Publications by authors named "Martine Antoine"

143 Publications

Diagnosis yield and safety of surgical biopsy in interstitial lung diseases: a prospective study.

Ann Thorac Surg 2021 Sep 29. Epub 2021 Sep 29.

APHP-Hôpital Bichat, Pneumologie A, Université de Paris, Paris, France.

Background: Surgical lung biopsy is essential in the diagnostic algorithm of interstitial lung disease (ILD) of unknown cause. Safety concerns have been recently reiterated. The aim of this study was to prospectively assess the yield of diagnosis and safety of video-assisted thoracoscopic surgical lung biopsy (VATS-LB) for ILD diagnosis.

Methods: This prospective study, conducted in 6 ILD-referral Paris hospitals, included 103 patients with ILD. After initial multidisciplinary discussion, VATS-LB was proposed. A final diagnosis was made after the procedure, during a second multidisciplinary discussion. The main outcome was to determine the final diagnoses and their proportion after VATS-LB. Other outcomes were the percentage of change in diagnosis and treatment propositions after VATS-LB and adverse events during 3 months after surgery, postoperative pulmonary function, quality of life and pain.

Results: A definite diagnosis was reached in 87 cases (84.4%), while 16 remained unclassifiable (15.6%). Hypothesized diagnosis and treatment changed after VATS-LB in 65 (63.1%) and in 41 patients (39.8%), respectively. There was one death due to acute exacerbation. In-hospital complications were predicted by a lower preoperative distance at 6-minute walking test and by forced vital capacity lower than 77%. Postoperative quality of life was not modified at 3 months while forced vital capacity decreased slightly. Postoperative neuropathic pain was revealed in 5% and 2% patients at 1 and 3 months, respectively.

Conclusions: VATS-LB dramatically changed preoperative hypothetical diagnoses and treatment in ILD of unknown cause with good patient survival in ILD-referral centers.
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http://dx.doi.org/10.1016/j.athoracsur.2021.08.056DOI Listing
September 2021

[2021 update of the GEFPICS' recommendations for HER2 status assessment in invasive breast cancer in France].

Ann Pathol 2021 Nov 12;41(6):507-520. Epub 2021 Aug 12.

Groupe d'étude des facteurs pronostiques immunohistochimiques dans le cancer du sein, Unicancer, 101, rue de Tolbiac, 75654 Paris cedex 13, France.

The last international guidelines on HER2 determination in breast cancer have been updated in 2018 by the American Society of Clinical Oncology and College of American Pathologists, on the basis of a twenty-year practice and results of numerous clinical trials. Moreover, the emerging HER2-low concept for 1+ and 2+ non amplified breast cancers lead to refine French practices for HER2 status assessment. The GEFPICS group, composed of expert pathologists, herein presents the latest French recommendations for HER2 status evaluation in breast cancer, taking into account the ASCO/CAP guidelines and introducing the HER2-low concept. In the era of personalized medicine, HER2 status assessment remains one of the most important biomarkers in breast cancer and its quality guaranties the optimal patients' care. French pathologists' commitment in theranostic biomarker quality is more than ever required to provide the most efficient cares in oncology.
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http://dx.doi.org/10.1016/j.annpat.2021.07.014DOI Listing
November 2021

Long-Term Outcome After Venoarterial Extracorporeal Membrane Oxygenation as Bridge to Left Ventricular Assist Device Preceding Heart Transplantation.

J Cardiothorac Vasc Anesth 2021 Jul 3. Epub 2021 Jul 3.

Department of Cardiac Surgery, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.

Objectives: To determine if venoarterial extracorporeal membrane oxygenation (VA ECMO) as a bridge to left ventricular assist device (LVAD) in heart transplant (HT) candidates (ie, double bridge to HT) was associated with increased morbidity and mortality when compared to LVAD bridging to HT (ie, single bridge to HT).

Design: A retrospective analysis of patients undergoing LVAD support from 2011 to 2020. A Kaplan-Meier survival curve and Cox-Mantel hazard ratios (HR) were calculated during LVAD support and after HT. Postoperative complications were collected.

Setting: University Hospital Erasme.

Participants: HT candidates requiring LVAD.

Interventions: VA ECMO bridging to LVAD (ECMO-LVAD group [n = 24]) versus LVAD (LVAD group [n = 64]).

Measurements And Main Results: Eighty-eight patients underwent HeartWare LVAD (HVAD, Medtronic) placement. Survival to hospital discharge and during the entire study period were lower in the ECMO-LVAD group (66.7% v 92.2%; p = 0.0027, and 37.5% v 62.5%; p = 0.035, respectively). Overall HR of death was 2.46 (95% confidence interval [CI]: 1.13-5.37; p = 0.005) in the ECMO-LVAD group and remained elevated throughout their time on LVAD support (HR 3.24 [95% CI: 1.15-9.14]; p = 0.0036). However, in patients who underwent HT (n = 50), mortality was similar between groups (HR 1.33 [95% CI: 0.33-5.31]; p = 0.66). Postoperative complications were more frequent in the ECMO-LVAD group (infection = 83.3% v 51.6%, p = 0.007; renal replacement therapy = 45.8% v 9.4%, p = 0.0001; post-LVAD ECMO = 25.0% v 1.6%; p = 0.0003).

Conclusions: VA ECMO as a bridge to LVAD support before HT was associated with increased morbidity and mortality during LVAD support. However, in patients who underwent HT, outcomes were similar regardless of VA ECMO bridging.
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http://dx.doi.org/10.1053/j.jvca.2021.06.035DOI Listing
July 2021

Risk of lung cancer among women in relation to lifetime history of tobacco smoking: a population-based case-control study in France (the WELCA study).

BMC Cancer 2021 Jun 16;21(1):711. Epub 2021 Jun 16.

Université Paris-Saclay, UVSQ, Inserm U1018, CESP, Team Exposome and Heredity, Villejuif, France.

Background: This study aims to provide new insights on the role of smoking patterns and cigarette dependence in female lung cancer, and to examine differences by histological subtype.

Methods: We conducted a population-based case-control study in the great Paris area among women including 716 incident cases diagnosed between 2014 and 2017 and 757 age-matched controls. Detailed data on smoking history was collected during in-person interviews to assess intensity and duration of tobacco smoking, time since cessation, smoking habits (depth of smoke inhalation, use of filter, type of tobacco, and type of cigarettes) and Fagerström test for cigarette dependence. The comprehensive smoking index (CSI), a score modelling the combined effects of intensity, duration and time since quitting smoking was determined for each subject. Multivariable logistic regression models were fitted to calculate odds ratios (ORs) and their confidence intervals (95%CI) of lung cancer associated with smoking variables.

