCR-based assays for the analysis of EGFR mutations from plasma samples in a centralized laboratory (LPCE, Nice, France). PATIENTS AND METHODS: A total of 345 samples were analyzed using the US Food and Drug Administration-approved Cobas EGFR Mutation Test v2 and 103 using the Therascreen EGFR Plasma RGQ PCR Kit over 3 years (395 samples from 324 patients). Eleven plasma samples were validated independently using Cobas at 3 institutions, and 130 samples were analyzed using Stilla digital PCR. Clinical data were collected for 175 (54%) of 324 patients. RESULTS: Cobas was superior to the Therascreen assay and demonstrated 100% reproducibility. Digital PCR showed only 48%, 83%, and 58% concordance with Cobas for exon 19 deletions, L858R mutations, and T790M mutations, respectively. Liquid biopsies helped inform and change treatment when resistance occurred and enabled the detection of EGFR mutations in patients when biopsy tissue results were unavailable. CONCLUSION: PCR-based assays are a fast and convenient test, allowing the detection of primary and secondary EGFR mutations from plasma. Cobas proved to be a reliable test, whereas digital PCR produced too many inconclusive results to be currently recommended as a principal testing device.


Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnosis , Clinical Laboratory Techniques/standards , DNA Mutational Analysis/methods , Lung Neoplasms/diagnosis , Mutation , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Female , France , Humans , Liquid Biopsy , Lung Neoplasms/blood , Lung Neoplasms/genetics , Male , Middle Aged , Reproducibility of Results
16.
J Thorac Dis ; 11(9): 3732-3737, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31656645

ABSTRACT

BACKGROUND: The aim of this study was to assess the feasibility of major pulmonary resection for a limited non-small cell lung cancer (NSCLC) in octogenarians within a dedicated care protocol. METHODS: We retrospectively analyzed data of 55 octogenarians operated on in a single institution between January 2005 and December 2016. They were all included in a specific care protocol with systematic geriatric assessment and adaptation of the peri-operative care. We describe the results of post-operative morbidity, mortality, and survival after anatomical resection and radical lymphadenectomy. RESULTS: Mean age at the time of surgery was 82.1 years (80-86 years). Median Charlson's comorbidity score was 0 (0-3). All patients were classified Balducci 1 or 2. We performed 2 pneumonectomies (3%), 3 bilobectomies (5%), 47 lobectomies (85%) and 3 segmentectomies (5%). The median hospital stay was 11.5 days (7-31 days). The 30-day mortality rate was 3%. The total of relevant clinical complications (Clavien 3 to 5) was 16% (n=9). The Overall Survival at one, three and five years were, respectively: 83% (95% CI: 75-95%); 70% (95% CI: 56-87%); 58% (95% CI: 43-79%). CONCLUSIONS: Major pulmonary resection for primary lung cancer in octogenarians seems to be safe, with an acceptable morbidity, mortality and long-term survival rate, when processing to rigorous selection of the patients, within a dedicated care protocol.

