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Article: Objective improvement in dexterity for trainees undergoing a video-assisted thoracoscopic surgery simulation program, a prospective single center study.

Koliakos, Evangelos / Abdelnour, Etienne / Hasenauer, Arpad / Forster, Celine / Ojanguren, Amaya / Ris, Hans-Beat / Gonzalez, Michel / Krueger, Thorsten / Perentes, Jean Y

Journal of thoracic disease

2023 Volume 15, Issue 12, Page(s) 6674–6686

Abstract: Background: Video-assisted thoracoscopic surgery (VATS) is the recommended approach for the management of early-stage operable non-small cell lung carcinoma as well as for other pathologies of the thoracic cavity. Although VATS approaches have been ... ...

Abstract	Background: Video-assisted thoracoscopic surgery (VATS) is the recommended approach for the management of early-stage operable non-small cell lung carcinoma as well as for other pathologies of the thoracic cavity. Although VATS approaches have been largely adopted in Europe and North America, teaching the technique to novice thoracic surgery trainees remains challenging and non-standardized. Our objective was to assess the impact of a VATS simulation training program on the dexterity of thoracic surgery residents in a prospective single institution study. Methods: We developed a 6-month VATS simulation training program on two different dry-lab simulators (Johnson & Johnson Ethicon Stupnik Results: After the 6-month VATS training program, all residents revealed a significant increase of their performance status with respect to instrument travel distances operation times and absence of periods of extreme motion in all three exercises performed. The performance of the control group was not different from the study group prior to the training program and remained unchanged 6 months later, for all exercises and parameters assessed. Conclusions: Our results suggest that the implementation of a VATS simulation training program objectively increases the dexterity of thoracic surgery residents and could be an interesting training tool for their surgical education.
Language	English
Publishing date	2023-12-21
Publishing country	China
Document type	Journal Article
ZDB-ID	2573571-8
ISSN	2077-6624 ; 2072-1439
ISSN (online)	2077-6624
ISSN	2072-1439
DOI	10.21037/jtd-23-1288
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Article ; Online: Use of a novel microbiome modulator improves anticancer immunity in a murine model of malignant pleural mesothelioma.

Gattlen, Christophe / Frank, Kirby R / Marie, Damien N / Trompette, Aurélien / Chriqui, Louis-Emmanuel / Hao, Yameng / Abdelnour, Etienne / Gonzalez, Michel / Krueger, Thorsten / Dyson, Paul J / Siankevich, Sviatlana / von Garnier, Christophe / Ubags, Niki D J / Cavin, Sabrina / Perentes, Jean Y

JTCVS open

2024 Volume 18, Page(s) 324–344

Abstract: Objective: Malignant pleural mesothelioma is a fatal disease and a clinical challenge, as few effective treatment modalities are available. Previous evidence links the gut microbiome to the host immunoreactivity to tumors. We thus evaluated the impact ... ...

Abstract	Objective: Malignant pleural mesothelioma is a fatal disease and a clinical challenge, as few effective treatment modalities are available. Previous evidence links the gut microbiome to the host immunoreactivity to tumors. We thus evaluated the impact of a novel microbiome modulator compound (MMC) on the gut microbiota composition, tumor immune microenvironment, and cancer control in a model of malignant pleural mesothelioma. Methods: Age- and weight-matched immunocompetent (n = 23) or athymic BALB/c mice (n = 15) were randomly assigned to MMC or no treatment (control) groups. MMC (31 ppm) was administered through the drinking water 14 days before AB12 malignant mesothelioma cell inoculation into the pleural cavity. The impact of MMC on tumor growth, animal survival, tumor-infiltrating leucocytes, gut microbiome, and fecal metabolome was evaluated and compared with those of control animals. Results: The MMC delayed tumor growth and significantly prolonged the survival of immunocompetent animals ( Conclusions: MMC administration boosts antitumor immunity, which correlates with a change in gut microbiome and metabolome. MMC may represent a valuable treatment option to combine with immunotherapy in patients with cancer.
Language	English
Publishing date	2024-02-17
Publishing country	Netherlands
Document type	Journal Article
ISSN	2666-2736
ISSN (online)	2666-2736
DOI	10.1016/j.xjon.2024.02.007
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Article: Limited Index of Clinical Suspicion and Underdiagnosis of Histopathologically Documented Invasive Mold Infections.