Results: Lung cancer risk increased linearly with intensity and duration of tobacco smoking while it decreased with time since cessation, to reach the risk in never-smokers after 20 years of abstinence. The combined effect of intensity and duration of tobacco smoking was more than multiplicative (p-interaction 0.012). The OR in the highest vs the lowest quartile of CSI was 12.64 (95%CI 8.50; 18.80) (p-trend < 0.001). The risk of small cell or squamous cell carcinomas increased with the CSI more sharply than the risk of adenocarcinomas. Deep smoke inhalation, dark vs blond tobacco, conventional vs light cigarettes, and unfiltered vs filtered cigarettes, as well as having mixed smoking habits, were found to be independent risk factors. Having high cigarette addiction behaviours also increased the risk after adjusting for CSI.

Conclusion: This study provides additional insights on the effects of tobacco smoking patterns on lung cancer risk among women.
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http://dx.doi.org/10.1186/s12885-021-08433-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207748PMC
June 2021

No evidence for a pathogen associated with pulmonary MALT lymphoma: a metagenomics investigation.

Infect Agent Cancer 2021 Feb 6;16(1):10. Epub 2021 Feb 6.

Service de Pneumologie et Oncologie thoracique, Centre de référence des maladies pulmonaires rares, AP-HP, Hôpital Tenon and GRC#4 Theranoscan, Sorbonne Université, Paris, France.

Mucosa-associated lymphoid tissue (MALT) lymphoma is generally associated with chronic antigen stimulation: auto-antigens or of microbial origin. Only one study suggested association between Achromobacter xylosoxidans and pulmonary MALT lymphoma. We aimed to investigate the presence of virus or any infectious agents in pulmonary MALT lymphoma by using metagenomic next-generation sequencing (mNGS).All lung samples were centrally reviewed. The t(11;18) (q21;q21) was evaluated by FISH analysis. The snap frozen large lung biopsies were analyzed by mNGS. After lung biopsies homogenization total nucleic acids (RNA and DNA) were extracted, amplified and classified according to their taxonomic assignment, after exclusion of host DNA.We included 13 samples from pulmonary MALT lymphoma (mean age: 60.3 years, 7 women, 3 with auto-immune background) and 10 controls. The diagnosis of MALT lymphoma was confirmed for the 13 samples, 3 showed API2-MALT1 translocation (23%). No evidence of the presence of a specific pathogen was clearly identified in the group of patients with pulmonary MALT lymphoma. We identifiedA. xylosoxidans sequence in 4/13 patients and in 4/10 controls.This study did not find evidence for a DNA or RNA virus, a fungi, a parasite or a bacteria associated with pulmonary MALT lymphoma either in the stroma or in tumor cells.
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http://dx.doi.org/10.1186/s13027-021-00351-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868019PMC
February 2021

Strong ALK and PD-L1 positive IHC expression related ALK amplification in an advanced lung sarcomatoid carcinoma: A therapeutic trap?

Lung Cancer 2021 02 21;152:94-97. Epub 2020 Dec 21.

Department of Pneumology and Thoracic Oncology, Tenon Hospital, Assistance Publique-Hôpitaux de Paris and GRC 4, Theranoscan, Sorbonne Université, 75970, Paris, France.

Objectives: Immunohistochemistry (IHC) is considered as a screening method for ALK rearrangement thanks to its excellent sensitivity. Strong marking on immunohistochemistry give the go-ahead to start ALK tyrosine kinase inhibitors (ALK TKI). Lack of therapeutic response may then lead to the suspicion of molecular alterations other than ALK rearrangements.

Methods: We present a patient with strong ALK and PD-L1 positive IHC expression lung sarcomatoid carcinoma with initial life-threatening disease progression after beginning ALK TKI. We also review the literature to summarize ALK amplification clinical features and therapeutic management in lung cancers.

Results: Fluorescence in situ Hybridization (FISH) revealed ALK amplification on the initial anatomopathological samples. Lack of ALK rearrangement and strong PD-L1 positive IHC expression led to the initiation of immune checkpoint inhibitor (ICI) as a second line of treatment, with an excellent response.

Conclusion: We demonstrated that IHC positive test, in these cases, must be interpreted with caution. FISH analysis has to be recommended to confirm IHC results in case of unusual phenotype, such as smoker or lung cancer other than adenocarcinoma. Although lung carcinoma with ALK rearrangement seems to be not sensitive to ICI, further investigations should be conducted on other types of ALK molecular alterations. ALK amplifications, as observed in the present case, should not be an impediment to taking into account the PD-L1 marking for the initiation of treatment by immunotherapy.
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http://dx.doi.org/10.1016/j.lungcan.2020.12.022DOI Listing
February 2021

Interstitial Lung Disease Associated with Lung Cancer: A Case-Control Study.

J Clin Med 2020 Mar 5;9(3). Epub 2020 Mar 5.

Service de Pneumologie, Site constitutif du centre de référence des maladies pulmonaires rares OrphaLung, APHP, Hôpital Tenon, 75020 Paris, France.

Interstitial lung disease (ILD) seems to be associated with an increased risk of lung cancer (LC) and to have a poorer prognosis than LC without ILD. The frequency of ILD in an LC cohort and its prognosis implication need to be better elucidated. This retrospective, observational, cohort study evaluated the frequency of ILD among LC patients (LC-ILD) diagnosed over a 2-year period. LC-ILD patients' characteristics were compared to those with LC without ILD (LC-noILD). Lastly, we conducted a case-control study within this cohort, matching three LC-noILDs to each LC-ILD patient, to evaluate the ILD impact on LC patients' prognoses. Among 906 LC patients, 49 (5.4%) also had ILD. Comparing LC-ILD to LC-noILD patients, respectively, more were men (85.7% vs. 66.2%; = 0.02); adenocarcinomas were less frequent (47.1% vs. 58.7%, = 0.08); median [range] and overall survival was shorter: (9 [range: 0.1-39.4] vs. 17.5 [range: 0.8-50.4] months; = 0.01). Multivariate analysis (hazard ratio [95% confidence interval]) retained two factors independently associated with LC risk of death: ILD (1.79 [1.22-2.62]; = 0.003) and standard-of-care management (0.49 [0.33-0.72]; < 0.001). Approximately 5% of patients with a new LC diagnosis had associated ILD. ILD was a major prognosis factor for LC and should be taken into consideration for LC management. Further studies are needed to determine the best therapeutic strategy for the LC-ILD population.
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http://dx.doi.org/10.3390/jcm9030700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141363PMC
March 2020

Efficacy of Immune Checkpoint Inhibitors in Lung Sarcomatoid Carcinoma.

J Thorac Oncol 2020 05 25;15(5):860-866. Epub 2020 Jan 25.

Department of Thoracic Oncology, AP-HP, Groupe Hospitalier HUPC, Hôpital Cochin, Paris, France; Centre de Recherche des Cordeliers, Université Paris Descartes, Complement, Inflammation and Cancer, Paris, France. Electronic address:

Introduction: Immune checkpoint inhibitors (ICIs) have improved cancer prognosis but have not been evaluated specifically in sarcomatoid carcinoma (SC), a rare lung cancer subtype with poor prognosis. As such, our study sought to retrospectively assess the efficacy of ICI in SC.