17.
Eur Respir J ; 54(1)2019 07.
Article in English | MEDLINE | ID: mdl-31023848

ABSTRACT

Club cell secretory protein (CCSP) knockout mice exhibit increased airway neutrophilia, as found in chronic obstructive pulmonary disease (COPD). We therefore investigated whether treating COPD airway epithelia with recombinant human CCSP (rhCCSP) could dampen exaggerated airway neutrophilia.Control, smoker and COPD air-liquid interface (ALI) cultures exposed to cigarette smoke extract (CSE) were treated with and without rhCCSP. The chemotactic properties of the supernatants were assessed using Dunn chambers. Neutrophil chemotaxis along recombinant human interleukin 8 (rhIL8) gradients (with and without rhCCSP) was also determined. rhCCSP-rhIL8 interactions were tested through co-immunoprecipitation, Biacore surface plasmon resonance (SPR) and in silico modelling. The relationship between CCSP/IL8 concentration ratios in the supernatant of induced sputum from COPD patients versus neutrophilic airway infiltration assessed in lung biopsies was assessed.Increased neutrophilic chemotactic activity of CSE-treated ALI cultures followed IL8 concentrations and returned to normal when supplemented with rhCCSP. rhIL8-induced chemotaxis of neutrophils was reduced by rhCCSP. rhCCSP and rhIL8 co-immunoprecipitated. SPR confirmed this in vitro interaction (equilibrium dissociation constant=8 µM). In silico modelling indicated that this interaction was highly likely. CCSP/IL8 ratios in induced sputum correlated well with the level of small airway neutrophilic infiltration (r2=0.746, p<0.001).CCSP is a biologically relevant counter-balancer of neutrophil chemotactic activity. These different approaches used in this study suggest that, among the possible mechanisms involved, CCSP may directly neutralise IL8.


Subject(s)
Bronchioles/pathology , Chemotaxis, Leukocyte , Neutrophils/cytology , Pulmonary Disease, Chronic Obstructive/pathology , Uteroglobin/pharmacology , Humans , Interleukin-8/metabolism , Interleukin-8/pharmacology , Neutrophils/drug effects , Pulmonary Disease, Chronic Obstructive/metabolism , Recombinant Proteins/pharmacology , Smoking , Sputum/cytology
18.
Am J Respir Crit Care Med ; 199(10): 1249-1256, 2019 05 15.
Article in English | MEDLINE | ID: mdl-30864813

ABSTRACT

Rationale: The diagnostic concordance between transbronchial lung cryobiopsy (TBLC)-versus surgical lung biopsy (SLB) as the current gold standard-in interstitial lung disease (ILD) cases requiring histology remains controversial. Objectives: To assess diagnostic concordance between TBLC and SLB sequentially performed in the same patients, the diagnostic yield of both techniques, and subsequent changes in multidisciplinary assessment (MDA) decisions. Methods: A two-center prospective study included patients with ILD with a nondefinite usual interstitial pneumonia pattern (on high-resolution computed tomography scan) confirmed at a first MDA. Patients underwent TBLC immediately followed by video-assisted thoracoscopy for SLB at the same anatomical locations. After open reading of both sample types by local pathologists and final diagnosis at a second MDA (MDA2), anonymized TBLC and SLB slides were blindly assessed by an external expert pathologist (T.V.C.). Kappa-concordance coefficients and percentage agreement were computed for: TBLC versus SLB, MDA2 versus TBLC, MDA2 versus SLB, and blinded pathology versus routine pathology. Measurements and Main Results: Twenty-one patients were included. The median TBLC biopsy size (longest axis) was 7 mm (interquartile range, 5-8 mm). SLB biopsy sizes averaged 46.1 ± 13.8 mm. Concordance coefficients and percentage agreement were: TBLC versus SLB: κ = 0.22 (95% confidence interval [CI], 0.01-0.44), percentage agreement = 38% (95% CI, 18-62%); MDA2 versus TBLC: κ = 0.31 (95% CI, 0.06-0.56), percentage agreement = 48% (95% CI, 26-70)%; MDA2 versus SLB: κ = 0.51 (95% CI, 0.27-0.75), percentage agreement = 62% (95% CI, 38-82%); two pneumothoraces (9.5%) were recorded during TBLC. TBLC would have led to a different treatment if SLB was not performed in 11 of 21 (52%) of cases. Conclusions: Pathological results from TBLC and SLB were poorly concordant in the assessment of ILD. SLBs were more frequently concordant with the final diagnosis retained at MDA.