Caudron de Coquereaumont, Grégoire / Couchepin, Jade / Perentes, Jean Y / Krueger, Thorsten / Lovis, Alban / Rotman, Samuel / Lamoth, Frederic

Open forum infectious diseases

2021 Volume 8, Issue 7, Page(s) ofab174

Abstract: Invasive mold infections (IMIs) are difficult to diagnose. This analysis of histopathologically proven IMIs at our institution (2010-2019) showed that 11/41 (27%) of them were not suspected at the time of biopsy/autopsy (9/17, 53% among autopsies). The ... ...

Abstract	Invasive mold infections (IMIs) are difficult to diagnose. This analysis of histopathologically proven IMIs at our institution (2010-2019) showed that 11/41 (27%) of them were not suspected at the time of biopsy/autopsy (9/17, 53% among autopsies). The rate of missed diagnosis was particularly high (8/16, 50%) among nonhematologic cancer patients.
Language	English
Publishing date	2021-04-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofab174
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Article: Outcome of parapneumonic empyema managed surgically or by fibrinolysis: a multicenter study.

Federici, Sara / Bédat, Benoit / Hayau, Justine / Gonzalez, Michel / Triponez, Frederic / Krueger, Thorsten / Karenovics, Wolfram / Perentes, Jean Y

Journal of thoracic disease

2021 Volume 13, Issue 11, Page(s) 6381–6389

Abstract: Background: Parapneumonic empyema (PPE) management remains debated. Here we present the outcome of a comparable population with PPE treated over a 4-year period in two Thoracic Surgery University Centers with different approaches: one with an early " ... ...

Abstract	Background: Parapneumonic empyema (PPE) management remains debated. Here we present the outcome of a comparable population with PPE treated over a 4-year period in two Thoracic Surgery University Centers with different approaches: one with an early "surgical" and the other with a "fibrinolytic" approach. Methods: All operable patients with PPE managed in both centers between January 2014 and January 2018 were reviewed. Patients with persistent pleural effusion/loculations following drainage were managed by a "surgical" approach in one center and by "fibrinolytic" approach in the other. For each patient, we recorded the age, sex, hospital stay, morbidity/mortality and change in pleural opacity on chest X-ray before and at the end of the treatment. Results: During the study period, 66 and 93 patients underwent PPE management in the "surgical" and "fibrinolytic" centers respectively. The population characteristics were comparable. Infection was controlled in all patients. In the "fibrinolytic" group, 20 patients (21.5%) underwent an additional drain placement while 12 patients (12.9%) required surgery to correct PPE. In the "surgical" group, 4 patients (6.1%) developed postoperative arrhythmia while 2 patients (3%) underwent a second surgery to evacuate a hemothorax. Median drainage {3 [2-4] Conclusions: Surgical management of PPE was associated with shorter chest tube and hospital duration and better pleural space control. Prospective randomized studies are mandatory.
Language	English
Publishing date	2021-12-17
Publishing country	China
Document type	Journal Article
ZDB-ID	2573571-8
ISSN	2077-6624 ; 2072-1439
ISSN (online)	2077-6624
ISSN	2072-1439
DOI	10.21037/jtd-21-1083
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Article ; Online: Effects of cold or warm ischemia and ex-vivo lung perfusion on the release of damage associated molecular patterns and inflammatory cytokines in experimental lung transplantation.

Hasenauer, Arpad / Bédat, Benoît / Parapanov, Roumen / Lugrin, Jérôme / Debonneville, Anne / Abdelnour-Berchtold, Etienne / Gonzalez, Michel / Perentes, Jean Y / Piquilloud, Lise / Szabo, Csaba / Krueger, Thorsten / Liaudet, Lucas

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

2021 Volume 40, Issue 9, Page(s) 905–916

Abstract: Background: Lung transplantation (LTx) is associated with sterile inflammation, possibly related to the release of damage associated molecular patterns (DAMPs) by injured allograft cells. We have measured cellular damage and the release of DAMPs and ... ...

