Publications of Bernard DUYSINX
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See detailGranulomatosis With Polyangiitis in a Patient on Programmed Death-1 Inhibitor for Advanced Non-small-cell Lung Cancer.
SIBILLE, Anne ULiege; Alfieri, Romain ULiege; MALAISE, Olivier ULiege et al

in Frontiers in oncology (2019), 9

Objectives: To contribute to a precise and thorough knowledge of immune-related adverse events (irAE) induced by immune checkpoint inhibitors (ICI) and to emphasize the importance of this specific form of ... [more ▼]

Objectives: To contribute to a precise and thorough knowledge of immune-related adverse events (irAE) induced by immune checkpoint inhibitors (ICI) and to emphasize the importance of this specific form of toxicity in terms of potential predictive value and long-term effects. Materials and Methods: We report the first case of granulomatosis with polyangiitis (GPA) in a patient treated with an anti-Programmed Death protein-1 (PD-1) antibody for advanced non-small-cell lung cancer (NSCLC). Results: After a single dose of this drug the patient showed severe myositis associated with a high anti-PR3 anti-neutrophil cytoplasmic antibody titer. Discontinuation of the anti-PD-1 and introduction of corticoids led to a remission of the irAE. Regarding tumor a partial response was noted. A year later a neutrophilic, sterile pleural exudate and cutaneous lesions appeared with the pathological findings of neutrophilic vasculitis. Retreatment with corticoids induced a new remission of symptoms. It remains unclear whether GPA was preexisting and clinically silent but revealed by the use of ICI or primarily induced by this treatment. Conclusions: irAE are rare when anti-PD-1 antibodies are used in monotherapy. They present with a distinct clinical picture and temporal course and require specific treatment. Patients with irAE usually have a favorable oncological outcome. [less ▲]

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See detailFirst report of probe based confocal laser endomicroscopy during medical thoracoscopy.
BONHOMME, Olivier ULiege; DUYSINX, Bernard ULiege; HEINEN, Vincent ULiege et al

in Respiratory Medicine (2019), 147

Probe based confocal laser endomicroscopy (pCLE) is a new optical endoscopic technique, generating fluorescent light emission from the tissue of interest and allowing in vivo live imaging at a cellular ... [more ▼]

Probe based confocal laser endomicroscopy (pCLE) is a new optical endoscopic technique, generating fluorescent light emission from the tissue of interest and allowing in vivo live imaging at a cellular level ("optical biopsies"). To the best of our knowledge, this article is the first to present pCLE images during medical thoracoscopy. We present here 3 different patients referred for various health problems. A precise description of pleural cavity pCLE images after intravenous fluorescein injection (a fluorophore) together with corresponding macroscopical and histological studies is performed. This led to the diagnosis of normal pleura in one case, carcinomatous pleuritis in another case and a malignant mesothelioma in the third case. We believe that optical biopsies could help clinicians to make an early diagnosis, thereby allowing rapid therapeutic intervention (talc pleurodesis for example). Furthermore, it could help to guide biopsies when affected zones are not obvious to macroscopic examination. In a near future, new fluorophores could be developed to stain some pathophysiological processes, therapeutic targets, or enzymes activities bringing new insights in endoscopic pleural disease work-up. [less ▲]

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See detailADAM10 mediates malignant pleural mesothelioma invasiveness
Sepult, Christelle ULiege; Bellefroid, Marine ULiege; Rocks, Natacha ULiege et al

in Oncogene (2019)

Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited therapeutic options and treatment efficiency. Even if the latency period between asbestos exposure, the main risk factor, and ... [more ▼]

Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited therapeutic options and treatment efficiency. Even if the latency period between asbestos exposure, the main risk factor, and mesothelioma development is very long, the local invasion of mesothelioma is very rapid leading to a mean survival of one year after diagnosis. ADAM10 (A Disintegrin And Metalloprotease) sheddase targets membrane-bound substrates and its overexpression is associated with progression in several cancers. However, nothing is known about ADAM10 implication in MPM. In this study, we demonstrated higher ADAM10 expression levels in human MPM as compared to control pleural samples and in human MPM cell line. This ADAM10 overexpression was also observed in murine MPM samples. Two mouse mesothelioma cell lines were used in this study including one primary cell line obtained by repeated asbestos fibre injections. We show, in vitro, that ADAM10 targeting through shRNA and pharmacological (GI254023X) approaches reduced drastically mesothelioma cell migration and invasion, as well as for human mesothelioma cells treated with siRNA targeting ADAM10. Moreover, ADAM10 downregulation in murine mesothelioma cells significantly impairs MPM progression in vivo after intrapleural cell injection. We also demonstrate that ADAM10 sheddase downregulation decreases the production of a soluble N-cadherin fragment through membrane N-cadherin, which stimulated mesothelioma cell migration. Taken together, we demonstrate that ADAM10 is overexpressed in MPM and takes part to MPM progression through the generation of N-cadherin fragment that stimulates mesothelioma cell migration. ADAM10 inhibition is worth considering as a therapeutic perspective in mesothelioma context. [less ▲]

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See detailIgG4-related pleural disease in a patient with a history of unknown origin acute pancreatitis: a case report and review of the literature.
Damas, François ULiege; Ghysen, K.; GESTER, Fanny ULiege et al

in Acta Clinica Belgica (2019), 8

Immunoglobulin G4-related disease is a rare autoimmune systemic disease with the capability of involving every organ. The disease is microscopically defined by a diffuse tissular inflammation with an ... [more ▼]

Immunoglobulin G4-related disease is a rare autoimmune systemic disease with the capability of involving every organ. The disease is microscopically defined by a diffuse tissular inflammation with an infiltration of IgG4 positive plasma cells in the affected organs. IgG4 disease has an increasing incidence in the last few years with a growing interest in its pathophysiology still misunderstood to date. Despite the growing recognition of this pathology, the literature still does not allow to propose a simple diagnostic algorithm. In this article, we present a case of a 56-year-old man with a history of unknown etiology acute pancreatitis and a unilateral pleural effusion. [less ▲]

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See detailComment j'explore... Les modifications biologiques dans les pathologies infiltrantes pulmonaires
GESTER, Fanny ULiege; DUYSINX, Bernard ULiege; VON FRENCKELL, Christian ULiege et al

in Revue medicale de Liege (2019), 74(1), 47-53

Interstitial lung diseases (ILD) are a part of a vast and heterogeneous clinicopathological entity. The work-up have to rule out a granulomatosis or a secondary cause, before making the diagnosis of an ... [more ▼]

Interstitial lung diseases (ILD) are a part of a vast and heterogeneous clinicopathological entity. The work-up have to rule out a granulomatosis or a secondary cause, before making the diagnosis of an idiopathic ILD. The etiological diagnosis is based on a multidisciplinary approach integrating a network of clinical and paraclinical datas. If the diagnosis remains unclear, a lung biopsy is suggested with a transbronchial approach (mainly cryobiopsy) or with a surgical approach (video-assisted thoracoscopy). This review article mainly describes the biological analyses that contribute to explore ILDs. [less ▲]

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See detailThermoplastie bronchique dans le traitement de l’asthme sévère. Analyse rétrospective de 10 cas traités au CHU de Liège
Frix, Anne-Noëlle ULiege; HEINEN, Vincent ULiege; SCHLEICH, FLorence ULiege et al

in Revue Médicale de Liège (2019), 74(2), 74-81

Summary: As treating severe forms of asthma represents a medical and economical challenge, research for new therapies in this area is extensive and expansive. Recently, bronchial thermoplasty (BT) – ie ... [more ▼]

Summary: As treating severe forms of asthma represents a medical and economical challenge, research for new therapies in this area is extensive and expansive. Recently, bronchial thermoplasty (BT) – ie. bronchoscopic procedure delivering a thermic form of energy through radiofrequency to the bronchi, in order to interfere with the components of the smooth muscle layer – arose as a promising technique. Our study followed the path of 10 patients from CHU Liège (University Hospital), who underwent this procedure in a context of severe asthma. We compared clinical and spirometric and treatment data in patients at 0 – 6 and 12 months post-procedural intervals, in order to determine whether thermoplasty had been improving asthma. Overall, we observed a stabilization and possibly a clinical improvement while reducing the total amount of exacerbation rate, and the burden of maintenance oral corticoids. © 2019 Revue Medicale de Liege. All Rights Reserved. [less ▲]