Subject(s)
Biopsy/methods , Bronchoscopy/methods , Cryosurgery/methods , Idiopathic Pulmonary Fibrosis/diagnosis , Lung Diseases, Interstitial/diagnosis , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Tomography, X-Ray Computed
19.
Thorac Cardiovasc Surg ; 67(7): 585-588, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30267389

ABSTRACT

BACKGROUND: Esophageal gastrointestinal stromal tumors (E-GISTs) represent less than 1% of all GISTs. The rarity of this lesion precludes the realization of randomized studies, and its treatment remains a matter of debate. We aimed to evaluate the feasibility of enucleation by video-assisted thoracic surgery (VATS) for low- to intermediate-risk E-GIST. METHODS: We performed a retrospective review of patients treated by enucleation through VATS between January 2004 and January 2014 and reviewed the literature. RESULTS: We included five patients (four men and one woman). Mean age was 53 years (range: 49-79). Three patients were diagnosed because of dysphagia and two others incidentally. The diagnosis was made by immunostaining demonstrating CD117 expression on tumor cells. The mitotic index of all E-GISTs was low (≤ 5 per 50 high-power field). Median postoperative follow-up was 5.5 years, and there was no recurrence. CONCLUSION: Thoracoscopic enucleation of E-GIST seems to represent a valuable option as the postoperative morbidity/mortality is low and the oncological outcome is good for low-to-intermediate grade of malignity tumors.This is a retrospective study focused on minimally invasive treatment of E-GIST. We evaluated the feasibility of VATS enucleation of low-to-medium grade of malignity E-GIST.


Subject(s)
Esophageal Neoplasms/surgery , Esophagectomy/methods , Gastrointestinal Stromal Tumors/surgery , Thoracic Surgery, Video-Assisted , Aged , Databases, Factual , Esophageal Neoplasms/pathology , Esophagectomy/adverse effects , Feasibility Studies , Female , Gastrointestinal Stromal Tumors/pathology , Humans , Male , Middle Aged , Neoplasm Grading , Retrospective Studies , Thoracic Surgery, Video-Assisted/adverse effects , Treatment Outcome
20.
World Neurosurg ; 122: e1542-e1550, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30471449

ABSTRACT

OBJECTIVE: It is unknown whether spinal instrumentation is required to prevent deformity after partial vertebrectomy in the treatment of primary bronchogenic carcinomas invading the spine (PBCIS). In this study, we focus on the postoperative spine deformity in patients who underwent operation for partial vertebrectomies without instrumentation during en bloc PBCIS resection. Our objective was to determine whether deformity depends on the type of vertebral resection and if any vertebral resection threshold can be observed to justify additional spinal instrumentation. METHODS: This is a retrospective study, including all patients with PBCIS operated without spinal instrumentation from 2009 to 2018. Partial vertebrectomies were classified into categories A, B, and C depending on vertebral resection. Patients had long-term radiologic follow-up to assess the spine deformity evolution. RESULTS: Eighteen patients were included. The median follow-up was 27 months. Four patients underwent a secondary posterior instrumentation surgical procedure due to progressive spinal deformity. A low-risk group of deformation was characterized as type A resection and type B resection on less than 3 vertebrae. CONCLUSIONS: There are no validated criteria to justify a systematic spinal instrumentation when performing a partial vertebrectomy during en bloc resection of PBCIS. Performed alone without spine instrumentation, both type A and type B resections on less than 3 resected vertebrae were not subject to sagittal and coronal deformity even after a long follow-up, emphasizing that a systematic stabilization is not needed in this low-risk group. These results could help to reduce the perioperative morbidity of these procedures that are usually long and complex.


Subject(s)
Lung Neoplasms/surgery , Orthopedic Procedures , Postoperative Complications , Spinal Curvatures/etiology , Spinal Neoplasms/surgery , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Feasibility Studies , Female , Follow-Up Studies , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Male , Middle Aged , Orthopedic Procedures/methods , Postoperative Complications/diagnostic imaging , Retrospective Studies , Spinal Curvatures/diagnostic imaging , Spinal Neoplasms/diagnostic imaging , Spinal Neoplasms/secondary
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