Methods: All consecutive patients with centrally confirmed SC treated using ICI as a second-line treatment or beyond between 2011 and 2017 were enrolled. Programmed death-ligand 1 (PD-L1) tumor expression was assessed using immunohistochemistry (SP263 clone) and the tumor mutational burden (TMB) with the Foundation One panel. TMB was considered high if it was greater than or equal to 10 mutations per megabase.

Results: Overall, 37 patients with SC were evaluated, predominantly men (73%) with a median age of 63.2 years (36.8-79.7) and who were current or former smokers (94.6%). Immunotherapy (nivolumab, 86.5% of cases) was given as a second-line treatment in 54% of the patients and as third-line treatment or beyond in 46% of the patients. The objective response rate was 40.5% and disease control rate was 64.8%, regardless of PD-L1 status. Median overall survival was 12.7 months (range: 0.3-45.7). One-third of patients exhibited early progression. The median PD-L1 expression was 70% (0-100). There was a trend toward higher PD-L1 expression in responsive diseases, with an objective response rate of 58.8% in patients with PD-L1+ and 0% in the one patient with PD-L1- (p = 0.44). The median TMB was 18 (4-39) mutations per megabase, with 87.5% of the cases displaying a high TMB. There was a trend toward higher TMB in responders versus stable or progressive diseases (p = 0.2).

Conclusions: Patients with SC exhibited high response rates and prolonged overall survival under ICI treatment. These data support the prospective investigation of ICI in patients with SC who are under first-line treatment.
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http://dx.doi.org/10.1016/j.jtho.2020.01.014DOI Listing
May 2020

Role of the YAP-1 Transcriptional Target cIAP2 in the Differential Susceptibility to Chemotherapy of Non-Small-Cell Lung Cancer (NSCLC) Patients with Tumor RASSF1A Gene Methylation from the Phase 3 IFCT-0002 Trial.

Cancers (Basel) 2019 Nov 21;11(12). Epub 2019 Nov 21.

Normandie Université, UNICAEN, CEA, CNRS, ISTCT/CERVOxy group, GIP CYCERON, 14074 Caen, France.

gene methylation predicts longer disease-free survival (DFS) and overall survival (OS) in patients with early-stage non-small-cell lung cancer treated using paclitaxel-based neo-adjuvant chemotherapy compared to patients receiving a gemcitabine-based regimen, according to the randomized Phase 3 IFCT (Intergroupe Francophone de Cancérologie Thoracique)-0002 trial. To better understand these results, this study used four human bronchial epithelial cell (HBEC) models (HBEC-3, HBEC-3-RasV12, A549, and H1299) and modulated the expression of RASSF1A or YAP-1. Wound-healing, invasion, proliferation and apoptosis assays were then carried out and the expression of YAP-1 transcriptional targets was quantified using a quantitative polymerase chain reaction. This study reports herein that gemcitabine synergizes with RASSF1A, silencing to increase the IAP-2 expression, which in turn not only interferes with cell proliferation but also promotes cell migration. This contributes to the aggressive behavior of RASSF1A-depleted cells, as confirmed by a combined knockdown of IAP-2 and RASSF1A. Conversely, paclitaxel does not increase the IAP-2 expression but limits the invasiveness of RASSF1A-depleted cells, presumably by rescuing microtubule stabilization. Overall, these data provide a functional insight that supports the prognostic value of gene methylation on survival of early-stage lung cancer patients receiving perioperative paclitaxel-based treatment compared to gemcitabine-based treatment, identifying IAP-2 as a novel biomarker indicative of YAP-1-mediated modulation of chemo-sensitivity in lung cancer.
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http://dx.doi.org/10.3390/cancers11121835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966477PMC
November 2019

High MET Overexpression Does Not Predict the presence of MET exon 14 Splice Mutations in NSCLC: Results From the IFCT PREDICT.amm study.

J Thorac Oncol 2020 01 9;15(1):120-124. Epub 2019 Oct 9.

Lille University Hospital, CHU Lille, Thoracic Oncology Department, Lille, France. Electronic address:

Introduction: MET proto-oncogene (MET) exon 14 splice site (METex14) mutations were recently described in NSCLC and has been reported to correlate with efficacy of MET tyrosine kinase inhibitors. High diversity of these alterations makes them hard to detect by DNA sequencing in clinical practice. Because METex14 mutations induce increased stabilization of the MET receptor, it is anticipated that these mutations are associated with MET overexpression. We aim to determine whether NSCLC with high MET overexpression could define a subset of patients with a high rate of METex14 mutations.

Methods: From The French Cooperative Thoracic Intergroup PREDICT.amm cohort of 843 consecutive patients with a treatment-naive advanced NSCLC who were eligible for a first-line therapy, 108 NSCLC samples with high MET overexpression defined by an immunochemistry score 3+ were tested for METex14 mutations using fragment length analysis combined with optimized targeted next-generation sequencing. MET copy number analysis was also derived from the sequencing data.

Results: METex14 mutations were detected in two patients (2.2%) who also displayed a TP53 mutation and a PIK3CA mutation, respectively. An MET gene copy number increase was observed in seven additional patients (7.7%). Next-generation sequencing analysis revealed inactivating mutations in TP53 (52.7%) and PTEN (1.1%), and oncogenic mutations in KRAS (28.6%), EGFR (7.7%), PIK3CA (4.4%), BRAF (4.4%), NRAS (2.2%), GNAS (1.1%), and IDH1 (1.1%).

Conclusions: The rate of METex14 mutations in NSCLC with high MET overexpression was similar to that found in unselected NSCLC. Moreover, we observed a high frequency of driver alterations in other oncogenes. Consequently these findings do not support the use of MET immunohistochemistry as a surrogate marker for METex14 mutations.
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http://dx.doi.org/10.1016/j.jtho.2019.09.196DOI Listing
January 2020

[Guidelines for the macroscopic management of surgically resected lung carcinoma].

Ann Pathol 2019 Dec 8;39(6):425-432. Epub 2019 Oct 8.

Département de biopathologie et département de recherche translationnelle et d'innovations, centre Léon-Bérard UNICANCER, université Grenoble-Alpes, 28, rue Laennec, 69008 Lyon, France.

Gross examination is an essential step for pathological report of a surgical sample. It includes the description of the surgical specimen and their disease(s), the precise and exhaustive sampling of tumoral and adjacent tumoral tissue areas. This examination requires a good knowledge of the updated pTNM classification. Pathologists from the PATTERN group have collaborated with thoracic surgeons, under the auspices of the Sociéte française de pathologie, to propose guidelines for resected specimen management. This approach fits into the context of the elaboration of structured pathological report proposed by the société française de pathologie, which is necessary for a standardized management of patients.
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http://dx.doi.org/10.1016/j.annpat.2019.05.008DOI Listing
December 2019

Shorter Survival in Malignant Pleural Mesothelioma Patients With High PD-L1 Expression Associated With Sarcomatoid or Biphasic Histology Subtype: A Series of 214 Cases From the Bio-MAPS Cohort.