Abstract	Background: Lung transplantation (LTx) is associated with sterile inflammation, possibly related to the release of damage associated molecular patterns (DAMPs) by injured allograft cells. We have measured cellular damage and the release of DAMPs and cytokines in an experimental model of LTx after cold or warm ischemia and examined the effect of pretreatment with ex-vivo lung perfusion (EVLP). Methods: Rat lungs were exposed to cold ischemia alone (CI group) or with 3h EVLP (CI-E group), warm ischemia alone (WI group) or with 3 hour EVLP (WI-E group), followed by LTx (2 hour). Bronchoalveolar lavage (BAL) was performed before (right lung) or after (left lung) LTx to measure LDH (marker of cellular injury), the DAMPs HMGB1, IL-33, HSP-70 and S100A8, and the cytokines IL-1β, IL-6, TNFα, and CXCL-1. Graft oxygenation capacity and static compliance after LTx were also determined. Results: Compared to CI, WI displayed cellular damage and inflammation without any increase of DAMPs after ischemia alone, but with a significant increase of HMGB1 and functional impairment after LTx. EVLP promoted significant inflammation in both cold (CI-E) and warm (WI-E) groups, which was not associated with cell death or DAMP release at the end of EVLP, but with the release of S100A8 after LTx. EVLP reduced graft damage and dysfunction in warm ischemic, but not cold ischemic, lungs. Conclusions: The pathomechanisms of sterile lung inflammation during LTx are significantly dependent on the conditions. The release of HMGB1 (in the absence of EVLP) and S100A8 (following EVLP) may be important factors in the pathogenesis of LTx.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Bronchoalveolar Lavage Fluid/chemistry ; Cold Ischemia/methods ; Cytokines/metabolism ; Disease Models, Animal ; Extracorporeal Circulation/methods ; Inflammation/etiology ; Inflammation/metabolism ; Lung/metabolism ; Lung Transplantation ; Organ Preservation/methods ; Perfusion/methods ; Rats ; Rats, Sprague-Dawley ; Tissue Donors ; Warm Ischemia/methods
Chemical Substances	Biomarkers ; Cytokines
Language	English
Publishing date	2021-06-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1062522-7
ISSN	1557-3117 ; 1053-2498
ISSN (online)	1557-3117
ISSN	1053-2498
DOI	10.1016/j.healun.2021.05.015
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Zs.A 2056: Show issues

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Article ; Online: Cyclooxygenase-2 Expression in Non-Small Cell Lung Cancer Correlates With Hypertrophic Osteoarthropathy.

Rotas, Ioannis / Cito, Giovanni / Letovanec, Igor / Christodoulou, Michel / Perentes, Jean Y

The Annals of thoracic surgery

2016 Volume 101, Issue 2, Page(s) e51–3

Abstract: Hypertrophic osteoarthrpathy (HO) is a rare paraneoplasic syndrome associated with non-small cell lung cancer (NSCLC). The pathophysiology of HO is unknown but was recently related to enhanced levels of urine prostaglandin E2 (PGE2). Here, we report the ... ...

Abstract	Hypertrophic osteoarthrpathy (HO) is a rare paraneoplasic syndrome associated with non-small cell lung cancer (NSCLC). The pathophysiology of HO is unknown but was recently related to enhanced levels of urine prostaglandin E2 (PGE2). Here, we report the case of a patient that presented HO in association with a resectable left upper lobe NSCLC. Following surgery and adjuvant chemotherapy, HO resolved and did not recur with development of a brain metastasis 1 year later. Interestingly, tumor cyclooxygenase-2, an enzyme responsible the synthesis of PGE2, was expressed in the primary tumor but not in the resected metastasis.
MeSH term(s)	Aged ; Carcinoma, Non-Small-Cell Lung/metabolism ; Cyclooxygenase 2/biosynthesis ; Humans ; Lung Neoplasms/metabolism ; Male ; Osteoarthropathy, Secondary Hypertrophic/metabolism ; Paraneoplastic Syndromes/metabolism
Chemical Substances	Cyclooxygenase 2 (EC 1.14.99.1)
Language	English
Publishing date	2016-02
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	211007-6
ISSN	1552-6259 ; 0003-4975
ISSN (online)	1552-6259
ISSN	0003-4975
DOI	10.1016/j.athoracsur.2015.09.023
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Article ; Online: Low-dose photodynamic therapy promotes a cytotoxic immunological response in a murine model of pleural mesothelioma.

Cavin, Sabrina / Gkasti, Aspasia / Faget, Julien / Hao, Yameng / Letovanec, Igor / Reichenbach, Maxime / Gonzalez, Michel / Krueger, Thorsten / Dyson, Paul J / Meylan, Etienne / Perentes, Jean Y

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery

2020 Volume 58, Issue 4, Page(s) 783–791

Abstract: Objectives: Malignant pleural mesothelioma (MPM) is a deadly disease with limited treatment options. Approaches to enhance patient immunity against MPM have been tested but shown variable results. Previously, we have demonstrated interesting vascular ... ...