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See detailLa thoracoscopie médicale en pratique pneumologique: expérience du CHU de Liège
DUYSINX, Bernard ULiege; HEINEN, Vincent ULiege; Corhay, Jean-Louis ULiege et al

in Revue des Maladies Respiratoires (2019), 36

Introduction: The incidence of pleural disease continues to increase worldwide. Medical thoracoscopy remains the standard method for exploration of the pleural cavity. Method: We report the retrospective ... [more ▼]

Introduction: The incidence of pleural disease continues to increase worldwide. Medical thoracoscopy remains the standard method for exploration of the pleural cavity. Method: We report the retrospective evaluation, the efficacy and the observed complications in 1024 medical thoracoscopies undertaken in the University Hospital of Liège between 2000 and 2017. Results: In total, 100 pneumothoraces and 400 benign and 501 malignant pleural diseases were identified. The main indication for thoracoscopy remains the diagnosis of an exudative, lymphocytic pleural effusion of unknown aetiology after thoracocentesis. The diagnostic sensibility of thoracoscopy was 99.2% in distinguishing benign from malignant pleural disease. Talc pleurodesis was performed in 69.5% of the total population and in 66.1% of pleural effusions or thickening. Failure of pleurodesis was observed in 11% of the patients with recurrent pneumothorax and in 7.8% of neoplastic pleural effusion. We report a mortality of 0.6% in the 30 days post procedure, long duration of drainage in 8.3% and serious complications in 4.7%. In 22/1024 (2.1%) thoracoscopic evaluation was not feasible because of dense pleural fibrosis. Conclusion: Medical thoracoscopy is a safe, well-tolerated procedure with high accuracy in the diagnostic and therapeutic management of pleural disease. © 2019 SPLF [less ▲]

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See detailInhibition of EZH2 methyltransferase decreases immunoediting of mesothelioma cells by autologous macrophages through a PD-1-dependent mechanism.
Hamaïdia, Malik ULiege; Gazon, Hélène ULiege; Hoyos, Clotilde ULiege et al

in JCI Insight (2019), 4(18),

The roles of macrophages in orchestrating innate immunity through phagocytosis and T lymphocyte activation have been extensively investigated. Much less understood is the unexpected role of macrophages in ... [more ▼]

The roles of macrophages in orchestrating innate immunity through phagocytosis and T lymphocyte activation have been extensively investigated. Much less understood is the unexpected role of macrophages in direct tumor regression. Tumoricidal macrophages can indeed manifest cancer immunoediting activity in the absence of adaptive immunity. We investigated direct macrophage cytotoxicity in malignant pleural mesothelioma, a lethal cancer that develops from mesothelial cells of the pleural cavity after occupational asbestos exposure. In particular, we analyzed the cytotoxic activity of mouse RAW264.7 macrophages upon cell-cell contact with autologous AB1/AB12 mesothelioma cells. We show that macrophages killed mesothelioma cells by oxeiptosis via a mechanism involving enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27-specific (H3K27-specific) methyltransferase of the polycomb repressive complex 2 (PRC2). A selective inhibitor of EZH2 indeed impaired RAW264.7-directed cytotoxicity and concomitantly stimulated the PD-1 immune checkpoint. In the immunocompetent BALB/c model, RAW264.7 macrophages pretreated with the EZH2 inhibitor failed to control tumor growth of AB1 and AB12 mesothelioma cells. Blockade of PD-1 engagement restored macrophage-dependent antitumor activity. We conclude that macrophages can be directly cytotoxic for mesothelioma cells independent of phagocytosis. Inhibition of the PRC2 EZH2 methyltransferase reduces this activity because of PD-1 overexpression. Combination of PD-1 blockade and EZH2 inhibition restores macrophage cytotoxicity. [less ▲]