Clin Lung Cancer 2019 09 13;20(5):e564-e575. Epub 2019 May 13.

Normandie Université, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Caen, France; Department of Pathology, CHU de Caen, Caen, France.

Background: Anticancer immune responses are negatively regulated by programmed cell death 1 (PD-1) T-cell membrane protein interaction with its ligand, programmed death ligand 1 (PD-L1), on cancer cells. We sought to assess the prognostic role of PD-L1 expression in tumor samples from patients enrolled onto the IFCT-0701 MAPS randomized phase 3 trial (NCT00651456).

Patients And Methods: Tumor samples were analyzed by immunohistochemistry for percentages of PD-L1 membrane-stained tumor cells using the E1L3N clone, and data were correlated to survival by multivariate Cox models including stratification variables.

Results: PD-L1 staining was assessed in 214 (47.75%) of 448 patients. Epithelioid subtype represented 83.7% (179/214). Absence of PD-L1 staining occurred in 137 (64.1%) of 214 malignant pleural mesothelioma (MPM) samples, while 77 (35.9%) of 214 were PD-L1 positive, with 50 (64.9%) of 77 showing < 50% PD-L1-expressing tumor cells. Sarcomatoid/biphasic subtypes were more commonly PD-L1 positive than epithelioid subtype (P < .001). In patients with 1% or more PD-L1-stained tumor cells, median overall survival (OS) was 12.3 months versus 22.2 months for other patients (hazard ratio [HR] = 1.25; 95% confidence interval [CI], 0.93-1.67; P = .14). OS did not differ according to PD-L1 positivity in multivariate analyses (adjusted HR = 1.10; 95% CI, 0.81-1.49; P = .55). With a 50% cutoff, PD-L1-positive patients displayed a 10.5 months median OS versus 19.3 months for patients with lower PD-L1 expression (HR = 1.93; 95% CI, 1.27-2.93; P = .002). OS did not significantly differ in adjusted Cox models (adjusted HR = 1.20; 95% CI, 0.74-1.94; P = .47). In the 179 epithelioid MPM patients, high PD-L1 staining (≥ 50% of tumor cells) negatively affected OS, although not significantly, showing a 12.3-month median OS (95% CI, 4.3-21.6) versus 23-month (95% CI, 18.5-25.2) for patients with tumor PD-L1 staining in < 50% cells (P = .071). The progression-free survival (PFS) differences were statistically significant, with a longer 9.9-month median PFS in patients with low PD-L1 staining (< 50% cells) compared to 6.7 months of median PFS in patients with high PD-L1 expression (≥ 50% cells) (P = .0047).

Conclusion: Although high PD-L1 tumor cell expression was associated with poorer OS in MPM patients from the MAPS trial, its prognostic influence was lost in multivariate analyses in the whole cohort, while PD-L1 expression was strongly associated with the sarcomatoid/biphasic subtypes. In the epithelioid MPM subset of patients, high PD-L1 tumor expression (≥ 50%) negatively affected OS and PFS, with this prognostic influence remaining statistically significant for PFS after adjustment in multivariate Cox model.
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http://dx.doi.org/10.1016/j.cllc.2019.04.010DOI Listing
September 2019

[GEFPICS' guidelines for management of breast cancer tissue samples in the neoadjuvant setting].

Ann Pathol 2019 Dec 27;39(6):383-398. Epub 2019 Jun 27.

Groupe d'étude des facteurs pronostiques immunohistochimiques dans le cancer du sein, Unicancer, France.

Neoadjuvant therapy is an increasing treatment option in the management of breast cancer. The tumor response to neoadjuvant therapy, especially the pathological complete response, is a validated endpoint frequently used in clinical trials. However, there is still a lack of standardization for the surgical specimen management in the neoadjuvant setting. This leads to heterogeneity in the specimen handling and might lead to significant bias for the prognostic assessment of patients or in clinical trials. The GEFPICS group, composed of expert breast cancer pathologists, herein presents guidelines for the management of breast and axillary specimen before treatment (management of biopsy, items of the pathological report) and after neoadjuvant therapy (specimen handling, histological assessment of response, items of the pathological report and response grading systems).
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http://dx.doi.org/10.1016/j.annpat.2019.04.004DOI Listing
December 2019

Calpain 1 in bronchoalveolar lavage fluid is associated with poor prognosis in lepidic predominant pulmonary adenocarcinoma.

Bull Cancer 2019 Mar 23;106(3):179-188. Epub 2019 Jan 23.

Sorbonne université, GRC n(o) 04, Theranoscan, 75252 Paris, France; Hôpitaux universitaires de l'est parisien, hôpital Tenon (AP-HP), service de pneumologie, 75970 Paris, France; Paris Descartes université, équipe « cancer, immune control and escape », centre de recherche des Cordeliers, Inserm UMR_S1138, 75006 Paris, France; AP-HP, hôpitaux universitaires Paris centre, hôpital Cochin, unité d'oncologie thoracique, service de pneumologie, 75014 Paris, France. Electronic address:

Calpain 1 is a proinflammatory calcium-activated cysteine protease, which can be partly externalized. Extracellular calpains limit inflammatory processes and promote tissue repair, through cell proliferation and migration. Toll like receptor (TLR) 2 has been identified as a target of extracellular calpains in lymphocytes. The aim was to investigate the externalization of calpain 1 and the release of soluble TLR2 during tumor progression of pulmonary lepidic predominant adenocarcinoma (LPA). Extracellular calpain 1, soluble fragment of TLR2 and cytokines were analyzed by ELISA in bronchoalveolar lavage fluid (BALF) supernatants from patients with LPA (n=68). Source of calpain was analyzed by immunohistochemistry and soluble TLR2 by flow cytometry on polymorphonuclear neutrophils (PMN) and human lung cancer cell lines. Extracellular calpain 1, secreted by tumor cells, was associated to tumor progression, neutrophilic inflammation, with a poor prognostic factor on survival (P=0.003). TLR2 was expressed on PMN and tumor cells and decreased after calpain exposure. Soluble fragment of TLR2 in BALF supernatants was correlated to the extracellular calpain 1 concentration (r=0.624; P<0.001), and its high level was associated with tumor progression and a pro-inflammatory environment. Extracellular calpain 1 secreted by tumor cells, could participate in inflammatory microenvironment and tumor progression through TLR2 in LPA.
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http://dx.doi.org/10.1016/j.bulcan.2018.11.014DOI Listing
March 2019

A Randomized Non-Comparative Phase II Study of Anti-Programmed Cell Death-Ligand 1 Atezolizumab or Chemotherapy as Second-Line Therapy in Patients With Small Cell Lung Cancer: Results From the IFCT-1603 Trial.