Abstract	Objectives: Malignant pleural mesothelioma (MPM) is a deadly disease with limited treatment options. Approaches to enhance patient immunity against MPM have been tested but shown variable results. Previously, we have demonstrated interesting vascular modulating properties of low-dose photodynamic therapy (L-PDT) on MPM. Here, we hypothesized that L-PDT vascular modulation could favour immune cell extravasation in MPM and improve tumour control in combination with immune checkpoint inhibitors. Methods: First, we assessed the impact of L-PDT on vascular endothelial E-selectin expression, a key molecule for immune cell extravasation, in vitro and in a syngeneic murine model of MPM. Second, we characterized the tumour immune cell infiltrate by 15-colour flow cytometry analysis 2 and 7 days after L-PDT treatment of the murine MPM model. Third, we determined how L-PDT combined with immune checkpoint inhibitor anti-CTLA4 affected tumour growth in a murine MPM model. Results: L-PDT significantly enhanced E-selectin expression by endothelial cells in vitro and in vivo. This correlated with increased CD8+ T cells and activated antigen-presenting cells (CD11b+ dendritic cells and macrophages) infiltration in MPM. Also, compared to anti-CTLA4 that only affects tumour growth, the combination of L-PDT with anti-CTLA4 caused complete MPM regression in 37.5% of animals. Conclusions: L-PDT enhances E-selectin expression in the MPM endothelium, which favours immune infiltration of tumours. The combination of L-PDT with immune checkpoint inhibitor anti-CTLA4 allows best tumour control and regression.
MeSH term(s)	Animals ; Cell Line, Tumor ; Disease Models, Animal ; Endothelial Cells ; Humans ; Lung Neoplasms/drug therapy ; Mesothelioma/drug therapy ; Mice ; Photochemotherapy ; Pleural Neoplasms/drug therapy
Language	English
Publishing date	2020-05-05
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639293-3
ISSN	1873-734X ; 1010-7940 ; 1567-4258
ISSN (online)	1873-734X
ISSN	1010-7940 ; 1567-4258
DOI	10.1093/ejcts/ezaa145
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Article ; Online: Chemo-manipulation of tumor blood vessels by a metal-based anticancer complex enhances antitumor therapy.

Riedel, Tina / Cavin, Sabrina / van den Bergh, Hubert / Krueger, Thorsten / Liaudet, Lucas / Ris, Hans-Beat / Dyson, Paul J / Perentes, Jean Y

Scientific reports

2018 Volume 8, Issue 1, Page(s) 10263

Abstract: Human pleural mesothelioma is an incurable and chemoresistant cancer. Using a nude mouse xenograft model of human pleural mesothelioma, we show that RAPTA-T, a compound undergoing preclinical evaluation, enhances tumor vascular function by decreasing ... ...

Abstract	Human pleural mesothelioma is an incurable and chemoresistant cancer. Using a nude mouse xenograft model of human pleural mesothelioma, we show that RAPTA-T, a compound undergoing preclinical evaluation, enhances tumor vascular function by decreasing blood vessel tortuosity and dilation, while increasing the coverage of endothelial cells by pericytes and vessel perfusion within tumors. This in turn significantly reduces the interstitial fluid pressure and increases oxygenation in the tumor. Consequently, RAPTA-T pre-treatment followed by the application of cisplatin or liposomal cisplatin (Lipoplatin) leads to increased levels of the cytotoxin in the tumor and enhanced mesothelioma growth inhibition. We demonstrate that the vascular changes induced by RAPTA-T are related, in part, to the inhibition of poly-(ADP-ribose) polymerase 1 (PARP-1) which is associated to tumor vascular stabilization. These findings suggest novel therapeutic implications for RAPTA-T to create conditions for superior drug uptake and efficacy of approved cytotoxic anti-cancer drugs in malignant pleural mesothelioma and potentially other chemoresistant tumors.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Cisplatin/pharmacology ; Drug Synergism ; Drug Therapy, Combination ; Endothelial Cells/drug effects ; Endothelial Cells/pathology ; Female ; Humans ; Lung Neoplasms/blood supply ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology ; Mesothelioma/blood supply ; Mesothelioma/drug therapy ; Mesothelioma/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Nude ; Organometallic Compounds/pharmacology ; Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents ; Organometallic Compounds ; RAPTA-T ; PARP1 protein, human (EC 2.4.2.30) ; Poly (ADP-Ribose) Polymerase-1 (EC 2.4.2.30) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2018-07-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-28589-2
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Article ; Online: Vascular-targeted low dose photodynamic therapy stabilizes tumor vessels by modulating pericyte contractility.