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See detailActualités concernant l’immunothérapie en oncologie pulmonaire
VAILLANT, Frédérique ULiege; Canivet, P.; DUYSINX, Bernard ULiege et al

in Revue Médicale Suisse (2018), 14(615), 1451-1454

Immunotherapy, based on the immune response to tumor cells, gives a new therapeutic hope for lung cancer whose prognosis remains dark. Four molecules are currently available in clinical practice. They ... [more ▼]

Immunotherapy, based on the immune response to tumor cells, gives a new therapeutic hope for lung cancer whose prognosis remains dark. Four molecules are currently available in clinical practice. They were first studied for non-small cell cancers in the second and third line of treatment with a significant improvement in overall survival, then in maintenance treatment and more recently in the front line with a significant response. Their complications, mainly dysimmune adverse effects, are protean but immunotherapy remains better tolerated than chemotherapy. It opens many perspectives but further studies, including biomarkers, are still needed. © 2018 Editions Medecine et Hygiene. All rights reserved. [less ▲]

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See detailImplication of ADAM10 protease in malignant pleural mesothelioma
Bellefroid, Marine ULiege; Sepult, Christelle ULiege; Rocks, Natacha ULiege et al

Conference (2018, May 03)

Detailed reference viewed: 33 (11 ULiège)
See detailImplication of ADAM10 protease in malignant mesohelioma
Sepult, Christelle ULiege; Bellefroid, Marine ULiege; Rocks, Natacha ULiege et al

Poster (2018, March 09)

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See detailComment j'explore... Techniques diagnostiques invasives des pneumopathies interstitielles diffuses
DUYSINX, Bernard ULiege; GUIOT, Julien ULiege; PELLEGRINI, Ivan ULiege et al

in Revue Médicale de Liège (2018), 73(3), 147-155

Interstitial lung diseases represent a very heterogeneous group of diseases mainly affecting connective lung tissue even if alveolar space may sometimes be involved. The identification of their etiology ... [more ▼]

Interstitial lung diseases represent a very heterogeneous group of diseases mainly affecting connective lung tissue even if alveolar space may sometimes be involved. The identification of their etiology is the key stage in their management. It requires the integration of anamnestic, clinical, biological, radiological data and, sometimes relies on, cytology or histology. In this review, we assess the contribution and feasibility of the different invasive techniques used for interstitial lung disease diagnosis. In particular we focus on the yield of lung endoscopy in casting light on the multidisciplinary confrontation, which is the gold standard of the interstitial lung disease care management. [less ▲]

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See detailClinical experience in idiopathic pulmonary fibrosis: a retrospective study
GUIOT, Julien ULiege; CORHAY, Jean-Louis ULiege; LOUIS, Renaud ULiege et al

in Acta Clinica Belgica (2017)

Introduction Idiopathic pulmonary fibrosis (IPF) is a rare lung disease with an increased incidence since the last few years. Here, we report our eight-year clinical experience in CHU of Liège, Belgium ... [more ▼]

Introduction Idiopathic pulmonary fibrosis (IPF) is a rare lung disease with an increased incidence since the last few years. Here, we report our eight-year clinical experience in CHU of Liège, Belgium. Methods We have studied retrospectively patients recruited from our ambulatory care polyclinic at CHU of Liège from 1 January 2009 to 1 January 2017. We have excluded all patients treated with a specific anti-fibrotic therapy due to incomplete follow-up. The diagnosis of IPF was made according to the ATS/ERS international recommendations (2015). Results Out of the 114 patients initially selected, 82 cases were found to be suitable for the analysis. The average age was 71.1 ± 9.35 years with a male predominance. The median survival was 43.7 months (23.6–71.7) with a majority (45%) of patients in the group II of the GAP index. The median rate of annual decline in diffusion capacity of CO (DLCO) was 11%, whereas the sub analysis for group III (according to GAP index) showed a decrease annual rate of 30%. Conclusion Our results are in keeping with the literature. One of our major finding is that patients in GAP III exhibit an annual rate of mortality of 42% and a median annual decline in DLCO of 30%. This observation highlights the fact that this specific subgroup of patients presents a high risk of morbi-mortality. [less ▲]