J Thorac Oncol 2019 05 18;14(5):903-913. Epub 2019 Jan 18.

Service de Pneumologie Aiguë Spécialisée et Cancérologie Thoracique, Centre Hospitalier Lyon, Lyon, France.

Introduction: This randomized phase II trial aimed at evaluating the engineered programmed cell death ligand 1 (PD-L1) antibody atezolizumab in SCLC progressing after first-line platinum-etoposide chemotherapy.

Methods: Patients were randomized 2:1 to atezolizumab (1200 mg intravenously every 3 weeks) until progression or unacceptable toxicity, or conventional chemotherapy (up to 6 cycles of topotecan or re-induction of initial chemotherapy). Patients were not selected based on PD-L1 tissue expression. The primary endpoint was objective response rate at 6 weeks. A two-stage design with 2:1 randomization and O'Brien-Fleming stopping rules was used. The null hypothesis was rejected if more than 12 of 45 patients were responders.

Results: Overall, 73 patients were randomized (atezolizumab n = 49; chemotherapy n = 24). At 6 weeks, 1 of 43 eligible atezolizumab patients achieved an objective response (2.3%, 95% confidence interval [CI]: 0.0-6.8), whereas 8 others had stable disease (20.9% disease control rate; 95% CI: 8.8-33.1). Among eligible chemotherapy patients (n = 20), 10% achieved an objective response (65% disease control rate). Median progression-free survival was 1.4 months (95% CI: 1.2-1.5) with atezolizumab and 4.3 months (95% CI: 1.5-5.9) with chemotherapy. Overall survival did not significantly differ between groups. Median overall survival was 9.5 months versus 8.7 months for the atezolizumab and the chemotherapy group, respectively (adjusted hazard ratio : 0.84, 95% CI: 0.45-1.58; p = 0.60). Two atezolizumab patients (4.2%) experienced grade 3 fatigue, and two others grade 1 dysthyroidism. Among 53 evaluable specimens, only 1 (2%) had positive immunohistochemical PD-L1 staining (SP142 clone).

Conclusions: Atezolizumab monotherapy in relapsed SCLC failed to show significant efficacy. No unexpected safety concerns were observed.
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http://dx.doi.org/10.1016/j.jtho.2019.01.008DOI Listing
May 2019

A Brief Report of Transformation From NSCLC to SCLC: Molecular and Therapeutic Characteristics.

J Thorac Oncol 2019 01 11;14(1):130-134. Epub 2018 Sep 11.

Thoracic Oncology unit, PTV, CHU Grenoble CS10217-38043 Grenoble cedex 9, France et INSERM U 823. Electronic address:

Introduction: Histologic transformation from NSCLC to SCLC is a mechanism of resistance in EGFR-mutant tumors but is also occasionally observed in nonmutated NSCLC.

Methods: We performed a multicenter retrospective collection of cases presenting between 2005 and 2017. The objectives were to analyze survival data and to define epidemiologic, clinical, treatment and histomolecular characteristics at both the time of diagnosis of NSCLC and of SCLC.

Results: Forty-eight EGFR-mutant NSCLC and 13 non-EGFR-mutant cases were registered. Most EGFR-mutant tumors retained the same EGFR mutation after transformation. The median time to SCLC transformation was shorter in the EGFR-mutant group than in non-EFGR mutants (16 months versus 26 months (p = 0.01)). Both tumors were responsive to platinum etoposide regimens (45% partial response for the EGFR-mutant group versus 40% for non-EFGR mutants). The median overall survival rates were 28 months in the EGFR-mutant group versus 37 months in the non-EFGR-mutant group, respectively. After transformation, the median overall survival was 9 months in the non-EGFR-mutant group versus 10 months in the EGFR-mutant group.

Conclusions: Transformation into SCLC seems to occur more quickly in EGFR mutated tumors; however, once the tumor is transformed its survival and response to treatment seems comparable to that of classical SCLC.
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http://dx.doi.org/10.1016/j.jtho.2018.08.2028DOI Listing
January 2019

c-MET Overexpression as a Poor Predictor of MET Amplifications or Exon 14 Mutations in Lung Sarcomatoid Carcinomas.

J Thorac Oncol 2018 12 24;13(12):1962-1967. Epub 2018 Aug 24.

Sorbonne University, GRC n°04, Theranoscan, F-75252, Paris, France; AP-HP, GH HUEP, Tenon Hospital, Chest Department and Thoracic Oncology, F-75970, Paris, France. Electronic address:

Introduction: MNNG HOS transforming gene (MET) abnormalities such as amplification and exon 14 mutations may be responsive to targeted therapies. They are prevalent in lung sarcomatoid carcinomas (LSCs) and must be diagnosed as efficiently as possible. Hypothetically, c-MET overexpression by immunohistochemistry (IHC) may prove effective as a screening test for MET abnormalities.

Methods: Tissue samples were obtained from consecutive patients with a resected LSC in four oncologic centers. IHC was performed using the SP44 antibody (Ventana, Tucson, Arizona) and evaluated using the MetMab score and H-score. Fluorescence in situ hybridization was applied with the dual color probe set from Zytovision (Clinisciences, Nanterre, France). True MET amplification was diagnosed when MET gene copy number was 5 or greater and the ratio between MET gene copy number and chromosome 7 number was greater than 2. All MET exon 14 alterations including those affecting splice sites occurring within splice donor and acceptor sites were detected in the routine molecular testing on genetic platforms.

Results: A total of 81 LSCs were included. Fourteen (17%) exhibited positive IHC using the MetMab score and 15 (18.5%) using the H-score. MET amplification was detected in six tumors (8.5%) and MET exon 14 mutation in five (6%). A weak positive correlation between IHC and fluorescence in situ hybridization was found (r = 0.27, p = 0.0001). IHC sensitivity for MET amplification was 50%, with a specificity of 83%, positive predictive value of 21.4%, and negative predictive value of 94.7%. IHC sensitivity for MET exon 14 mutations was 20%, with a specificity of 83%, positive predictive value of 7%, and negative predictive value of 94%.

Conclusion: IHC is not a relevant screening tool for MET abnormalities in LSC.
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http://dx.doi.org/10.1016/j.jtho.2018.08.008DOI Listing
December 2018

Lung cancer and interstitial lung disease: a literature review.

J Thorac Dis 2018 Jun;10(6):3829-3844

Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Service de Pneumologie, Paris, France.