Cavin, Sabrina / Riedel, Tina / Rosskopfova, Petra / Gonzalez, Michel / Baldini, Greg / Zellweger, Matthieu / Wagnières, Georges / Dyson, Paul J / Ris, Hans-Beat / Krueger, Thorsten / Perentes, Jean Y

Lasers in surgery and medicine

2019 Volume 51, Issue 6, Page(s) 550–561

Abstract: Vascular-targeted low-dose photodynamic therapy (L-PDT) was shown to improve chemotherapy distribution in malignant pleural tumors such as malignant pleural mesothelioma (MPM). However, the mechanisms triggered by L-PDT on the tumor vasculature are still ...

Abstract	Vascular-targeted low-dose photodynamic therapy (L-PDT) was shown to improve chemotherapy distribution in malignant pleural tumors such as malignant pleural mesothelioma (MPM). However, the mechanisms triggered by L-PDT on the tumor vasculature are still debated. In pericyte and endothelial cell co-cultures, we show that pericytes exhibit enhanced sensitivity towards L-PDT compared to endothelial cells, displaying actin stress fibers and cellular contraction via Rho/ROCK kinase signaling myosin light chain and focal adhesion kinase phosphorylation (MLC-P, FAK-P). We then confirm, in two separate MPM models, in mice the phosphorylation of the MLC in pericytes specifically following L-PDT. Furthermore, while L-PDT does not affect tumor vascular density or diameter, we show that it enhances tumor vascular pericyte coverage, leads to a drop in tumor interstitial fluid pressure and enhances the transport of FITC-dextran throughout tumors. In conclusion, L-PDT has the potential to stabilize the tumor vascular bed which improves vascular transport. The mechanism described in the present study may help translate and optimize this approach in patients. Lasers Surg. Med. 51:550-561, 2019. © 2019 Wiley Periodicals, Inc.
MeSH term(s)	Animals ; Cell Culture Techniques ; Coculture Techniques ; Disease Models, Animal ; Endothelial Cells/drug effects ; Female ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology ; Mesothelioma/drug therapy ; Mesothelioma/pathology ; Mesothelioma, Malignant ; Pericytes/drug effects ; Photochemotherapy ; Photosensitizing Agents/therapeutic use ; Pleural Neoplasms/drug therapy ; Pleural Neoplasms/pathology ; Verteporfin/therapeutic use
Chemical Substances	Photosensitizing Agents ; Verteporfin (0X9PA28K43)
Language	English
Publishing date	2019-02-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604493-1
ISSN	1096-9101 ; 0196-8092
ISSN (online)	1096-9101
ISSN	0196-8092
DOI	10.1002/lsm.23069
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Article ; Online: Visualizing anti-tumor immune responses in vivo.

Perentes, Jean Y / Duda, Dan G / Jain, Rakesh K

Disease models & mechanisms

2009 Volume 2, Issue 3-4, Page(s) 107–110

Abstract: Real-time imaging of stromal and immune cells in tumors is an emerging field that will greatly help us to understand the role of these non-malignant tumor components in tumor progression and therapy. ...

Abstract	Real-time imaging of stromal and immune cells in tumors is an emerging field that will greatly help us to understand the role of these non-malignant tumor components in tumor progression and therapy.
MeSH term(s)	Animals ; Disease Models, Animal ; Disease Progression ; Humans ; Immune System ; Immunotherapy/methods ; Lymphocyte Activation ; Medical Oncology/methods ; Mice ; Microscopy/methods ; Models, Biological ; Neoplasms/immunology ; Neoplasms/therapy ; Neovascularization, Pathologic ; Stromal Cells/cytology
Language	English
Publishing date	2009-02-24
Publishing country	England
Document type	Editorial
ZDB-ID	2451104-3
ISSN	1754-8411 ; 1754-8403
ISSN (online)	1754-8411
ISSN	1754-8403
DOI	10.1242/dmm.001842
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