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See detailComment je traite ⋯ une fibrose pulmonaire idiopathique
GUIOT, Julien ULiege; Duysinx, Bernard ULiege; BONHOMME, Olivier ULiege et al

in Revue Médicale de Liège (2017), 72(9), 381-383

Idiopathic pulmonary fibrosis (IPF) is a rare disorder of unknown origin, which is associated with a high mortality and whose incidence has been increasing for several years. Nowadays there are two anti ... [more ▼]

Idiopathic pulmonary fibrosis (IPF) is a rare disorder of unknown origin, which is associated with a high mortality and whose incidence has been increasing for several years. Nowadays there are two anti-fibrotic therapies (pirfenidone - nintedanib) known to reduce significantly the decline in respiratory function tests of patients suffering from this condition. The only curative therapeutic option remains the pulmonary transplantation whose accessibility remains limited. Pulmonary rehabilitation is also central in the treatment of patients. A major challenge for patients remains early and aggressive management to reduce as early as possible the evolution towards severe pulmonary fibrosis. [less ▲]

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See detailEGFR tyrosine kinase inhibitors overcome resistance to chemotherapy in malignant pleural mesothelioma.
Staumont, Bernard ULiege; Costa, Christostome; Vandermeers, Fabian et al

Poster (2017, February 01)

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See detailFrom Valeriana officinalis to cancer therapy: the success of a bio-sourced compound
Hamaïdia, Malik ULiege; Barez, Pierre-Yves ULiege; Carpentier, Alexandre ULiege et al

in Biotechnologie, Agronomie, Société et Environnement (2016), 20

Over the centuries, bio-sourced compounds isolated from plants, insects and microorganisms have been a potent source of drugs for the treatment of human diseases. In this review, we recapitulate the story ... [more ▼]

Over the centuries, bio-sourced compounds isolated from plants, insects and microorganisms have been a potent source of drugs for the treatment of human diseases. In this review, we recapitulate the story of one of these compounds, 2-propylpentanoic acid, derived from the Valeriana officinalis flowering plant and its path to validation as a cancer treatment. [less ▲]

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See detailImprovement of malignant pleural mesothelioma immunotherapy by epigenetic modulators
Hamaïdia, Malik ULiege; Staumont, Bernard ULiege; DUYSINX, Bernard ULiege et al

in Current Topics in Medicinal Chemistry (2016), 16

In the absence of a satisfactory treatment of malignant pleural mesothelioma (MPM), novel therapeutic strategies are urgently needed. Among these, immunotherapy offers a series of advantages such as tumor ... [more ▼]

In the absence of a satisfactory treatment of malignant pleural mesothelioma (MPM), novel therapeutic strategies are urgently needed. Among these, immunotherapy offers a series of advantages such as tumor specificity and good tolerability. Unfortunately, MPM immunotherapy is frequently limited by incomplete cell differentiation or feedback loop regulatory mechanisms. In this review, we describe different components of the innate immune system and discuss strategies to improve MPM immunotherapy by using epigenetic modulators. [less ▲]

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See detailApport de l'échographie thoracique aux urgences : à propos d'un cas de dyspnée aiguë durant la grossesse
MARISSIAUX, Laurent ULiege; GENSBURGER, Mathieu ULiege; TROMBA, A et al

in Revue Médicale de Liège (2016), 71(7-8), 349-355

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See detailFacteurs pronostiques du cancer pulmonaire non à petites cellules
GESTER, Fanny ULiege; PAULUS, Astrid ULiege; SIBILLE, Anne ULiege et al

in Revue Médicale de Liège (2016), 71(1), 34-39

Summary : Non small cell lung cancer is the most frequent type of lung cancer and its prognosis is still very poor. Relapse is frequent and can be observed even in early stages of the disease, in spite of ... [more ▼]

Summary : Non small cell lung cancer is the most frequent type of lung cancer and its prognosis is still very poor. Relapse is frequent and can be observed even in early stages of the disease, in spite of a surgical management with curative intent. This paper gives an overview of the main prognostic factors, the two most important of which remain the staging and tumor histology. These also determine the therapeutic strategy. Other factors of poor prognosis might also be useful for clinicians, particularly in their decision to refer patients for adjuvant therapies. Keywords : Non-small cell lung cancer – Prognostic factors – Pulmonary oncology – Surgery [less ▲]

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