The association between lung cancer (LC) and interstitial lung disease (ILD) can be explained by the shared risk factors like smoking and physiopathology of fibrogenesis and cancerogenesis. The relative LC risk is shown to be 3.5- to 7.3-times higher in ILD, with LC occurrence estimated at 10-20% in ILD, with >15% of ILD patients likely to die from LC. ILD incidence upon LC diagnosis varied from 2.4-10.9%. Primary radiological presentations consist of peripheral lesions, mostly in the inferior pulmonary lobes, either close to or within the ILD areas. There is a trend towards inverted proportion of adenocarcinomas and squamous-cell carcinomas, with EGFR mutations very rarely found. ILD negatively impacted LC prognosis, with surgery associated with increased morbidity-mortality, particularly due to acute exacerbation (AE) of ILD. Limited resection reduced this risk, whilst increasing that of cancer mortality. Studies on radiotherapy that can induce AE-ILD are scarce. Chemotherapy was associated with similar response rates to those in LC patients without ILD, yet worse survival. This difference may be accounted for by ILD patients' poorer health and higher risk of drug-induced pneumonitis. Further studies are warranted to better understand cancer physiopathology within the fibrotic areas, along with the therapeutic strategies required.
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http://dx.doi.org/10.21037/jtd.2018.05.75DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051867PMC
June 2018

Bronchial Dieulafoy's Disease: Visualization of Embolization Particles in Bronchial Aspirate.

Am J Respir Crit Care Med 2018 10;198(7):954-955

1 Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Service de Réanimation Médico-Chirurgicale.

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http://dx.doi.org/10.1164/rccm.201711-2184IMDOI Listing
October 2018

[PD-L1 testing in non-small cell lung carcinoma: Guidelines from the PATTERN group of thoracic pathologists].

Ann Pathol 2018 Apr 21;38(2):110-125. Epub 2018 Mar 21.

Département de pathologie, hôpital Cochin, université Paris Descartes, Assistance publique-hôpitaux de Paris, 74014 Paris, France.

Lung cancer is the leading cause of cancer death in France with low response rates to conventional chemotherapy. Nevertheless, new therapies have emerged recently, among which PD1 immune checkpoint inhibitors (ICI), such as nivolumab (OPDIVO, Bristol-Myers Squibb) and pembrolizumab (KEYTRUDA, Merck & Co), or PD-L1 ICI, such as atezolizumab (TECENTRIQ, Genentech), durvalumab (IMFINZI, Astra-Zeneca), and avelumab (BAVENCIO, EMD Serono). The prescription of pembrolizumab for advanced stage non-small cell lung carcinoma (NSCLC) patients requires the demonstration of PD-L1 expression by tumor cells by immunohistochemistry (IHC) (minimum of 50% of positive tumor cells is required for first-line setting, and of 1% for second-line and beyond) and PD-L1 assay is now considered as a companion diagnostic tool for this drug. Numerous standardized PD-L1 assays performed on dedicated platforms have been validated in clinical trials, each antibody being associated to one specific PD1 or PD-L1 inhibitor. However, not all pathologists have access to the dedicated platforms and the high cost of these assays is still a limitation to their implementation; in addition, the small size of the NSCLC tumor samples does not allow to perform at the same time multiple assays for multiple drugs. The use of laboratory-developed tests seems feasible but their validation must guarantee the same sensitivities and specificities as standardized tests. In this context, the French group of thoracic pathologists PATTERN has teamed up with thoracic oncologists to provide recommendations on the indication, the critical technical steps and the interpretation of the PD-L1 IHC test to help pathologists to implement quickly and in the best conditions this new theranostic test.
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http://dx.doi.org/10.1016/j.annpat.2018.01.007DOI Listing
April 2018

Cost-effectiveness of , and testing for decision making in advanced nonsmall cell lung carcinoma: the French IFCT-PREDICT.amm study.

Eur Respir J 2018 03 15;51(3). Epub 2018 Mar 15.

Service de Pneumologie, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Sorbonne Universités, UPMC Université Paris 06, GRC 04, Theranoscan, Paris, France.

rearrangement and / mutations constitute the primary biomarkers tested to provide targeted or nontargeted therapies in advanced nonsmall cell lung cancer (NSCLC) patients. Our objective was to assess the cost-effectiveness of biomarker testing for NSCLC.Between 2013 and 2014, 843 treatment-naive patients were prospectively recruited at 19 French hospitals into a longitudinal observational cohort study. Two testing strategies were compared, with "at least one biomarker status known" and "at least status known", in addition to "no biomarker testing" as the reference strategy. The Kaplan-Meier approach was employed to assess restricted mean survival time. Direct medical costs incurred by hospitals were estimated with regard to treatment, inpatient care and biomarker testing.Compared with "no biomarker testing", the "at least one biomarker status known" strategy yielded an incremental cost-effectiveness ratio of EUR13 230 per life-year saved, which decreased to EUR7444 per life-year saved with the "at least status known" testing strategy. In sensitivity analyses, biomarker testing strategies were less costly and more effective in 41% of iterations.In summary, molecular testing prior to treatment initiation proves to be cost-effective in advanced NSCLC management and may assist decision makers in defining conditions for further implementation of these innovations in general practice.
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http://dx.doi.org/10.1183/13993003.01467-2017DOI Listing
March 2018

High p95HER2/HER2 Ratio Associated With Poor Outcome in Trastuzumab-Treated HER2-Positive Metastatic Breast Cancer NCCTG N0337 and NCCTG 98-32-52 (Alliance).

Clin Cancer Res 2018 07 12;24(13):3053-3058. Epub 2018 Mar 12.

Center for Breast Health, Mayo Clinic, Jacksonville, Florida.

p95HER2 is a truncated form of HER2 that confers resistance to trastuzumab , but clinical results have been conflicting to date. Given that p95HER2 levels correlate with total HER2 expression levels, which confer better outcomes, we sought to evaluate the p95HER2/HER2 ratio in the North Central Cancer Treatment Group N0337 and N98-32-52 trials. The HERmark assay and VeraTag technology (Monogram Biosciences) were used to measure total HER2 and p95HER2 expression levels in 91 patient samples. In the multivariate model, increasing total HER2 level was significantly associated with longer (OS; HR, 0.33; = 0.002) and decreasing p95HER2 level was significantly associated with longer OS (HR, 4.2; = 0.01). Total HER2 expression level was significantly associated with longer progression-free survival (PFS) (HR, 0.57; = 0.04), whereas p95HER2 level was not (HR, 1.7; = 0.25). However, there was a positive association between p95HER2 and total HER2 expression levels ( = 0.48; < 0.001). Consistent with our hypothesis, the ratio of p95HER2/HER2 was significantly associated with worsening PFS (HR, 1.7; = 0.04) and OS (HR, 2.8; = 0.002). Patients with the highest tertile of p95HER2/HER2 values had significantly less favorable PFS (HR, 1.8; = 0.06) and OS (HR, 2.3; = 0.02). A high p95HER2/HER2 ratio identified patients with metastatic breast cancer with poor outcomes on trastuzumab-based therapies. Further investigation of the p95HER2/HER2 ratio as a potential prognostic or predictive biomarker for HER2-targeted therapy is warranted. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-1864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314664PMC
July 2018

Transcatheter embolotherapy of pulmonary artery aneurysms as emergency treatment of hemoptysis in Behcet patients: experience of a referral center and a review of the literature.

Intern Emerg Med 2018 06 7;13(4):491-500. Epub 2018 Mar 7.

Service de Radiologie, Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique-Hôpitaux de Paris, Paris, France.

Hemoptysis is a life-threatening complication of Behcet's disease that is likely related to pulmonary artery aneurysm (PAA). Vascular interventional radiology may offer effective emergency therapeutic option, but has not been thoroughly investigated in this setting. A case series of a French referral center for hemoptysis combined with a literature review of case reports was conducted. Between 1995 and 2016, 12 patients were referred to our center for hemoptysis revealing or complicating the course of Behcet's disease. Pulmonary artery aneurysm (PAA) was the mechanism of hemoptysis in ten patients, nine of whom were treated by a transcatheter embolotherapy. Combining an additional 8 case reports from the literature, 17 patients treated by transcatheter embolotherapy for PAA were analyzed. The duration of the course of Behcet's disease was 22 months [IQR 3-45] at the time of PAA diagnosis. Transcatheter embolotherapy of PAA was successful for immediately controlling hemoptysis in all patients, without major complication except for one. Hemoptysis recurred in seven patients (41%) within 5 months [IQR 1-12]. The use of coils for transcatheter embolotherapy was associated with hemoptysis recurrence. A bronchosystemic hypervascularization related to the previously occluded PAA was the main mechanism of bleeding recurrence, leading to bronchosystemic artery embolization in four patients and surgery in two patients. Behcet's disease-related hemoptysis is mainly due to PAA. Transcatheter embolotherapy should be considered as the first-line emergency treatment for PAA-related hemoptysis, in association with the immunosuppressive regimen. Hemoptysis may recur in half of the cases, involving preferentially a bronchosystemic arterial mechanism.
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http://dx.doi.org/10.1007/s11739-018-1817-yDOI Listing
June 2018

[Lung cancer in HIV-infected patients].

Bull Cancer 2018 Jan 22;105(1):111-119. Epub 2017 Dec 22.

Assistance publique-Hôpitaux de Paris, hôpital Tenon, service de pneumologie, 4, rue de la Chine, 75020 Paris, France; Université Paris-VI, université Pierre-et-Marie-Curie, GRC-UPMC 04 Théranoscan, 4, place Jussieu, 75252 Paris cedex 05, France. Electronic address:

Until 1996, AIDS was the leading cause of deaths from HIV infection. In 2010, because of introduction of powerful antiretroviral therapies, AIDS represented less than 25% of deaths. Cancer has become the leading cause of death in this population, and, because of smoking and immunosuppression, lung cancer risk is more important than in general population. Furthermore, treatment is more difficult, due to potential interactions between antiretroviral and anticancer therapies, to comorbidities and to tumor aggressiveness. Research will focus on molecular biology, immunotherapies and lung cancer screening in order to improve survival of HIV patients with lung cancer. For all these reasons, HIV patients must be included in clinical trials.
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http://dx.doi.org/10.1016/j.bulcan.2017.11.002DOI Listing
January 2018

Nonsmall cell lung cancer from HIV-infected patients expressed programmed cell death-ligand 1 with marked inflammatory infiltrates.

AIDS 2018 02;32(4):461-468

Sorbonne Universités, UPMC Univ Paris 06, GRC n°04, Theranoscan.

Objective: Immunotherapies targeting the programmed cell death-1 (PD-1)/PD-ligand 1 (PD-L1) checkpoint improved prognosis in lung cancer. PD-1/PD-L1 status, however, has not been investigated in human immunodeficiency virus (HIV)-positive patients. This study assessed PD-L1 status and tumor immune-cell infiltration in nonsmall cell lung cancer (NSCLC) in HIV patients.

Methods: Consecutive HIV patients treated between 1996 and 2014 were enrolled. PD-L1 tumor expression was assessed using immunohistochemistry with two antibodies (clones 5H1 and E1L3N), and tumor immune-cell infiltration with CD3, CD4, CD8, CD20, CD163, and MPO. PD-L1 expression and immune infiltration results were compared with those of 54 NSCLCs from unknown HIV status patients.

Results: Thirty-four HIV-positive patients were evaluated: predominantly men (88.2%) (median age: 51.1 years) presenting stage IV (38.2%) adenocarcinomas (76.5%). The median blood CD4 count was 480 cells/μL (86-1120) and 64% exhibited undetectable viral load. The PD-L1 score (percentage of positive cells × intensity) was higher in HIV-positive than HIV-undetermined patients with the E1L3N clone [median (range) 0 (0-150) versus 0 (0-26.7), P = 0.047], yet not with the 5H1 clone [0 (0-120) versus 0 (0-26.7) P = 0.07, respectively]. PD-L1 expression frequency did not differ between both cohorts (18.7 versus 9.3% using E1L3N and 10 versus 5.6% using 5H1 clone, respectively). There were significantly greater cytotoxic T-cell (P < 0.001), B-lymphocyte (P = 0.005), and activated macrophage (P < 0.001) infiltrations in the HIV-positive patients, but no differences for CD4 T cells.

Conclusion: Tumors in HIV-positive patients seem to express higher PD-L1 levels with increased immune infiltration, supporting their inclusion in clinical trials assessing immune checkpoint inhibitors.
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http://dx.doi.org/10.1097/QAD.0000000000001713DOI Listing
February 2018

Prevalence of Microsatellite Instability in Intraductal Papillary Mucinous Neoplasms of the Pancreas.

Gastroenterology 2018 03 20;154(4):1061-1065. Epub 2017 Nov 20.

INSERM, UMR S 938 - Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, Equipe labellisée par la Ligue Nationale contre le Cancer, F-75012, Paris, France; Sorbonne Université, Université Pierre et Marie Curie - Paris 6, Paris, France. Electronic address:

Microsatellite instability (MSI) caused by mismatch repair deficiency (dMMR) is detected in a small proportion of pancreatic ductal adenocarcinomas (PDACs). dMMR and MSI have been associated with responses of metastatic tumors, including PDACs, to immune checkpoint inhibitor therapy. We performed immunohistochemical analyses of a 445 PDAC specimens, collected from consecutive patients at multiple centers, to identify those with dMMR, based on loss of mismatch repair proteins MLH1, MSH2, MSH6, and/or PMS2. We detected dMMR in 1.6% of tumor samples; we found dMMR in a larger proportion of intraductal papillary mucinous neoplasms-related tumors (4/58, 6.9%) than non- intraductal papillary mucinous neoplasms PDAC (5/385, 1.3%) (P = .02). PDACs with dMMR contained potentially immunogenic mutations because of MSI in coding repeat sequences. PDACs with dMMR or MSI had a higher density of CD8+ T cells at the invasive front than PDACs without dMMR or MSI (P = .08; Fisher exact test). A higher proportion of PDACs with dMMR or MSI expressed the CD274 molecule (PD-L1, 8/9) than PDACs without dMMR or MSI (4/10) (P = .05). Times of disease-free survival and overall survival did not differ significantly between patients with PDACs with dMMR or MSI vs without dMMR or MSI. Studies are needed to determine whether these features of PDACs with dMMR or MSI might serve as prognostic factors.
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http://dx.doi.org/10.1053/j.gastro.2017.11.009DOI Listing
March 2018

False-positive galactomannan assay in broncho-alveolar lavage after enteral nutrition solution inhalation: a case report.

JMM Case Rep 2017 Sep 18;4(9):e005116. Epub 2017 Sep 18.

Department of Intensive Care, CUB - Erasme, Université Libre de Bruxelles (ULB), Route de Lennik 808, 1070 Brussels, Belgium.

Diagnosis of invasive aspergillosis is challenging and the gold standard for definite diagnosis remains histopathological tissue examination. However, invasive procedures such as lung biopsy are often not feasible in critically ill patients. The detection of fungal cell wall components like galactomannan in broncho-alveolar lavage remains a key component of the diagnostic procedure. False-positive of the galactomannan assay is not frequent. We report a case of positive galactomannan in broncho-alveolar lavage fluid after enteral nutrition aspiration without signs of invasive aspergillosis. Galactomannan was positive in the enteral nutrition solution. Physicians should be aware of this previously unrecognized cause of false-positive galactomannan in broncho-alveolar fluid which can result in unnecessary treatments.
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http://dx.doi.org/10.1099/jmmcr.0.005116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643004PMC
September 2017

Severe Hemoptysis Associated with Bacterial Pulmonary Infection: Clinical Features, Significance of Parenchymal Necrosis, and Outcome.

Lung 2018 02 12;196(1):33-42. Epub 2017 Oct 12.

Faculté de Médecine de Créteil, Groupe de recherche clinique CARMAS, Université Paris Est Créteil, 94010, Paris, Créteil, France.

Purpose: Severe hemoptysis (SH) associated with non-tuberculosis bacterial lower respiratory tract infection (LRTI) is poorly described, and the efficacy of the usual decision-making process is unknown. This study aimed at describing the clinical, radiological patterns, mechanism, and microbiological spectrum of SH related to bacterial LRTI, and assessing whether the severity of hemoptysis and the results of usual therapeutic strategy are influenced by the presence of parenchymal necrosis.

Methods: A single-center analysis of patients with SH related to bacterial LRTI from a prospective registry of consecutive patients with SH admitted to the intensive care unit of a tertiary referral center between November 1996 and May 2013.

Results: Of 1504 patients with SH during the study period, 65 (4.3%) had SH related to bacterial LRTI, including non-necrotizing infections (n = 31), necrotizing pneumonia (n = 23), pulmonary abscess (n = 10), and excavated nodule (n = 1). The presence of parenchymal necrosis (n = 34, 52%) was associated with a more abundant bleeding (volume: 200 ml [70-300] vs. 80 ml [30-170]; p = 0.01) and a more frequent need for endovascular procedure (26/34; 76% vs. 9/31; 29%; p < 0.001). Additionally, in case of parenchymal necrosis, the pulmonary artery vasculature was involved in 16 patients (47%), and the failure rate of endovascular treatment was up to 25% despite multiple procedures.

Conclusions: Bacterial LRTI is a rare cause of SH. The presence of parenchymal necrosis is more likely associated with bleeding severity, pulmonary vasculature involvement, and endovascular treatment failure.
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http://dx.doi.org/10.1007/s00408-017-0064-8DOI Listing
February 2018

Left ventricular assist device: exercise capacity evolution and rehabilitation added value.

Acta Cardiol 2018 Jun 28;73(3):248-255. Epub 2017 Aug 28.

c Department of Cardiac Surgery , Erasme Hospital , Brussels , Belgium.

Background: With more than 15,000 implanted patients worldwide and a survival rate of 80% at 1-year and 59% at 5-years, left ventricular assist device (LVAD) implantation has become an interesting strategy in the management of heart failure patients who are resistant to other kinds of treatment. There are limited data in the literature on the change over time of exercise capacity in LVAD patients, as well as limited knowledge about the beneficial effects that rehabilitation might have on these patients. Therefore, the aim of our study was to evaluate the evolution of exercise capacity on a cohort of patients implanted with the same device (HeartWare) and to analyse the potential impact of rehabilitation.

Methods: Sixty-two patients implanted with a LVAD between June 2011 and June 2015 were screened. Exercise capacity was evaluated by cardiopulmonary exercise testing at 6 weeks, 6 and 12 months after implantation.

Results: We have observed significant differences in the exercise capacity and evolution between the trained and non-trained patients. Some of the trained patients nearly normalised their exercise capacity at the end of the rehabilitation programme.

Conclusions: Exercise capacity of patient implanted with a HeartWare LVAD increased in the early period after implantation. Rehabilitation allowed implanted patients to have a significantly better evolution compared to non-rehabilitated patients.
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http://dx.doi.org/10.1080/00015385.2017.1368947DOI Listing
June 2018

Pro-tumoural CXCL10/CXCR3-A autocrine loop in invasive mucinous lung adenocarcinoma.

ERJ Open Res 2017 Jan 31;3(1). Epub 2017 Mar 31.

Sorbonne Universités, UPMC University Paris 06, GRC n°04, Theranoscan, F-75252, Paris, France.

Invasive mucinous adenocarcinoma (IMA) is a mucinous variant of lepidic predominant lung adenocarcinoma (LPA) and associated with a worse prognosis. We postulated that cytokine expression would enable us to differentiate IMA from LPA in terms of prognosis and acquisition of pro-tumoural capacities. A 30-cytokine panel was assessed in bronchoalveolar lavage fluids (BALF) from IMA (n=38), LPA (n=25) and control samples (n=7). We investigated the expression of differentially expressed cytokines and splice variants of their receptors in surgical samples. The presence of and mutations were determined. We also examined the expression of cytokines and splice variants of their receptors in different cell lines, exploring their functional impact on signalling pathways, proliferation and migration. Only C-X-C motif chemokine 10 (CXCL10) was differentially expressed, namely overexpressed in IMA BALF compared with LPA. CXCL10 overexpression in BALF was linked to a worse prognosis. In surgical samples, CXCL10 and its receptor C-X-C motif chemokine receptor 3 (CXCR3) were overexpressed in IMA compared to LPA. A pro-tumoural CXCR3-A splice variant was overexpressed in IMA, suggesting a CXCL10/CXCR3-A autocrine loop in IMA. CXCL10 and CXCR3 expression were not correlated with or status. CXCL10 up-regulated CXCR3-A expression, Erk1/2 phosphorylation and enhanced migration in the mucinous H2228 cell line. CXCL10/CXCR3-A may play a pro-tumoural role in IMA an autocrine mechanism.
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http://dx.doi.org/10.1183/23120541.00047-2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566270PMC
January 2017
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